What are the evaluation and management strategies for a patient with carcinoma of the penis, including signs of inoperability?

Evaluation and Management of Penile Carcinoma

Initial Evaluation

The initial assessment must document specific physical characteristics: diameter, location, number of lesions, morphology (papillary, nodular, ulcerous, or flat), and relationship to anatomical structures including submucosa, tunica albuginea, urethra, corpus spongiosum, and corpus cavernosum. 1

Primary Tumor Assessment

• Obtain tissue diagnosis via punch, excisional, or incisional biopsy—avoid superficial scrapings as they may not be sufficiently representative 1
• MRI or ultrasound are optional studies to further define concerning physical exam findings and provide detailed anatomic assessment 1, 2
• MRI is the most accurate technique for local staging and depicts penile anatomy in detail 2

Regional Lymph Node Evaluation

The lymph node status provides the strongest prognostic factor for survival 1:

For clinically negative nodes (cN0):

• Dynamic sentinel node biopsy (DSNB) is indicated for intermediate-risk (T1G2) or high-risk disease (T1G3 or worse, lymphovascular invasion, >50% poorly differentiated) 1
• DSNB has a 97% sentinel node identification rate, 7% false-negative rate, and 4.7% complication rate 1
• If DSNB unavailable, use ultrasound-guided fine-needle aspiration cytology (FNAC) of visualized nodes 1, 2
• Note: approximately 50% of palpable inguinal nodes at diagnosis are inflammatory rather than metastatic 1

For palpable nodes:

• Perform percutaneous FNAC biopsy and/or histology 1
• If biopsy negative but nodes remain clinically suspicious, repeat biopsy or perform node excision 1
• Nodes becoming palpable during follow-up are malignant in nearly 100% of cases 1

Distant Metastasis Evaluation

• Pelvic CT scan or PET-CT for patients with metastatic inguinal nodes 1
• 18F-FDG PET/CT appears most accurate for detecting pelvic lymph node metastases and identifying distant metastases in node-positive disease 1, 3

Management Strategies

Primary Tumor Treatment

Organ-sparing approaches should be prioritized when oncologically appropriate:

For Tis/Ta disease:

• Topical therapy (imiquimod or fluorouracil cream) 1
• Laser therapy (Category 2B) with ~18% local recurrence rate 1, 4
• Wide local excision including circumcision 1, 5

For T1 disease:

• Wide local excision including circumcision 1
• Laser therapy (Category 2B) for carefully selected G1-2 lesions with close follow-up 4
• Complete glansectomy (Category 2B) 1

For T2 or greater:

• Partial penectomy is the standard for high-grade tumors provided functional penile stump can be preserved and negative margins obtained 1
• Total penectomy for extensive disease 1

Radiation Therapy (Category 2B for Penile Preservation)

For T1-2, N0, tumor <4 cm:

• Circumcision followed by brachytherapy alone (interstitial implant) OR external beam radiotherapy (EBRT) ± chemotherapy: 65-70 Gy to primary with 2 cm margins 1
• Consider prophylactic inguinal lymph node irradiation 1

For T1-2, N0, tumor >4 cm:

• Circumcision followed by EBRT with chemotherapy: 45-50.4 Gy to penile shaft ± pelvis/inguinal nodes, then boost primary to 60-70 Gy 1

For T3-4 or N1:

• Circumcision followed by EBRT with chemotherapy: 45-50.4 Gy to whole penile shaft, pelvic and bilateral inguinal lymph nodes, then boost to 60-70 Gy 1

Lymph Node Management

Standard or modified inguinal lymph node dissection (ILND) or DSNB (Category 2B) is indicated for high-risk features even without palpable adenopathy: 1

• Lymphovascular invasion
• pT1G3 or ≥T2 any grade

• 50% poorly differentiated histology

Pelvic lymph node dissection (PLND) should be considered at time of ILND if ≥2 inguinal nodes positive on frozen section or delayed procedure if extranodal extension present 1

Neoadjuvant cisplatin-based chemotherapy should be considered standard prior to ILND in patients with 2-4 cm inguinal lymph nodes (fixed or mobile) if FNA positive 1

Signs of Inoperability

Inoperability is suggested by:

• Fixed inguinal lymph nodes requiring neoadjuvant chemotherapy before attempting surgical resection 1
• Extensive pelvic lymph node involvement detected on CT or PET-CT 1, 3
• Distant metastases on staging imaging 1
• T4 disease with extensive local invasion into adjacent structures that precludes adequate surgical margins 1
• Poor performance status precluding major surgery or multimodal therapy 6

Surveillance

For patients treated with organ-sparing approaches:

• Clinical exam every 3 months year 1-2, then every 6 months year 3-5, then annually year 5-10 1

For patients treated with penectomy:

• Clinical exam every 6 months year 1-2, then annually year 3-5 1

For node-negative patients on active surveillance:

• Clinical exam every 3-6 months year 1-2, then every 6-12 months year 3-5 1
• Imaging (chest CT/X-ray and abdominopelvic CT/MRI) as clinically indicated 1

Critical Prognostic Factors

Lymphovascular invasion and venous embolization are the main factors predicting lymph node metastasis, which represents the strongest prognostic factor for survival 1, 7. The presence and extent of nodal metastases, number of positive nodes, and extracapsular extension provide the most critical prognostic information 1, 7.