UrologySchool.com

OTHER GU ONCOLOGY: PENILE TUMOURS

Benign Tumours

Pearly penile papules
- Also known as papillomas
- Normal and generally found on the glans penis or corona

Pearly penile papules

Source: Wikipedia

Zoon balanitis

Also called plasma cell balanitis and balanitis plasmacellularis
Occurs in uncircumcised men from the 3rd decade onward
Appearance: smooth, moist, erythematous, well-circumscribed plaques on the glans penis; shallow erosions are often present and lesions can be quite large (up to 2cm); difficult to distinguish from carcinoma in situ
- See Figure
Pathology:
- Angiofibromas, similar to the lesions seen on the face in tuberous sclerosis
- Plasma cell infiltrate
Diagnosis and evaluation: biopsy
- Malignancy and extra-mammary Paget’s disease must be excluded
Management

Circumcision
- Curative in the majority of cases
- Prevents against development of the disease
- For patients wanting to avoid circumcision, topical corticosteroids may provide symptomatic relief; topical calcineurin inhibitors (tacrolimus or pimecrolimus) and laser therapy may also play a role

Premalignant cutaneous lesions

Classified as HPV-related vs. non-HPV related§
- HPV related (3): bowenoid papulosis, verrucous carcinoma, CIS
  1. Bowenoid papulosis
    - Appearance: multiple reddish-brown verrucous papules on the penile skin; occurs on the shaft of young men in most cases
      - See Figure
    - Histologically similar to low-grade carcinoma in situ [Bowen’s disease]
    - HPV 16 has been suspected as a cause
    - Progression rate to invasive cancer: 1%
    - Diagnosis: biopsy (gold standard)
    - Management: options include excision, electrocautery, cryotherapy, laser, or 5-fluorouracil topical therapy
  2. Verrucous carcinoma (also known as classic Buschke-Löwenstein Tumor and giant condyloma)
    - DNA from HPV types 6 and 11 has been identified in these tumors
    - Progression rate to invasive cancer: 30%
      - Exhibits progressive local growth but does not metastasize
      - Results in invasion and destruction of adjacent tissues by compression
        
        Buschke-Löwenstein tumor differs from condyloma acuminatum in that condylomata, regardless of size, always remain superficial and never invade adjacent tissue.
    - Management: often requires surgical excision for definitive treatment; radiation is ineffective

Verrucous Carcinoma of the Penis

Source: Wikipedia

CIS
- Erythroplasia of Queyrat
  - CIS of the glans or foreskin
  - Progression rate to invasive cancer: 30%
- Bowen’s disease
  - CIS the penile shaft or the remainder of the genitalia or perineal region
  - Progression rate to invasive cancer: 5%
  - See Figure
- Metastasis extremely rare
- Not associated with visceral malignancies

Non-HPV related (5):
1. Penile Kaposi sarcoma
  - Often associated with herpes-virus 8
  - Should prompt an investigation into whether patient is also infected with HIV or otherwise immunosuppressed
  - Appears as a raised, painful, bleeding papule or ulcer with bluish discolouration
    - See Figure
  - Categories of Kaposi sarcoma (4):
    1. Classic: occurs in patients without known immunodeficiency and typically has an indolent course
    2. Immunosuppressive treatment-related: occurs in patients undergoing immunosuppression for organ transplantation or other reasons
    3. African Kaposi sarcoma: occurs in young men and can be indolent or aggressive
    4. Epidemic or HIV-related: occurs in patients with AIDS
    - The classic and immunosuppressive forms of the disease are considered non-epidemic
      - Non-epidemic Kaposi sarcoma limited to penile involvement should be aggressively treated because it is rarely associated with diffuse organ involvement
  - Management
    - The first step in treatment of Kaposi's sarcoma in patients with HIV is to initiate HAART or to optimize the HAART regimen, which generally results in remission of Kaposi's sarcoma.
    - Local treatment can include laser therapy, cryotherapy, surgical excision, application of topical retinoids.
    - Disseminated or visceral Kaposi's sarcoma is treated with combination chemotherapy.
2. Penile cutaneous horn
  - Rare
  - Usually develops over a pre-existing skin lesion (wart, nevus, traumatic abrasion, or malignant neoplasm)
  - Characterized by overgrowth and cornification of the epithelium, which forms a solid protuberance
    - See Figure
  - May recur and may demonstrate malignant change on subsequent biopsy, even when initial histological appearance is benign. As a result, careful histological evaluation of the base and close follow-up of the excision site are essential
3. Leucoplakia
4. Lichen sclerosis (see Penis and Urethra Surgery Chapter Notes)
5. Pseudoepitheliomatous micaceous and keratotic balanitis

