All Title Author
Keywords Abstract


Current and Future Strategies in the Diagnosis and Management of Penile Cancer

DOI: 10.1155/2011/593751

Full-Text   Cite this paper   Add to My Lib

Abstract:

Penile cancer is an uncommon malignancy that has a devastating effect on the patient while also being challenging to diagnose and treat. By implementing preventive measures, we can decrease the incidence of this disease and improve the quality of life of our patients. Early detection plays an important role in disease control and proper diagnostic modalities must be used in order to accurately identify the cancer and its progression. Primary penile lesions should be initially approached when surgically feasible and clinically appropriate with penile preserving surgical techniques. Advances in inguinal lymph node detection and management, has improved the clinical outcome of penile cancer. Advanced penile cancer still portends a poor prognosis and should be approached via a multimodal treatment regimen. In this review, we address the importance of prevention, early detection, and the contemporary management of primary penile lesions, as well as the advances in inguinal lymph node disease detection and surgical treatment, for both localized and advanced disease. 1. Introduction Penile cancer is an uncommon disease in the US and Europe that has a devastating effect on the patient while also being challenging to diagnose and treat. A distinction between benign and malignant penile neoplasms must be made in order to offer the most effective treatment [1]. In 2010, the new cases of penile cancer in the United States are about 1,250 with 310 deaths, with an incidence rate of 0.3 to 1.8 per 100,000 [2, 3]. Penile cancer is much more common in African, Asian, and South American countries, constituting about 10% of malignant disease in these countries and thus posing a considerable health concern [1, 4]. Notably, Paraguay and Uganda have an incidence rate of 4.2 and 4.4 per 100,000, respectively [4]. The lowest incidence is found in Israeli Jews (0.1/100,000) [3]. Cancer of the penis most commonly affects men between the ages of 50–70, with only 19% at ages <40 and 7% <30 [3]. Squamous cell carcinoma of the penis was found to be 43% greater in men from countries where the poverty level is >20% [3]. 2. Risk Factors The presence of an intact foreskin has been identified as an important risk factor for developing penile cancer. Maden et al. [5] found that the risk of penile cancer was 3.2-times greater among men who had never been circumcised relative to men circumcised at birth and 3.0-times greater among men circumcised after the neonatal period [3, 5]. In addition, penile cancer is rarely seen in Jews, as they are circumcised at birth [3]. A history of phimosis

References

[1]  A. J. Wein, L. R. Kavoussi, A. C. Novick, A. W. Partin, and C. A. Peters, Campbell-Walsh Urology, Saunders-Elsevier, Philadelphia, Pa, USA, 9th edition, 2006.
[2]  National Cancer Institute, “Penile Cancer,” http://www.cancer.gov/cancertopics/types/penile.
[3]  M. R. Pow-Sang, U. Ferreira, J. M. Pow-Sang, A. C. Nardi, and V. Destefano, “Epidemiology and natural history of penile cancer,” Urology, vol. 76, no. 2, supplement 1, pp. S2–S6, 2010.
[4]  M. C. Bleeker, D. A. Heideman, P. J. Snijders, S. Horenblas, J. Dillner, and C. J. Meijer, “Penile cancer: epidemiology, pathogenesis and prevention,” World Journal of Urology, vol. 27, no. 2, pp. 141–150, 2009.
[5]  C. Maden, K. J. Sherman, A. M. Beckmann et al., “History of circumcision, medical conditions, and sexual activity and risk of penile cancer,” Journal of the National Cancer Institute, vol. 85, no. 1, pp. 19–24, 1993.
[6]  D. Hellberg, J. Valentin, T. Eklund, and S. Nilsson, “Penile cancer: is there an epidemiological role for smoking and sexual behaviour?” British Medical Journal Clinical research ed, vol. 295, no. 6609, pp. 1306–1308, 1987.
[7]  J. Dillner, G. Von Krogh, S. Horenblas, and C. J. L. M. Meijer, “Etiology of squamous cell carcinoma of the penis,” Scandinavian Journal of Urology and Nephrology, vol. 34, no. 205, pp. 189–193, 2000.
[8]  J. R. Daling, M. M. Madeleine, L. G. Johnson et al., “Penile cancer: importance of circumcision, human papillomavirus and smoking in in situ and invasive disease,” International Journal of Cancer, vol. 116, no. 4, pp. 606–616, 2005.
