Penile carcinoma

Penile carcinoma dr kiran

1. Carcinoma Penis DR KIRAN KUMAR BR

2. Benign Lesions Non cutaneous Cutaneous In c lu s ion/R e t e n t ion cysts Syringoma Neurilemmoma Angioma, Fibroma, Neuroma, Lipoma, Myoma Pseudotumors Penile papules Hirsute papillomas Coronal papillae Zoons erythroplasia Rashes & ulcerations secondary to irritation, allergy and infections

3. Premalignant lesions 42% of pts with SCC had hx of pre existing penile lesions. (Bouchot etal 1989) Cutaneous Horn P s e udo e pith e l i om a tous Micaceous & Keratotic Balanitis Balanitis Xerotica Obliterans Leukoplakia

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) Condylomata Acuminatum Bowenoid Papulosis Kaposi’s Sarcoma

5. 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) Condylomata Acuminatum Bowenoid Papulosis Kaposi’s Sarcoma

6. 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.

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

8. Carcinoma in situ • • • Penile 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 & CO 2 laser, liquid nitrogen Kelley etal 1974, Graham & Helwig 1973, Mortimer etal 1983

9. 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, 6 th 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)

10. E t i o l og y • • • • • • • Circumcission practice. Hygiene standards. Phimosis. No. of sexual partners. HPV(16,18) infection. Exposure to tobacco products. No convincing association with occupation, gonorrhea, syphillis & alcohol intake. Barrasso etal 1987, Maiche 1992, Maden etal 1993

11. P r e v en t i on Routine neonatal circumcission. AAP Paediatric guidelines 1999. Good hygiene practice. Avoid HPV infection and tobacco .

12. 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.

13. Pr e se n t a t i o n Symptoms malaise, wt loss, fatigue, weakness, hemorrhage, pain. Signs penile lesion. rarely nodal mass, ulceration, suppuration.

14. D i agn o s is Primary lesion. Regional lymph nodes. Distant metastasis. Physical examination. Ultrasound. MRI. CT. Cavernosography. Lymphangiography.

15. D i agn o s is Histological diagnosis is absolutely necessary prior to treatment decision. Growth pattern of SCC superficial spreading. vertical growth. multicentric. verrucous. Cubilla etal 1993

16. Grading systems 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 into 3 grades 5 year survival Grade 1 Grade 2,3 Grade 4 80% 50% 30%

17. S t a g i n g Jackson’s staging system, 1966.

18. TNM staging system

19. Management depends on: Location Size T stage N stage Histopathological characteristics Patient preference (Organ preservation?)

20. O p tions Surgery Radiotherapy EBRT Brachytherapy Chemotherapy Local Systemic

21. Su r g e r y

22. Overview Mainstay of treatment May involve Circumcision Laser ablation Mohs micrographic surgery Penectomy Partial or total Radical Surgery Emasculation/ Hemipelvectomy Not performed in common practice

23. Cirumcision Indications/Reasons Definitive treatment of carcinoma-in-situ ( Tis ) If phimosis is present, allows better visualization of disease If prepuce is involved, removes some of the tumor bulk → facilitates planning of treatment. Allows the radiation oncologist to better deal with RT toxicities (edema/phimosis/painful ulceration)

24. Laser ablation CO 2 or Nd:YAG lasers have been reported to provide good functional and cosmetic results. 1 Tis or T 1 ; high recurrence rates are seen with > T2 lesions 1 . Local recurrences of ~20% are reported; these can be salvaged by re-treatment, RT or surgery. 2 Extended, careful follow-up required; only 57% of local recurrences occur within the first 2 years, 30% between 6 and 10 years, and 15% after 10 years. 2 Meijer et al, Urol 2007 Windahl et al, J Urol 2003

25. Excision of tissue in successive layers with microscopic scanning of each layer to identify any tumor outgrowths Successive layers removed until margins are histologically clear. Local recurrences in upto 1/3 rd patients; usually salvageable by repeat procedures/surgery. 1 May be offered to selected patients (Tis, ? T1 ) who are reliable for follow up. 1. Shinde et al, J Urol 2007 Mohs M ic r og r aphic surgery

26. P ene c t o m y Done for bulky lesions; usually T2 and beyond. The goal is to leave adequate penile length for hygienic upright micturition and intercourse. Margin needed: 2cm has been tradiationally advocated. Current data suggests 5-10mm margins are as safe as 2cm margins. 1 When a total penectomy has to be done, perineal urethrostomy is needed. Phalloplasty may be done at equipped centres. 1. Minhas et al. BJU Int 2005