Squamous Cell Carcinoma of the Penis

Accounts for > 95% of penile malignancies

Epidemiology of Invasive Squamous Cell Carcinoma of the Penis

Abrupt increase of incidence in the 6th decade of life

Risk factors (9)
1. Lack of circumcision
  - Neonatal circumcision
    - Almost eliminates risk of invasive penile cancer
      - The controversial discussion about neonatal circumcision should take into account that circumcision removes approximately half the tissue that can develop into penile cancer
    - Does not demonstrate the same level of protection for CIS
  - Adult circumcision
    - Offers little to no protection
2. Phimosis
3. Lichen sclerosus, chronic penile inflammation
4. HPV (subtype 16 most frequently; oncologic subtypes: 16 and 18, non-oncologic subtypes: 6 and 11)
5. Tobacco exposure (smoking, chewing tobacco)
6. Poor hygiene, rural areas, low socioeconomic status, unmarried
7. Number of sexual partners, early age of sexual intercourse
8. Penile trauma
9. Sporalene and ultraviolet A phototherapy (PUVA) for various dermatological conditions such as psoriasis
  - PUVA is a combination treatment which consists of Psoralens (P) and then exposing the skin to UVA (long wave ultraviolet radiation)

TNM Staging AJCC 8th edition

Primary tumour (T)

TX: Primary tumour cannot be assessed
T0: No evidence of primary tumour
Tis: Carcinoma in situ
Ta: non-invasive squamous cell carcinoma types including basaloid, warty, verrucous, papillary, and mixed types
T1: invades subepithelial connective tissue

T1a: WITHOUT lymphovascular invasion, perineural invasion, and is not high grade (i.e. grade 3-4 or sarcomatoid)
T1b: WITH lymphovascular invasion, perineural invasion, or high grade (i.e. grade 3-4 or sarcomatoid)

T2: invades corpora spongiosum
T3: invades corpus cavernosum
T4: invades other adjacent structures

Lymph nodes (N)

Clinical

cNX: Regional nodes cannot be assessed
cN0: No palpable or visibly enlarged inguinal lymph nodes
cN1: unilateral, solitary, mobile inguinal lymph node
cN2: ≥2 unilateral, mobile inguinal lymph nodes or bilateral inguinal lymph nodes
cN3: fixed nodal mass, regardless of the size or unilateral/bilateral involvement

Pathological

pNX: Regional nodes cannot be assessed
pN0: No regional lymph node metastasis
pN1: up to 2 unilateral positive inguinal lymph nodes
pN2: ≥3 unilateral lymph nodes or bilateral inguinal lymph nodes
pN3: extra-nodal extension or pelvic lymph node(s)
- A lymph node > 4 cm is often associated with extranodal extension of cancer.

Distant metastasis (M)

M0: No distant metastasis (no pathologic M0; use clinical M to complete staging group)
M1: Distant metastasis: lymph node metastasis outside the true pelvis, or to visceral or bone sites

Natural history

Tumour architecture
- Flat tumours are associated with earlier nodal metastasis and worse survival than papillary tumours
Earliest route of dissemination is metastasis to the regional inguinal and pelvic nodes

Superficial lymphatic system
- Drains the foreskin and skin of the penile shaft
- Empties into the right and left superficial inguinal nodes
Deep lymphatic system
- Drains the glans penis
- Empties into the superficial inguinal nodes and the deep inguinal nodes of the femoral triangle
Penile cancer can metastasize to contralateral inguinal nodes because of crossover in the symphyseal region
Drainage subsequently proceeds from the inguinal nodes to the ipsilateral pelvic lymph nodes (external iliac, internal iliac, and obturator)

