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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="Table of Contents Page" href="/books/n/pdqcis/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-pdqcis-lrg.png" alt="Cover of PDQ Cancer Information Summaries" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>PDQ Cancer Information Summaries [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK65918_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK65918_dtls__"><div>Bethesda (MD): <a href="http://www.cancer.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Cancer Institute (US)</a>; 2002-.</div></div><div class="half_rhythm"></div><div class="bk_noprnt"><form method="get" action="/books/n/pdqcis/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search this book" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search this book" submit="false" style="padding: 0.1em 0.4em;" /></div></form></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK65918_"><span class="title" itemprop="name">Urethral Cancer Treatment (PDQ®)</span></h1><div class="subtitle whole_rhythm">Health Professional Version</div><p class="contrib-group"><span itemprop="author">PDQ Adult Treatment Editorial Board</span>.</p><p class="small">Published online: July 19, 2024.</p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="_abs_rndgid_" itemprop="description"><p id="CDR0000062925__228">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of urethral cancer. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.</p><p id="CDR0000062925__229">This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).</p></div><div id="CDR0000062925__1"><h2 id="_CDR0000062925__1_">General Information About Urethral Cancer</h2><div id="CDR0000062925__198"><h3>Incidence and Mortality</h3><p id="CDR0000062925__199">Urethral cancer is rare. The annual incidence rate for urethral cancer in the Surveillance, Epidemiology, and End Results (SEER) Program database from 1973 to 2002 in the United States was 4.3 per million for men and 1.5 per million for women, with downward trends over the three decades.[<a class="bk_pop" href="#CDR0000062925_rl_1_1">1</a>] The incidence was twice as high in African American individuals as in White individuals (5 per million vs. 2.5 per million). Urethral cancers appear to be associated with human papillomavirus (HPV) infection, particularly HPV16, a strain known to cause cervical cancer.[<a class="bk_pop" href="#CDR0000062925_rl_1_2">2</a>,<a class="bk_pop" href="#CDR0000062925_rl_1_3">3</a>]</p><p id="CDR0000062925__200">Because urethral cancer is rare, nearly all information about its treatment and the outcomes of therapy is derived from retrospective, single-center case series, which represents a very low <a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000810039/" class="def">Level of evidence C3</a>. Most information comes from cases accumulated over many decades at major academic centers.</p></div><div id="CDR0000062925__201"><h3>Anatomy</h3><p id="CDR0000062925__202">The female urethra is largely contained within the anterior vaginal wall. In adults, it is about 4 cm in length. </p><p id="CDR0000062925__203">The male urethra, which averages about 20 cm in length, is divided into distal and proximal portions. The distal urethra, which extends from the tip of the penis to just before the prostate, includes the meatus, the fossa navicularis, the penile or pendulous urethra, and the bulbar urethra. The proximal urethra, which extends from the bulbar urethra to the bladder neck, includes the membranous urethra and the prostatic urethra.</p><div id="CDR0000062925__227" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Anatomy%20of%20the%20male%20urinary%20system%20(left%20panel)%20and%20female%20urinary%20system%20(right%20panel)%20showing%20the%20kidneys%2C%20ureters%2C%20bladder%2C%20and%20urethra&p=BOOKS&id=605091_CDR0000765031.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK65918/bin/CDR0000765031.jpg" alt="Anatomy of the male urinary system (left panel) and female urinary system (right panel); two-panel drawing showing the right and left kidneys, the ureters, the bladder filled with urine, and the urethra. The inside of the left kidney shows the renal pelvis. An inset shows the renal tubules and urine. Also shown are the prostate and penis (left panel) and the uterus (right panel)." class="tileshop" title="Click on image to zoom" /></a></div><div class="caption"><p>Anatomy of the male urinary system (left panel) and female urinary system (right panel) showing the kidneys, ureters, bladder, and urethra. The inside of the left kidney shows the renal pelvis. An inset shows the renal tubules and urine. Also shown are the prostate and penis (left panel) and the uterus (right panel). Urine is made in the renal tubules and collects in the renal pelvis of each kidney. The urine flows from the kidneys through the ureters to the bladder. The urine is stored in the bladder until it leaves the body through the urethra.</p></div></div></div><div id="CDR0000062925__205"><h3>Prognosis</h3><p id="CDR0000062925__206">The prognosis of urethral cancer depends on the following factors:[<a class="bk_pop" href="#CDR0000062925_rl_1_4">4</a>-<a class="bk_pop" href="#CDR0000062925_rl_1_6">6</a>] </p><ul id="CDR0000062925__207"><li class="half_rhythm"><div>Anatomical location. </div></li><li class="half_rhythm"><div>Size. </div></li><li class="half_rhythm"><div>Stage. </div></li><li class="half_rhythm"><div>Depth of invasion.</div></li></ul><p id="CDR0000062925__208">Superficial tumors in the distal urethra in both women and men are generally curable. However, deeply invasive lesions are rarely curable by any combination of therapies.
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In men, the prognosis of tumors in the distal (pendulous) urethra is better than for tumors of the proximal (bulbomembranous) and prostatic urethra, which tend to present at more advanced stages.[<a class="bk_pop" href="#CDR0000062925_rl_1_7">7</a>,<a class="bk_pop" href="#CDR0000062925_rl_1_8">8</a>] Likewise, distal urethral tumors tend to occur at earlier stages in women and to have a better prognosis than proximal tumors.[<a class="bk_pop" href="#CDR0000062925_rl_1_9">9</a>] </p></div><div id="CDR0000062925_rl_1"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062925_rl_1_1">Swartz MA, Porter MP, Lin DW, et al.: Incidence of primary urethral carcinoma in the United States. Urology 68 (6): 1164-8, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/17141838" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17141838</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_1_2">Wiener JS, Liu ET, Walther PJ: Oncogenic human papillomavirus type 16 is associated with squamous cell cancer of the male urethra. Cancer Res 52 (18): 5018-23, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1325290" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1325290</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_1_3">Wiener JS, Walther PJ: A high association of oncogenic human papillomaviruses with carcinomas of the female urethra: polymerase chain reaction-based analysis of multiple histological types. J Urol 151 (1): 49-53, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/8254831" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8254831</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_1_4">Urethra. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp. 767–76.</div></li><li><div class="bk_ref" id="CDR0000062925_rl_1_5">Rabbani F: Prognostic factors in male urethral cancer. Cancer 117 (11): 2426-34, 2011. [<a href="https://pubmed.ncbi.nlm.nih.gov/24048790" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24048790</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_1_6">Dalbagni G, Zhang ZF, Lacombe L, et al.: Female urethral carcinoma: an analysis of treatment outcome and a plea for a standardized management strategy. Br J Urol 82 (6): 835-41, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9883221" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9883221</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_1_7">Dinney CP, Johnson DE, Swanson DA, et al.: Therapy and prognosis for male anterior urethral carcinoma: an update. Urology 43 (4): 506-14, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/8154072" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8154072</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_1_8">Dalbagni G, Zhang ZF, Lacombe L, et al.: Male urethral carcinoma: analysis of treatment outcome. Urology 53 (6): 1126-32, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10367840" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10367840</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_1_9">Gheiler EL, Tefilli MV, Tiguert R, et al.: Management of primary urethral cancer. Urology 52 (3): 487-93, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9730466" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9730466</span></a>]</div></li></ol></div></div><div id="CDR0000062925__4"><h2 id="_CDR0000062925__4_">Cellular Classification of Urethral Cancer</h2><p id="CDR0000062925__178">In an analysis of Surveillance, Epidemiology, and End Results (SEER) Program data from 1973 to 2002, the most common histological types of urethral cancer were the following:[<a class="bk_pop" href="#CDR0000062925_rl_4_1">1</a>] </p><ul id="CDR0000062925__209"><li class="half_rhythm"><div>Transitional cell (55%). </div></li><li class="half_rhythm"><div>Squamous cell (21.5%). </div></li><li class="half_rhythm"><div>Adenocarcinoma (16.4%). </div></li></ul><p id="CDR0000062925__210">Other cell types, such as melanoma, were extremely rare.[<a class="bk_pop" href="#CDR0000062925_rl_4_1">1</a>]</p><p id="CDR0000062925__5">The female urethra is lined by transitional cell mucosa proximally and
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stratified squamous cells distally. Therefore, transitional cell carcinoma is most common in the proximal urethra, and squamous cell carcinoma predominates
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in the distal urethra. Adenocarcinoma may occur in both locations and arises
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from metaplasia of the numerous periurethral glands.
