The vast majority of penile cancers — approximately 95% — are squamous cell carcinomas (SCC) arising from the skin of the glans, foreskin, or shaft. Like other SCCs, they typically grow slowly and give warning signs before reaching advanced stage.
Penile cancer is rare in developed countries, affecting approximately 1 in 100,000 men, with about 2,200 new cases diagnosed in the United States each year. Despite its rarity, it carries significant physical and psychological impact — particularly when diagnosis is delayed and more extensive surgery becomes necessary.
The glans (head of the penis) and the inner foreskin are the most common sites of origin, accounting for roughly 70–80% of cases. The coronal sulcus and penile shaft account for most remaining cases. Urethral involvement is uncommon but important to assess at diagnosis.
HPV infection — particularly high-risk strains 16 and 18 — is the most significant causal factor, detectable in approximately 40–50% of penile squamous cell carcinomas. Understanding this connection is important both for prevention (HPV vaccination) and for understanding the biology of the disease.
Several well-established risk factors increase the likelihood of developing penile cancer. Some — like HPV status and smoking — are modifiable; others, like age, are not.
High-risk HPV strains (16, 18) are present in 40–50% of penile SCC cases. HPV-positive tumors tend to be higher-grade but may respond better to immune-based treatments. HPV vaccination before exposure substantially reduces risk.
Inability to retract the foreskin creates a warm, moist environment that promotes HPV persistence, chronic inflammation, and smegma accumulation — all of which raise cancer risk. Phimosis is present in approximately 25–75% of penile cancer cases at diagnosis.
Smoking significantly increases penile cancer risk, independent of HPV status. It is thought to act through both direct carcinogen exposure and through impairment of local immune surveillance of HPV-infected cells.
Conditions including balanitis xerotica obliterans (BXO, also called lichen sclerosus), chronic balanitis, and other persistent inflammatory states of the glans or foreskin are recognized risk factors and precursors to invasive cancer.
Infrequent cleaning under the foreskin allows smegma accumulation and chronic microbial irritation, promoting the inflammatory and HPV-permissive environment associated with cancer development.
Most cases occur in men over 60, though HPV-related cases can present earlier. Immunosuppressed patients — including solid organ transplant recipients and HIV-positive individuals — have substantially elevated risk due to impaired HPV clearance.
Neonatal circumcision is associated with a significantly reduced risk of penile cancer, likely by eliminating phimosis and reducing HPV persistence. Adult circumcision provides less protection but may be appropriate in cases of recurrent phimosis or lichen sclerosus.
Several well-defined precancerous conditions of the penis can progress to invasive carcinoma if untreated. Recognizing and treating these early offers an opportunity to prevent cancer before it develops. Any persistent, unexplained lesion on the penis should be evaluated — many precancerous lesions are not visually distinguishable from early invasive cancer without biopsy.
PeIN / CIS
The spectrum of non-invasive squamous dysplasia, ranging from low-grade (PeIN I) to carcinoma in situ (PeIN III / Bowen’s disease / erythroplasia of Queyrat). High-grade PeIN carries a significant risk of progression to invasive SCC and should be treated.
Treatment options include topical 5-fluorouracil or imiquimod, laser ablation, glans resurfacing, or excision depending on extent and location.
LS / BXO
Balanitis xerotica obliterans is a chronic, progressive inflammatory condition causing white, scarred patches on the glans and foreskin. It is associated with a 2–9% risk of progression to invasive penile SCC and requires long-term surveillance and treatment.
Managed with topical steroids, tacrolimus, or surgery (circumcision, glansectomy) depending on severity.
HPV lesions
Common genital warts (condylomata acuminata) from low-risk HPV strains are generally benign but warrant treatment. Giant condyloma acuminatum (Buschke-Löwenstein tumor) is a locally destructive, borderline malignant lesion with significant risk of malignant transformation.
Requires wide local excision; surveillance for recurrence and progression is essential.
Penile cancer most commonly presents as a visible or palpable change on the penis that persists for more than a few weeks. Because the lesion is visible, early detection is possible — but many men delay seeking care. Any of the following that does not resolve within 2–4 weeks should be evaluated by a urologist.