Metastatic enlargement of the regional nodes eventually leads to skin necrosis, chronic infection, and death from sepsis, or hemorrhage secondary to erosion into the femoral vessels

Most common sites of distant metastasis are lung, bone, liver

Clinically detectable distant metastatic lesions to the lung, liver, bone, or brain are uncommon
Usually occur late in the course of the disease after the local lesion has been treated

Death occurs in the majority of untreated patients within 2 years

Diagnosis and Evaluation:
- UrologySchool.com Summary:
  - H+P (including exam of inguinal nodes)
  - Laboratory (1): serum calcium
  - Imaging (2):
    - Local: penile US for large/invasive lesions
    - Metastasis: if indicated (see below)
  - Other (1): biopsy

History and physical exam
- History
  - Delay in seeking medical attention is common
  - Pain is uncommon
- Physical exam
  - Assess penile lesion for size, location, fixation, and involvement of corporeal bodies
    - Lesions are most commonly on the glans (48%) and foreskin (21%)
    - Physical exam incorrectly establishes pathologic tumour stage in 26% of cases
  - Careful palpation of the inguinal area for adenopathy is important
    - EAU Guidelines: Palpably enlarged lymph nodes are highly indicative of lymph node metastases. Physical examination should note the number of palpable nodes on each side and whether these are fixed or mobile. Additional imaging does not alter management and is not required
Laboratory

Serum calcium
- Hypercalcemia may occur without detectable osseous metastases from elevated PTH and related substances produced by tumour

Imaging

Primary tumour

For small-volume glanular lesions, imaging studies are not needed
For larger lesions/lesions suspicious for invasion, US can provide information about infiltration of the corpora

Penile Doppler US has been reported to have a higher staging accuracy than an MRI in detecting corporal infiltration
- MRI with an artificially induced erection can be used to detect corporal invasion but is very unpleasant for the patient

CT has poor soft-tissue resolution and is not useful for imaging the extent of the primary tumour

Metastases

Regional

Physical exam of the inguinal region remains the clinical gold standard for evaluating the presence of metastasis in the non-obese patients

EAU Guidelines: Imaging studies are not helpful in staging clinically normal inguinal regions; however, CT or MRI should also be performed in obese patients and those who have had prior inguinal surgery, whose physical examination findings may be unreliable
EAU Guidelines: A pelvic CT/PET scan can be used to assess the pelvic lymph nodes
Campbell's: some patients may have a challenging inguinal nodal examination because of body habitus or lymphedema from prior procedures. In these patients ultrasound can be used. The role of computed tomography (CT), positron emission tomography (PET)-CT, or magnetic resonance imaging (MRI) is not well defined

Distant

CT scan of the chest, abdomen, pelvis; bone scintigraphy; or CT/PET scan

Other
- Biopsy
  - Before initiation of therapy, biopsy is necessary to (4):
    1. Confirm the diagnosis of penile carcinoma
    2. Evaluate the depth of invasion
    3. Evaluate presence of vascular invasion
    4. Evaluate histologic grade
  - Risk factors for nodal metastases (4):

High-grade disease
Depth of invasion [pT stage]
Perineural invasion
Vascular invasion

Differential diagnosis of penile cancer
1. Condyloma acuminatum (HPV warts)
2. Verrucous carcinoma (Buschke-Lowenstein tumour)
3. Lichen sclerosis
4. STI lesion: Chancre, chancroid, herpes, lymphogranuloma venereum, granuloma inguinale
5. Tuberculosis

Management of penile cancer

CIS

Non-surgical

Topical

EAU: Circumcision is advisable prior to the use of topical agents
Options (2):
1. 5-fluorouracil cream (5% concentration BID x 6 weeks)
2. Imiquimod 5% cream
Patient adherence and strict follow-up is a must, and prompt re-biopsy is necessary for lesions that fail to respond
If topical treatment fails, it should not be repeated.

