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Penile Cancer

Penile Cancer. Kashif Siddiqui, T. McDermott RCSI, March 29, 2004. Benign Lesions. Premalignant lesions. 42% of pts with SCC had hx of pre existing penile lesions. (Bouchot etal 1989). Viral related conditions. Human Papilloma virus (HPV)

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Penile Cancer

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  1. Penile Cancer Kashif Siddiqui, T. McDermott RCSI, March 29, 2004.

  2. Benign Lesions

  3. Premalignant lesions • 42% of pts with SCC had hx of pre existing penile lesions. (Bouchot etal 1989)

  4. Viral related conditions • Human Papilloma virus (HPV) Types 6,11,42,43 & 44 associated with low grade dysplasia. Types 16,18,31,33,35 & 39 have higher association with malignancy. • Human Herpesvirus 8 (HHV 8)

  5. Buschke-Lowenstein Tumor(Verrucous Carcinoma, Giant Condyloma Acuminatum) • initially described in 1925. • true incidence is unknown. • Does not metastasize rather invades locally. • Treatment is excision. • Recurrence is common. • Topical therapy with Podophyllin, 5FU, radiation and chemotherapy have all been tried with no great success.

  6. Penile Cancer • Squamous cell carcinoma. > 95% • Mesenchymal tumors. < 3% e.g Kaposi sarcoma, angiosarcoma etc • Maligannt Melanoma. • Basal cell carcinoma. • Metastasis. Sufrin & Huben 1991

  7. Carcinoma in situPenile intraepithelial neoplasia, Erythroplasia of Queyrat, Bowen’s disease • can progress to invasive carcinoma. • Histological confirmation with proper determination of invasion. • Treatment Circumcission------------Preputial lesions Local excision------------small & non invasive Radiotherapy Topical 5FU as 5% base Nd:YAG & CO2 laser, liquid nitrogen Kelley etal 1974, Graham & Helwig 1973, Mortimer etal 1983

  8. Invasive carcinoma • Uncommon. • 0.1 – 0.9 per 100,000 in USA, Europe. • Upto 10% in some asian, african and south american countries, (Vatamasapt etal 1995) • Disease of older men, 6th decade, reported in younger men & children. (Narsimharao 1985) • Primary tumor localized to glans (48%), prepuce (21%), both glans & prepuce (9%), coronal (6%), shaft (<2%). (Sufrin & Huben 1991)

  9. Etiology • Circumcission practice. • Hygiene standards. • Phimosis. • No. of sexual partners. • HPV infection. • Exposure to tobacco products. • No convincing association with occupation, gonorrhea, syphillis & alcohol intake. Barrasso etal 1987, Maiche 1992, Maden etal 1993

  10. Prevention • Routine neonatal circumcission. AAP Paediatric guidelines 1999. • Good hygiene practice. • Avoid HPV infection and tobacco.

  11. Natural History • Begins as small lesion, papillary & exophytic or flat & ulcerative. • Flat & ulcerative lesions >5cm and extending >75% of the shaft have higher incidence of metastasis and poor survival. • Pattern in lymphatic spread. • Metastatic nodes cause erosion into vessels, skin necrosis & chronic infection. • Distant metastasis uncommon 1 – 10% • Death within 2 years for most untreated cases.

  12. Presentation • Symptoms malaise, wt loss, fatigue, weakness, hemorrhage, pain. • Signs penile lesion. rarely nodal mass, ulceration, suppuration.

  13. Primary lesion. Regional lymph nodes. Distant metastasis. Physical examination. Ultrasound. MRI. CT. Cavernosography. Lymphangiography. Diagnosis

  14. Diagnosis • Histological diagnosis is absolutely necessary prior to treatment decision. • Growth pattern of SCC superficial spreading. vertical growth. multicentric. verrucous. Cubilla etal 1993

  15. Broders grading system (Ann Surg 1921;73:141) divided into 4 grades depends on differentiation based on keratinization, nuclear pleomorphism, no. of mitosis Maiche system score (Br J Urol 1991;67:522-526) modified into3 grades 5 year survival Grade 1 80% Grade 2,3 50% Grade 4 30% Maiche etal 1991 Grading systems

  16. Staging • Jackson’s staging system, 1966.

  17. TNM staging system

  18. Treatment of Penile lesion Penile intraepithelial neoplasia Penis preserving strategy • Laser therapy. • Local excision. • 5 FU cream. • Cryotherapy. • Photodynamic therapy. • 5% topical imiquimod.

  19. Treatment of Penile lesion Ta-1 G1-2 Penis preserving strategy with regular follow up. • Local excision plus reconstruction, recurrence 11-30% • Laser therapy, recurrence 15-25%. • Radiotherapy / Brachytherapy, recurrence 15-25%. • Glansectomy.

  20. Treatment of Penile lesion T1 G3, T ≥ 2 • Partial / total amputation. • Conservative strategy is an alternative in very carefully selected patients.

  21. Treatment of Penile lesion Local recurrence • Second conservative procedure. • Partial / total amputation. • External beam radiotherapy / brachytherapy for lesions < 4cm diameter.