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</p><p id="CDR0000062925__6">The male urethra is lined by transitional cells in its prostatic and membranous
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portion and stratified columnar epithelium to stratified squamous epithelium in
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the bulbous and penile portions. The submucosa of the urethra contains
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numerous glands. Therefore, urethral cancer in men can manifest the
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histological characteristics of transitional cell carcinoma, squamous cell
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carcinoma, or adenocarcinoma.
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</p><p id="CDR0000062925__7">Except for the prostatic urethra, where transitional cell carcinoma is most
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common, squamous cell carcinoma is the predominant histology of urethral
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neoplasms. Because transitional cell carcinoma of the prostatic urethra may be associated with transitional cell carcinoma of the bladder and/or
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transitional cell carcinoma arising in prostatic ducts, it is often treated similarly to these primaries and should be separated from
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the more distal carcinomas of the urethra.
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</p><div id="CDR0000062925_rl_4"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062925_rl_4_1">Swartz MA, Porter MP, Lin DW, et al.: Incidence of primary urethral carcinoma in the United States. Urology 68 (6): 1164-8, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/17141838" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17141838</span></a>]</div></li></ol></div></div><div id="CDR0000062925__8"><h2 id="_CDR0000062925__8_">Stage Information for Urethral Cancer</h2><p id="CDR0000062925__9">Prognosis and treatment decisions are determined by the following:[<a class="bk_pop" href="#CDR0000062925_rl_8_1">1</a>]</p><ul id="CDR0000062925__211"><li class="half_rhythm"><div>The anatomical location of the primary tumor.</div></li><li class="half_rhythm"><div>The size of the tumor.</div></li><li class="half_rhythm"><div>The stage of the cancer.</div></li><li class="half_rhythm"><div>The depth of invasion of the tumor.</div></li></ul><p id="CDR0000062925__212">The histology of the
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primary tumor is of less importance in estimating response to therapy and
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survival.[<a class="bk_pop" href="#CDR0000062925_rl_8_2">2</a>]
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Endoscopic examination, urethrography, and magnetic resonance imaging are useful in determining the local extent of the tumor.[<a class="bk_pop" href="#CDR0000062925_rl_8_3">3</a>,<a class="bk_pop" href="#CDR0000062925_rl_8_4">4</a>] </p><div id="CDR0000062925__10"><h3>Distal Urethral Cancer</h3><p id="CDR0000062925__11">These lesions are often superficial.
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</p><ul id="CDR0000062925__73"><li class="half_rhythm"><div>Female: Lesions of the distal third of the urethra.</div></li><li class="half_rhythm"><div>Male: Anterior, or penile, portion of the urethra, including the meatus and
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pendulous urethra.
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</div></li></ul></div><div id="CDR0000062925__15"><h3>Proximal Urethral Cancer</h3><p id="CDR0000062925__16">These lesions are often deeply invasive.
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</p><ul id="CDR0000062925__74"><li class="half_rhythm"><div>Female: Lesions not clearly limited to the distal
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third of the urethra.
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</div></li><li class="half_rhythm"><div>Male: Bulbomembranous and prostatic urethra.</div></li></ul></div><div id="CDR0000062925__19"><h3>Urethral Cancer Associated With Invasive Bladder Cancer</h3><p id="CDR0000062925__20">Approximately 5% to 10% of men with cystectomy for bladder cancer may have or may develop urethral cancer distal to the urogenital diaphragm.[<a class="bk_pop" href="#CDR0000062925_rl_8_5">5</a>,<a class="bk_pop" href="#CDR0000062925_rl_8_6">6</a>]
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</p></div><div id="CDR0000062925__116"><h3>American Joint Committee on Cancer (AJCC) Stage Groupings and TNM Definitions</h3><p id="CDR0000062925__95">The AJCC has designated staging by TNM
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(tumor, node, metastasis) classification to define urethral cancer.[<a class="bk_pop" href="#CDR0000062925_rl_8_1">1</a>]
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</p><div id="CDR0000062925__233"><h4>Male penile urethra and female urethra</h4><div id="CDR0000062925__234" class="table"><h3><span class="title">Table 1. Definitions of TNM Stages 0is and 0a<sup>a</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65918/table/CDR0000062925__234/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062925__234_lrgtbl__"><table class="no_margin"><thead><tr><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Stage</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">TNM</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Description</th></tr></thead><tbody><tr><td colspan="1" rowspan="3" style="vertical-align:top;">0is</td><td colspan="1" rowspan="3" style="vertical-align:top;">Tis, N0, M0</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tis = Carcinoma <i>in situ</i>.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N0 = No regional lymph node metastasis.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">M0 = No distant metastasis.</td></tr><tr><td colspan="1" rowspan="3" style="vertical-align:top;">0a</td><td colspan="1" rowspan="3" style="vertical-align:top;">Ta, N0, M0</td><td colspan="1" rowspan="1" style="vertical-align:top;">Ta = Noninvasive papillary carcinoma.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N0 = No regional lymph node metastasis. </td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">M0 = No distant metastasis.</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">T = primary tumor; N = regional lymph node; M = distant metastasis.</p></div></dd><dt></dt><dd><div><p class="no_margin"><sup>a</sup>Reprinted with permission from AJCC: Urethra. In: Amin MB, Edge SB, Greene FL, et al., eds.: <i>AJCC Cancer Staging Manual</i>. 8th ed. New York, NY: Springer, 2017, pp. 767–76.</p></div></dd></dl></div></div></div><div id="CDR0000062925__239" class="table"><h3><span class="title">Table 2. Definition of TNM Stage I<sup>a</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65918/table/CDR0000062925__239/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062925__239_lrgtbl__"><table class="no_margin"><thead><tr><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Stage</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">TNM</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Description</th></tr></thead><tbody><tr><td colspan="1" rowspan="3" style="vertical-align:top;">I</td><td colspan="1" rowspan="3" style="vertical-align:top;">T1, N0, M0</td><td colspan="1" rowspan="1" style="vertical-align:top;">T1 = Tumor invades subepithelial connective tissue.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N0 = No regional lymph node metastasis.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">M0 = No distant metastasis.</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">T = primary tumor; N = regional lymph node; M = distant metastasis.</p></div></dd><dt></dt><dd><div><p class="no_margin"><sup>a</sup>Reprinted with permission from AJCC: Urethra. In: Amin MB, Edge SB, Greene FL, et al., eds.: <i>AJCC Cancer Staging Manual</i>. 8th ed. New York, NY: Springer, 2017, pp. 767–76.</p></div></dd></dl></div></div></div><div id="CDR0000062925__240" class="table"><h3><span class="title">Table 3. Definition of TNM Stage II<sup>a</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65918/table/CDR0000062925__240/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062925__240_lrgtbl__"><table class="no_margin"><thead><tr><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Stage</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">TNM</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Description</th></tr></thead><tbody><tr><td colspan="1" rowspan="3" style="vertical-align:top;">II</td><td colspan="1" rowspan="3" style="vertical-align:top;">T2, N0, M0</td><td colspan="1" rowspan="1" style="vertical-align:top;">T2 = Tumor invades any of the following: corpus spongiosum, periurethral muscle.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N0 = No regional lymph node metastasis.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">M0 = No distant metastasis.</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">T = primary tumor; N = regional lymph node; M = distant metastasis.