Management of Groin in Cancer of the Penis Hemant B. Tongaonkar Professor & Head Urologic Oncology Services Tata Memorial Hospital, Mumbai

Penile Cancer Presence and extent of inguinal nodal metastases most important prognostic factor for survival

Penile Cancer Prolonged locoregional phase before mets occur Superficial inguinal LN most frequent site of lymphatic mets LN involvement generally stepwise LN mets beyond pelvis considered distant Lymphadenectomy can be curative & need not be treated as systemic disease

Penile cancer Problems in management of groin LN mets single most imp prognostic parameter 10-20% have occult LN mets in patients with clinically negative groin 50% of patients with palpable groin nodes do not have metastasis Clinical prediction of nodal spread unreliable & inaccurate

Penile Cancer Assessment of groin Clinical examination Lymphangiography High resolution USG with FNAC Fine needle aspiration cytology Sentinel node biopsy with patent blue dye or lymphoscintigraphy Histological evaluation at surgery is the Gold Standard

Penile Cancer: Management of Groin Nodes Crucial questions Predictors of lymph node mets Indications for lymphadenectomy Prophylactic vs therapeutic Extent of lymphadenectomy Superficial vs deep inguinal Inguinal or inguinopelvic Unilateral vs bilateral No prospective or randomized trials

Inguinopelvic Lymphadenectomy Good Prognostic Factors Minimal nodal disease (2 or less nodes) Unilateral involvement No extranodal extension Absence of pelvic node metastases

Penile Cancer Lymphadenectomy is indicated in patients with palpable inguinal lymphadenopathy that persists after treatment of the primary penile lesion following a course of antibiotic therapy Srinivas 1987, Ornellas 1994

Penile Cancer Management of No groin Early prophylactic lymphadenectomy Versus Surveillance (delayed lymphadenectomy)

Penile Cancer Early Prophylactic Lymphadenectomy for N0 Groin Cure rate may be as high as 80% Lymph node metastases in nearly 30% Reluctance due to substantial morbidity Less likely in prophylactic setting Modified extent of dissection Better surgical technique Preservation of dermis, scarpa’s fascia & saphenous veins Myocutaneous flap coverage

Early vs Delayed Lymphadenectomy Early better Baker 1976 (n=37): 59% vs 61% McDougal 1986 (n=23): 83% vs 36% (66% in patients with N1 with GND) Fraley 1989, Johnson & Lo 1984, Lynch 1997, Ornellas 1999 Delayed LND unable to salvage relapses (Fossa 1987, Fraley 1989, Johnson 1984, Ravi 1993, Srinivas 1987) Early prophylactic better than delayed therapeutic “Window of opportunity” Reluctance due to morbidity

Early vs Delayed Lymphadenectomy No difference Ravi 1993: (n=371): 100% vs. 76% (NS) Probably due to: Patient selection Strict follow up Aggressive treatment at relapse Can delayed therapeutic dissection reliably & Effectively salvage inguinal recurrences?

N0 Groin: Treatment Options Fine needle aspiration cytology Isolated node biopsy Sentinel node biopsy Extended sentinel LN dissection Intraoperative lymphatic mapping Superficial dissection Modified complete dissection Is there a role for Spiral CT or PET scan?

Fine needle aspiration cytology Requires pedal / penile lymphangiograhy for node localization & aspiration under fluoroscopy guidance Multiple nodes to be sampled Sensitivity 71% (Scappini 1986, Horenblas 1993) Can provide useful information to plan therapy when +ve

Unreliable method: Not recommended Sentinel Node Biopsy Based on penile lymphangiographic studies of Cabanas (1977) Accuracy questioned: False –ve 10=50% (Cabanas 1977, McDougal 1986, Fossa 1987) Extended sentinel node biopsy: 25% false –ve False –ve due to anatomic variation in position of sentinel node Unreliable method: Not recommended

Intraoperative Lymphatic Mapping Potential for precise localization of sentinel node Intradermal inj of vital blue dye or Tc- labeled colloid adjacent to the lesion Horenblas 11/55: All +ve False –ve in 3 Pettaway 3/20: All +ve No false –ve Tanis (2002): 18/23 +ve detected (Sensitivity 78%) Promising technique for early localization of nodal metastases Long-term data needed

Superficial Inguinal LND Removal of nodes superficial to fascia lata If nodes +ve on FS: Complete inguino-pelvic LND Rationale: No spread to deep inguinal nodes when superficial nodes –ve (Pompeo 1995, Parra 1996) No clinical evidence of direct deep node mets when corporal invasion present

Complete Modified LND (Catalona 1988) Smaller incision Limited inguinal dissection (superficial + fossa ovalis) Preservation of saphenous vein Thicker skin flaps No sartorius transposition Identifies microscopic mets without morbidity (Colberg 1997, Parra 1996)

Limited Inguinal LND: Advantages Provides more information than does biopsy of a single node or group of nodes Avoids missing the sentinel node by removing all potential first echelon nodes Spares patients the morbid consequences associated with traditional LND Can be performed by any surgeon