An open sore or ulcer on the glans, foreskin, or shaft that doesn't heal — even if painless. This is the most common initial presentation.
A firm, painless lump anywhere on the penis, often on the glans or under the foreskin where it may not be immediately visible.
Discoloration, thickening, rash, white or red patches, or flat areas of abnormal skin on the glans or shaft.
Unusual discharge or foul smell from under the foreskin — may be associated with concurrent infection but warrants evaluation to rule out underlying tumor.
Bleeding from the penis not explained by trauma, especially from under the foreskin or from a lesion
Firm, enlarged lymph nodes in one or both groins — may indicate regional lymph node involvement, though reactive lymphadenopathy from infection is more common.
Many men mistake early penile cancer for a skin infection or sexually transmitted infection. If a skin change, sore, or lump does not resolve completely after treatment of any suspected infection, biopsy is essential. Early-stage penile cancer is highly curable and often treatable without major surgery.
Diagnosis requires tissue confirmation — imaging and physical examination alone cannot diagnose penile cancer. A biopsy of the primary lesion is the essential first step, followed by imaging to assess regional and distant spread.
Complete examination of the penis — including retraction of the foreskin if present — with characterization of the lesion's size, location, depth of invasion on palpation, and involvement of the urethra. Both groins are examined for palpable lymphadenopathy.
An incisional or punch biopsy of the lesion provides tissue for histological diagnosis and grading. This is mandatory before treatment planning. The pathology report should include: cell type (SCC in 95% of cases), grade (well, moderately, or poorly differentiated), depth of invasion, and presence of lymphovascular invasion (LVI) or perineural invasion — all of which influence prognosis and lymph node management.
MRI of the penis — performed after pharmacological erection induction with intracavernosal prostaglandin — is the most accurate modality for determining depth of invasion into the corpus cavernosum or spongiosum. This is critical for staging and for planning whether organ-sparing surgery is feasible.
Nodal staging is one of the most important prognostic factors in penile cancer. Clinically palpable nodes are evaluated with CT scan and fine needle aspiration (FNA). Non-palpable nodes in intermediate- and high-risk tumors are assessed with dynamic sentinel lymph node biopsy (DSNB) — the gold-standard minimally invasive staging technique — or modified inguinal lymph node dissection (ILND). PET-CT may add sensitivity for nodal and distant staging in high-risk cases.
Cross-sectional imaging of the abdomen and pelvis assesses pelvic lymph nodes and distant metastases. Chest CT is added for patients with palpable inguinal lymphadenopathy or high-stage primary tumors. Bone scan is performed if skeletal metastases are suspected.
Penile cancer is staged using the AJCC TNM system. The T stage reflects depth of local invasion; the N stage reflects regional lymph node involvement; and the M stage reflects distant metastases. Nodal status is the single most important prognostic factor.
Cancer cells are present in the top layer of skin only (carcinoma in situ / PeIN III). No invasion into underlying tissue. Highly curable with local treatment. Organ-sparing therapy is virtually always possible.
T1a: Invades subepithelial connective tissue; no LVI or perineural invasion; well/moderately differentiated. T1b: Invades subepithelial connective tissue with high-grade features, LVI, or perineural invasion. T2: Invades corpus spongiosum with or without urethral invasion. T3: Invades corpus cavernosum. All node-negative. Organ-sparing surgery is often feasible for T1–T2; partial penectomy may be required for T3.
Cancer has spread to inguinal lymph nodes (N1: mobile, unilateral; N2: bilateral or multiple; N3: fixed or pelvic nodes). Lymph node involvement dramatically worsens prognosis. Combined surgical and systemic (chemotherapy) management is required. 5-year survival falls to approximately 20–50% depending on nodal burden.