</p></div></dd><dt></dt><dd><div><p class="no_margin"><sup>a</sup>Reprinted with permission from AJCC: Urethra. In: Amin MB, Edge SB, Greene FL, et al., eds.: <i>AJCC Cancer Staging Manual</i>. 8th ed. New York, NY: Springer, 2017, pp. 767–76.</p></div></dd></dl></div></div></div><div id="CDR0000062925__241" class="table"><h3><span class="title">Table 4. Definitions of TNM Stage III<sup>a</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65918/table/CDR0000062925__241/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062925__241_lrgtbl__"><table class="no_margin"><thead><tr><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Stage</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">TNM</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Description</th></tr></thead><tbody><tr><td colspan="1" rowspan="12" style="vertical-align:top;">III</td><td colspan="1" rowspan="3" style="vertical-align:top;">T1, N1, M0</td><td colspan="1" rowspan="1" style="vertical-align:top;">T1 = Tumor invades subepithelial connective tissue.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N1 = Single regional lymph node metastasis in the inguinal region or true pelvis (perivesical, obturator, internal [hypogastric] and external iliac), or presacral lymph node. </td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">M0 = No distant metastasis.</td></tr><tr><td colspan="1" rowspan="3" style="vertical-align:top;">T2, N1, M0</td><td colspan="1" rowspan="1" style="vertical-align:top;">T2 = Tumor invades any of the following: corpus spongiosum, periurethral muscle.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N1 = Single regional lymph node metastasis in the inguinal region or true pelvis (perivesical, obturator, internal [hypogastric] and external iliac), or presacral lymph node. </td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">M0 = No distant metastasis.</td></tr><tr><td colspan="1" rowspan="3" style="vertical-align:top;">T3, N0, M0</td><td colspan="1" rowspan="1" style="vertical-align:top;">T3 = Tumor invades any of the following: corpus cavernosum, anterior vagina.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N0 = No regional lymph node metastasis.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">M0 = No distant metastasis.</td></tr><tr><td colspan="1" rowspan="3" style="vertical-align:top;">T3, N1, M0</td><td colspan="1" rowspan="1" style="vertical-align:top;">T3 = Tumor invades any of the following: corpus cavernosum, anterior vagina.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N1 = Single regional lymph node metastasis in the inguinal region or true pelvis (perivesical, obturator, internal [hypogastric] and external iliac), or presacral lymph node.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">M0 = No distant metastasis.</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">T = primary tumor; N = regional lymph node; M = distant metastasis.</p></div></dd><dt></dt><dd><div><p class="no_margin"><sup>a</sup>Reprinted with permission from AJCC: Urethra. In: Amin MB, Edge SB, Greene FL, et al., eds.: <i>AJCC Cancer Staging Manual</i>. 8th ed. New York, NY: Springer, 2017, pp. 767–76.</p></div></dd></dl></div></div></div><div id="CDR0000062925__242" class="table"><h3><span class="title">Table 5. Definitions of TNM Stage IV<sup>a</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65918/table/CDR0000062925__242/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062925__242_lrgtbl__"><table class="no_margin"><thead><tr><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Stage</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">TNM</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Description</th></tr></thead><tbody><tr><td colspan="1" rowspan="22" style="vertical-align:top;">IV</td><td colspan="1" rowspan="3" style="vertical-align:top;">T4, N0, M0</td><td colspan="1" rowspan="1" style="vertical-align:top;">T4 = Tumor invades other adjacent organs (e.g., invasion of the bladder wall).</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N0 = No regional lymph node metastasis.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">M0 = No distant metastasis.</td></tr><tr><td colspan="1" rowspan="3" style="vertical-align:top;">T4, N1, M0</td><td colspan="1" rowspan="1" style="vertical-align:top;">T4 = Tumor invades other adjacent organs (e.g., invasion of the bladder wall).</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N1 = Single regional lymph node metastasis in the inguinal region or true pelvis (perivesical, obturator, internal [hypogastric] and external iliac), or presacral lymph node.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">M0 = No distant metastasis.</td></tr><tr><td colspan="1" rowspan="10" style="vertical-align:top;">Any T, N2, M0</td><td colspan="1" rowspan="1" style="vertical-align:top;">TX = Primary tumor cannot be assessed.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T0 = No evidence of primary tumor.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Ta = Noninvasive papillary carcinoma.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Tis = Carcinoma <i>in situ</i>.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T1 = Tumor invades subepithelial connective tissue.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T2 = Tumor invades any of the following: corpus spongiosum, periurethral muscle.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T3 = Tumor invades any of the following: corpus cavernosum, anterior vagina.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T4 = Tumor invades other adjacent organs (e.g., invasion of the bladder wall).</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N2 = Multiple regional lymph node metastasis in the inguinal region or true pelvis (perivesical, obturator, internal [hypogastric] and external iliac), or presacral lymph node.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">M0 = No distant metastasis.</td></tr><tr><td colspan="1" rowspan="6" style="vertical-align:top;">Any T, Any N, M1</td><td colspan="1" rowspan="1" style="vertical-align:top;">Any T = See descriptions above in this table, stage IV, Any T, N2, M0.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">NX = Regional lymph nodes cannot be assessed.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N0 = No regional lymph node metastasis.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N1 = Single regional lymph node metastasis in the inguinal region or true pelvis (perivesical, obturator, internal [hypogastric] and external iliac), or presacral lymph node.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N2 = Multiple regional lymph node metastasis in the inguinal region or true pelvis (perivesical, obturator, internal [hypogastric] and external iliac), or presacral lymph node.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">M1 = Distant metastasis.</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">T = primary tumor; N = regional lymph node; M = distant metastasis.</p></div></dd><dt></dt><dd><div><p class="no_margin"><sup>a</sup>Reprinted with permission from AJCC: Urethra. In: Amin MB, Edge SB, Greene FL, et al., eds.: <i>AJCC Cancer Staging Manual</i>. 8th ed. New York, NY: Springer, 2017, pp. 767–76.</p></div></dd></dl></div></div></div></div></div><div id="CDR0000062925_rl_8"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062925_rl_8_1">Urethra. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp. 767–76.</div></li><li><div class="bk_ref" id="CDR0000062925_rl_8_2">Grigsby PW, Corn BW: Localized urethral tumors in women: indications for conservative versus exenterative therapies. J Urol 147 (6): 1516-20, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1593679" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1593679</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_8_3">Ryu J, Kim B: MR imaging of the male and female urethra. Radiographics 21 (5): 1169-85, 2001 Sep-Oct. [<a href="https://pubmed.ncbi.nlm.nih.gov/11553824" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11553824</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_8_4">Pavlica P, Barozzi L, Menchi I: Imaging of male urethra. Eur Radiol 13 (7): 1583-96, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/12835971" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12835971</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_8_5">Mark JR, Hurwitz M, Gomella LG: Cancer of the urethra and penis. In: DeVita VT Jr, Lawrence TS, Rosenberg SA, et al., eds.: DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer, 2019, pp 1136-44.