  22. Treatment of regional nodes Non palpable nodes 20% harbour micrometastasis. Low risk pTis, pTaG1-2, pT1G1 • Surveillance. • Occult micrometastasis in < 16.5%. Solsona J Urol 2001;165:1506-1509, Horenblas J Urol 1994;151:1239-1243,Theodoreson 1996 J Urol;155:1626-1631

  23. Treatment of regional nodes Non palpable nodes Intermediate risk T1G2 • Vascular / lymphatic invasion & growth pattern. • Surveillance for superficial pattern & no invasion. • Modified lymphadenectomy in infiltrating growth pattern or invasion. • ? Role of sentinnel node biopsy. Solsona J Urol 2001;165:1506-1509, Horenblas J Urol 1994;151:1239-1243,Theodoreson 1996 J Urol;155:1626-1631

  24. Treatment of regional nodes Non palpable nodes High risk T (2 or G3) • Modified or radical lymphadenectomy. • 70% may have occult metastasis. Solsona J Urol 2001;165:1506-1509, Horenblas J Urol 1994;151:1239-1243,Theodoreson 1996 J Urol;155:1626-1631

  25. Treatment of regional nodes Palpable nodes • Present at diagnosis in 58% patients. • Of these 17-45% have nodal metastasis while remaining have iflammatory disease. Horenblas J Urol 1993;149:492-497, Ornellas J Urol 1994;151:1244-1249

  26. Treatment of regional nodes Positive palpable nodes • Bilateral radical inguinal lymphadenectomy. • Probability of pelvic node involvement 23% , 2-3 nodes +ve & 56%, >3 nodes +ve Culkin J Urol 2003;170:359-365 • Incidence of pelvic nodes ↑ to 30% in 2-3 node group with delayed pelvic lymphadenectomy. Ornellas J Urol 1994;151:1244-1249

  27. Treatment of regional nodes Fixed inguinal mass / clinically +ve pelvic nodes • Chemotherapy, partial / complete clinical response in 21-60%. (Ficarra Int Urol Nephrol 2002;34:245-250, Culkin J Urol 2003;170:359-365, Pizzocaro J Urol 1995;153:246) • Subsequent radical ilioinguinal lymphadenectomy. • Radiotherapy followed by lymphadenectomy but higher morbidity.

  28. Treatment of regional nodes Inguinal palpable nodes during surveillance • Bilateral radical inguinal lymphadenectomy • Inguinal lymphadenectomy at site of +ve nodes in cases of long disease free interval.

  29. Treatment Integrated therapy • In pts presenting with primary tumor and +ve nodes, both issues should be managed simultaneously. • In pts presenting initially with +ve pelvic nodes, induction chemotherapy followed by radical / palliative surgery or DTx is administered according to tumor response.

  30. Treatment Distant metastasis • Chemotherapy. • Palliative therapy.

  31. Treatment Technical aspects • Surgeons experience. • Formal circumcission before radiotherapy. • ~ 2 cm tumor free margin. • Landmarks for RIL include inguinal lig, adductor & sartorius muscle, femoral vessels. • MIL, saphenous vein should be preserved, boundaries 1-2 cm less than radical surgery. • PL includes external iliac & ilio obturator chains with boundaries of iliac bifurcation, ilioinguinal & obturator nerve.

  32. Treatment Technical aspects • Complications of LND. • Sentinnel node biopsy & its limitations. 92% identified, 23 % +ve for tumor. • Various lasers, CO2 0.1cm & NdYAG 0.4cm absorption, local recurrence +/- 25%.

  33. Treatment Quality of Life • Age, performance status. • Socioeconomic factors. • Sexual function. • Patient motivation. • Psychological aspects. • Morbidity of various procedures. • Tumor biology.

  34. Chemotherapy • cis platin +/- 5FU, VMB, CMB. • Adjuvant following RLND, 82% 5 yr survival. Pizzocaro Acta Oncol 1988;27:823-4 • Neo adjuvant, fixed inguinal nodes, 56% resectable & 31% cured. Pizzocaro J Urol 1995;153:246 • Advanced disease, 32% response rate, 12% Rx related deaths. Haas J Urol 1999;161:1823-1825, Kattan Urol 1993;42:559-62

  35. Radiotherapy Primary tumor • EBR, response rate 56%, failure 40%. • Brachytherapy, response rate 70%, failure 16%. • Tumor size < 4 cm. • Complications telengiectasia >90%, meatal stenosis 30%, urethral strictures / fistula 35%, penile necrosis.

  36. Radiotherapy Prophylaxis • NOT recommended. (fails to prevent mets, morbidity, difficult to follow) Neo adjuvant • can render fixed nodes operable. Adjuvant • may be used to reduce local recurrence.

  37. Follow up • Most relapses in first 2 years. • 0-7% chance of relapse after partial / total penectomy. • Development of palpable nodes with non palpable nodes initially means metastasis ~ 100%. • Physical exam, CT & CXR.

  38. EAU guidelines on diagnosis

  39. EAU guidelines on diagnosis

  40. EAU guidelines on treatmentPrimary Lesion

  41. EAU guidelines on treatmentRN therapy in non palpable nodes

  42. EAU guidelines on treatmentPalpable positive RLN

  43. EAU guidelines for follow up

  44. Thank you all Discussion & Questions

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