Advanced Penile Carcinoma (2003)

No AccessJournal of UrologyCLINICAL UROLOGY: Review Article1 Aug 2003Advanced Penile Carcinoma DANIEL J. CULKIN and TOMASZ M. BEER DANIEL J. CULKINDANIEL J. CULKIN and TOMASZ M. BEERTOMASZ M. BEER View All Author Informationhttps://doi.org/10.1097/01.ju.0000062829.43654.5eAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: In the United States penile carcinoma is an uncommon malignancy that represents only 0.4% of all male malignancies and 2% to 4% of genitourinary malignancies. Of penile cancer cases 30% are diagnosed with advanced disease. Improved understanding of the natural history, appropriate and accurate staging, and tailored, less morbid lymphadenectomy have led to improved survival and decreased the adverse effects of therapy. However, the management of advanced penile carcinoma remains a challenge to urological, medical and radiation oncologists. The rarity and paucity of well designed clinical studies of medical and/or surgical therapy for advanced penile cancer have hampered progress in the treatment of this disease. However, there is clear evidence that identifies active chemotherapy and radiation treatments. This review aims to provide the treating physician with an overview of available data for surgical, chemotherapeutic and radiation treatments, and provide guidelines for appropriate patient selection for these therapies. Materials and Methods: We performed a detailed review of the available literature regarding advanced penile carcinoma to include its etiology, epidemiology, natural history, staging classification and treatment. Results: Penile carcinoma typically spreads along an echelon of nodal pathways that permits fairly accurate staging. Prognosis correlates well with clinical nodal status and grade, and the TNM classification developed by the UICC should be uniformly used by clinicians. Treatment recommendations are tightly associated with disease stage. Although tailored lymphadenectomy as currently recommended has greatly decreased morbidity, improved staging accuracy and improved treatment results, controversies still exist regarding the need for lymphadenectomy in patients with impalpable lymph node (cN0) disease, and the role and timing of pelvic lymphadenectomy. There is evidence of modest activity for chemotherapy in advanced penile carcinoma. Active agents include cisplatin, bleomycin and methotrexate. Combination chemotherapy regimens with promising activity and toxicity profiles include cisplatin and 5-fluorouracil, and vincristine, bleomycin and methotrexate. Radiation in combination with surgery and/or chemotherapy in advanced disease have also demonstrated activity. Conclusions: The natural history of penile carcinoma and its proclivity to spread via regional lymphatics has been well defined. This understanding has led to the development of effective locoregional treatment strategies. Penile carcinoma is sensitive to radiation and certain chemotherapeutic agents. A threshold volume of nodal metastases is associated with significant mortality. The optimal application of these strategies remains to be determined. Improvements in survival and quality of life likely require the incorporation of multiple modalities into the treatment of advanced penile carcinoma. A multi-institutional, international effort is essential to perform appropriately powered clinical trials to advance the standard of care in this rare disease. References 1 : Cancer Statistics Review. Bethesda: National Institute of Health1990. Google Scholar 2 : Squamous cell carcinoma of the penis: accuracy of tumor, nodes and metastasis classification system, and role of lymphangiography, computerized tomography scan and fine needle aspiration cytology. J Urol1991; 146: 1279. Link, Google Scholar 3 : Surgical treatment of invasive