[9]  M. A. Rubin, B. Kleter, M. Zhou et al., “Detection and typing of human papillomavirus DNA in penile carcinoma: evidence for multiple independent pathways of penile carcinogenesis,” American Journal of Pathology, vol. 159, no. 4, pp. 1211–1218, 2001.
[10]  F. H. Sarkar, B. J. Miles, D. H. Plieth, and J. D. Crissman, “Detection of human papillomavirus in squamous neoplasm of the penis,” Journal of Urology, vol. 147, no. 2, pp. 389–392, 1992.
[11]  M. Senba, A. Kumatori, S. Fujita et al., “The prevalence of human papillomavirus genotypes in penile cancers from northern Thailand,” Journal of Medical Virology, vol. 78, no. 10, pp. 1341–1346, 2006.
[12]  S. Minhas, A. Manseck, S. Watya, and P. K. Hegarty, “Penile cancer-prevention and premalignant conditions,” Urology, vol. 76, no. 2, supplement 1, pp. S24–S35, 2010.
[13]  R. U. Levine, C. P. Crum, E. Herman, D. Silvers, A. Ferenczy, and R. M. Richart, “Cervical papillomavirus infection and intraepithelial neoplasia: a study of male sexual partners,” Obstetrics and Gynecology, vol. 64, no. 1, pp. 16–20, 1984.
[14]  X. Castellsagué, F. X. Bosch, N. Mu?oz et al., “Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners,” New England Journal of Medicine, vol. 346, no. 15, pp. 1105–1112, 2002.
[15]  A. R. Giuliano, “Human papillomavirus vaccination in males,” Gynecologic Oncology, vol. 107, supplement 1, no. 2, pp. S24–S26, 2007.
[16]  S. L. Block, T. Nolan, C. Sattler et al., “Comparison of the immunogenicity and reactogenicity of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in male and female adolescents and young adult women,” Pediatrics, vol. 118, no. 5, pp. 2135–2145, 2006.
[17]  M. C. Bleeker, C. J. Hogewoning, F. J. Voorhorst et al., “Condom use promotes regression of human papillomavirus-associated penile lesions in male sexual partners of women with cervical intraepithelial neoplasia,” International Journal of Cancer, vol. 107, no. 5, pp. 804–810, 2003.
[18]  N. O'Farrell, M. Quigley, and P. Fox, “Association between the intact foreskin and inferior standards of male genital hygiene behaviour: a cross-sectional study,” International Journal of STD and AIDS, vol. 16, no. 8, pp. 556–559, 2005.
[19]  D. W. Tam, S. E. J. Van, and F. Urbach, “Bowen's disease and squamous cell carcinoma. occurrence in a patient with psoriasis after topical, systemic, and PUVA therapy,” Archives of Dermatology, vol. 115, no. 2, pp. 203–204, 1979.
[20]  R. S. Stern, E. Abel, B. Wintroub et al., “Genital tumors among men with psoriasis exposed to psoralens and ultraviolet A radiation (PUVA) and ultraviolet B radiation: the photochemotherapy follow-up study,” New England Journal of Medicine, vol. 322, no. 16, pp. 1093–1097, 1990.
[21]  D. A. Barocas and S. S. Chang, “Penile cancer: clinical presentation, diagnosis, and staging,” Urologic Clinics of North America, vol. 37, no. 3, pp. 343–352, 2010.
[22]  B. Y. Hernandez, J. Barnholtz-Sloan, R. R. German et al., “Burden of invasive squamous cell carcinoma of the penis in the United States, 1998-2003,” Cancer, vol. 113, no. 10, pp. 2883–2891, 2008.
[23]  A. S. Narayana, L. E. Olney, and S. A. Loening, “Carcinoma of the penis. analysis of 219 cases,” Cancer, vol. 49, no. 10, pp. 2185–2191, 1982.
[24]  S. Horenblas, R. Kr?ger, M. P. Gallee, D. W. W. Newling, and H. Van Tinteren, “Ultrasound in squamous cell carcinoma of the penis; a useful addition to clinical staging? a comparison of ultrasound with histopathology,” Urology, vol. 43, no. 5, pp. 702–707, 1994.