Penile Cancer Predictors of lymph node metastases Tumour histology Corporal invasion Urethral involvement Tumour grade Lymphatic & vascular invasion DNA ploidy

Penile Cancer LN mets in stage T1 G1-2 cancers Author Stage/Grade N % LN mets Fraley T1G1 19 1 (5.2%) Theodorescu 8 2 (25%) Solsona T1G1-2 23 1 (4.3%) McDougal 24 1 (4%) Heyns 91 5 (6%) 17 1 (6%) Total 182 11 (6%)

Penile Cancer Corporal Invasion vs. LN Mets Author N +ve nodes McDougal 23 11 (48%) Fraley 29 26 (90%) Theodorescu 18 12 (67%) Villavicencio 37 14 (38%) Lopes 44 28 (64%) Heyns 32 15 (47%) Solsona 42 27 (64%) Total 225 133 (59%)

Penile Cancer Risk Grouping for Inguinal Nodal Metastases Low risk Tis / Ta T1 Grade I-II No vascular invasion <10% LN mets Surveillance High risk T2-T3 Grade III Vascular invasion Non-compliance >50% LN mets Early lymphadenectomy

Penile Cancer: N0 High Risk Group Goals of Treatment To determine whether occult metastases exist in inguinal nodes To maximise detection & treatment for those with proven nodal metastases To limit treatment morbidity in those with histologically negative nodes

Management: High risk patients Bilateral N0 groin Bilateral superficial or modified inguinal LND Node -ve Unilat +ve Bilat +ve Conclude Unilat inguino- Bilat inguino- pelvic LND pelvic LND

Cancer Penis Management of N+ groin Surgical treatment recommended for operable inguinal metastatic disease Most patients with inguinal LN mets will die if untreated. 20-67% patients with metastatic inguinal LN disease free 5 years after LND. Better survival 82-88% with single / limited mets

Resectable Inguinal Lymphadenopathy Complete inguinopelvic lymphadenectomy Therapeutic value justifies morbidity Goals: To eradicate all cancer To cover the vasculature To ensure rapid wound healing

Lymphadenectomy Unilateral vs. Bilateral Anatomic crossover well-established & bilateral drainage a rule (Lymphangiography & IOLM studies) Synchronous: Contralateral nodes in 50% (Ekstrom 58) Bilateral LND must Contralateral side: Superficial – FS Metachronous: Unilateral may be justified if RFS >12 mo

Should pelvic lymphadenectomy be performed in patients with positive inguinal nodes? Pelvic LN mets related to inguinal LN mets (Ravi 1993, Srinivas 1987, Kamat 1993) Inguinal nodes Pelvic nodes -ve -ve 1-3 +ve 22% >3 +ve 57% Although overall survival 10%, occasional long-term survivals reported

Pelvic Lymphadenectomy Staging tool Identifies patients likely to benefit from adjuvant chemo Adds to locoregional control No additional morbidity If pre-op pelvic node identified : NACT followed by surgery in responders Value of pelvic LND unproven Patients with minimal inguinal disease & limited pelvic LN mets may benefit

Inguinopelvic Lymphadenectomy Pathologic criteria for long-term survival Minimal nodal metastases (upto 2) Unilateral involvement No extranodal extension Absence of pelvic node metastases 80% five year survival

Penile Cancer Pelvic LN Mets vs. Survival Author Pts with +ve LN 5 yr survival Dekernion 2 1 (50%) Horenblas Srinivas 11 Pow-Sang 3 2 (66%) Kamat 6 2 (33%) Ravi 30 Total 54 5 (10%)

Cancer Penis Substratification of LN vs survival Survival with metastatic inguinal LN 20-25% Survival related to : - No. of metastatic nodes - Bilaterality - Level of metastatic nodes - Perinodal extension (Srinivas 1989, Tongaonkar 1992)

Inguinopelvic Lymphadenectomy Indications for adjuvant therapy >2 metastatic inguinal nodes Extranodal extension of disease Pelvic lymph node metastases

Penile Cancer Management of fixed nodes Neoadjuvant chemo + surgery in responders Palliative chemotherapy Chemotherapy + radiation therapy

Complications of lymphadenectomy Persistent lymphorrhoea Wound breakdown, necrosis, infection Lymphocyst Femoral blowout Lymphangitis Lymphoedema of lower extremity

Cancer Penis Measures to reduce morbidity of GND Choice of incision Downscaling of template Saphenous vein sparing Reconstructive techniques Lymphovenous shunts

Tensor fascia lata myocutaneous flap

Measures to reduce morbidity of GND TMH experience (n = 100) Elective excision of skin overlying the lymph node area Reconstruction with TFL or anterolateral thigh flap Significant reduction in early & late morbidity ? Improved disease control

Penile Cancer: Conclusions Uncommon disease No systematic study & complete absence of RCTs Small no of patients over a long time Poor decision making, treatment delays, poor compliance to treatment & follow up RCTs to develop guidelines essential