squamous cell carcinoma of the penis: retrospective analysis of 350 cases. J Urol1994; 151: 1244. Link, Google Scholar 4 : Prophylactic lymphadenectomy vs observation vs inguinal biopsy in node-negative patients with invasive carcinoma of the penis. Jpn J Clin Oncol1993; 23: 53. Google Scholar 5 : Penile cancer. Urology1973; 1: 569. Crossref, Medline, Google Scholar 6 : History of circumcision, medical conditions, and sexual activity and risk of penile cancer. J Natl Cancer Inst1993; 85: 19. Google Scholar 7 : Human papillomavirus 16 and 18 L1 serology compared across anogenital cancer sites. Cancer Res2001; 61: 1934. Google Scholar 8 : Human papillomavirus as a prognostic factor in carcinoma of the penis: analysis of 82 patients treated with amputation and bilateral lymphadenectomy. Cancer2001; 91: 2315. Google Scholar 9 : Epidermoid carcinoma of the penis. J Urol1964; 91: 166. Link, Google Scholar 10 : Cancer of the penis: a clinical study of 229 cases. Acta Chir Scand1958; 115: 25. Google Scholar 11 : Combined bleomycin and radiation therapy in carcinoma of the penis. Cancer1985; 56: 1257. Google Scholar 12 : Squamous cell carcinoma of the penis. III. Treatment of regional lymph nodes. J Urol1993; 149: 492. Link, Google Scholar 13 : Treatment of carcinoma of the penis: the case for primary lymphadenectomy. J Urol1986; 136: 38. Link, Google Scholar 14 : Prospective validation of the association of local tumor stage and grade as a predictive factor for occult lymph node micrometastasis in patients with penile carcinoma and clinically negative inguinal lymph nodes. J Urol2001; 165: 1506. Link, Google Scholar 15 : Tumor stage, vascular invasion and the percentage of poorly differentiated cancer: independent prognosticators for inguinal lymph node metastasis in penile squamous cancer. J Urol2001; 165: 1138. Link, Google Scholar 16 : Reappraisal of the role of radiotherapy and surgery in the management of carcinoma of the penis. Br J Urol1984; 56: 724. Google Scholar 17 : Conservative treatment of carcinoma of the penis. Br J Urol1979; 51: 32. Google Scholar 18 : Carcinoma of the penis: analysis of therapy in 100 consecutive cases. J Urol1972; 108: 428. Link, Google Scholar 19 : Management of regional lymph nodes in carcinoma of the penis. Eur Urol1989; 16: 410. Google Scholar 20 : Iridium-192 interstitial therapy for squamous cell carcinoma of the penis. Int J Radiat Oncol Biol Phys1992; 24: 479. Google Scholar 21 : Cancer of the penis. Experience at the Norwegian Radium Hospital 1974–1985. Eur Urol1987; 13: 372. Google Scholar 22 : The role of ilioinguinal lymphadenectomy and significance of histological differentiation in treatment of carcinoma of the penis. J Urol1989; 142: 1478. Link, Google Scholar 23 : Clinical staging of cancer of the penis: by size? By localization? Or by depth of infiltration?. Eur Urol1990; 18: 16. Google Scholar 24 : The results of primary radiation therapy in the management of squamous cell carcinoma of the penis. Int J Radiat Oncol Biol Phys1993; 25: 623. Crossref, Medline, Google Scholar 25 : Carcinoma of the penis. Treatment by surgery or combined bleomycin and radiation therapy. Acta Oncol1993; 32: 653. Google Scholar 26 : Carcinoma of the penis: a retrospective review of treatment with iridium mould and external beam irradiation. Clin Oncol1993; 5: 207. Google Scholar 27 : Penile cancer: relation of extent of nodal metastasis to survival. J Urol1987; 137: 880. Link, Google Scholar 28 : Correlation between the extent of nodal involvement and survival following groin dissection for carcinoma of the penis. Br J Urol1993; 72: 817. Crossref, Medline, Google Scholar 29 : Analyses of 200 lymphadenectomies in patients with penile carcinoma. J Urol1991; 146: 330. Link, Google Scholar 30 : Unreliability of sentinel lymph node biopsy for staging