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Penile carcinoma
This document discusses the management of penile carcinoma. Surgery is the mainstay of treatment and may involve circumcision, laser ablation, Mohs micrographic surgery, or penectomy depending on the location, size, and stage of the tumor. Radiotherapy options include brachytherapy and external beam radiation therapy. Chemotherapy has a limited role and is mainly used perioperatively for unresectable disease. Treatment aims to balance tumor control with organ preservation and minimizing psychosocial and sexual morbidity. Close multidisciplinary care and discussion of treatment expectations is important.
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Penile carcinoma
- 1. Penile Carcinoma: Management Dr. AnimeshAgrawal Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow
- 2. • Management dependson: • Location • Size • T stage • N stage • Histopathological characteristics • Patient preference (Organ preservation?)
- 3. Options • Surgery • Radiotherapy •EBRT • Brachytherapy • Chemotherapy • Local • Systemic
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- 5. Overview • Mainstay oftreatment • May involve • Circumcision • Laser ablation • Mohs micrographic surgery • Penectomy • Partial or total • Radical Surgery • Emasculation/ Hemipelvectomy • Not performed in common practice
- 6. Cirumcision • Indications/Reasons • Definitivetreatment 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)
- 7. Laser ablation • CO2or Nd:YAG lasers have been reported to provide good functional and cosmetic results.1 • Tis or T1; high recurrence rates are seen with > T2 lesions1. • 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 1. Meijer et al, Urol 2007 2. Windahl et al, J Urol 2003
- 8. • Excision oftissue 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 1/3rd 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 Micrographic surgery
- 9. Penectomy • Done forbulky 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
- 10. 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
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- 12. 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
- 13. SLN Biopsy • Sentinellymph 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
- 14. 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
- 15. 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 Nodal disease Regression Tissue Diagnosis Treat if Positive Follow up No Yes Adapted from DeVita’s Cancer, 10th edition.
- 16. Inguinal Lymph Nodes NCCN,2015 S U R V E I L L A C E
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- 19. Overview • Brachytherapy • Interstitital •Mould based • EBRT • Patient position • Fields (primary/nodal) • Dose (Primary/Nodal) • Indications? • Control rates • Complications
- 20. 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).
- 21. • Adjuvant RT 1.After Circumcision for T1-T2, N0 a. Brachytherapy alone b. EBRT + Chemotherapy 2. After Pelvic LN dissection. • Multiple nodes +ve for mets • Nodal disease > 4cm • Extranodal extension • B/L Nodes +ve
- 22. Brachytherapy • May beinterstitial 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.
- 23. • Ir-192 isthe 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.
- 24. • For anexterior plane, tissue equivalent bolus is placed between the needle and surface. a. Active length b. 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
- 25. 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
- 26. • Factors determiningprognosis 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.
- 27. Preparing and applyingthe mould
- 28. EBRT • 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
- 29. EBRT (contd) • Waterbath 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.
- 30. EBRT: Planning andDoses • 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.
- 31. EBRT: Planning andDoses • 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.
- 32. 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
- 33. 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
- 34. • (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.
- 35. • Tis: Topical5-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) 1. Haas et al, J Urol 1999 2. Bahl et al, JCO 2012 3. Pizzocaro et al, Eur Urol 2009 Chemotherapy
- 36. • Indication • Mostlyemployed perioperatively for unresectable disease. • Very high toxicity coupled with dismal disease control rates
- 37. (brachytx not available) PenileConservation Non penile conserving t/t Management of CA Penis: Summary Outline Laser Circumcision T1a T1b
- 38. Psychosocial issues • Primarysurgical 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.
- 39. Summary • A curabletumor 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.
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