Penile cancer

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  • Solsona J Urol 2001;165:1506-1509, Horenblas J Urol 1994;151:1239-1243, Theodoreson 1996 J Urol;155:1626-1631
  • Penile cancer

    1. 1. Management of Carcinoma Penis Dr Akhilesh Mishra Senior Resident Radiation Oncology IRCH , AIIMS
    2. 2. Lymphatics <ul><li>Skin : B/L Superficial Inguinal Lymph Nodes </li></ul><ul><li>Glans : B/L Inguinal or Iliac Nodes </li></ul><ul><li>Corpora: B/L Deep Inguinal and Iliac Nodes </li></ul>
    3. 3. Benign Lesions Non cutaneous Cutaneous <ul><li>Inclusion/Retention cysts </li></ul><ul><li>Syringoma </li></ul><ul><li>Neurilemmoma </li></ul><ul><li>Angioma, Fibroma, Neuroma, Lipoma, Myoma </li></ul><ul><li>Pseudotumors </li></ul><ul><li>Penile papules </li></ul><ul><li>Hirsute papillomas </li></ul><ul><li>Coronal papillae </li></ul><ul><li>Zoons erythroplasia </li></ul><ul><li>Rashes & ulcerations secondary to irritation, allergy and infections </li></ul>
    4. 4. Premalignant lesions <ul><li>42% of pts with SCC had hx of pre existing penile lesions. </li></ul><ul><li>(Bouchot etal 1989) </li></ul><ul><li>Cutaneous Horn </li></ul><ul><li>Pseudoepitheliomatous Micaceous & Keratotic Balanitis </li></ul><ul><li>Balanitis Xerotica Obliterans </li></ul><ul><li>Leukoplakia </li></ul>
    5. 5. Viral related conditions <ul><li>Human Papilloma virus (HPV) </li></ul><ul><li>Types 6,11,42,43 & 44 associated with low grade dysplasia. </li></ul><ul><li>Types 16,18,31,33,35 & 39 have higher association with malignancy. </li></ul><ul><li>Human Herpesvirus 8 (HHV 8) </li></ul><ul><li>Condylomata Acuminatum </li></ul><ul><li>Bowenoid Papulosis </li></ul><ul><li>Kaposi’s Sarcoma </li></ul>
    6. 6. Buschke-Lowenstein Tumor (Verrucous Carcinoma, Giant Condyloma Acuminatum) <ul><li>initially described in 1925. </li></ul><ul><li>true incidence is unknown. </li></ul><ul><li>Does not metastasize rather invades locally. </li></ul><ul><li>Treatment is excision. </li></ul><ul><li>Recurrence is common. </li></ul><ul><li>Topical therapy with Podophyllin, 5FU, radiation and chemotherapy have all been tried with no great success. </li></ul>
    7. 7. Penile Cancer <ul><li>Squamous cell carcinoma. > 95% </li></ul><ul><li>Mesenchymal tumors. < 3% </li></ul><ul><li>e.g Kaposi sarcoma, angiosarcoma etc </li></ul><ul><li>Maligannt Melanoma. </li></ul><ul><li>Basal cell carcinoma. </li></ul><ul><li>Metastasis. </li></ul><ul><li>Sufrin & Huben 1991 </li></ul>
    8. 8. Carcinoma in situ Penile intraepithelial neoplasia, Erythroplasia of Queyrat, Bowen’s disease <ul><li>can progress to invasive carcinoma. </li></ul><ul><li>Histological confirmation with proper determination of invasion. </li></ul><ul><li>Treatment </li></ul><ul><li>Circumcission------------Preputial lesions </li></ul><ul><li>Local excision------------small & non invasive </li></ul><ul><li>Radiotherapy </li></ul><ul><li>Topical 5FU as 5% base </li></ul><ul><li>Nd:YAG & CO 2 laser, liquid nitrogen </li></ul><ul><li>Kelley etal 1974, Graham & Helwig 1973, Mortimer etal 1983 </li></ul>
    9. 9. Invasive carcinoma <ul><li>Uncommon. </li></ul><ul><li>0.1 – 0.9 per 100,000 in USA, Europe. </li></ul><ul><li>Upto 10% in some asian, african and south american countries, (Vatamasapt etal 1995) </li></ul><ul><li>Disease of older men, 6 th decade, reported in younger men & children. (Narsimharao 1985) </li></ul><ul><li>Primary tumor localized to glans (48%), prepuce (21%), both glans & prepuce (9%), coronal (6%), shaft (<2%). (Sufrin & Huben 1991) </li></ul>