</div></li><li><div class="bk_ref" id="CDR0000062925_rl_8_6">Erckert M, Stenzl A, Falk M, et al.: Incidence of urethral tumor involvement in 910 men with bladder cancer. World J Urol 14 (1): 3-8, 1996. [<a href="https://pubmed.ncbi.nlm.nih.gov/8646239" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8646239</span></a>]</div></li></ol></div></div><div id="CDR0000062925__179"><h2 id="_CDR0000062925__179_">Treatment Option Overview for Urethral Cancer</h2><p id="CDR0000062925__180">Information about the treatment of urethral cancer and the outcomes of therapy is derived from retrospective, single-center case series and represents a very low <a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000810039/" class="def">Level of evidence C3</a>. Most of this information comes from the small numbers of cases accumulated over many decades at major academic centers. Therefore, the treatment in these reports is usually not standardized and spans eras of shifting supportive care practices. Because urethral cancer is rare, its treatment may also reflect extrapolation from the management of other urothelial malignancies, such as bladder cancer in the case of transitional cancers and anal cancer in the case of squamous cell carcinomas. </p><div id="CDR0000062925__181"><h3>Surgery</h3><p id="CDR0000062925__182">Surgery is the mainstay of therapy for urethral cancers in both women and men.[<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000810039/" class="def">Level of evidence C3</a>] The surgical approach depends on tumor stage and anatomic location, and tumor grade plays a less important role in treatment decisions.[<a class="bk_pop" href="#CDR0000062925_rl_179_1">1</a>,<a class="bk_pop" href="#CDR0000062925_rl_179_2">2</a>] Although the traditional recommendation has been to achieve a 2-cm tumor-free margin, the optimal surgical margin has not been rigorously studied and is not well defined. The role of lymph node dissection is not clear in the absence of clinical involvement, and the role of prophylactic dissection is controversial.[<a class="bk_pop" href="#CDR0000062925_rl_179_2">2</a>] Radiation therapy and/or chemotherapy may be added in some cases in patients with extensive disease or in an attempt at organ preservation. However, there are no clear guidelines for patient selection, and the low level of evidence precludes confident conclusions about their incremental benefit.[<a class="bk_pop" href="#CDR0000062925_rl_179_2">2</a>,<a class="bk_pop" href="#CDR0000062925_rl_179_3">3</a>] </p><p id="CDR0000062925__183">Ablative techniques, such as transurethral resection, electroresection and fulguration, or laser vaporization-coagulation, are used to preserve organ function in cases of superficial anterior tumors, although the supporting literature is scant.[<a class="bk_pop" href="#CDR0000062925_rl_179_2">2</a>]</p></div><div id="CDR0000062925__184"><h3>Radiation Therapy</h3><p id="CDR0000062925__185">External-beam radiation therapy, brachytherapy, or a combination is sometimes used as the primary therapy for early-stage proximal urethral cancers, particularly in women.[<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000810039/" class="def">Level of evidence C3</a>] Brachytherapy may be delivered with low-dose-rate iridium Ir 192 sources using a template or urethral catheter. Definitive radiation is also sometimes used for advanced-stage tumors, but because monotherapy of large tumors has shown poor tumor control, it is more frequently incorporated into combined modality therapy after surgery or with chemotherapy.[<a class="bk_pop" href="#CDR0000062925_rl_179_4">4</a>] There are no head-to-head comparisons of these various approaches, and patient selection may explain differences in outcomes among the regimens.[<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000810039/" class="def">Level of evidence C3</a>] </p><p id="CDR0000062925__186">The most commonly used tumor doses are in the range of 60 Gy to 70 Gy. Severe complication rates for definitive radiation therapy are about 16% to 20% and include fistula development, especially for large tumors invading the vagina, bladder, or rectum. Urethral strictures also occur in the setting of urethral-sparing treatment. Toxicity rates increase at doses greater than 65 Gy to 70 Gy. Intensity-modulated radiation therapy has become more common in an attempt to decrease local morbidity of the radiation.[<a class="bk_pop" href="#CDR0000062925_rl_179_4">4</a>]</p></div><div id="CDR0000062925__187"><h3>Chemotherapy</h3><p id="CDR0000062925__219">The literature on chemotherapy for urethral carcinoma is anecdotal in nature and restricted to retrospective, single-center case series or case reports.[<a class="bk_pop" href="#CDR0000062925_rl_179_5">5</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000810039/" class="def">Level of evidence C3</a>] A wide variety of agents used alone or in combination have been reported over the years, and their use has largely been extrapolated from experience with other urinary tract tumors. </p><p id="CDR0000062925__220">For squamous cell cancers, agents that have been used in penile cancer or anal carcinoma include the following:[<a class="bk_pop" href="#CDR0000062925_rl_179_3">3</a>,<a class="bk_pop" href="#CDR0000062925_rl_179_5">5</a>]</p><ul id="CDR0000062925__221"><li class="half_rhythm"><div>Cisplatin.</div></li><li class="half_rhythm"><div>Fluorouracil.</div></li><li class="half_rhythm"><div>Bleomycin.</div></li><li class="half_rhythm"><div>Methotrexate.</div></li><li class="half_rhythm"><div>Irinotecan.</div></li><li class="half_rhythm"><div>Gemcitabine.</div></li><li class="half_rhythm"><div>Paclitaxel.</div></li><li class="half_rhythm"><div>Docetaxel.</div></li><li class="half_rhythm"><div>Mitomycin.</div></li></ul><p id="CDR0000062925__223">Chemotherapy for transitional cell urethral tumors is extrapolated from experience with transitional cell bladder tumors and, therefore, usually contains the following:[<a class="bk_pop" href="#CDR0000062925_rl_179_1">1</a>,<a class="bk_pop" href="#CDR0000062925_rl_179_4">4</a>-<a class="bk_pop" href="#CDR0000062925_rl_179_7">7</a>]</p><ul id="CDR0000062925__224"><li class="half_rhythm"><div> Methotrexate, vinblastine, doxorubicin, and cisplatin.</div></li><li class="half_rhythm"><div>Paclitaxel.</div></li><li class="half_rhythm"><div>Carboplatin.</div></li><li class="half_rhythm"><div>Ifosfamide, with occasional complete responses. </div></li></ul><p id="CDR0000062925__197">Chemotherapy has been used alone for metastatic disease or in combination with radiation therapy and/or surgery for locally advanced urethral cancer. It may be used in the neoadjuvant setting with radiation therapy in an attempt to increase the resectability rate or to preserve organs.[<a class="bk_pop" href="#CDR0000062925_rl_179_3">3</a>] However, the impact of any of these regimens on survival is not known for any stage or setting. </p><div id="CDR0000062925__260"><h4>Fluorouracil dosing</h4><p id="CDR0000062925__sm_CDR0000813769_4"><div class="milestone-start" id="CDR0000062925__sm_CDR0000813769_3"></div>The <i>DPYD</i> gene encodes an enzyme that catabolizes pyrimidines and fluoropyrimidines, like capecitabine and fluorouracil. An estimated 1% to 2% of the population has germline pathogenic variants in <i>DPYD</i>, which lead to reduced DPD protein function and an accumulation of pyrimidines and fluoropyrimidines in the body.[<a class="bk_pop" href="#CDR0000062925_rl_179_8">8</a>,<a class="bk_pop" href="#CDR0000062925_rl_179_9">9</a>] Patients with the <i>DPYD*2A</i> variant who receive fluoropyrimidines may experience severe, life-threatening toxicities that are sometimes fatal. Many other <i>DPYD</i> variants have been identified, with a range of clinical effects.[<a class="bk_pop" href="#CDR0000062925_rl_179_8">8</a>-<a class="bk_pop" href="#CDR0000062925_rl_179_10">10</a>] Fluoropyrimidine avoidance or a dose reduction of 50% may be recommended based on the patient's <i>DPYD</i> genotype and number of functioning <i>DPYD</i> alleles.[<a class="bk_pop" href="#CDR0000062925_rl_179_11">11</a>-<a class="bk_pop" href="#CDR0000062925_rl_179_13">13</a>] <i>DPYD</i> genetic testing costs less than $200, but insurance coverage varies due to a lack of national guidelines.[<a class="bk_pop" href="#CDR0000062925_rl_179_14">14</a>] In addition, testing may delay therapy by 2 weeks, which would not be advisable in urgent situations. This controversial issue requires further evaluation.<div class="milestone-end"></div>[<a class="bk_pop" href="#CDR0000062925_rl_179_15">15</a>]</p></div></div><div id="CDR0000062925_rl_179"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062925_rl_179_1">Mark JR, Hurwitz M, Gomella LG: Cancer of the urethra and penis. In: DeVita VT Jr, Lawrence TS, Rosenberg SA, et al., eds.: DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer, 2019, pp 1136-44.