Chapter 37: Penile Tumors

What is an appropriate surgical margin for penile sparing surgical methods?

0.5-1cm

What are 4 pathological criteria post lymphadenectomy associated with improved survival for penile cancer with nodal mets?

1) 2 or less nodes involved 2) Unilateral involvement 3) No extra-nodal extension 4) No pelvic LN mets

When you are doing ILND, when should PLND be performed (2 nodal characteristics)?

1) 2 or more positive ILN 2) ENE present

List 6 types of non-squamous penile cancers.

1) Basal cell (A) 2) Melanoma (B) 3) Sarcoma (C) 4) Extramammary Paget disease (D,E) 5) Adenosquamous carcinoma 6) Lymphoreticular malignant neoplasm

What are 3 organs that can result in metastatic spread of their cancers to the penis?

1) Bladder 2) Prostate 3) Rectum

What are 4 types of lasers used for laser ablation for lower stage/grade penile cancers?

1) CO2 2) Argon 3) Nd:YAG 4) KTP

List 4 infectious lesions that could be on the differential for penile tumors.

1) Chancre 2) Herpes lesion 3) Granuloma inguinale 4) TB

What are 6 types of pre-malignant penile lesions?

1) Cutaneous horn 2) Pseudoepitheliomatous, micaceous, and keratotic balanitis 3) Male lichen sclerosus (BXO) 4) Condylomata acuminata (HPV lesion) 5) Bowenoid papulosis 6) Kaposi sarcoma 7) Buschke-Lowenstein tumor

For clinically palpable nodes, ILND is still best option for treatment. When can adjuvant radiation be considered as well?

1) ENE present 2) 2 or more nodes involved

What are 2 radiation modalities to treat the primary lesion for penile cancer, should surgery not be opted for?

1) External beam 2) Brachytherapy

What are 4 options for node sampling in HIGH risk penile tumor patients who have non-palpable lymph nodes?

1) FNA 2) Sentinel node biopsy (extended) 3) Dynamic sentinel node biopsy 4) Superficial and modified ILND

How do you treat hypercalcemia in penile cancer? (3)

1) Fluid resuscitation 2) Bisphosphonates 3) Calcitonin (severe)

What are 3 methods of organ preservation surgery for penile cancers? (if partial or total penectomy is not necessary)

1) Limited excision/circumcision 2) Mohs surgery 3) Laser ablation

What are 2 of the most common late side effects of radiotherapy to the penis?

1) Meatal stenosis (1.5-2 years later) - up to 40% 2) Soft tissue ulceration

What are 2 ways to assess the primary tumor for depth of invasion?

1) Physical exam (small lesions) 2) Contrast enhanced MRI (for large lesions with suspicion for corporal invasion), maybe with artificial erection as well

What are 3 signs of mets to the penis? Which is the most common?

1) Priapism (most common) - tumor replaces cavernosa 2) Swelling 3) Nodularity 4) Ulceration

What are 3 benefits that the American Academy of Pediatrics has cited as benefits of neonatal circumcision?

1) Reduces UTI risk 2) Reduces STI transmission and prevents HIV-1 infection 3) Prevents penile cancer

List 4 complications from inguinal lymphadenectomy for penile cancer.

1) Skin necrosis 2) Lymphedema 3) Seroma formation 4) Wound infection

What are 4 pathological predictors of increased metastatic risk?

1) Stage 2) Grade 3) LVI 4) Perineural invasion

What are 3 histological features of primary penile tumor that would put them in the HIGH RISK for inguinal mets category?

1) T1b and above 2) Grade 3 or 4 3) LVI

What are 3 characteristics of penile cancers where penile amputation (ie: partial/total penectomy) is the gold standard treatment? (HINT: stage, grade, size)

1) T2 and above 2) Grade 3 and 4 3) Tumor >4cm

What are 2 characteristics of the primary penile tumor that make radiotherapy more successfull (HINT: stage, size)?

1) T2 and below 2) Size <4cm

What are 3 histological features of the primary penile tumor that would put them in the LOW RISK for inguinal mets category? (ie: these patients can be observed without ILND)

1) Ta 2) Tis 3) T1, grade 1

What are 4 RF for contracting HPV?

1) Uncircumcised 2) Smoker 3) Lack of condom 4) High number of sexual partners

List 8 RF for developing penile cancer.

1) Uncircumcised (neonatal) 2) Phimosis 3) HPV 4) Exposure to tobacco 5) BXO (male LS) 6) Penile trauma 7) Exposure to ultraviolet photochemotherapy (PUVA) 8) Increased sexual partners and lack of condom use

Histologically, SCC of the penis is classified into 6 categories. What are they (in order of incidence)?

1) Usual (59%) 2) Papillary (15%) 3) Basaloid (10%) 4) Warty (condylomatous) (10%) 5) Verrucous (3%) 6) Sarcomatoid (3%)

What are 4 nodal characteristics of any risk group that are associated with a higher cure rate?

1) no more than 2 nodes involved 2) no ENE 3) unilateral involvement 4) no pelvic nodal mets

What are treatments for condylomata acuminata (6)? Which one is the treatment of choice? What should you do prior to applying podophyllotoxin?