    10. 10. Etiology <ul><li>Circumcission practice. </li></ul><ul><li>Hygiene standards. </li></ul><ul><li>Phimosis. </li></ul><ul><li>No. of sexual partners. </li></ul><ul><li>HPV(16,18) infection. </li></ul><ul><li>Exposure to tobacco products. </li></ul><ul><li>No convincing association with occupation, gonorrhea, syphillis & alcohol intake. </li></ul><ul><li>Barrasso etal 1987, Maiche 1992, Maden etal 1993 </li></ul>
    11. 11. Prevention <ul><li>Routine neonatal circumcission. </li></ul><ul><li>AAP Paediatric guidelines 1999. </li></ul><ul><li>Good hygiene practice. </li></ul><ul><li>Avoid HPV infection and tobacco. </li></ul>
    12. 12. Natural History <ul><li>Begins as small lesion, papillary & exophytic or flat & ulcerative. </li></ul><ul><li>Flat & ulcerative lesions >5cm and extending >75% of the shaft have higher incidence of metastasis and poor survival. </li></ul><ul><li>Pattern in lymphatic spread. </li></ul><ul><li>Metastatic nodes cause erosion into vessels, skin necrosis & chronic infection. </li></ul><ul><li>Distant metastasis uncommon 1 – 10% </li></ul><ul><li>Death within 2 years for most untreated cases. </li></ul>
    13. 13. Presentation <ul><li>Symptoms </li></ul><ul><li>malaise, wt loss, fatigue, weakness, hemorrhage, pain. </li></ul><ul><li>Signs </li></ul><ul><li>penile lesion. </li></ul><ul><li>rarely nodal mass, ulceration, suppuration. </li></ul>
    14. 14. Diagnosis <ul><li>Primary lesion. </li></ul><ul><li>Regional lymph nodes. </li></ul><ul><li>Distant metastasis. </li></ul><ul><li>Physical examination. </li></ul><ul><li>Ultrasound. </li></ul><ul><li>MRI. </li></ul><ul><li>CT. </li></ul><ul><li>Cavernosography. </li></ul><ul><li>Lymphangiography. </li></ul>
    15. 15. Diagnosis <ul><li>Histological diagnosis is absolutely necessary prior to treatment decision. </li></ul><ul><li>Growth pattern of SCC </li></ul><ul><li>superficial spreading. </li></ul><ul><li>vertical growth. </li></ul><ul><li>multicentric. </li></ul><ul><li>verrucous. </li></ul><ul><li>Cubilla etal 1993 </li></ul>
    16. 16. Grading systems <ul><li>Broders grading system (Ann Surg 1921;73:141) </li></ul><ul><li>divided into 4 grades </li></ul><ul><li>depends on differentiation based on keratinization, nuclear pleomorphism, no. of mitosis </li></ul><ul><li>Maiche system score </li></ul><ul><li>(Br J Urol 1991;67:522-526) </li></ul><ul><li>modified into 3 grades </li></ul><ul><li>5 year survival </li></ul><ul><li>Grade 1 80% </li></ul><ul><li>Grade 2,3 50% </li></ul><ul><li>Grade 4 30% </li></ul><ul><li>Maiche etal 1991 </li></ul>
    17. 17. Staging <ul><li>Jackson’s staging system, 1966. </li></ul>
    18. 18. TNM staging system
    19. 19. Treatment of Penile lesion <ul><li>Penile intraepithelial neoplasia </li></ul><ul><li>Penis preserving strategy </li></ul><ul><li>Laser therapy. </li></ul><ul><li>Local excision. </li></ul><ul><li>5 FU cream. </li></ul><ul><li>Cryotherapy. </li></ul><ul><li>Photodynamic therapy. </li></ul><ul><li>5% topical imiquimod. </li></ul>
    20. 20. Treatment of Penile lesion <ul><li>Ta-1 G1-2 </li></ul><ul><li>Penis preserving strategy with regular follow up. </li></ul><ul><li>Local excision plus reconstruction, recurrence 11-30% </li></ul><ul><li>Laser therapy, recurrence 15-25%. </li></ul><ul><li>Radiotherapy / Brachytherapy, recurrence 15-25%. </li></ul><ul><li>Glansectomy. </li></ul>