</div></li><li><div class="bk_ref" id="CDR0000062925_rl_179_2">Karnes RJ, Breau RH, Lightner DJ: Surgery for urethral cancer. Urol Clin North Am 37 (3): 445-57, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/20674699" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20674699</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_179_3">Cohen MS, Triaca V, Billmeyer B, et al.: Coordinated chemoradiation therapy with genital preservation for the treatment of primary invasive carcinoma of the male urethra. J Urol 179 (2): 536-41; discussion 541, 2008. [<a href="https://pubmed.ncbi.nlm.nih.gov/18076921" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18076921</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_179_4">Koontz BF, Lee WR: Carcinoma of the urethra: radiation oncology. Urol Clin North Am 37 (3): 459-66, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/20674700" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20674700</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_179_5">Trabulsi EJ, Hoffman-Censits J: Chemotherapy for penile and urethral carcinoma. Urol Clin North Am 37 (3): 467-74, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/20674701" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20674701</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_179_6">VanderMolen LA, Sheehy PF, Dillman RO: Successful treatment of transitional cell carcinoma of the urethra with chemotherapy. Cancer Invest 20 (2): 206-7, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/11901541" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11901541</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_179_7">Lin CC, Hsu CH, Huang CY, et al.: Phase II trial of weekly paclitaxel, cisplatin plus infusional high dose 5-fluorouracil and leucovorin for metastatic urothelial carcinoma. J Urol 177 (1): 84-9; discussion 89, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/17162009" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17162009</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_179_8">Sharma BB, Rai K, Blunt H, et al.: Pathogenic DPYD Variants and Treatment-Related Mortality in Patients Receiving Fluoropyrimidine Chemotherapy: A Systematic Review and Meta-Analysis. Oncologist 26 (12): 1008-1016, 2021. [<a href="/pmc/articles/PMC8649021/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8649021</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/34506675" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34506675</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_179_9">Lam SW, Guchelaar HJ, Boven E: The role of pharmacogenetics in capecitabine efficacy and toxicity. Cancer Treat Rev 50: 9-22, 2016. [<a href="https://pubmed.ncbi.nlm.nih.gov/27569869" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27569869</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_179_10">Shakeel F, Fang F, Kwon JW, et al.: Patients carrying DPYD variant alleles have increased risk of severe toxicity and related treatment modifications during fluoropyrimidine chemotherapy. Pharmacogenomics 22 (3): 145-155, 2021. [<a href="https://pubmed.ncbi.nlm.nih.gov/33410339" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33410339</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_179_11">Amstutz U, Henricks LM, Offer SM, et al.: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update. Clin Pharmacol Ther 103 (2): 210-216, 2018. [<a href="/pmc/articles/PMC5760397/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5760397</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29152729" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29152729</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_179_12">Henricks LM, Lunenburg CATC, de Man FM, et al.: DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis. Lancet Oncol 19 (11): 1459-1467, 2018. [<a href="https://pubmed.ncbi.nlm.nih.gov/30348537" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30348537</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_179_13">Lau-Min KS, Varughese LA, Nelson MN, et al.: Preemptive pharmacogenetic testing to guide chemotherapy dosing in patients with gastrointestinal malignancies: a qualitative study of barriers to implementation. BMC Cancer 22 (1): 47, 2022. [<a href="/pmc/articles/PMC8742388/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8742388</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/34996412" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34996412</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_179_14">Brooks GA, Tapp S, Daly AT, et al.: Cost-effectiveness of DPYD Genotyping Prior to Fluoropyrimidine-based Adjuvant Chemotherapy for Colon Cancer. Clin Colorectal Cancer 21 (3): e189-e195, 2022. [<a href="/pmc/articles/PMC10496767/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10496767</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35668003" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35668003</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_179_15">Baker SD, Bates SE, Brooks GA, et al.: DPYD Testing: Time to Put Patient Safety First. J Clin Oncol 41 (15): 2701-2705, 2023. [<a href="/pmc/articles/PMC10414691/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10414691</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36821823" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36821823</span></a>]</div></li></ol></div></div><div id="CDR0000062925__32"><h2 id="_CDR0000062925__32_">Treatment of Distal Urethral Cancer</h2><div id="CDR0000062925__33"><h3>Treatment Options for Female Distal Urethral Cancer</h3><p id="CDR0000062925__34">If the malignancy is at or just within the meatus and superficial parameters (stage 0/Tis,
|
|
Ta), open excision or electroresection and fulguration may be possible. Tumor
|
|
destruction using neodymium:yttrium-aluminum-garnet (Nd:YAG) or CO<sub>2</sub> laser vaporization-coagulation represents an
|
|
alternative option. For large lesions (T1) and more invasive lesions (T2), brachytherapy or a combination of brachytherapy and
|
|
external-beam radiation therapy (EBRT) are alternatives to surgical resection of the distal third of
|
|
the urethra. Patients with T3 distal urethral lesions or lesions that recur after treatment with
|
|
local excision or radiation therapy require anterior
|
|
exenteration and urinary diversion.
|
|
</p><p id="CDR0000062925__35">If inguinal lymph nodes are palpable, frozen section confirmation of a tumor should be
|
|
obtained. If positive for malignancy, ipsilateral lymph node dissection is indicated. If no
|
|
inguinal adenopathy exists, lymph node dissection is not generally performed, and the nodes are monitored clinically.
|
|
</p><p id="CDR0000062925__36">Treatment options for female distal urethral cancer include the following:
|
|
</p><ol id="CDR0000062925__76"><li class="half_rhythm"><div>Open excision and organ-sparing conservative surgical therapy.[<a class="bk_pop" href="#CDR0000062925_rl_32_1">1</a>]</div></li><li class="half_rhythm"><div>Ablative techniques, such as transurethral resection, electroresection and fulguration, or laser vaporization-coagulation (Tis, Ta, T1 lesions).[<a class="bk_pop" href="#CDR0000062925_rl_32_2">2</a>,<a class="bk_pop" href="#CDR0000062925_rl_32_3">3</a>]
|
|
</div></li><li class="half_rhythm"><div> EBRT, brachytherapy, or a combination of the two (T1, T2 lesions).[<a class="bk_pop" href="#CDR0000062925_rl_32_4">4</a>]
|
|
</div></li><li class="half_rhythm"><div>Anterior exenteration with or without preoperative radiation and diversion
|
|
(T3 lesions or recurrent lesions).[<a class="bk_pop" href="#CDR0000062925_rl_32_2">2</a>,<a class="bk_pop" href="#CDR0000062925_rl_32_3">3</a>]</div></li></ol><p id="CDR0000062925__189">The level of evidence for these treatment options is <a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000810039/" class="def">Level of evidence C3</a>.</p></div><div id="CDR0000062925__40"><h3>Treatment Options for Male Distal Urethral Cancer</h3><p id="CDR0000062925__41">If the malignancy is in the pendulous urethra and is superficial, there is potential
|
|
for long-term disease-free survival. In the rare cases that involve mucosa only (Tis, Ta),
|
|
resection and fulguration may be used. For infiltrating
|
|
lesions in the fossa navicularis, amputation of the glans penis may be adequate
|
|
treatment. For lesions involving more proximal portions of the distal urethra,
|
|
excision of the involved segment of the urethra, preserving the penile corpora,
|
|
may be feasible for superficial tumors. Penile amputation is used for infiltrating lesions. Traditionally, a 2-cm margin proximal to the tumor is used, but the optimal margin has not been well studied. Local recurrences after amputation
|
|
are rare.
|
|
</p><p id="CDR0000062925__213">The role of radiation therapy in the treatment of anterior urethral
|
|
carcinoma in men is not well defined. Some anterior urethral cancers have
|
|
been cured with radiation alone or a combination of chemotherapy and radiation therapy.[<a class="bk_pop" href="#CDR0000062925_rl_32_4">4</a>,<a class="bk_pop" href="#CDR0000062925_rl_32_5">5</a>]</p><p id="CDR0000062925__42">If inguinal lymph nodes are palpable, ipsilateral node dissection is indicated after
|
|
frozen section confirmation of a tumor because a cure is still achievable with limited
|
|
regional nodal metastases. If no inguinal adenopathy exists, lymph node dissection
|
|
is not generally performed, and the nodes are monitored clinically.</p><p id="CDR0000062925__43">Treatment options for male distal urethral cancer include the following:</p><ol id="CDR0000062925__77"><li class="half_rhythm"><div>Open-excision and organ-sparing conservative surgery.[<a class="bk_pop" href="#CDR0000062925_rl_32_1">1</a>,<a class="bk_pop" href="#CDR0000062925_rl_32_3">3</a>]</div></li><li class="half_rhythm"><div>Ablative techniques, such as transurethral resection, electroresection and fulguration, or laser vaporization-coagulation (Tis, Ta, T1 lesions).[<a class="bk_pop" href="#CDR0000062925_rl_32_2">2</a>,<a class="bk_pop" href="#CDR0000062925_rl_32_3">3</a>]</div></li><li class="half_rhythm"><div> Amputation of the penis (T1, T2, T3 lesions).
