Penile cancer

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Most penile cancers are squamous-cell carcinomas arising on glans, prepuce or shaft, sometimes through HPV-related penile intraepithelial neoplasia and sometimes through differentiated inflammation-related pathways. Oncogenic HPV, particularly type 16, drives a proportion of penile intraepithelial neoplasia and squamous cancers through E6 and E7 oncoproteins. Lichen sclerosus, phimosis, poor foreskin retractability and chronic inflammation contribute to differentiated precursor disease independent of HPV. Penile intraepithelial neoplasia remains above the basement membrane but can progress to invasive squamous carcinoma if persistent. Tumour extends from epithelium into corpus spongiosum, corpora cavernosa, urethra and adjacent structures, determining organ-preserving feasibility.

Recognition depends on the tempo, host context and anatomical pattern rather than one isolated result. Ulcer, plaque, nodule, warty growth, colour change or induration is suspicious when persistent or progressive. Contact bleeding, malodorous discharge or infection can occur, particularly when phimosis conceals the tumour. Inability to retract the foreskin plus a palpable lesion or unexplained discharge requires examination and often dorsal slit or circumcision planning. Investigation should answer immediate safety, diagnostic confirmation and extent in that order. Clinical examination and photography with consent Record foreskin, glans, corporal and urethral features and node size or mobility; sensitive consent and chaperoning support accurate follow-up. Incisional, punch or excisional biopsy Choose a representative edge and adequate depth; avoid destructive laser or topical therapy without histology when invasion is possible. Penile MRI An induced erection or dedicated protocol can improve local staging; MRI does not replace histology of the primary lesion.

Management is determined by physiological urgency, disease extent, treatment intent and the person's priorities. The pathway moves through confirm before destructive treatment, then preserve organ where safe, then stage nodes according to primary risk; each transition requires named multidisciplinary ownership. Follow-up must anticipate inguinal and pelvic nodal metastasis, loss of penile function, groin-wound and lymphatic morbidity while measuring function and treatment toxicity.

Key points

Persistent surface lesion is a pivotal clue in Penile cancer: Ulcer, plaque, nodule, warty growth, colour change or induration is suspicious when persistent or progressive.
Immediate priority in unstable Penile cancer: Stabilise bleeding and infection, provide analgesia and urinary drainage by an oncologically safe route with urology, and involve the specialist penile cancer centre urgently rather than performing unplanned local excision.
Clinical examination and photography with consent is used early to map lesion site, size, surface, shaft involvement and both groins before biopsy. Record foreskin, glans, corporal and urethral features and node size or mobility; sensitive consent and chaperoning support accurate follow-up.
Incisional, punch or excisional biopsy refines the next decision because choose a representative edge and adequate depth; avoid destructive laser or topical therapy without histology when invasion is possible.
Confirm before destructive treatment: Examine and document the entire penis and both groins, address phimosis enough to visualise the lesion and make an urgent specialist referral.
Preserve organ where safe: For superficial invasive disease, consider wide local excision, glans resurfacing, glansectomy or radiotherapy through an experienced organ-preserving service.
A major avoidable harm is inguinal and pelvic nodal metastasis; Nodal burden is the dominant prognostic factor and may remain curable when identified and resected before bulky fixation.
A common diagnostic trap is inflammatory balanitis: Candidal, irritant or plasma-cell inflammation can cause erythema and soreness, but persistence after appropriate care requires biopsy.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

High-risk HPV

Oncogenic HPV, particularly type 16, drives a proportion of penile intraepithelial neoplasia and squamous cancers through E6 and E7 oncoproteins.

Chronic inflammatory disease

Lichen sclerosus, phimosis, poor foreskin retractability and chronic inflammation contribute to differentiated precursor disease independent of HPV.

Smoking and immunosuppression

Tobacco exposure, HIV and other immune compromise reduce viral clearance and increase dysplastic and invasive risk.

Age and delayed presentation

Risk rises with age, while embarrassment and lesion concealment under phimosis can allow otherwise visible disease to progress.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Epithelial precursor
Penile intraepithelial neoplasia remains above the basement membrane but can progress to invasive squamous carcinoma if persistent.
2
Local infiltration
Tumour extends from epithelium into corpus spongiosum, corpora cavernosa, urethra and adjacent structures, determining organ-preserving feasibility.
3
Stepwise lymphatic spread
Drainage reaches superficial and deep inguinal nodes before pelvic nodes, making occult groin staging central even when examination is normal.
4
Nodal inflammatory mimic
Ulcerated primary tumours commonly cause reactive enlarged groin nodes, but delaying reassessment risks missing curable metastatic nodes.
5
Advanced dissemination
Bulky nodal disease can ulcerate, infect and invade vessels before lung, liver, bone or distant nodal metastasis develops.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Persistent surface lesion

Ulcer, plaque, nodule, warty growth, colour change or induration is suspicious when persistent or progressive.