    21. 21. Treatment of Penile lesion <ul><li>T1 G3, T ≥ 2 </li></ul><ul><li>Partial / total amputation. </li></ul><ul><li>Conservative strategy is an alternative in very carefully selected patients. </li></ul>
    22. 22. Treatment of Penile lesion <ul><li>Local recurrence </li></ul><ul><li>Second conservative procedure. </li></ul><ul><li>Partial / total amputation. </li></ul><ul><li>External beam radiotherapy / brachytherapy for lesions < 4cm diameter. </li></ul>
    23. 23. Penile Preservation <ul><li>RT Alone- </li></ul><ul><li>Steps : </li></ul><ul><li>1. Circumcision; f/b EBRT / Brachytherapy alone / Chemo–RT. </li></ul><ul><li>EBRT: 45-50 Gy to whole penile shaft (+/-) nodes f/b Boost to primary with 2cm margin upto 60-65 Gy. </li></ul>
    24. 24. Penile Preservation <ul><li>Brachytherapy: </li></ul><ul><li>1. Radioactive mold,60 Gy to Tumour, 50 Gy to Urethra. </li></ul><ul><li>2. Interstitial by Ir 192, upto 65 Gy (t/t of choice in Europe) </li></ul><ul><li>Contraindicated if tumour >4cm, or >1cm invasion in Corpus Cavernosa. </li></ul>
    25. 26. Penile Cancer Risk Grouping for Inguinal Nodal Metastases <ul><li>Low risk </li></ul><ul><li>Tis / Ta </li></ul><ul><li>T1 Grade I-II </li></ul><ul><li>No vascular invasion </li></ul><ul><li><10% LN mets </li></ul><ul><li>Surveillance </li></ul><ul><li>High risk </li></ul><ul><li>T2-T3 </li></ul><ul><li>Grade III </li></ul><ul><li>Vascular invasion </li></ul><ul><li>Non-compliance </li></ul><ul><li>>50% LN mets </li></ul><ul><li>Early lymphadenectomy </li></ul>
    26. 27. Cancer Penis Substratification of LN vs survival <ul><li>Survival with metastatic inguinal LN 20-25% </li></ul><ul><li>Survival related to : - No. of metastatic nodes - Bilaterality - Level of metastatic nodes - Perinodal extension </li></ul><ul><li>(Srinivas 1989, Tongaonkar 1992) </li></ul>
    27. 28. Treatment of regional nodes <ul><li>Non palpable nodes </li></ul><ul><li>20% harbour micrometastasis. </li></ul><ul><li>Low risk pTis, pTaG1-2, pT1G1 </li></ul><ul><li>Surveillance. </li></ul><ul><li>Occult micrometastasis in < 16.5%. </li></ul><ul><li>Solsona J Urol 2001;165:1506-1509, Horenblas J Urol 1994;151:1239-1243, Theodoreson 1996 J Urol;155:1626-1631 </li></ul>
    28. 29. Treatment of regional nodes <ul><li>Non palpable nodes </li></ul><ul><li>Intermediate risk T1G2 </li></ul><ul><li>Vascular / lymphatic invasion & growth pattern. </li></ul><ul><li>Surveillance for superficial pattern & no invasion. </li></ul><ul><li>Modified lymphadenectomy in infiltrating growth pattern or invasion. </li></ul><ul><li>? Role of sentinnel node biopsy. </li></ul><ul><li>Solsona J Urol 2001;165:1506-1509, Horenblas J Urol 1994;151:1239-1243, Theodoreson 1996 J Urol;155:1626-1631 </li></ul>
    29. 30. Treatment of regional nodes <ul><li>Non palpable nodes </li></ul><ul><li>High risk T (2 or G3) </li></ul><ul><li>Modified or radical lymphadenectomy. </li></ul><ul><li>70% may have occult metastasis. </li></ul><ul><li>Solsona J Urol 2001;165:1506-1509, Horenblas J Urol 1994;151:1239-1243, Theodoreson 1996 J Urol;155:1626-1631 </li></ul>
    30. 31. Treatment of regional nodes <ul><li>Palpable nodes </li></ul><ul><li>Present at diagnosis in 58% patients. </li></ul><ul><li>Of these 17-45% have nodal metastasis while remaining have iflammatory disease. </li></ul><ul><li>Horenblas J Urol 1993;149:492-497, Ornellas J Urol 1994;151:1244-1249 </li></ul>