|
|
</div></li><li class="half_rhythm"><div> Radiation (T1, T2, T3 lesions, if amputation is refused).[<a class="bk_pop" href="#CDR0000062925_rl_32_4">4</a>]
|
|
</div></li><li class="half_rhythm"><div>Combined chemotherapy and radiation therapy.[<a class="bk_pop" href="#CDR0000062925_rl_32_5">5</a>]</div></li></ol><p id="CDR0000062925__190">The level of evidence for these treatment options is <a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000810039/" class="def">Level of evidence C3</a>.</p></div><div id="CDR0000062925__TrialSearch_32_sid_5"><h3>Current Clinical Trials</h3><p id="CDR0000062925__TrialSearch_32_22">Use our <a href="https://www.cancer.gov/research/participate/clinical-trials-search/advanced" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">advanced clinical trial search</a> to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. <a href="https://www.cancer.gov/research/participate/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">General information</a> about clinical trials is also available.</p></div><div id="CDR0000062925_rl_32"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062925_rl_32_1">Davis JW, Schellhammer PF, Schlossberg SM: Conservative surgical therapy for penile and urethral carcinoma. Urology 53 (2): 386-92, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/9933060" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9933060</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_32_2">Mark JR, Hurwitz M, Gomella LG: Cancer of the urethra and penis. In: DeVita VT Jr, Lawrence TS, Rosenberg SA, et al., eds.: DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer, 2019, pp 1136-44.</div></li><li><div class="bk_ref" id="CDR0000062925_rl_32_3">Karnes RJ, Breau RH, Lightner DJ: Surgery for urethral cancer. Urol Clin North Am 37 (3): 445-57, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/20674699" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20674699</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_32_4">Koontz BF, Lee WR: Carcinoma of the urethra: radiation oncology. Urol Clin North Am 37 (3): 459-66, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/20674700" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20674700</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_32_5">Cohen MS, Triaca V, Billmeyer B, et al.: Coordinated chemoradiation therapy with genital preservation for the treatment of primary invasive carcinoma of the male urethra. J Urol 179 (2): 536-41; discussion 541, 2008. [<a href="https://pubmed.ncbi.nlm.nih.gov/18076921" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18076921</span></a>]</div></li></ol></div></div><div id="CDR0000062925__47"><h2 id="_CDR0000062925__47_">Treatment of Proximal Urethral Cancer</h2><div id="CDR0000062925__48"><h3>Treatment Options for Female Proximal Urethral Cancer</h3><p id="CDR0000062925__49">Lesions of the proximal urethra or the entire length of the urethra are usually associated with invasion
|
|
and a high incidence of pelvic nodal metastases. The prospects for cure are
|
|
limited except in the case of small tumors. The best results have been
|
|
achieved with exenterative surgery and urinary diversion, with 5-year survival rates
|
|
ranging from 10% to 20%.
|
|
</p><p id="CDR0000062925__214">In an effort to shrink tumor margins, increase the resectability rate of gross tumor, and decrease local recurrence, adjunctive preoperative radiation
|
|
therapy is a reasonable option. Pelvic
|
|
lymphadenectomy is performed concomitantly. Ipsilateral inguinal lymph node dissection is
|
|
indicated only if biopsy specimens of ipsilateral palpable adenopathy are positive on a
|
|
frozen section. For tumors that do not exceed 2 cm in greatest
|
|
dimension, radiation alone, nonexenterative surgery alone, or a combination
|
|
of the two may be sufficient to provide an excellent outcome.</p><p id="CDR0000062925__50">It is reasonable to consider removal of
|
|
part of the pubic symphysis and the inferior pubic rami to maximize the
|
|
surgical margin and reduce local recurrence. The perineal closure
|
|
and vaginal reconstruction can be accomplished with the use of myocutaneous
|
|
flaps.
|
|
</p><p id="CDR0000062925__51">The prognosis of female urethral cancer is related to the size of the
|
|
lesion at presentation. For lesions smaller than 2 cm in diameter, a 5-year survival rate of 60% can be anticipated. For lesions larger than 4 cm in
|
|
diameter, the 5-year survival rate falls to 13%.
|
|
</p><p id="CDR0000062925__52">Treatment options for female proximal urethral cancer include the following:
|
|
</p><ol id="CDR0000062925__78"><li class="half_rhythm"><div>Preoperative radiation followed by anterior exenteration and urinary
|
|
diversion with bilateral pelvic lymph node dissection, with or without inguinal lymph node
|
|
dissection.[<a class="bk_pop" href="#CDR0000062925_rl_47_1">1</a>]
|
|
</div></li><li class="half_rhythm"><div>For tumors that do not exceed 2 cm in greatest dimension,
|
|
radiation alone, nonexenterative surgery alone, or a combination of the two may be
|
|
sufficient to provide an excellent outcome.[<a class="bk_pop" href="#CDR0000062925_rl_47_1">1</a>,<a class="bk_pop" href="#CDR0000062925_rl_47_2">2</a>]</div></li></ol><p id="CDR0000062925__191">The level of evidence for these treatment options is <a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000810039/" class="def">Level of evidence C3</a>.</p></div><div id="CDR0000062925__55"><h3>Treatment Options for Male Proximal Urethral Cancer</h3><p id="CDR0000062925__56">Lesions of the bulbomembranous urethra require radical cystoprostatectomy and
|
|
en bloc penectomy to achieve adequate margins of resection, minimize local
|
|
recurrence, and achieve long-term, disease-free survival. Pelvic lymphadenectomy is also performed because of the high incidence of positive lymph nodes and the limited added
|
|
morbidity.
|
|
</p><p id="CDR0000062925__215">Despite extensive surgery, local recurrence is common, and this event is invariably associated with eventual death from
|
|
the disease. Five-year survival rates are only 15% to 20%.
|
|
In an effort to shrink tumor margins, the use of preoperative adjunctive
|
|
radiation therapy may be considered. In an effort to increase the surgical
|
|
margins of dissection, resection of the inferior pubic rami and the lower
|
|
portion of the pubic symphysis has been used. Urinary diversion is
|
|
required.[<a class="bk_pop" href="#CDR0000062925_rl_47_3">3</a>]</p><p id="CDR0000062925__57">Ipsilateral inguinal lymph node dissection is indicated if palpable ipsilateral
|
|
inguinal adenopathy is found on physical examination and confirmed to be
|
|
neoplasm by frozen section.
|
|
</p><p id="CDR0000062925__58">Treatment options for male proximal urethral cancer include the following:
|
|
</p><ul id="CDR0000062925__263" class="simple-list"><li class="half_rhythm"><div>Preoperative radiation or combined chemotherapy and radiation therapy followed by cystoprostatectomy, urinary diversion, and
|
|
penectomy with bilateral pelvic lymph node dissection, with or without inguinal lymph node
|
|
dissection.[<a class="bk_pop" href="#CDR0000062925_rl_47_4">4</a>]
|
|
</div></li></ul><p id="CDR0000062925__192">The level of evidence for these treatment options is <a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000810039/" class="def">Level of evidence C3</a>.</p></div><div id="CDR0000062925__TrialSearch_47_sid_6"><h3>Current Clinical Trials</h3><p id="CDR0000062925__TrialSearch_47_22">Use our <a href="https://www.cancer.gov/research/participate/clinical-trials-search/advanced" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">advanced clinical trial search</a> to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. <a href="https://www.cancer.gov/research/participate/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">General information</a> about clinical trials is also available.</p></div><div id="CDR0000062925_rl_47"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062925_rl_47_1">Koontz BF, Lee WR: Carcinoma of the urethra: radiation oncology. Urol Clin North Am 37 (3): 459-66, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/20674700" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20674700</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_47_2">Grigsby PW, Corn BW: Localized urethral tumors in women: indications for conservative versus exenterative therapies. J Urol 147 (6): 1516-20, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1593679" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1593679</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_47_3">Su LM, Smith JA Jr.: Laparoscopic and robotic-assisted laparoscopic radical prostatectomy and pelvic lymphadenectomy. In: Wein AJ, Kavoussi LR, Novick AC, et al.: Campbell-Walsh Urology. 10th ed. Elsevier Saunders, 2012, pp 2830-2849.</div></li><li><div class="bk_ref" id="CDR0000062925_rl_47_4">Karnes RJ, Breau RH, Lightner DJ: Surgery for urethral cancer. Urol Clin North Am 37 (3): 445-57, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/20674699" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20674699</span></a>]</div></li></ol></div></div><div id="CDR0000062925__60"><h2 id="_CDR0000062925__60_">Treatment of Urethral Cancer Associated With Invasive Bladder Cancer</h2><p id="CDR0000062925__61">Approximately 10% (range, 4%–17%) of patients who undergo cystectomy for bladder cancer can be
|
|
expected to have or to later develop clinical neoplasm of the urethra distal to
|
|
the urogenital diaphragm.