27. Results with Surgery 5 year overall survivals: Early stage disease 55-80% 87% DFS at 5 years in Node negative patients. 1 1. Ornellas et al. J Urol 1994

28. Inguinal Lymph Nodes

29. Clinical Node Negative (N0) ~ 20% have occult metastases on prophylactic lymph node dissection. Divided into low and high risk. 1 Low-Risk Group: Patients with carcinoma in situ (Tis), verrucous carcinoma (Ta), and T1 tumors who have grade 1 or 2 tumor histology <10% chance of developing lymph node metastases Surveillance / DSNB High-Risk Group T2 and T3 with grade 3 tumors and vascular invasion. >50% incidence of inguinal lymph node metastases. ILND / DSNB 1. Slaton et al, J Urol 2001 DSNB: Dynamic Sentinel Node Biopsy

30. SLN Biopsy Sentinel lymph node biopsy as originally described by Cabanas is no longer recommended in view of the high false-negative rate. 1 Dynamic SLN biopsy can decreased the false-negatives and morbidity. 2-4 Difficult to adopt at smaller, low volume centres. Other approaches involve evaluation of micrometastases and the size of the SLN to determine whether to perform lymphadenectomy . 5 Lymphotropic nanoparticle-enhanced MRI (LNMRI) has been investigated. 6

31. Dynamic SLN Biopsy Advocated by modern high volume centres. Suggested algorithm by the EAU. 1 Resource intensive. Has a high sensitivity and specificity; false negatives <5%. Prospective validation awaited. 1. Yeung LL, Brandes SB. Urol Oncol 2013

32. Clinically Node Positive (N+) ~ 50% present with palpable inguinal nodes. Half of these have inflammatory adenopathy secondary to infection of the primary lesion. Two possible approaches. Node +ve Treat the Primary Antibiotics for 4-6 weeks Tissue Diagnosis Treat if Positive Follow up Nodal disease Regression No Yes Adapted from DeVita’s Cancer, 10 th edition.

33. Inguinal Lymph Nodes NCCN, 2015 S U R V E I L L A C E

34. Inguinal Lymph Nodes ESMO, 2013

35. Radiotherapy

36. Overview Brachytherapy Interstitital Mould based EBRT Patient position Fields (primary/nodal) Dose (Primary/Nodal) Indications? Control rates Complications

37. Indications Definitive brachytherapy (ABS consensus statement, 2013): Node negative disease, with: T1b disease T2 lesion < 4cm (ideally restricted to the glans) T3 disease without disruption of urethral mucosa Definitive EBRT as organ preserving treatment: When brachytherapy is not available. Patient not a surgical candidate Neoadjuvant External beam chemoradiotherapy Fixed inguinal nodes +ve for mets (ESMO; no role as per NCCN).

38. Adjuvant RT After Circumcision for T1-T2, N0 Brachytherapy alone EBRT + Chemotherapy After Pelvic LN dissection. Multiple nodes +ve for mets Nodal disease > 4cm Extranodal extension B/L Nodes +ve

39. B r ac h y the r a p y May be interstitial or mould based. Mould based treatments are non-invasive and can be performed without anesthesia. Not suitable for T2 or T3 disease. Interstitial treatment may be performed under Local/regional anesthesia.

40. Ir-192 is the source employed (LDR, PDR and HDR). Two to three planes of needles/catheters are usually sufficient for disease coverage. These can be held in place by predrilled templates (needles) or fixing buttons. A Foley’s catheter is placed during application to assist urethral localization.

41. For an exterior plane, tissue equivalent bolus is placed between the needle and surface. Active length Treated length d. Lateral margin c. Space between planes c. Instersource spacing Dose: LDR: 60 Gy @ 0.5-0.6 Gy/hr, over 5 days (12 hrs/day) PDR: 60 Gy, Pulses equal to the hourly dose rate, each hour HDR: 38.4 Gy @ 3.2 Gy twice daily for 6 days

42. Results with Brachytherapy Long-term (5–10 years) local control rates vary between 60% and 90% and seem more related to tumour characteristics than treatment parameters. Compare favourably with surgical series. 1. Sarin et al, IJROBP 1997

43. Factors determining prognosis after brachytherapy* Tumor size (< 4cm) 1 Depth of invasion (< 1cm) 2 Tumor volume (< 8ml) 3 No. of brachytherapy needles (< 6) 3 Spacing between individual needles (wider spacing) 4 Bracketed parameters suggest a good prognosis.