    31. 32. Treatment of regional nodes <ul><li>Positive palpable nodes </li></ul><ul><li>Bilateral radical inguinal lymphadenectomy. </li></ul><ul><li>Probability of pelvic node involvement </li></ul><ul><li>23% , 2-3 nodes +ve & 56%, >3 nodes +ve </li></ul><ul><li>Culkin J Urol 2003;170:359-365 </li></ul><ul><li>Incidence of pelvic nodes ↑ to 30% in 2-3 node group with delayed pelvic lymphadenectomy. </li></ul><ul><li>Ornellas J Urol 1994;151:1244-1249 </li></ul>
    32. 33. Treatment of regional nodes <ul><li>Fixed inguinal mass / clinically +ve pelvic nodes </li></ul><ul><li>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) </li></ul><ul><li>Subsequent radical ilioinguinal lymphadenectomy. </li></ul><ul><li>Radiotherapy followed by lymphadenectomy but higher morbidity. </li></ul>
    33. 34. Treatment of regional nodes <ul><li>Inguinal palpable nodes during surveillance </li></ul><ul><li>Bilateral radical inguinal lymphadenectomy </li></ul><ul><li>Inguinal lymphadenectomy at site of +ve nodes in cases of long disease free interval. </li></ul>
    34. 35. Inguinopelvic Lymphadenectomy Indications for adjuvant therapy <ul><li>>2 metastatic inguinal nodes </li></ul><ul><li>Extranodal extension of disease </li></ul><ul><li>Pelvic lymph node metastases </li></ul>
    35. 36. Treatment <ul><li>Integrated therapy </li></ul><ul><li>In pts presenting with primary tumor and +ve nodes, both issues should be managed simultaneously. </li></ul><ul><li>In pts presenting initially with +ve pelvic nodes, induction chemotherapy followed by radical / palliative surgery or DTx is administered according to tumor response. </li></ul>
    36. 37. Treatment <ul><li>Distant metastasis </li></ul><ul><li>Chemotherapy. </li></ul><ul><li>Palliative therapy. </li></ul>
    37. 38. Treatment <ul><li>Technical aspects </li></ul><ul><li>Surgeons experience. </li></ul><ul><li>Formal circumcission before radiotherapy. </li></ul><ul><li>~ 2 cm tumor free margin. </li></ul><ul><li>Landmarks for RIL include inguinal lig, adductor & sartorius muscle, femoral vessels. </li></ul><ul><li>MIL, saphenous vein should be preserved, boundaries 1-2 cm less than radical surgery. </li></ul><ul><li>PL includes external iliac & ilio obturator chains with boundaries of iliac bifurcation, ilioinguinal & obturator nerve. </li></ul>
    38. 39. Treatment <ul><li>Technical aspects </li></ul><ul><li>Complications of LND. </li></ul><ul><li>Sentinnel node biopsy & its limitations. </li></ul><ul><li>92% identified, 23 % +ve for tumor. </li></ul><ul><li>Various lasers, CO 2 0.1cm & NdYAG 0.4cm absorption, local recurrence +/- 25%. </li></ul>
    39. 40. Treatment <ul><li>Quality of Life </li></ul><ul><li>Age, performance status. </li></ul><ul><li>Socioeconomic factors. </li></ul><ul><li>Sexual function. </li></ul><ul><li>Patient motivation. </li></ul><ul><li>Psychological aspects. </li></ul><ul><li>Morbidity of various procedures. </li></ul><ul><li>Tumor biology. </li></ul>
    40. 41. Chemotherapy <ul><li>cis platin +/- 5FU, VMB, CMB. </li></ul><ul><li>Adjuvant following RLND, 82% 5 yr survival. </li></ul><ul><li>Pizzocaro Acta Oncol 1988;27:823-4 </li></ul><ul><li>Neo adjuvant, fixed inguinal nodes, 56% resectable & 31% cured. Pizzocaro J Urol 1995;153:246 </li></ul><ul><li>Advanced disease, 32% response rate, 12% Rx related deaths. </li></ul><ul><li>Haas J Urol 1999;161:1823-1825, Kattan Urol 1993;42:559-62 </li></ul>