T4: tumor invades adjacent structures (scrotum, prostate, pubic bone). M1: distant metastases (lungs, liver, bone). Primary treatment is systemic chemotherapy; surgery or radiation may be used for local palliation. Prognosis is poor, though emerging immunotherapy combinations are showing activity.
| Stage / T Category | Preferred Approach | Lymph Node Management |
|---|---|---|
| Tis / PeIN (in situ) | Topical / Laser / Glans resurfacing | No nodal intervention |
| T1a (low-grade, no LVI) | Wide local excision or glansectomy | Surveillance; DSNB if intermediate risk |
| T1b (high-grade or LVI) | Glansectomy or partial penectomy | DSNB or modified ILND (bilateral) |
| T2 (corpus spongiosum) | Glansectomy ± partial penectomy | DSNB or modified ILND (bilateral) |
| T3 (corpus cavernosum) | Partial penectomy | Bilateral ILND |
| T4 / locally advanced | Neoadjuvant chemo → surgery | Bilateral ILND ± pelvic dissection |
| N1–N2 (resectable nodes) | Surgical ILND ± adjuvant chemo | Bilateral inguinal ± pelvic LND |
The overriding principle in primary tumor management is to achieve adequate oncologic margins while preserving as much penile length and function as safely possible. Modern penile cancer surgery has shifted strongly toward organ-sparing approaches, supported by evidence that conservative surgery with adequate margins achieves equivalent cancer control to more radical resection for most tumors.
Organ-sparing treatment is appropriate for the majority of penile cancer presentations — particularly Tis, T1, and selected T2 tumors. A surgical margin of at least 3–5 mm of normal tissue is required. Local recurrence after conservative surgery is more common than after penectomy but is highly salvageable with further treatment; overall survival is not compromised.
Tis / PeIN only
5-fluorouracil (5-FU) cream or imiquimod applied directly to the lesion. Appropriate for flat, non-invasive in-situ disease (PeIN).
Requires prolonged treatment (weeks), careful follow-up, and repeat biopsy to confirm complete response. Local recurrence rate is 10–15%; requires ongoing surveillance.
Tis / T1a
CO₂ or Nd:YAG laser ablation of superficial lesions. Preserves penile anatomy and function. Can be repeated for recurrence.
Limited to superficial, non-invasive, or minimally invasive disease. Requires biopsy confirmation of depth before use. Local recurrence ~10–20%.
T1a / small T1b
Surgical excision of the tumor with a margin of normal tissue, preserving the glans and shaft. Most suitable for smaller lesions on the shaft or foreskin.
Simple circumcision is appropriate when the tumor is confined to the foreskin. Mohs micrographic surgery is used at some centers for precise margin control.
Tis / T1a (diffuse)
The outer epithelial layer of the glans is removed and replaced with a split-thickness skin graft from the thigh. Achieves excellent oncologic control of surface disease while preserving glans shape and sensation.
Indicated for diffuse PeIN or early T1a disease across the glans surface where topical therapy has failed or is unsuitable.
T1b / T2
Surgical removal of the glans with reconstruction using a skin graft over the preserved tips of the corpora cavernosa. Achieves adequate oncologic margins for most T1b and T2 tumors while preserving penile length and the ability to have erections.
Gold-standard organ-sparing operation for glans-confined invasive disease. Reconstruction typically uses a split-thickness graft from the inner thigh.
Functional outcomes
Most patients retain the ability to achieve erections and maintain sexual activity after glansectomy with skin graft reconstruction. Urinary function is preserved in almost all cases.
Patient satisfaction with glansectomy and reconstruction is generally high. Sensitivity of the neoglans may be reduced but improves over time.
When organ-sparing surgery cannot achieve adequate margins — typically for T3 tumors or tumors with deep corpus cavernosum invasion — partial or total penectomy is required. These procedures remove the affected penile tissue to achieve a tumor-free margin, with priority given to maintaining as much length as safely oncologically possible.
T2–T3 tumors
The distal penis is removed, with the transection point chosen to achieve a clear pathological margin. A neo-urethral meatus is fashioned to allow normal urination.
A penile stump of adequate length (>3 cm standing) is sufficient for sexual intercourse in many patients. Penile prostheses or reconstruction may be considered post-operatively.
Local recurrence after partial penectomy is uncommon — approximately 5–8%. If recurrence does occur at the stump, completion penectomy with perineal urethrostomy can still achieve cure.
Proximal or extensive T3–T4 tumors
Complete removal of the penis with creation of a perineal urethrostomy — a new urinary opening in the perineum through which the patient urinates sitting down.