Ablation with lasers

Two commonly used laser mediums are carbon dioxide (CO2) and Nd:YAG; conflicting literature regarding their efficacy for cancerous lesions

Surgical

Foreskin lesion

Circumcision or excision with a 5-mm margin is adequate

Glans lesion

Excisional strategies while maintaining normal penile anatomy

Radiation

Can be used for tumours that are resistant to topical treatment, especially among patients who are not surgical candidates

Moh's surgery

Favourable histologic features (stage Ta, T1; grade 1 and 2)

Organ-sparing or glans-sparing surgical procedures

Goal is to preserve glans sensation and maximize shaft length
Options (5):
1. Moh's surgery
2. Laser ablation
3. Radiation therapy
4. Limited excision strategies
5. Glansectomy

Moh's micrographic surgery
- Least invasive of the organ-sparing approaches, with favourable functional outcomes
- High recurrence rates have been reported during long-term follow-up.
- Due to the low radicality of the procedure, Moh’s surgery has greater benefit for small superficial shaft lesions, but should not be used for large or high-risk tumours
Glansectomy
- Most radical of the organ-sparing procedures
- Has the highest local control rate
- The glans is separated from the corporal heads and urethra transected with a distal urethrostomy constructed. The shaft skin can be advanced or split, or a full-thickness skin graft used.

Because recurrence rates are higher with organ-preserving strategies, compliance with follow-up is also a consideration in recommending organ preservation versus amputation

Indications for partial or total penectomy (3):
1. High grade (grade ≥ 3) lesions
2. [stage ≥ T2]; deep invasion into the glans urethra or corpora cavernosa
3. Tumours >4cm

EAU Guidelines treatment of primary penile tumour summary
- Tis (glans): Laser therapy, glans resurfacing; alternative: topical therapy
- Ta, Tis (foreskin, shaft skin): Surgical excision to achieve negative margin; alternatives: laser therapy, topical therapy (Tis only)
- Ta, T1 grade 1-3
  - Glans: Therapy based on size and position of lesion as well as potential side effects, excision, glans resurfacing procedures, glansectomy, radiotherapy (not indicated for Ta)
  - Foreskin, shaft: Complete surgical excision to achieve negative margin
- T2 (glans) without gross cavernosum involvement: Total glansectomy with or without corpora cavernosa transection to achieve negative surgical margins, partial penectomy, radiotherapy
- T2 (corporeal invasion), T3: Partial or total penectomy
- T4 (adjacent structures): Consider neoadjuvant chemotherapy with surgical consolidation for responding patients if baseline resectability is a concern
- Local disease recurrence after conservative therapy: Complete surgical excision to achieve negative surgical margins; may require partial or total penectomy; select patients with superficial low-grade recurrences may be candidates for repeat penile-conserving procedure
- Radiotherapy: Select patients with T1-T2 tumors involving glans, coronal sulcus <4 cm

Treatment of inguinal nodes

Lymph node involvement is most important prognostic factor for survival

5-year survival: lymph node involvement vs. without: 73% vs. 60% (range 0-86% depending on extent of lymph node involvement)

Clinically negative groins

≈20% of patients with clinically nonpalpable inguinal nodes harbor occult metastases
Patients with stage ≥pT2 have high risk of metastasis, patients with pTis, pTa, pT1, grade 1 tumours have low risk of metastasis
- Immediate resection of clinically occult lymph node metastases is associated with improved survival when compared with delayed resection of involved nodes at the time of clinical detection
Patients with high-risk disease (high-grade or ≥pT2) should undergo lymph node staging with either bilateral modified inguinal lymphadenectomy or dynamic sentinel node biopsy
- Dynamic Sentinel Node Biopsy (DNSB)
- Inguinal staging procedure