    41. 42. Radiotherapy <ul><li>Primary tumor </li></ul><ul><li>EBR, response rate 56%, failure 40%. </li></ul><ul><li>Brachytherapy, response rate 70%, failure 16%. </li></ul><ul><li>Tumor size < 4 cm. </li></ul><ul><li>Complications </li></ul><ul><li>telengiectasia >90%, meatal stenosis 30%, urethral strictures / fistula 35%, penile necrosis. </li></ul>
    42. 43. Radiotherapy <ul><li>Prophylaxis </li></ul><ul><li>NOT recommended. (fails to prevent mets, morbidity, difficult to follow) </li></ul><ul><li>Neo adjuvant </li></ul><ul><li>can render fixed nodes operable. </li></ul><ul><li>Adjuvant </li></ul><ul><li>may be used to reduce local recurrence. </li></ul>
    43. 44. Follow up <ul><li>Most relapses in first 2 years. </li></ul><ul><li>0-7% chance of relapse after partial / total penectomy. </li></ul><ul><li>Development of palpable nodes with non palpable nodes initially means metastasis ~ 100%. </li></ul><ul><li>Physical exam, CT & CXR. </li></ul>
    44. 45. EAU guidelines on diagnosis Primary tumor PE mandatory, recording morphology & characteristics of lesion. Histological diagnosis or cytology is mandatory. Penile US advisable, if inconclusive MRI optional. Regional lymph nodes PE mandatory. Impalpable nodes, no indication for imaging or histology, DSNB adviable in intermediate & high risk pts. Palpable nodes, record morphology and characteristics, histology reqd
    45. 46. EAU guidelines on diagnosis Distant metastasis (only in pts with inguinal nodes) Pelvic / abdominal CT (pelvic nodes) Chest xray Bone scan only if symptomatic Laboratory determinations for specific conditions optional
    46. 47. EAU guidelines on treatment Primary Lesion Penile intraepithelial neoplasia Penis preserving strategy. Ta-1 G1-2 Penis conservation, partial amputation in non compliance to follow up. T1G3, T ≥ 2 Partial / total amputation standard, conservative option in selected pts Local recurrence following conservative therapy Second conservative procedure in no invasion cases Partial / total amputation in infiltrating recurrences.
    47. 48. EAU guidelines on treatment RN therapy in non palpable nodes Low risk of occult mets (pTis, pTaG1-2, pT1G1) Surveillance, MLND is optional in unreliable to follow pts. Intermediate risk (pT1G2) Strict surveillance is an option in cases with no lymphovas invasion & favourable growth pattern MLND is an option with poor histology, role of DSLNB MLND enlarged to RLND in presence of + ve nodes High risk (pT ≥2 or G3) MLND or RLND recommended.
    48. 49. EAU guidelines on treatment Palpable positive RLN Bilateral radical inguinal LND is standard recommendation. PLND can be performed in cases with at least 2 +ve LNs or extracapsular invasion. MLND can be considered on contralateral groin with no palpable nodes. Induction chemo followed by RLND for fixed inguinal mass or clinically +ve pelvic nodes, alternative is neo adjuvant DTx. Bilat RLND or LND at site of palpable nodes during surveillance, adjuvant chemo & DTx are options.
    49. 50. EAU guidelines for follow up Primary tumor Conservative therapy, every 2/12 for 2 yrs, 3/12 for 1yr, 6/12 long term. Partial / total penectomy, every 4/12 for 2 yrs, twice during third yr, then annually long term. Regional nodes & distant metastasis Primary tumor removed, 2/12 for 2 yrs, 3/12 for 1 yr, 6/12 for 2 yrs Lymphadenectomy (pN0), 4/12 for 2 yrs, 3/12 for 1 more yr Lymphadenectomy (pN1-3), PE, CT & CXR at regular intervals Bone scan if symptomatic
    50. 51. THANKS <ul><li>VENERATION </li></ul><ul><li>NEGELECT </li></ul>

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