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Pre-Cancerous/Malignant Lesions

Penile Intraepithelial Neoplasia (PEIN/PIN)

• Associated with HPV in 90% cases
• Erythroplasia of Queyrat: CiS of glans or prepuce, progression in 10-33%
• Bowen disease: CiS of penile shaft, genitalia, or perineal region, progression in 5%
• Bowenoid papulosis: similar-appearing to CiS but benign, multiple papules
• Treat with circumcision if located on foreskin
• Margin: 5mm adequate for local control, glans defects can be repaired with skin graft
• Consider 5-FU or 5% imiquimod cream, laser excision

Balanitis Xerotica Obliterans (BXO, male lichen sclerosis)

• Whitish patches on prepuce/glans/meatus/fossa navicularis
• Treat with clobetasol cream for 2-3 months
• treat stenosis with dilation, steroids, or reconstruction

Condyloma acuminata (genital warts)

• Rare before puberty (consider sexual abuse)
• 5% have urethral involvement, may require 5-FU, pediatric resectoscope, or urethroplasty
• HPV present in 50-70% specimens
• HPV infection risk increased with uncircumcised state, increased sexual partners, non-condom use, and smoking
• Subclinical lesions diagnosed via applying 5% acetic acid, lesions will be white under magnifying glass
• Treatments: trichloroacetic acid 35-85%, cryotherapy, electrofulguration, CO₂ laser, imiquimod 5% cream
• Consider circumcision to remove preputial lesions and provide better glans exposure

Buschke-Lowenstein Tumor

• Uncontrolled local growth of condylomas causing destruction/displacement of adjacent tissues without metastasis
• Excisional or deep biopsies required to differentiate from penile cancer
• Treat with complete excision and possible skin grafts
• XRT and topical therapies non-beneficial

Kaposi Sarcoma

• Varieties: classic (indolent), immunosuppressive, African (young, indolent or aggressive), epidemic or HIV-related
• Treat nonepidemic forms aggressively due to rarity of diffuse organ involvement, surgery or EBRT effective
• Consider withdrawing immunosuppression to treat
• AIDS increases risk x7000, can treat with surgery, XRT, or laser removal

Penile Cancer

Risk Factors

• Neonatal circumcision eliminates risk due to lack of smegma irritation, no benefit for adult circumcision
• HPV seen in 31-63% penile cancers
• Other risk factors: HIV, tobacco use, increased sexual partners, trauma, BXO

Natural History

• Invasion through Buck fascia can lead to vascular dissemination of tumor
• Regional nodal metastases can cause skin necrosis, infection, hemorrhage from erosion into femoral vessels
• Clinically detectable metastases seen in 1-10%, presence in absence of regional nodal metastases is rare
• Mortality rates high within 2 years, no spontaneous remission reported, second primary develops in 5-17%

Presentation

• Penile lesion is first sign - according to Campbell's, may present as a "luxuriant exophytic lesion"
• Phimosis can obscure a lesion, presenting with erosion through prepuce, odor, discharge/bleeding
• Location: glans (48%), prepuce (21%), prepuce + glans (9%), coronal sulcus (6%), shaft (< 2%)
• Pain is not a common symptom
• Inguinal lymph node exam is important and more informative than imaging, although exam understages in 10% and overstages in 16%
• Care delays seen in 15-50% for more than 1 year, high levels of denial regarding condition

Diagnosis

• Perform biopsy to assess depth, vascular invasion, and histologic grade
• Biopsy can be separate from definitive surgical treatment
• Low-grade lesions make up 70-80% cases
• Imaging is not currently indicated due to poor accuracy
• If palpable nodal disease, obtain CT A/P to assess for poor prognostic features - central necrosis or irregular nodal border were predictive of 3+ positive LN, ENE, or positive pelvic nodes

Staging Tips

• T1a vs T1b: inguinal metastasis (10-18% vs 33-50%)
• T2 (78%) vs T3 (53%): disease specific survival (78% vs 53%), inguinal metastasis (33-35% vs 49-53%)
• N1 vs N2: disease specific survival (90% vs 60%)