penile carcinoma. J Urol1980; 124: 734. Link, Google Scholar 31 : Sentinel lymph node dissection for penile carcinoma: the M. D. Anderson Cancer Center experience. J Urol1995; 154: 1999. Link, Google Scholar 32 : Penile lymphoscintigraphy for sentinel node identification. Eur J Nucl Med2001; 28: 581. Google Scholar 33 : Lymphatic mapping and intraoperative lymphoscintigraphy for identifying the sentinel node in penile tumors. Urology2000; 55: 582. Google Scholar 34 : Accurate staging of carcinoma of the penis in men with nonpalpable inguinal lymph nodes by modified inguinal lymphadenectomy. J Urol1996; 155: 560. Link, Google Scholar 35 : Prognostic factors in carcinoma of the penis: multivariate analysis of 145 patients treated with amputation and lymphadenectomy. J Urol1996; 156: 1637. Link, Google Scholar 36 : Detection of occult metastasis in squamous cell carcinoma of the penis using a dynamic sentinel node procedure. J Urol2000; 163: 100. Link, Google Scholar 37 : Role of radiation therapy in the treatment of carcinoma of the penis. Br J Urol1994; 74: 646. Google Scholar 38 : Dynamic sentinel node biopsy for penile cancer: reliability of a staging technique. J Urol2002; 168: 76. Link, Google Scholar 39 : Early experience in intermediate-risk penile cancer with sentinel node identification using the gamma probe. Urology2001; 58: 65. Google Scholar 40 : Penile cancer–the sentinel lymph node controversy. Urol Int1991; 47: 108. Google Scholar 41 : First experience with gamma probe guided sentinel lymph node surgery in penile cancer. Urol Res2000; 28: 246. Google Scholar 42 : Sentinel lymph node biopsy for staging penile cancer. Urology1984; 23: 352. Google Scholar 43 : Radical excision of the inguinal and iliac lymph glands: a study based on 450 anatomical dissections and upon supportive clinical observations. Surg Gynec Obst1948; 87: 679. Google Scholar 44 : Radical ilio-inguinal node dissection: the skin bridge technique. A new procedure. J Urol1972; 108: 279. Link, Google Scholar 45 : The treatment of carcinoma of the penis. Brit J Surg1966; 53: 33. Google Scholar 46 : Results of surgical treatment of carcinoma of the penis. Aust N Z J Surg1971; 41: 157. Google Scholar 47 : The surgical management of squamous cell carcinoma of the penis. J Urol1972; 107: 273. Link, Google Scholar 48 : A technique of ilioinguinal lymph node dissection for carcinoma of the penis. Surg Gynecol Obstet1984; 159: 573. Google Scholar 49 : Modified inguinal lymphadenectomy for carcinoma of the penis with preservation of saphenous veins: technique and preliminary results. J Urol1988; 140: 306. Link, Google Scholar 50 : Lymphedema after groin dissection. Am J Surg1983; 145: 205. Google Scholar 51 : Role of laparoscopic pelvic lymph node dissection in the management of patients with penile cancer and inguinal adenopathy. J Endourol1994; 8: 365. Google Scholar 52 : Treatment of penis carcinoma. Urol Int1983; 38: 243. Google Scholar 53 : Sexuality in patients treated for penile cancer: patients' experience and doctors' judgement. Br J Urol1994; 73: 554. Google Scholar 54 : Treatment results and prognostic factors in 101 men treated for squamous carcinoma of the penis. Int J Radiat Oncol Biol Phys1997; 38: 713. Crossref, Medline, Google Scholar 55 : Interstitial brachytherapy for penile carcinoma: a multicentric survey (259 patients). Radiother Oncol1995; 36: 83. Crossref, Medline, Google Scholar 56 : Radiation therapy of cancer of the penis. Indications, advantages, and pitfalls. Urol Clin North Am1992; 19: 325. Google Scholar 57 : Radiotherapy of penile carcinoma, indications and results. Strahlentherapie1976; 152: 333. Google Scholar 58 : Current management of unusual genitourinary cancers. Part 1: penile cancer. Oncology1999; 13: 1347. Google Scholar 59 : Radiotherapy in treatment of