Reserved for tumors involving the penile base or where partial penectomy cannot achieve adequate margins. Psychological impact is significant; pre-operative counseling and post-operative psychological support are strongly recommended.
Penile reconstruction (phalloplasty) using free flap techniques can be considered at experienced reconstructive centers, though this is a complex undertaking.
Intraoperative frozen section analysis of surgical margins is performed routinely to confirm tumor-free resection and avoid the need for re-excision.
If the urethra is involved at the tumor margin, urethral reconstruction or urinary diversion may be required at the same operation.
Radiation therapy offers an organ-preserving alternative for selected patients with T1–T2 tumors who wish to avoid surgery or are poor surgical candidates. It is not the standard first-line approach in most centers but is a legitimate curative option for appropriately selected patients.
Delivered to the primary tumor and, in some protocols, the regional inguinal nodes. Modern techniques (IMRT) allow dose escalation to the tumor while limiting dose to the urethra and surrounding structures. Typically administered over 5–7 weeks.
Radioactive seeds or wires are implanted directly into the tumor (interstitial brachytherapy) or applied to the surface (surface mold). Brachytherapy offers highly localized radiation dose and is considered the preferred radiation modality for T1–T2 tumors at experienced centers. Local control rates of 70–85% have been reported for T1–T2 disease. Circumcision is required prior to brachytherapy to reduce the risk of foreskin necrosis.
Radiation carries a risk of late toxicities including urethral stricture (requiring dilation or surgery), meatal stenosis, and in some cases penile fibrosis or necrosis. Approximately 20–30% of patients treated with radiation require salvage surgery for local recurrence or late complications. Patients treated with radiation require close, lifelong surveillance with penile examination and urethroplasty if stricture develops.
Lymph node status is the most important determinant of survival in penile cancer. The inguinal lymph nodes are the primary drainage basin, followed by pelvic nodes. Accurate staging and appropriate treatment of the lymph nodes is essential — this is one of the most complex and consequential parts of penile cancer management.
Approximately 20–30% of patients with clinically node-negative disease harbor occult (microscopic) lymph node metastases detectable only on pathology. Delaying lymph node treatment until nodes become clinically palpable significantly worsens survival. Early, prophylactic nodal staging in intermediate- and high-risk patients improves outcomes.
Tis / T1a low-grade only
Active surveillance of the groins with regular physical examination and imaging is appropriate only for low-risk T1a tumors (low-grade, no LVI, no perineural invasion).
Risk of occult nodal disease in this group is <5%. Any new groin mass prompts immediate evaluation with CT and FNA.
T1b and above, cN0
Radioactive tracer and blue dye are injected around the primary tumor. The sentinel node (the first node draining the tumor) is identified intraoperatively and removed for pathological analysis.
If sentinel node is negative: no further nodal surgery. If positive: completion inguinal lymph node dissection (ILND). False-negative rate ~7%. Preferred over routine ILND to avoid unnecessary morbidity.
Where DSNB not available
A modified inguinal lymph node dissection removes the nodes in the central and superomedial inguinal region (where penile drainage is concentrated) rather than the full inguinal field.
More morbid than DSNB (lymphedema risk ~5–10%) but provides definitive staging when sentinel node biopsy is not available or technically feasible
When inguinal lymph nodes are palpable, CT imaging and fine needle aspiration (FNA) confirm malignant involvement. Four weeks of antibiotic therapy may be given first to exclude reactive (infection-related) lymphadenopathy, particularly if there is concurrent penile infection or ulceration.
N1–N2 (resectable)
Complete removal of inguinal lymph nodes on the affected side(s). Bilateral dissection is recommended in most guidelines given the high rate of bilateral drainage from the penis.
Significant morbidity: lymphedema of the lower limb occurs in 30–50% of patients, wound complications in 20–40%. Minimally invasive video-endoscopic inguinal lymphadenectomy (VEIL) reduces wound complications while achieving equivalent oncologic outcomes.
≥2 positive inguinal nodes or pN3
Pelvic lymph node dissection is recommended when 2 or more inguinal nodes are involved or when extranodal extension is present — both of which predict a high risk of pelvic nodal metastasis.