Bleeding or discharge

Contact bleeding, malodorous discharge or infection can occur, particularly when phimosis conceals the tumour.

Phimosis with mass

Inability to retract the foreskin plus a palpable lesion or unexplained discharge requires examination and often dorsal slit or circumcision planning.

Inguinal nodes

Palpable groin nodes may be reactive or metastatic; hard, fixed, bilateral or persistent nodes demand urgent staging.

Locally advanced effects

Pain, urinary spraying, retention, fistula or invasion of adjacent perineal structures indicates greater local burden.

Fungating emergencyRed flag

Major bleeding, sepsis or urinary obstruction from advanced disease requires acute stabilisation and specialist transfer.

Red flags requiring action

A painless ulcer, nodule, induration, warty growth or bleeding lesion persists on glans, prepuce or shaft.
Phimosis conceals discharge, odour, bleeding or a palpable subpreputial mass.
A lesion fails to resolve after a short appropriate treatment for presumed infection or dermatitis.
Palpable inguinal nodes persist after treatment of infection or are hard, fixed or enlarging.
Urinary obstruction, severe pain, haemorrhage, cellulitis or sepsis accompanies an advanced penile lesion.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Clinical examination and photography with consentFirst step
Why
Map lesion site, size, surface, shaft involvement and both groins before biopsy.
Interpretation and limitations
Record foreskin, glans, corporal and urethral features and node size or mobility; sensitive consent and chaperoning support accurate follow-up.
02
Incisional, punch or excisional biopsy
Why
Confirm invasive versus intraepithelial disease, histological subtype, grade and depth before definitive treatment.
Interpretation and limitations
Choose a representative edge and adequate depth; avoid destructive laser or topical therapy without histology when invasion is possible.
03
Penile MRI
Why
Define corporal invasion and residual penile length when organ-preserving or partial surgery is considered.
Interpretation and limitations
An induced erection or dedicated protocol can improve local staging; MRI does not replace histology of the primary lesion.
04
Inguinal-node ultrasound with FNAC or core
Why
Assess palpable nodes and obtain cytology or histology from suspicious nodal disease.
Interpretation and limitations
Negative sampling of a clinically suspicious node needs repeat or surgical staging; treat overt infection briefly but do not allow prolonged observation.
05
Dynamic sentinel-node biopsy
Why
Detect occult inguinal metastasis in clinically node-negative patients with intermediate- or high-risk primary pathology.
Interpretation and limitations
Perform only in an experienced penile cancer centre with validated technique; low-risk primary disease can usually avoid invasive nodal staging.
06
CT or PET-CT staging
Why
Define pelvic and distant disease in node-positive or advanced cancer.
Interpretation and limitations
Imaging is insensitive for microscopic groin disease and cannot replace sentinel or surgical nodal staging when indicated.
07
HPV and pathology dataset
Why
Classify HPV-associated or independent morphology and adverse features.
Interpretation and limitations
Report depth, grade, lymphovascular and perineural invasion, margins and p16 or HPV according to the RCPath dataset.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Inflammatory balanitis

Candidal, irritant or plasma-cell inflammation can cause erythema and soreness, but persistence after appropriate care requires biopsy.

Lichen sclerosus

White atrophic plaques and phimosis are inflammatory yet confer cancer risk; focal ulceration or induration warrants sampling.

Genital wart

Condyloma is often multifocal and soft, but verrucous carcinoma and warty squamous cancer can look similar clinically.

Syphilitic or herpetic ulcer

Sexual history and microbiology help, but empirical infection treatment must not postpone biopsy of a persistent atypical ulcer.

Fixed drug eruption or psoriasis

Recurrent or patterned dermatoses can affect the glans; failure to respond or focal induration changes the diagnostic priority.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01BiopsyConfirm before destructive treatmentFirst stepA persistent penile lesion is suspicious for intraepithelial or invasive cancer.

1Examine and document the entire penis and both groins, address phimosis enough to visualise the lesion and make an urgent specialist referral.
2Obtain representative incisional, punch or excisional biopsy with adequate depth before topical, laser or major surgery.
3Report subtype, grade, depth, lymphovascular or perineural invasion, HPV association and margin through expert pathology review.

02PrimaryPreserve organ where safePathology and local staging define intraepithelial or localised invasive disease.

1For penile intraepithelial neoplasia, use circumcision, topical treatment, laser or resurfacing according to site, extent and adherence, with biopsy of non-response.
2For superficial invasive disease, consider wide local excision, glans resurfacing, glansectomy or radiotherapy through an experienced organ-preserving service.
3Use partial or total penectomy when invasion cannot be controlled safely with preservation, providing reconstructive, urinary, sexual and psychological support.

03GroinStage nodes according to primary riskPrimary pathology creates an intermediate or high occult-node risk, or inguinal nodes are palpable.