[25]  A. Agrawal, D. Pai, N. Ananthakrishnan, S. Robinson Smile, and C. Ratnakar, “Clinical and sonographic findings in carcinoma of the penis,” Journal of Clinical Ultrasound, vol. 28, no. 8, pp. 399–406, 2000.
[26]  A. P. Lont, A. P. Besnard, M. P. W. Gallee, H. Van Tinteren, and S. Horenblas, “A comparison of physical examination and imaging in determining the extent of primary penile carcinoma,” British Journal of Urology International, vol. 91, no. 6, pp. 493–495, 2003.
[27]  S. B. Stewart, R. A. Leder, and B. A. Inman, “Imaging tumors of the penis and urethra,” Urologic Clinics of North America, vol. 37, no. 3, pp. 353–367, 2010.
[28]  E. Solsona, F. Algaba, S. Horenblas, G. Pizzocaro, and T. Windahl, “EAU guidelines on penile cancer,” European Urology, vol. 46, no. 1, pp. 1–8, 2004.
[29]  B. Scher, M. Seitz, M. Reiser et al., “18F-FDG PET/CT for staging of penile cancer,” Journal of Nuclear Medicine, vol. 46, no. 9, pp. 1460–1465, 2005.
[30]  N. V. Raghavaiah, “Corpus cavernosogram in the evaluation of carcinoma of the penis,” Journal of Urology, vol. 120, no. 4, pp. 423–424, 1978.
[31]  G. Petralia, G. Villa, E. Scardino et al., “Local staging of penile cancer using magnetic resonance imaging with pharmacologically induced penile erection,” Radiologia Medica, vol. 113, no. 4, pp. 517–528, 2008.
[32]  H. Fujita, “New horizons in MR technology: RF coil designs and trends,” Magnetic Resonance in Medical Sciences, vol. 6, no. 1, pp. 29–42, 2007.
[33]  American Joint Committee on Cancer, “Penis,” in American Joint Committee on Cancer, S. B. Edge, D. R. Byrd, and C. C. Compton, Eds., p. 447, Springer, New York, NY, USA, 7th edition, 2010.
[34]  P. K. Hegarty, M. Shabbir, B. Hughes et al., “Penile preserving surgery and surgical strategies to maximize penile form and function in penile cancer: recommendations from the United Kingdom experience,” World Journal of Urology, vol. 27, no. 2, pp. 179–187, 2009.
[35]  J. R. Rossari, T. Vora, and T. Gil, “Advances in penile cancer management,” Current Opinion in Oncology, vol. 22, no. 3, pp. 226–235, 2010.
[36]  S. Minhas, O. Kayes, P. Hegarty, P. Kumar, A. Freeman, and D. Ralph, “What surgical resection margins are required to achieve oncological control in men with primary penile cancer?” British Journal of Urology International, vol. 96, no. 7, pp. 1040–1043, 2005.
[37]  G. Pizzocaro, F. Algaba, and S. Horenblas, “EAU guidelines on penile cancer,” http://www.uroweb.org/fileadmin/tx_eauguidelines/2009/Full/Penile_Cancer.pdf/.
[38]  M. Hovman, A. Renshaw, and K. R. Loughlin, “Squamous cell carcinoma of the penis and microscopic pathologic margins: How much margin is needed for local cure?” Cancer, vol. 85, no. 7, pp. 1565–1568, 1999.
[39]  A. Agrawal, D. Pai, N. Ananthakrishnan, S. R. Smile, and C. Ratnakar, “The histological extent of the local spread of carcinoma of the penis and its therapeutic implications,” British Journal of Urology International, vol. 85, no. 3, pp. 299–301, 2000.
[40]  D. K. Goette, M. Elgart, and R. L. Devillez, “Erythroplasia of queyrat. treatment with topically applied fluorouracil,” Journal of the American Medical Association, vol. 232, no. 9, pp. 934–937, 1975.
[41]  G. Micali, M. R. Nasca, and A. Tedeschi, “Topical treatment of intraepithelial penile carcinoma with imiquimod,” Clinical and Experimental Dermatology, vol. 28, no. 1, supplement 1, pp. 4–6, 2003.