Extends the dissection along the iliac vessels. Adjuvant chemotherapy is recommended post-operatively for patients with ≥2 positive inguinal nodes or pelvic node involvement.
When inguinal lymph nodes are fixed, matted, or there is skin involvement (N3), surgery alone is unlikely to achieve complete resection. Neoadjuvant chemotherapy (typically TIP: taxol, ifosfamide, cisplatin) is recommended to downstage the nodes before surgical dissection. Patients who respond to neoadjuvant chemotherapy and subsequently undergo complete surgical resection have meaningfully improved survival compared to those treated with chemotherapy alone.
After inguinal dissection, all patients should receive education on lower limb lymphedema prevention, including skin care, compression garments, and lymphatic massage. Early referral to a lymphedema therapist significantly reduces the severity of long-term swelling.
Video-endoscopic inguinal lymphadenectomy (VEIL) achieves equivalent lymph node yield to open ILND with significantly fewer wound complications. Ask about minimally invasive lymphadenectomy when surgical nodal treatment is indicated.
Chemotherapy and, increasingly, immunotherapy play important roles in locally advanced and metastatic penile cancer. Penile SCC is a chemotherapy-sensitive tumor — response rates to combination platinum-based regimens are meaningful, particularly in the neoadjuvant (pre-surgery) setting.
| Regimen | Class | Setting | Notes |
|---|---|---|---|
| TIP (Taxol + Ifosfamide + Cisplatin) | Chemotherapy | Neoadjuvant (N3 / bulky nodes); first-line metastatic | Most widely used regimen; response rates ~40–50% neoadjuvant; allows conversion of unresectable to resectable disease in some patients |
| Gemcitabine + Cisplatin (GP) | Chemotherapy | First-line metastatic; adjuvant (pN2–N3) | Active alternative to TIP; better tolerability profile; used as adjuvant after surgery for ≥2 positive nodes |
| Paclitaxel + Carboplatin | Chemotherapy | Cisplatin-ineligible first-line | Reasonable alternative when cisplatin is contraindicated due to renal function or neuropathy |
| Pembrolizumab | Immunotherapy | Second-line; PD-L1+ or TMB-high tumors | FDA-approved for TMB-high solid tumors (tumor agnostic); response rates ~25–30% in penile SCC; active in HPV-positive tumors |
| Nivolumab ± Ipilimumab | Immunotherapy | Second-line; clinical trial / selected cases | Active investigation in penile SCC; combination checkpoint blockade shows promising activity in HPV-associated SCC; preferred in clinical trial setting |
| Cetuximab ± chemotherapy | Anti-EGFR | EGFR-overexpressing tumors; second-line | EGFR is overexpressed in ~70% of penile SCC; cetuximab has demonstrated activity; optimal sequencing under investigation |
Tumor tissue from advanced penile SCC should undergo comprehensive genomic profiling (TMB, MSI, EGFR, PIK3CA, CDKN2A) to identify potentially actionable targets. PD-L1 expression and HPV status should be assessed — both influence immunotherapy response and are increasingly incorporated into treatment decisions. Ask about clinical trial eligibility at each stage of treatment.
Penile cancer surgery — particularly glansectomy, partial penectomy, or total penectomy — has significant physical, functional, and psychological consequences. Reconstruction and rehabilitation planning should begin before surgery and continue through recovery. At Bansal Urology, we view penile reconstruction and quality-of-life support as integral parts of cancer care, not optional additions.
A split-thickness skin graft from the inner thigh is applied to the corpora tips after glansectomy, reconstituting a functional neoglans. Most patients retain the ability to achieve erections, maintain sexual activity, and urinate normally. Graft contraction over 3–6 months leads to satisfactory cosmetic and functional outcomes for the majority of patients.
Many patients with a residual penile stump of adequate length (>3 cm) can achieve satisfactory sexual function. For patients who wish to restore length or girth, a penile prosthesis placed into the residual corpora may be possible in select cases. Phalloplasty (penile reconstruction using free flap tissue transfer) is available at specialized reconstructive centers for patients who have undergone total penectomy and wish to restore penile form.