1In clinically node-negative intermediate- or high-risk disease, use dynamic sentinel-node biopsy or modified dissection in a validated specialist pathway.
2Sample palpable nodes by ultrasound-guided FNAC or core; if infection is plausible, give only a short treatment interval with scheduled reassessment.
3Perform therapeutic inguinal and, when indicated, pelvic node dissection for proven disease, considering neoadjuvant chemotherapy for bulky fixed nodes.

04AdvancedIntegrate systemic and palliative treatmentDisease is unresectable locally, bulky node-positive, recurrent or metastatic.

1Obtain adequate pathology and staging, assess renal and performance status and discuss cisplatin-based combination chemotherapy in the specialist MDT.
2Use radiotherapy, embolisation, surgery or wound care for bleeding, pain, odour and threatening groin disease according to urgency.
3Provide lymphoedema, sexual, urinary, psychological and palliative support and revisit treatment burden and goals at each progression.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Induces local immune clearance in selected biopsy-proven non-invasive penile disease when adherence and surveillance are reliable.

Imiquimod 5% cream for penile intraepithelial neoplasia

Apply a thin layer to the affected area three times weekly at night, leave for about 6–10 hours and wash off, commonly for up to 12 weeks under specialist supervision with response checks.

Do not use for unbiopsied possible invasion; expect inflammation, pause or reduce for severe ulceration, and re-biopsy persistent or recurrent disease rather than repeating indefinitely.

Provides an organ-preserving option for selected biopsy-proven superficial intraepithelial disease.

Topical fluorouracil for penile intraepithelial neoplasia

A specialist regimen commonly applies fluorouracil 5% cream thinly once or twice daily for 4–6 weeks, with exact frequency adjusted to local reaction and product guidance.

Avoid on invasive or unconfirmed lesions, counsel about marked local inflammation and safe handling, and arrange biopsy of incomplete response.

Provides neoadjuvant systemic treatment for selected bulky or fixed inguinal nodal penile squamous cancer before attempted surgery.

TIP chemotherapy

A commonly used 21-day specialist regimen gives paclitaxel 175 mg/m² IV day 1, ifosfamide 1,200 mg/m² IV days 1–3 with mesna, and cisplatin 25 mg/m² IV days 1–3, often for 4 cycles.

Requires high-volume-centre prescribing with hydration, mesna and antiemesis; monitor marrow, sepsis, renal, hearing, neuropathy and ifosfamide neurological and bladder toxicity.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Inguinal and pelvic nodal metastasis

Nodal burden is the dominant prognostic factor and may remain curable when identified and resected before bulky fixation.

Loss of penile function

Surgery or radiotherapy can alter length, voiding, sensation, erection, sexual identity and psychological wellbeing. In Penile cancer, this distinction materially changes complication assessment.

Groin-wound and lymphatic morbidity

Node dissection can cause infection, skin necrosis, lymphocele and chronic lower-limb or genital lymphoedema. In Penile cancer, this distinction materially changes complication assessment.

Fungation and haemorrhage

Locally advanced tumour or nodes can ulcerate, become infected, smell, bleed and erode major femoral vessels.

Urethral obstruction

Progressive local invasion or treatment-related stenosis can impair voiding and require reconstruction or diversion. In Penile cancer, this distinction materially changes complication assessment.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

After organ-preserving treatment, inspect the primary site at short risk-based intervals and biopsy any persistent, recurrent or indurated change.
Examine both groins throughout follow-up because occult nodal relapse can remain treatable if detected before fixation.
After sentinel or node dissection, monitor wound, infection, lymphocele and lower-limb or genital lymphoedema and refer early for therapy.
Assess urinary stream, meatal or urethral stenosis, sexual function, body image and psychological distress explicitly.
During systemic therapy, track counts, renal function, hearing, neuropathy, infection and response of each nodal basin.
Document smoking cessation, HPV-related partner questions and vaccination information without implying vaccination treats established cancer.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Biopsy before cream or laser

Destructive treatment can erase the surface while leaving unrecognised invasive cancer beneath, so histology must establish depth first.

Normal imaging misses microscopic nodes

Clinically node-negative higher-risk primary cancer still needs sentinel or surgical staging because CT size cannot exclude micrometastasis.

Reactive nodes need a deadline

Infection can enlarge groin nodes, but a vague prolonged antibiotic course delays curative nodal treatment.

Preservation needs surveillance

An organ-preserving operation trades functional benefit for a higher local-recurrence burden that is acceptable only with reliable inspection and re-biopsy.

Nodal status drives prognosis

A modest penile primary with untreated occult inguinal disease can be more dangerous than a larger organ-confined lesion.

11Common pitfallsFrequent interpretation and management errors.

01
Treating a persistent penile lesion empirically without biopsy.
02
Using topical therapy when invasion has not been excluded.
03
Relying on CT to exclude microscopic inguinal metastasis.
04
Observing enlarged groin nodes for months as presumed infection.
05
Performing unplanned local excision outside a penile cancer pathway.
06
Ignoring sexual, urinary and lymphoedema consequences during consent.