[42]  B. P. Van Bezooijen, S. Horenblas, W. Meinhardt, and D. W. Newling, “Laser therapy for carcinoma in situ of the penis,” Journal of Urology, vol. 166, no. 5, pp. 1670–1671, 2001.
[43]  S. Horenblas, H. Van Tinteren, J. F. Delemarre, T. A. Boon, L. M. F. Moonen, and V. Lustig, “Squamous cell carcinoma of the penis. II. treatment of the primary tumor,” Journal of Urology, vol. 147, no. 6, pp. 1533–1538, 1992.
[44]  R. P. Meijer, T. A. Boon, G. E. Van Venrooij, and C. J. Wijburg, “Long-term follow-up after laser therapy for penile carcinoma,” Urology, vol. 69, no. 4, pp. 759–762, 2007.
[45]  I. Depasquale, A. J. Park, and A. Bracka, “The treatment of balanitis xerotica obliterans,” British Journal of Urology International, vol. 86, no. 4, pp. 459–465, 2000.
[46]  P. Hadway, C. M. Corbishley, and N. A. Watkin, “Total glans resurfacing for premalignant lesions of the penis: initial outcome data,” British Journal of Urology International, vol. 98, no. 3, pp. 532–536, 2006.
[47]  P. Pietrzak, C. Corbishley, and N. Watkin, “Organ-sparing surgery for invasive penile cancer: early follow-up data,” British Journal of Urology International, vol. 94, no. 9, pp. 1253–1257, 2004.
[48]  S. Horenblas and H. Van Tinteren, “Squamous cell carcinoma of the penis. IV. prognostic factors of survival: Analysis of tumor, nodes and metastasis classification system,” Journal of Urology, vol. 151, no. 5, pp. 1239–1243, 1994.
[49]  G. Bandieramonte, M. Colecchia, L. Mariani et al., “Peniscopically controlled CO2 laser excision for conservative treatment of in situ and T1 penile carcinoma: report on 224 patients,” European Urology, vol. 54, no. 4, pp. 875–882, 2008.
[50]  M. Azrif, J. P. Logue, R. Swindell, R. A. Cowan, J. P. Wylie, and J. E. Livsey, “External-beam radiotherapy in T1-2 N0 penile carcinoma,” Clinical Oncology, vol. 18, no. 4, pp. 320–325, 2006.
[51]  J. M. Crook, J. Jezioranski, L. Grimard, B. Esche, and G. Pond, “Penile brachytherapy: results for 49 patients,” International Journal of Radiation Oncology Biology Physics, vol. 62, no. 2, pp. 460–467, 2005.
[52]  R. Salvioni, A. Necchi, L. Piva, M. Colecchia, and N. Nicolai, “Penile cancer,” Urologic Oncology, vol. 27, no. 6, pp. 677–685, 2009.
[53]  M. Shabbir, B. E. Hughes, T. Swallow, C. Corbishley, M. J. A. Perry, and N. Watkin, “Management of chronic ulceration after radiotherapy for penile cancer,” Journal of Urology, vol. 179, no. 4, p. 785, 2008.
[54]  J. A. Bonner, P. M. Harari, J. Giralt et al., “Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck,” New England Journal of Medicine, vol. 354, no. 6, pp. 567–578, 2006.
[55]  K. A. Gold, H. Y. Lee, and E. S. Kim, “Targeted therapies in squamous cell carcinoma of the head and neck,” Cancer, vol. 115, no. 5, pp. 922–935, 2009.
[56]  P. E. Spiess, M. S. Hernandez, and C. A. Pettaway, “Contemporary inguinal lymph node dissection: minimizing complications,” World Journal of Urology, vol. 27, no. 2, pp. 205–212, 2009.
[57]  P. K. Hegarty, C. P. Dinney, and C. A. Pettaway, “Controversies in ilioinguinal lymphadenectomy,” Urologic Clinics of North America, vol. 37, no. 3, pp. 421–434, 2010.
[58]  G. Sufrin and R. Huben, “Benign and malignant lesions of the penis,” in Adult and Pediatric Urology, J. Y. Gillenwate, Ed., pp. 1975–2009, Lippincott Williams and Wilkins, Philadelphia, Pa, USA, 4th edition, 2002.