Palpable adenopathy
- Associated with metastasis in 43% of cases, secondary to inflammation in the remainder; can consider fine-needle aspiration to differentiate
- Lymphadenectomy can be curative due to the prolonged locoregional phase before distant dissemination
- Inguinal lymphadenectomy is still recommended
  - The superficial lymph node dissection should be bilateral even if adenopathy is unilateral at presentation
  - Complete ilionguinal lymph node dissection (removal of those nodes deep to the fascia lata contained within the femoral triangle as well as the pelvic nodes) is then performed if the superficial nodes are positive at surgery by frozen-section analysis.
- Exception is verrucous carcinoma, also known as a Buschke-Lowenstein tumor
  - Unlike penile squamous cell carcinoma, verrucous carcinoma of the penis has a very low likelihood of metastasis.
  - Palpable adenopathy in the context of verrucous carcinoma is very likely to be reactive and should be initially observed. Biopsy should be reserved unless the node remains persistently enlarged
    or grows over time.
  - Lymphadenectomy in the context of verrucous carcinoma should be reserved for cases of biopsy-proven metastases.
Fixed inguinal lymph nodes (cN3)
- Neoadjuvant chemotherapy followed by radical inguinal lymphadenectomy in responders

2018 EAU Penile Cancer Guidelines: Summary of treatment strategies for nodal metastases

Lymph node status	Management
No palpable inguinal nodes (cN0)	Tis, Ta G1, T1G1: surveillance.
No palpable inguinal nodes (cN0)	> T1G2 [2019 NCCN guidelines: T1b or ≥T2]: invasive lymph node staging by either bilateral modified inguinal lymphadenectomy (the medial superficial inguinal lymph nodes and those from the central zone are removed bilaterally, leaving the greater saphenous vein untouched) or dynamic sentinel node biopsy
Palpable inguinal nodes (cN1/cN2)	Palpably enlarged groin lymph nodes should be surgically removed, pathologically assessed (by frozen section) and, if positive, a radical [bilateral?] inguinal lymphadenectomy should be performed
Fixed inguinal lymph nodes (cN3)	Neoadjuvant chemotherapy followed by radical inguinal lymphadenectomy in responders
Pelvic lymph nodes	Ipsilateral pelvic lymphadenectomy if ≥2 inguinal nodes are involved on one side or if extracapsular nodal metastasis (pN3) reported.
Adjuvant chemotherapy	In pN2/pN3 patients after radical lymphadenectomy
Radiotherapy	Not recommended for nodal disease except as a palliative option

Pathologic criteria associated with improved long-term survival after attempted curative surgical resection of inguinal metastases include:

Unilateral involvement
Minimal nodal disease (≤2 involved nodes in most series (pN1))
No evidence of extra nodal extension of cancer (pN3)
Absence of pelvic nodal metastases (pN3)

i.e. pN1, and lack of features associated with pN2 and pN3

Indications for pelvic lymph node dissection in patients indergoing inguinal lymph node dissection for curative intent (no pelvic adenopathy):
1. ≥2 positive inguinal lymph nodes
2. Extra-nodal extension is present

PLND in this setting serves as staging tool to identify patients who should be considered for adjunctive therapy
PLND includes the distal common iliac, external iliac, and obturator groups of nodes.

Radiation
- An option for those with invasive SCC refusing surgical treatment
- May be delivered as brachytherapy with interstitial implant or external beam radiation
- Primary radiation therapy may be successfully applied to select patients with T1-2 tumours that are < 4cm; circumcision is necessary before
  - Brachytherapy more likely to preserve erectile function compared to EBRT
- Adverse effects: desquamation, meatal stenosis, and soft-tissue ulceration
- Salvage penectomy may be required for persistent or recurrent disease after radiation
- For patients undergoing primary radiotherapy, surgical management of inguinal lymph nodes should be recommended by the same criteria as for patients selected for surgical management of the primary tumour
  - Radiation to the inguinal area is not as effective as surgery for the treatment of inguinal nodes
- Prophylactic radiotherapy has not been shown to alter the natural history of inguinal metastases and is not recommended
- Palliative radiotherapy among patients with inoperable inguinal nodes may provide some benefit
Chemotherapy
- Treatment with a cisplatin-containing regimen in advanced metastatic penile cancer should be considered and this may facilitate curative resection. The optimal regimen has yet to be determined.
- Among patients whose tumour progresses through chemotherapy, surgery is not recommended