|
|
Factors associated with the risk of urethral recurrence after cystectomy include the following:[<a class="bk_pop" href="#CDR0000062925_rl_60_1">1</a>,<a class="bk_pop" href="#CDR0000062925_rl_60_2">2</a>]</p><ul id="CDR0000062925__193"><li class="half_rhythm"><div>Tumor multiplicity.</div></li><li class="half_rhythm"><div>Papillary pattern.</div></li><li class="half_rhythm"><div>Carcinoma <i>in situ</i>.</div></li><li class="half_rhythm"><div>Tumor location at the bladder neck.</div></li><li class="half_rhythm"><div>Prostatic urethral mucosal or stromal involvement.</div></li></ul><p id="CDR0000062925__62">The benefits of urethrectomy at the time of cystectomy need to be weighed
|
|
against the morbidity factors, which include added operating time, hemorrhage, and the
|
|
potential for perineal hernia. Tumors found incidentally on
|
|
pathological examination are much more likely to be superficial or <i>in situ</i> in
|
|
contrast to those that present with clinical symptoms at a later date, when
|
|
the likelihood of invasion within the corporal bodies is high. The former
|
|
lesions are often curable, and the latter are only rarely so. Indications for
|
|
urethrectomy in continuity with cystoprostatectomy are the following:
|
|
</p><ul id="CDR0000062925__63"><li class="half_rhythm"><div>Visible tumor in the urethra.
|
|
</div></li><li class="half_rhythm"><div>Positive swab cytology of the urethra.
|
|
</div></li><li class="half_rhythm"><div>Positive margins of the membranous urethra on frozen section taken at the
|
|
time of cystoprostatectomy.
|
|
</div></li><li class="half_rhythm"><div>Multiple <i>in situ</i> bladder tumors that extend onto the bladder
|
|
neck and proximal prostatic urethra.
|
|
</div></li></ul><p id="CDR0000062925__64">If the urethra is not removed at the time of cystectomy, follow-up
|
|
includes periodic cytologic evaluation of saline urethral washings.[<a class="bk_pop" href="#CDR0000062925_rl_60_2">2</a>]
|
|
</p><p id="CDR0000062925__65">Treatment options for urethral cancer associated with invasive bladder cancer include the following:
|
|
</p><ol id="CDR0000062925__80"><li class="half_rhythm"><div>In continuity cystourethrectomy.
|
|
</div></li><li class="half_rhythm"><div>Monitor urethral cytology and delayed urethrectomy, if necessary.
|
|
</div></li></ol><p id="CDR0000062925__194">The level of evidence for these treatment options is <a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000810039/" class="def">Level of evidence C3</a>.</p><div id="CDR0000062925__TrialSearch_60_sid_7"><h3>Current Clinical Trials</h3><p id="CDR0000062925__TrialSearch_60_22">Use our <a href="https://www.cancer.gov/research/participate/clinical-trials-search/advanced" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">advanced clinical trial search</a> to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. <a href="https://www.cancer.gov/research/participate/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">General information</a> about clinical trials is also available.</p></div><div id="CDR0000062925_rl_60"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062925_rl_60_1">Mark JR, Hurwitz M, Gomella LG: Cancer of the urethra and penis. In: DeVita VT Jr, Lawrence TS, Rosenberg SA, et al., eds.: DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer, 2019, pp 1136-44.</div></li><li><div class="bk_ref" id="CDR0000062925_rl_60_2">Sherwood JB, Sagalowsky AI: The diagnosis and treatment of urethral recurrence after radical cystectomy. Urol Oncol 24 (4): 356-61, 2006 Jul-Aug. [<a href="https://pubmed.ncbi.nlm.nih.gov/16818191" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16818191</span></a>]</div></li></ol></div></div><div id="CDR0000062925__68"><h2 id="_CDR0000062925__68_">Treatment of Metastatic or Recurrent Urethral Cancer</h2><p id="CDR0000062925__195">Local recurrences of urethral cancer may be amenable to local modality therapy with radiation or surgery, with or without chemotherapy. For more information, see the <a href="#CDR0000062925__179">Treatment Option Overview for Urethral Cancer</a> section. Metastatic disease may be treated with regimens in common use for other urothelial transitional cell or squamous cell carcinomas, or anal carcinomas, depending on the histology.[<a class="bk_pop" href="#CDR0000062925_rl_68_1">1</a>-<a class="bk_pop" href="#CDR0000062925_rl_68_3">3</a>]</p><p id="CDR0000062925__69">Treatment options for metastatic or recurrent urethral cancer include the following:</p><ol id="CDR0000062925__81"><li class="half_rhythm"><div>
|
|
Surgical excision of locally recurrent urethral cancer after radiation therapy should be considered, if feasible.
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|
</div></li><li class="half_rhythm"><div>Combination radiation therapy and wider surgical resection should be considered for locally recurrent urethral cancer after surgery alone.</div></li><li class="half_rhythm"><div>Clinical trials using chemotherapy should be considered for metastatic urethral cancer. Transitional cell cancer of the urethra may respond favorably to the same chemotherapy regimens used for advanced transitional cell cancer of the bladder.[<a class="bk_pop" href="#CDR0000062925_rl_68_1">1</a>-<a class="bk_pop" href="#CDR0000062925_rl_68_4">4</a>]</div></li></ol><p id="CDR0000062925__196">The level of evidence for these treatment options is <a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000810039/" class="def">Level of evidence C3</a>.</p><div id="CDR0000062925__TrialSearch_68_sid_8"><h3>Current Clinical Trials</h3><p id="CDR0000062925__TrialSearch_68_22">Use our <a href="https://www.cancer.gov/research/participate/clinical-trials-search/advanced" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">advanced clinical trial search</a> to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. <a href="https://www.cancer.gov/research/participate/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">General information</a> about clinical trials is also available.</p></div><div id="CDR0000062925_rl_68"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062925_rl_68_1">Mark JR, Hurwitz M, Gomella LG: Cancer of the urethra and penis. In: DeVita VT Jr, Lawrence TS, Rosenberg SA, et al., eds.: DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer, 2019, pp 1136-44.</div></li><li><div class="bk_ref" id="CDR0000062925_rl_68_2">Trabulsi EJ, Hoffman-Censits J: Chemotherapy for penile and urethral carcinoma. Urol Clin North Am 37 (3): 467-74, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/20674701" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20674701</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_68_3">Lin CC, Hsu CH, Huang CY, et al.: Phase II trial of weekly paclitaxel, cisplatin plus infusional high dose 5-fluorouracil and leucovorin for metastatic urothelial carcinoma. J Urol 177 (1): 84-9; discussion 89, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/17162009" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17162009</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062925_rl_68_4">VanderMolen LA, Sheehy PF, Dillman RO: Successful treatment of transitional cell carcinoma of the urethra with chemotherapy. Cancer Invest 20 (2): 206-7, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/11901541" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11901541</span></a>]</div></li></ol></div></div><div id="CDR0000062925__83"><h2 id="_CDR0000062925__83_">Latest Updates to This Summary (07/19/2024)</h2><p id="CDR0000062925__84">The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
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<b>
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<a href="#CDR0000062925__179">Treatment Option Overview for Urethral Cancer</a>
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</b>
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</p><p id="CDR0000062925__262">Added <a href="#CDR0000062925__260">Fluorouracil dosing</a> as a new subsection.</p><p id="CDR0000062925__disclaimerHP_3">This summary is written and maintained by the <a href="https://www.cancer.gov/publications/pdq/editorial-boards/adult-treatment" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Adult Treatment Editorial Board</a>, which is
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editorially independent of NCI. The summary reflects an independent review of
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the literature and does not represent a policy statement of NCI or NIH. More
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information about summary policies and the role of the PDQ Editorial Boards in
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maintaining the PDQ summaries can be found on the <a href="#CDR0000062925__AboutThis_1">About This PDQ Summary</a> and <a href="https://www.cancer.gov/publications/pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ® Cancer Information for Health Professionals</a> pages.