[59]  I. Saisorn, N. Lawrentschuk, S. Leewansangtong, and D. M. Bolton, “Fine-needle aspiration cytology predicts inguinal lymph node metastasis without antibiotic pretreatment in penile carcinoma,” British Journal of Urology International, vol. 97, no. 6, pp. 1225–1228, 2006.
[60]  V. Ficarra, F. Zattoni, W. Artibani et al., “Nomogram predictive of pathological inguinal lymph node involvement in patients with squamous cell carcinoma of the penis,” Journal of Urology, vol. 175, no. 5, pp. 1700–1704, 2006.
[61]  H. J. Steinkamp, M. Mueffelmann, J. C. B?ck, T. Thiel, P. Kenzel, and R. Felix, “Differential diagnosis of lymph node lesions: a semiquantitative approach with colour doppler ultrasound,” British Journal of Radiology, vol. 71, pp. 828–833, 1998.
[62]  J. W. Crawshaw, P. Hadway, D. Hoffland et al., “Sentinel lymph node biopsy using dynamic lymphoscintigraphy combined with ultrasound-guided fine needle aspiration in penile carcinoma,” British Journal of Radiology, vol. 82, no. 973, pp. 41–48, 2009.
[63]  B. K. Kroon, S. Horenblas, E. E. Deurloo, O. E. Nieweg, and H. J. Teertstra, “Ultrasonography-guided fine-needle aspiration cytology before sentinel node biopsy in patients with penile carcinoma,” British Journal of Urology International, vol. 95, no. 4, pp. 517–520, 2005.
[64]  C. F. Heyns, N. Fleshner, V. Sangar, B. Schlenker, T. B. Yuvaraja, and H. Van Poppel, “Management of the lymph nodes in penile cancer,” Urology, vol. 76, no. 2, supplement 1, pp. S43–S57, 2010.
[65]  N. M. Graafland, J. A. P. Leijte, R. A. Valdés Olmos, C. A. Hoefnagel, H. J. Teertstra, and S. Horenblas, “Scanning with 18F-FDG-PET/CT for detection of pelvic nodal involvement in inguinal node-positive penile carcinoma,” European Urology, vol. 56, no. 2, pp. 339–345, 2009.
[66]  J. A. Leijte, N. M. Graafland, R. A. Valdés Olmos, H. H. Van Boven, C. A. Hoefnagel, and S. Horenblas, “Prospective evaluation of hybrid F-fluorodeoxyglucose positron emission tomography/computed tomography in staging clinically node-negative patients with penile carcinoma,” British Journal of Urology International, vol. 104, no. 5, pp. 640–644, 2009.
[67]  S. Tabatabaei, M. Harisinghani, and W. S. McDougal, “Regional lymph node staging using lymphotropic nanoparticle enhanced magnetic resonance imaging with ferumoxtran-10 in patients with penile cancer,” Journal of Urology, vol. 174, no. 3, pp. 923–927, 2005.
[68]  H. C. Thoeny, M. Triantafyllou, F. D. Birkhaeuser et al., “Combined ultrasmall superparamagnetic particles of iron oxide-enhanced and diffusion-weighted magnetic resonance imaging reliably detect pelvic lymph node metastases in normal-sized nodes of bladder and prostate cancer patients,” European Urology, vol. 55, no. 4, pp. 761–769, 2009.
[69]  J. A. Leijte, B. Hughes, N. M. Graafland et al., “Two-center evaluation of dynamic sentinel node biopsy for squamous cell carcinoma of the penis,” Journal of Clinical Oncology, vol. 27, no. 20, pp. 3325–3329, 2009.
[70]  W. J. Catalona, “Modified inguinal lymphadenectomy for carcinoma of the penis with preservation of saphenous veins: technique and preliminary results,” Journal of Urology, vol. 140, no. 2, pp. 306–310, 1988.
[71]  C. A. L. D'Ancona, R. Gon?alves De Lucena, F. A. De Oliveira Querne, M. H. Tavares Martins, F. Denardi, and N. Rodrigues Netto, “Long-term followup of penile carcinoma treated with penectomy and bilateral modified inguinal lymphadenectomy,” Journal of Urology, vol. 172, no. 2, pp. 498–501, 2004.