Urinary function is preserved in all patients after glansectomy and most patients after partial penectomy. After total penectomy with perineal urethrostomy, patients urinate in a sitting position through the perineal opening — most patients adapt well to this change. Urethral stricture at the meatus can occur after radiation therapy or surgery and is managed with dilation or revision surgery.
A penile cancer diagnosis and its treatment can have profound effects on self-image, sexual identity, and relationships. Psychological counseling, sex therapy, and partner support are important components of comprehensive care. Many patients benefit from referral to a psycho-oncologist or sexual health specialist, particularly after partial or total penectomy. Support groups for men with penile cancer are available through organizations such as the Penile Cancer Support Network.
Lower limb lymphedema following inguinal lymph node dissection is a common and impactful complication. Early referral to a certified lymphedema therapist, use of compression garments, meticulous skin care, and manual lymphatic drainage are the cornerstones of management. Prevention through careful surgical technique and minimally invasive lymphadenectomy (VEIL) reduces but does not eliminate this risk.
Penile cancer is highly curable when detected early. Prognosis depends primarily on the depth of invasion at the primary tumor, nodal status, and — in node-positive disease — the number of nodes involved and whether extranodal extension is present
| Stage / Nodal Status | 5-Year Disease-Specific Survival | Key Determinants |
|---|---|---|
| Tis / Stage 0 (in situ) | ~100% | Essentially curable; recurrence usually superficial and re-treatable |
| Stage I–II (localized, node-negative) | 79–100% | Lymphovascular invasion and grade are most important risk factors within this group |
| Stage III (1–2 positive inguinal nodes) | ~50% | Number of nodes, extranodal extension, and pelvic node involvement are critical |
| Stage III (≥3 nodes or pelvic N+) | ~20–30% | Combined chemo + surgery improves outcomes vs. either alone |
| Stage IV (T4 or M1) | <15% | Systemic therapy; immunotherapy combinations under active investigation |
The difference in survival between node-negative and node-positive disease is dramatic. Prompt evaluation and treatment — before lymph node involvement develops — is the single most impactful thing a patient can do to improve their outcome.
These figures reflect population-level estimates. Individual outcomes depend on histological grade, LVI status, response to treatment, and overall health.
Because penile cancer has well-established, modifiable risk factors, meaningful primary prevention is possible. These measures are most impactful when adopted early in life but benefit men at any age.
The HPV vaccine (Gardasil-9) protects against the high-risk strains (16, 18) most associated with penile cancer. Vaccination is recommended for males up to age 26, and is available to men 27–45 after discussion with a physician. It is most effective before sexual debut but provides partial protection in sexually active individuals.
Daily retraction of the foreskin and washing with mild soap and water removes smegma and reduces chronic microbial irritation. This simple habit meaningfully reduces the local inflammatory environment that promotes cancer development in uncircumcised men.
Smoking is an independent, modifiable risk factor for penile cancer. Quitting smoking reduces risk over time and also lowers the risk of many other cancers and cardiovascular disease. Resources for smoking cessation are available through your primary care physician or 1-800-QUIT-NOW.
Phimosis, recurrent balanitis, and lichen sclerosus (BXO) should be treated promptly. Circumcision may be recommended in cases of recurrent or refractory phimosis, repeated balanitis, or lichen sclerosus involving the foreskin. These conditions, left untreated, provide sustained promotion of malignant transformation.
Men — particularly those with risk factors — should be familiar with the appearance of their penis and report any persistent change (sore, lump, skin change, discoloration) to a urologist if it does not resolve within 2–4 weeks. Early lesions are far more amenable to organ-sparing treatment.
Consistent condom use reduces the risk of HPV transmission and acquisition of other STIs that can cause chronic genital inflammation. While condoms do not fully protect against HPV (which spreads through skin-to-skin contact beyond the condom area), they significantly reduce transmission risk.
Whether you’re seeking expert care for a urological condition or looking for a second opinion, we’re here to support you every step of the way. Reach out to schedule an appointment, ask questions, or learn more about personalized, minimally invasive treatment options tailored to your needs.