carcinoma of the penis. Br J Urol1965; 37: 211. Google Scholar 60 : An appraisal of the efficacy of bleomycin in epidermoid carcinoma of the penis. Anticancer Res1984; 4: 289. Google Scholar 61 : Methotrexate in the treatment of penile carcinoma. Cancer1980; 45: 214. Google Scholar 62 : Sequential trials of methotrexate, cisplatin and bleomycin for penile cancer. J Urol1984; 132: 465. Link, Google Scholar 63 : Cis-diamminedichloroplatinum in the treatment of advanced epidermoid carcinoma of the penis: a Southwest Oncology Group Study. J Urol1989; 141: 66. Link, Google Scholar 64 : Neoadjuvant therapy with cisplatin and 5-fluorouracil for stage III squamous cell carcinoma of the penis. J Urol1990; 143: 352A. abstract 653. Google Scholar 65 : Chemotherapy with cisplatin and 5-fluorouracil for penile and urethral squamous cell carcinomas. Cancer1990; 65: 433. Google Scholar 66 : Cisplatin and 5-fluorouracil in advanced cancer of the penis. J Urol1992; 147: 630. Link, Google Scholar 67 : Combination chemotherapy with methotrexate, bleomycin and cisplatin for advanced squamous cell carcinoma of the male genital tract. J Urol1991; 146: 1284. Link, Google Scholar 68 : Cisplatin, methotrexate and bleomycin for the treatment of carcinoma of the penis: a Southwest Oncology Group study. J Urol1999; 161: 1823. Link, Google Scholar 69 : Chemotherapy for cancer of the penis. In: Principles and Practice of Genitourinary Oncology. Edited by . Philadelphia: Lippincott-Raven Publishers1997: 973. Google Scholar 70 : Penile cancer chemotherapy: twelve years' experience at Institut Gustave-Roussy. Urology1993; 42: 559. Google Scholar 71 : Adjuvant and neoadjuvant vincristine, bleomycin, and methotrexate for inguinal metastases from squamous cell carcinoma of the penis. Acta Oncol1988; 27: 823. Google Scholar 72 : Contemporary chemotherapy and radiotherapy for inguinal metastases of carcinoma of the penis: a case report. Tumori1988; 74: 585. Google Scholar 73 : Combined modality therapy for locally advanced penile squamous cell carcinoma. Am J Clin Oncol1993; 16: 501. Google Scholar 74 : Combined approach to squamous cell carcinoma of the penis (SCP). Proc Am Soc Clin Oncol1987; 6: 109. Google Scholar From the Department of Urology, University of Oklahoma Health Sciences Center (DJC), Oklahoma City, Oklahoma, and Department of Medicine, Hematology/Medical Oncology Division (TMB), Oregon Health and Science University (TMB), Portland, Oregon© 2003 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byGraafland N, van Boven H, van Werkhoven E, Moonen L and Horenblas S (2010) Prognostic Significance of Extranodal Extension in Patients With Pathological Node Positive Penile CarcinomaJournal of Urology, VOL. 184, NO. 4, (1347-1353), Online publication date: 1-Oct-2010.Leijte J, Gallee M, Antonini N and Horenblas S (2008) Evaluation of Current TNM Classification of Penile CarcinomaJournal of Urology, VOL. 180, NO. 3, (933-938), Online publication date: 1-Sep-2008.Lont A, Kroon B, Gallee M, van Tinteren H, Moonen L and Horenblas S (2018) Pelvic Lymph Node Dissection for Penile Carcinoma: Extent of Inguinal Lymph Node Involvement as an Indicator for Pelvic Lymph Node Involvement and SurvivalJournal of Urology, VOL. 177, NO. 3, (947-952), Online publication date: 1-Mar-2007. Volume 170Issue 2August 2003Page: 359-365 Advertisement Copyright & Permissions© 2003 by American Urological Association, Inc.Keywordsneoplasm metastasisdrug therapypenile neoplasmspenisradiotherapyMetricsAuthor Information DANIEL J. CULKIN More articles by this author TOMASZ M. BEER Financial interest and/or other relationship with Aventis, Novacea, Inc., Bristol Myer Squibb, Dendreon Corp., Novartis, AVI BioPharma, Praecis Pharmaceuticals and Amgen. More articles by this author Expand All Advertisement PDF downloadLoading ...