Non-squamous penile malignant neoplasms

Extremely rare
Basal cell carcinoma
- Frequently encountered on other sun-exposed cutaneous surfaces, it is rare on the penis
- Treatment is by local excision, which is virtually always curative
Melanoma
- Aggressive form of cancer but can be cured if diagnosed and treated with the appropriate surgical treatment at an early stage
  - Surgery is the primary mode of treatment; radiation therapy and chemotherapy are of only adjunctive or palliative benefit
Sarcoma
- Prone to local recurrence; regional and distant metastases are rare.
- Superficial lesions can be treated with less radical procedures
Extramammary Paget Disease
- Appearance
  - Erythematous, eczematoid, well-demarcated area
  - Cannot be clinically distinguished from erythroplasia of Queyrat, Bowen disease, or carcinoma in situ of the penis
  - See Figure
- Clinical presentation
  - Local discomfort, pruritus, and occasionally a serosanguineous discharge involving the penis, the scrotum, or even the perianal area
- Behaves as a slow-growing intraepithelial adenocarcinoma
  - With time the cells may become invasive with dermal tumor deposits metastasizing to regional lymph nodes via dermal lymphatics penoscrotal
- May be associated with other malignancies of the genitourinary tract, such as prostate, bladder, and renal malignancies and should be evaluated for their presence
- Management
  - In most cases, only the skin and dermis must be resected with a gross margin of up to 3 cm. Positive margins may still occur, and frozen sections are recommended to guide the extent of resection.
    - Patients with a positive surgical margin are at a higher risk for recurrence, and additional resection is advised
  - Local skin or scrotal flaps can be used to cover the defects.
  - In a minority of cases the tumor may invade deeper structures, necessitating more extensive resection and reconstruction
  - If inguinal adenopathy is present, radical node dissection is advised but prognosis is poor
Adenosquamous carcinoma
Lymphoreticular malignant neoplasm
Metastases
- Most often represent spread from a clinically obvious existing primary tumor.
- Prognosis is poor, and therapy should be directed toward the primary tumor site histology and local palliation
- Priapism is the most frequently encountered sign of metastatic involvement of the penis
Lymphomatous infiltration of the penis is most likely secondary to diffuse disease

Questions

List the premalignant lesions of the penis.
What is the risk of progression of Bowenoid papulosis? Verrucous carcinoma? Erythroplaysia of Querat? Bowen disease?
List risk factors for penile cancer
Describe the lymphatic drainage of the penis
What is the work-up of a patient with suspected penile cancer?
What form of imaging of the primary tumour is preferred?
Which patients should undergo imaging to evaluate lymph node metastases?
What is the name of the classification system used in grading penile cancer?
What are the risk factors for nodal mestastasis?
Describe the pTNM staging of penile cancer
Describe the management options of the primary lesion in penile cancer
What is the recommended margin on circumcision for CIS?
What are the indications for partial or total penectomy
What is the most important prognostic factor for survival?
What are the prognostic factors following inguinal lymph node dissection for penile cancer?
Which patients may be treated with primary radiotherapy for invasive penile carcinoma?
What is the recommended margin in extra-mammary Paget’s disease?
What is the most presentation of metastasis to the penis?

Answers

List the premalignant lesions of the penis.
- HPV-related (4): Bowenoid papulosis, verrucous carcinoma, Erythroplasia of Querat, Bowen disease
- Non-HPV related (5): Kaposi sarcoma, cutaneous horn, leukoplakia, lichen schlerosis, pseudoepitheliomatous micaceous and keratotic balanitis
What is the risk of progression of Bowenoid papulosis? Verrucous carcinoma? Erythroplaysia of Querat? Bowen disease?
- 1%, 30%, 30%, 5%
List risk factors for penile cancer

Lack of circumcision
Phimosis
Lichen sclerosus, chronic penile inflammation
HPV (subtype 16 most frequently)
Tobacco exposure (smoking, chewing tobacco)
Poor hygiene, rural areas, low socioeconomic status, unmarried
Number of sexual partners, early age of sexual intercourse
Penile trauma
Sporalene and ultraviolet A phototherapy (PUVA)