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</p></div><div id="CDR0000062925__AboutThis_1"><h2 id="_CDR0000062925__AboutThis_1_">About This PDQ Summary</h2><div id="CDR0000062925__AboutThis_2"><h3>Purpose of This Summary</h3><p id="CDR0000062925__AboutThis_3">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of urethral cancer. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.</p></div><div id="CDR0000062925__AboutThis_4"><h3>Reviewers and Updates</h3><p id="CDR0000062925__AboutThis_5">This summary is reviewed regularly and updated as necessary by the <a href="https://www.cancer.gov/publications/pdq/editorial-boards/adult-treatment" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Adult Treatment Editorial Board</a>, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).</p><p id="CDR0000062925__AboutThis_22"> Board members review recently published articles each month to determine whether an article should:</p><ul id="CDR0000062925__AboutThis_6"><li class="half_rhythm"><div>be discussed at a meeting,</div></li><li class="half_rhythm"><div>be cited with text, or</div></li><li class="half_rhythm"><div>replace or update an existing article that is already cited.</div></li></ul><p id="CDR0000062925__AboutThis_7">Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.</p><p>The lead reviewers for Urethral Cancer Treatment are:</p><ul><li class="half_rhythm"><div>Juskaran S. Chadha, DO (Moffitt Cancer Center)</div></li><li class="half_rhythm"><div>Jad Chahoud, MD, MPH (Moffitt Cancer Center)</div></li><li class="half_rhythm"><div>Timothy Gilligan, MD (Cleveland Clinic Taussig Cancer Institute)</div></li></ul><p id="CDR0000062925__AboutThis_9">Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's <a href="https://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.</p></div><div id="CDR0000062925__AboutThis_10"><h3>Levels of Evidence</h3><p id="CDR0000062925__AboutThis_11">Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a <a href="/books/n/pdqcis/CDR0000062796/">formal evidence ranking system</a> in developing its level-of-evidence designations.</p></div><div id="CDR0000062925__AboutThis_12"><h3>Permission to Use This Summary</h3><p id="CDR0000062925__AboutThis_13">PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”</p><p id="CDR0000062925__AboutThis_14">The preferred citation for this PDQ summary is:</p><p id="CDR0000062925__AboutThis_15">PDQ® Adult Treatment Editorial Board. PDQ Urethral Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: <a href="https://www.cancer.gov/types/urethral/hp/urethral-treatment-pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://www.cancer.gov/types/urethral/hp/urethral-treatment-pdq</a>. Accessed <MM/DD/YYYY>. [PMID: 26389356]</p><p id="CDR0000062925__AboutThis_16">Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in <a href="https://visualsonline.cancer.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Visuals Online</a>, a collection of over 2,000 scientific images.
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</p></div><div id="CDR0000062925__AboutThis_17"><h3>Disclaimer</h3><p id="CDR0000062925__AboutThis_18">Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the <a href="https://www.cancer.gov/about-cancer/managing-care" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Managing Cancer Care</a> page.</p></div><div id="CDR0000062925__AboutThis_20"><h3>Contact Us</h3><p id="CDR0000062925__AboutThis_21">More information about contacting us or receiving help with the Cancer.gov website can be found on our <a href="https://www.cancer.gov/contact" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Contact Us for Help</a> page. Questions can also be submitted to Cancer.gov through the website’s <a href="https://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>.</p></div></div></div></div>
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK65918/?report=reader">PubReader</a></li><li><a href="/books/NBK65918/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK65918" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK65918" style="display:none" title="Cite this Page"><div class="bk_tt">PDQ Adult Treatment Editorial Board. Urethral Cancer Treatment (PDQ®): Health Professional Version. 2024 Jul 19. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. <span class="bk_cite_avail"></span></div></div></li><li><a href="#" class="toggle-glossary-link" title="Enable/disable links to the glossary">Disable Glossary Links</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Version History</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter shutter_closed" title="Show/hide content" remembercollapsed="true" pgsec_name="version_history" id="Shutter"></a></div><div class="portlet_content" style="display: none;"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><span class="bk_col_itm">NBK65918.9</span> July 19, 2024 (Displayed Version)</li><li><span class="bk_col_itm"><a href="/books/NBK65918.8/">NBK65918.8</a></span> August 19, 2022</li><li><span class="bk_col_itm"><a href="/books/NBK65918.7/">NBK65918.7</a></span> December 9, 2021</li><li><span class="bk_col_itm"><a href="/books/NBK65918.6/">NBK65918.6</a></span> June 18, 2021</li><li><span class="bk_col_itm"><a href="/books/NBK65918.5/">NBK65918.5</a></span> January 31, 2020</li><li><span class="bk_col_itm"><a href="/books/NBK65918.4/">NBK65918.4</a></span> November 27, 2019</li><li><span class="bk_col_itm"><a href="/books/NBK65918.3/">NBK65918.3</a></span> June 2, 2015</li><li><span class="bk_col_itm"><a href="/books/NBK65918.2/">NBK65918.2</a></span> October 2, 2015</li><li><span class="bk_col_itm"><a href="/books/NBK65918.1/">NBK65918.1</a></span> October 23, 2014</li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>In this Page</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="page-toc" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="#CDR0000062925__1" ref="log$=inpage&link_id=inpage">General Information About Urethral Cancer</a></li><li><a href="#CDR0000062925__4" ref="log$=inpage&link_id=inpage">Cellular Classification of Urethral Cancer</a></li><li><a href="#CDR0000062925__8" ref="log$=inpage&link_id=inpage">Stage Information for Urethral Cancer</a></li><li><a href="#CDR0000062925__179" ref="log$=inpage&link_id=inpage">Treatment Option Overview for Urethral Cancer</a></li><li><a href="#CDR0000062925__32" ref="log$=inpage&link_id=inpage">Treatment of Distal Urethral Cancer</a></li><li><a href="#CDR0000062925__47" ref="log$=inpage&link_id=inpage">Treatment of Proximal Urethral Cancer</a></li><li><a href="#CDR0000062925__60" ref="log$=inpage&link_id=inpage">Treatment of Urethral Cancer Associated With Invasive Bladder Cancer</a></li><li><a href="#CDR0000062925__68" ref="log$=inpage&link_id=inpage">Treatment of Metastatic or Recurrent Urethral Cancer</a></li><li><a href="#CDR0000062925__83" ref="log$=inpage&link_id=inpage">Latest Updates to This Summary (07/19/2024)</a></li><li><a href="#CDR0000062925__AboutThis_1" ref="log$=inpage&link_id=inpage">About This PDQ Summary</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related publications</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="document-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK65946/">Patient Version</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related information</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" 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two_line"><a class="brieflinkpopperctrl" href="/pubmed/26389236" ref="ordinalpos=1&linkpos=1&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Parathyroid Cancer Treatment (PDQ®): Health Professional Version.</a><span class="source">[PDQ Cancer Information Summari...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Parathyroid Cancer Treatment (PDQ®): Health Professional Version.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">PDQ Adult Treatment Editorial Board. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">PDQ Cancer Information Summaries. 2002</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/27583328" ref="ordinalpos=1&linkpos=2&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Financial Toxicity and Cancer Treatment (PDQ®): Health Professional Version.</a><span class="source">[PDQ Cancer Information Summari...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Financial Toxicity and Cancer Treatment (PDQ®): Health Professional Version.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">PDQ Adult Treatment Editorial Board. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">PDQ Cancer Information Summaries. 2002</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/26389173" ref="ordinalpos=1&linkpos=3&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Delirium (PDQ®): Health Professional Version.</a><span class="source">[PDQ Cancer Information Summari...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Delirium (PDQ®): Health Professional Version.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">PDQ Supportive and Palliative Care Editorial Board. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">PDQ Cancer Information Summaries. 2002</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/26389484" ref="ordinalpos=1&linkpos=4&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Fatigue (PDQ®): Health Professional Version.</a><span class="source">[PDQ Cancer Information Summari...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Fatigue (PDQ®): Health Professional Version.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">PDQ Supportive and Palliative Care Editorial Board. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">PDQ Cancer Information Summaries. 2002</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/26389421" ref="ordinalpos=1&linkpos=5&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> 714-X (PDQ®): Health Professional Version.</a><span class="source">[PDQ Cancer Information Summari...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> 714-X (PDQ®): Health Professional Version.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">PDQ Integrative, 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<script type="text/javascript" src="/portal/portal3rc.fcgi/static/js/hfjs2.js"> </script>
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</div><!-- /.twelve_col -->
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</div>
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<span class="PAFAppResources"></span>
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<noscript><img alt="statistics" src="/stat?jsdisabled=true&ncbi_db=books&ncbi_pdid=book-part&ncbi_acc=NBK65918&ncbi_domain=pdqcis&ncbi_report=record&ncbi_type=fulltext&ncbi_objectid=&ncbi_pcid=/NBK65918/&ncbi_pagename=Urethral Cancer Treatment (PDQ®) - PDQ Cancer Information Summaries - NCBI Bookshelf&ncbi_bookparttype=chapter&ncbi_app=bookshelf" /></noscript>
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<script type="text/javascript" src="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/js/3879255/4121861/3501987/4008961/3893018/3821238/4062932/4209313/4212053/4076480/3921943/3400083/3426610.js" snapshot="books"></script></body>
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