44. Preparing and applying the mould

45. EB R T Patient Positioning Supine or prone with hands above the head The organ has to be kept in position by a wax/acrylic block to create a reproducible setup. Figure shows a wax block with a central cylindrical chamber. Tissue equivalent material should be placed in the chamber distally. Catheterization may prevent slumping of the organ as disease regresses. Supine setup

46. EBRT (contd) Water bath technique: The patient lies prone on Styrofoam slabs such that the penis is suspended in a water bath. Transparent sides on the water bath permit a visual check of penile position. A: View from above of plastic box with central cylinder. Patient is treated in the prone position. The penis is placed in the central cylinder, and water is used to fill the surrounding volume. B: Lateral view.

47. EBRT: Planning and Doses Patient should be circumcised. B/L groins, external iliac and hypogastric nodes should be included. Unless the patient has a high disease burden/positive posterior pelvic nodes, these may be excluded. Bolus may be considered for tumor/nodal disease close to skin surface.

48. EBRT: Planning and Doses 4-6 MV Photons (Cobalt-60 or LINAC) EBRT Dose (when surgery not done) Node -ve: 60-65 Gy @ 2 Gy per fraction, 6-6.5 weeks with reduced fields (GTV boost with 2 cm margin) for the last 5-10 Gy. Node +ve: 70-75 Gy @ 2 Gy per fraction, 7-7.5 weeks with reduced fields after 50 Gy. Postoperative setting: 45-50.4 Gy to Nodal basins if Node +ve Boosted to 60-70 Gy for R1 resection Areas with gross nodal disease and with ECE If Nodal dissection not done, Nodal fields as before.

49. Results with EBRT Most data is from series spanning several years over which staging changed and management evolved; however results have been concordant. Sarin et al noted a higher incidence of local failure was observed with total dose <60 Gy, dose per fraction <2 Gy and treatment time exceeding 45 days. 1 1. Sarin et al, IJROBP 1997

50. Complications of Radiotherapy Acute Reactions: Erythema, dry or moist desquamation, swelling of the subcutaneous tissue of the shaft in virtually all patients. Peak at around 3-4 weeks after brachytherapy and towards the end of EBRT; resolve by 1-2 months post RT. Late sequelae: Telangiectasia: usually asymptomatic. Soft tissue necrosis: Most common cause of amputation. Peaks 7-18 months after RT Associated with a higher dose of RT

51. (Late sequelae) Urethral strictures Mostly meatal; occur in upto 40%. Usually before 3 years Correlates with urethral dose Adhesions in acute phase should be separated, and late phase stenoses should be managed by repeated dilatations. Sexual function Can resume as soon as patient is comfortable, but with lubricant Appears to correlate with dose to testes; can be shielded by placing a lead plate/sheet into the Styrofoam collar around the base of penis.

52. Tis: Topical 5-FU cream and imiquimod for glandular and meatal lesions. Cisplatin combination chemotherapy regimens are the most widely used and seem to be the most effective. No randomized evidence. Of the various combinations tested, the following have shown promise: 1-3 Cisplatin / Methotrexate / Bleomycin (CMB) Taxane / Cisplatin / 5 FU (TPF) Haas et al, J Urol 1999 Bahl et al, JCO 2012 Pizzocaro et al, Eur Urol 2009 Chemotherapy

53. Indication Mostly employed perioperatively for unresectable disease. Very high toxicity coupled with dismal disease control rates

54. (brachyt x not available) Penile Conservation Non penile conserving t/t Management of CA Penis: Summary Outline L a s er Circumcision T 1a T 1b

55. Psychosocial issues Primary surgical management permits durable response but causes considerable psychosexual morbidity. Treatment expectations, outcomes and post treatment rehabilitation must be discussed with both patient and his partner. Referral to a trained therapist may be warranted.

56. Summa r y A curable tumor but significant treatment associated morbidity. Treatment is mainly surgical. Radiotherapy may be Brachytherapy (early disease) or EBRT (unresectable ds/adjuvant). Role of chemotherapy still evolving. Education and awareness needed for early diagnosis and during management.

57. Thank You