Describe the lymphatic drainage of the penis
- Foreskin and skin of the penile shaft drain into the right and left superficial inguinal nodes
- Glans drains into the superficial inguinal nodes and the deep inguinal nodes
- Penile cancer can metastasize to contralateral inguinal nodes because of crossover in the symphyseal region
- Drainage subsequently proceeds from the inguinal nodes to the ipsilateral pelvic lymph nodes (external iliac, internal iliac, and obturator)
What is the work-up of a patient with suspected penile cancer?
- History and physical exam (including exam of nodes), serum calcium, penile doppler US for larger/invasive lesions, metastatic imaging (if indicated)
What form of imaging of the primary tumour is preferred?
- Penile doppler US
Which patients should undergo imaging to evaluate lymph node metastases?
- Patients in whom physical exam unreliable (obesity, previous surgery in inguinal area)
What is the name of the classification system used in grading penile cancer?
- Broder
What are the risk factors for nodal mestastasis?

Stage (depth of invasion)
Grade
Lymphovascular invasion
Perineural invasion

Describe the pTNM staging of penile cancer
- Primary tumour (T)
  - TX: Primary tumour cannot be assessed
  - T0: No evidence of primary tumour
  - Tis: Carcinoma in situ
  - Ta: non-invasive squamous cell carcinoma types including basaloid, warty, verrucous, papillary, and mixed types
  - T1
    - T1a: Tumour invades subepithelial connective tissue without lymphovascular invasion, perineural invasion, and is not high grade (i.e. grade 3-4 or sarcomatoid)
    - T1b: Tumour invades subepithelial connective tissue WITH lymphovascular invasion, perineural invasion, or high grade (i.e. grade 3-4 or sarcomatoid)
  - T2: Tumour invades corpora spongiosum
  - T3: Tumour invades corpus cavernosum
  - T4: Tumour invades other adjacent structures
- Lymph nodes (N)
  - Clinical
    - cNX: Regional nodes cannot be assessed
    - cN0: No palpable or visibly enlarged inguinal lymph nodes
    - cN1: unilateral, mobile inguinal lymph nodes
    - cN2: ≥2 unilateral, mobile inguinal lymph nodes or bilateral inguinal lymph nodes
    - cN3: palpable, fixed nodal mass, regardless of the size or unilateral/bilateral involvement
  - Pathological
    - pNX: Regional nodes cannot be assessed
    - pN0: No regional lymph node metastasis
    - pN1: up to 2 unilateral positive inguinal lymph nodes
    - pN2: ≥3 unilateral lymph nodes or bilateral inguinal lymph nodes
    - pN3: Extra-nodal extension or pelvic lymph node(s)
- Distant metastasis (M)
  - M0: No distant metastasis (no pathologic M0; use clinical M to complete staging group)
  - M1: Distant metastasis
    - Lymph node metastasis outside the true pelvis, or to visceral or bone sites
Describe the management options of the primary lesion in penile cancer
- CIS

Non-surgical
- Topical: 5-FU, imiquimod
- Laser ablation
Surgical: limited excision/circumcision
Radiation
Mohs surgery

Favourable histologic features (stage Ta, T1; grade 1 and 2)

Organ-sparing or glans-sparing surgical procedures: Mohs surgery, laser ablation, radiation therapy, limited excision strategies, and glansectomy

What is the recommended margin on circumcision for CIS?
- 5mm
What are the indications for partial or total penectomy

High grade (grade ≥ 3) lesions
[stage ≥ T2]; deep invasion into the glans urethra or corpora cavernosa
Tumours >4cm

What is the most important prognostic factor for survival?
- Lymph node metastasis
What are the prognostic factors following inguinal lymph node dissection for penile cancer?

Unilateral involvement
Minimal nodal disease (up to 2 involved nodes in most series)
No evidence of extra nodal extension of cancer
Absence of pelvic nodal metastases

Which patients may be treated with primary radiotherapy for invasive penile carcinoma?
- T1-2 tumours and <4cm; circumcision is necessary before
What is the recommended margin in extra-mammary Paget’s disease?
- 3cm
What is the most presentation of metastasis to the penis?
- Priapism

References

Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, vol 1, chap 37
Chipollini, Juan, et al."Patient presentation, differential diagnosis, and management of penile lesions." Canadian Urological Association Journal 13.2 Suppl 1 (2019): S2.