Penile Cancer Treatments

Surgical removal

• Penectomy: consider if > 4cm, grade 3-4, or T2+
• Consider organ-sparing treatments if Tis, Ta, or T1 (low grade), margins < 2cm reasonable
• Minimally invasive options include glans stripping and Mohs surgery, but may have no additional benefit over other options
• Consider topical therapies (imiquimod, 5-FU) for Ta, TiS
• Risk of local recurrence: penectomy (0-8%), organ-sparing (2-6%), laser ablation (7%), Mohs surgery (32%)
• Palliative resection: may improve short-term QoL but rarely provides cure, survival 21%, 8%, 4% at 1, 2, 3yrs

Nodal Treatments

• Recommended for any primary tumor besides Tis, Ta, or T1 (with low grade) - 0-16% +LN rate
• 25% risk LN metastases if nonpalpable LNs
• Delaying ILND by > 12 weeks decreases 5yr survival 64% to 40%
• Prognostic factors associated with longterm survival: ≤ 2 LNs +, unilateral disease, no ENE, and no pelvic metastases
• Screening FNA: 93% sensitivity and 91% specificity if palpable adenopathy, avoids giving patients 4-6 weeks antibiotics prior to considering surgery
• Perform bilateral ILND if unilateral adenopathy, due to presence of bilateral drainage - may not be indicated if delayed adenopathy after primary treatment
• Consider PLND if 2+ LN in ILND or ENE
• Make incision transverse to minimize risk for skin necrosis
• 5yr survival: 90-100% for negative ILND, 80% for 1 positive node, 50% for 2+ unilateral nodes, and 10% for bilateral positive nodes, extranodal extension, or positive pelvic nodes
• Early mobilization now recommended unless flap used (bedrest 48-72hr)
• Continue postoperative antibiotics x1 week or until drains removed (< 50mL/d)
• Continue drains until < 100-150mL/d
• Complications: wound issues (0.6-43%), lymphedema + lymphocele + seroma (2.4-26.5%)

Radiation

• Most appropriate if T1-T2, < 4cm, no/minimal extension beyond coronal sulcus
• Most often used if too old/sick for surgical therapy, or locoregionally advanced disease
• Option for primary tumors, may require pre-XRT circumcision, salvage surgery remains an option
• Results: 5yr local control 55-70%, penile preservation 39-66%
• Lower control if T3+, > 4cm, high grade tumors
• Brachytherapy (high/low) are options - 5yr local control 77-88% and penile preservation 74-88%, 10yr local control 70-80% and penile preservation 67-70%
• Side effects: acute desquamation, meatal stenosis (10-45%), soft-tissue ulceration (0-26%)
• Consider inguinal XRT if multiple positive LN or concern for ENE, can consider for multimodal therapy

Chemotherapy

• First-line for advanced or metastatic disease, TIP (paclitaxel, ifosfamide, cisplatin) is recommended regimen
• Adjuvant chemotherapy decreases relapse rates (16% vs 45%), but toxicity risk is high
• Adjuvant indications: 2+ positive nodes, ENE, or pelvic metastases
• Can consider cisplatin NAC if LN metastasis present

Follow-Up

• If Low Risk (Tis, Ta, T1a): physical exam q3m year 1-2, q4m year 3, q6m year 4, q12m year 5+
• If High Risk (T1b+): physical exam q2m year 1-2, q3m year 3, q6m year 4, q12m year 5+
• If penile-preserving treatment: q3m year 1-2, q6m year 3
• If partial penectomy: q6m year 1-2, q12m year 3
• If ILND with pN0: physical exam q4m year 1-2, q6m year 3, q12m year 4+
• if ILND with pN1+: physical exam + CT + CXR q3m year 1-2, q4m year 3, q6m year 4, q12m year 5+

References

• AUA Core Curriculum
• Kutikov, A., P. L. Crispen, and R. G. Uzzo. "Pathophysiology, evaluation, and medical management of adrenal disorders." Campbell-Walsh Urology 12 (2020).
• Pettaway, C., J. Crook, and L. Pagliaro. "Tumors of the Penis." Campbell-Walsh Urology 12 (2020).
• Sotelo, R., L. Medina, and M. Machado. "Inguinal Node Dissection." Campbell-Walsh Urology 12 (2020).