[72]  E. H. Daseler, B. J. Anson, and A. F. Reimann, “Radical excision of the inguinal and iliac lymph glands; a study based,” Surgery, gynecology & obstetrics, vol. 87, no. 6, pp. 679–694, 1948.
[73]  M. Tobias-Machado, E. Starling, A. Pompeu, and E. Wroclawski, “Video endoscopic inguinal lymphadenectomy (VEIL): a critical analysis after a 5-year experience,” in Genitourinary Cancers Symposium Proceedings Book, p. 193, American Society of Clinical Oncology, Alexandria, Va, USA, 2009.
[74]  H. Grabstald, “Controversies concerning lymph node dissection for cancer of the penis,” Urologic Clinics of North America, vol. 7, no. 3, pp. 793–799, 1980.
[75]  S. Horenblas, “Lymphadenectomy for squamous cell carcinoma of the penis. part 2: the role and technique of lymph node dissection,” British Journal of Urology International, vol. 88, no. 5, pp. 473–483, 2001.
[76]  B. K. Kroon, O. E. Nieweg, H. van Boven, and S. Horenblas, “Size of metastasis in the sentinel node predicts additional nodal involvement in penile carcinoma,” Journal of Urology, vol. 176, no. 1, pp. 105–108, 2006.
[77]  Y. Zhu, S. L. Zhang, D. W. Ye, X. D. Yao, Z. X. Jiang, and X. Y. Zhou, “Predicting pelvic lymph node metastases in penile cancer patients: a comparison of computed tomography, Cloquet's node, and disease burden of inguinal lymph nodes,” Onkologie, vol. 31, no. 1-2, pp. 37–41, 2008.
[78]  L. C. Pagliaro and J. Crook, “Multimodality therapy in penile cancer: when and which treatments?” World Journal of Urology, vol. 27, no. 2, pp. 221–225, 2009.
[79]  G. Pizzocaro, N. Nicolai, and L. Piva, “Chemotherapy for cancer of the penis,” in Principles and Practice of Genitourinary Oncology, D. Raghavan, S. A. Leibel, H. I. Scher, et al., Eds., pp. 973–977, Lippincot-Raven Publishers, Philadelphia, Pa, USA, 1997.
[80]  R. Salvioni, et al., “Penile cancer,” Urologic Oncology: Seminars and Original Investigations, vol. 27, no. 6, pp. 677–685, 2009.
[81]  D. J. Culkin and T. M. Beer, “Advanced penile carcinoma,” Journal of Urology, vol. 170, no. 2, pp. 359–365, 2003.
[82]  G. P. Haas, B. A. Blumenstein, R. G. Gagliano et al., “Cisplatin, methotrexate and bleomycin for the treatment of carcinoma of the penis: a southwest oncology group study,” Journal of Urology, vol. 161, no. 6, pp. 1823–1825, 1999.
[83]  C. Bermejo, J. E. Busby, P. E. Spiess, L. Heller, L. C. Pagliaro, and C. A. Pettaway, “Neoadjuvant chemotherapy followed by aggressive surgical consolidation for metastatic penile squamous cell carcinoma,” Journal of Urology, vol. 177, no. 4, pp. 1335–1338, 2007.
[84]  L. Pagliaro, D. Williams, D. Daliani, et al., “Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy prior to inguinal/pelvic lymphadenectomy for stage Tany, N2-3, M0 squamous carcinoma of the penis (abstract #602),” Journal of Urology, vol. 175, p. 195, 2006.
[85]  L. C. Pagliaro, D. L. Williams, D. Daliani, M. B. Williams, W. Osai, and M. Kincaid, “Neoadjuvant paclitaxol, ifosfamide, and cisplatin chemotherapy for metastatic penile cancer: a phase II study,” Journal of Clinical Oncology, vol. 28, no. 24, pp. 3851–3857, 2010.
[86]  E. J. Trabulsi and J. Hoffman-Censits, “Chemotherapy for penile and urethral carcinoma,” Urologic Clinics of North America, vol. 37, no. 3, pp. 467–474, 2010.
[87]  B. C. Carthon, C. A. Pettaway, and L. C. Pagliaro, “Epidermal growth factor receptor (EGFR) targeted therapy in advanced metastatic squamous cell carcinoma (AMSCC) of the penis,” [abstract #254].

Full-Text

comments powered by Disqus