1) podophyllotoxin 0.5% gel 2) trichloroacetic acid 3) cryotherapy 4) electrofulguration 5) laser 6) imiquimod cream 5%** **Imiquimod (immune moduator) is treatment of choice Biopsy before the podophyllotoxin as the histological changes afterwards can mimic SCC.

What is the incidence invasive penile carcinoma?

1/100,000

What is the risk of penile cancer in men with lichen sclerosis (BXO)?

2-9%

What percentage of penile cancer patients with clinically non-palpable nodes actually have nodal mets?

30%

What percentage of penile tumors are effectively locally controlled with radiation?

40-60% for external beam, 80% with brachy. The rest need curative salvage penile amputation.

To detect subclinical HPV of the penis, what can you apply in clinic?

5% acetic acid (lesions turn white, are flat)

What is the percentage of urethral involvement with condylomata acuminata?

5%. Any involvement warrants urethroscopy.

What is the risk of progression of penile CIS to invasive carcinoma?

5-30%

What percentage of high risk penile tumors have nodal mets?

50-70%

Treatment of CIS include any excisional technique and topical therapy. For excision, how large of a normal margin is needed for adequate control?

5mm

Which histological subtypes of SCC carry the worst prognosis (2)? The best (1)?

Basaloid and sarcomatoid (aggressive) Verrucous is most favorable.

What is the next step after a penile tumor has been recognized clinically?

Biopsy, ensuring adequate depth

Penile cancer starts off SF and goes deep (papillary or ulcerative lesion). What layer of fascia acts as a natural initial barrier for corporeal invasion?

Bucks fascia

If inguinal lymphadenopathy is detected clinically, what is the next step?

CT and/or PET Determine poor prognostic features and presence of pelvic/distant mets.

What should be done first prior to treating the primary penile lesion with radiation?

Circumcision (exposes lesion, prevents subsequent edema or phimosis)

Which chemotherapy agent has been shown to have good responses in advanced metastatic penile cancer?

Cisplatin-based chemo

How do you treat BXO?

Clobetasol propionate cream X 2-3 months. F/u closely, as SCC still a RF after treatment.

What sets Buscke-Lowenstein tumors apart from condylomata accuminata?

Condylomata accuminata are superficial and never invade/compress adjacent tissues BL tumors displace and destroys adjacent tissue by compression. No malignant activity though, never metastasizes. Basically a larger worse form of condylomata. Associated with HPV 6 and 11.

What is a significant cause of delay in penile cancer management?

Delay in seeking medical attention.

What was the purpose of giving antibiotics when inguinal lymphadenopathy was detected in penile cancer? Why is it no longer advised?

Discern infection from mets. No longer advised because it delays treatment.

How do you treat BL tumors (verrucous carcinoma)?

Excision and cryosurgery. Topical treatment and radiation is ineffective (thick tumor won't allow for penetration of medication) Close f/u needed.

Where do the majority of penile tumors occur on the penis?

Glans and prepuce

What are the grades of penile cancer?

Grade 1 and 2: well differentiated Grade 3 and 4: poor differentiation

What virus is associated with Kaposi sarcoma, along with HIV and severe immunosuppression?

HHV-8 (Kaposi sarcoma-related herpesvirus)

Although most labs are normal, what is one electrolyte imbalance associated with penile cancer?

Hypercalcemia (even without bony mets). Possible explanation: tumor secretes PTH (causes bone resorption)

What is pseudoepitheliomatous, micaceous, keratotic balanitis, and how to treat?

Hyperkeratosis, micaceous (thin scales) growths on glans. Treat: excise, laser, or cryo; close f/u

When is an ilioinguinal LND performed (ie: deep LND and pelvic LND)?

If the SF LN are positive on ILND.

What is the most common type of interstitial brachytherapy used for penile cancer?

Iridium-192

What is extramammary Paget disease?

It is an adenocarcinoma of cutaneous origin. Looks indistinguishable from CIS. Spreads intraepidermally. Invasive EMPD is fairly lethal.

What is the risk of mets with the primary penile tumor being verrucous carcinoma (Ta) or CIS (Tis)?

Little to no risk of mets.

What is a characteristic trait of sarcomas after you resect them?

Local recurrences are common!

What is a common complication of BXO that might require ongoing management?

Meatal stenosis. Manage with serial dilations, steroid injections, or even recon

What is the management for high risk patients (T1b and above, Grade 3-4, or LVI)?

NON-PALP: DSNB, SF ILND PALP: a) Unilateral: ipsilat ILND+PLND, contralateral SF ILND b) Bilat: start bilat SF ILND, go deeper based on frozen

What is the management for low risk patients (Ta, Tis, T1 grade 1)?

NON-PALP: Observation PALP: can give antibiotics, and if persists then FNA/excisional biopsy. ILND if abnormal.

What is the management for intermediate risk patients (T1 grade 2)?

NON-PALP: Observation or nodal staging PALP: FNA, and if positive do ILND. If negative, can give Abx and if still persists do excision bx or proceed to ILND

Is pain a common presenting symptom of penile tumors?

No

Organ sparing for penile cancer is associated with higher recurrence rates than traditional amputation (ie: partial/total penectomy). How is early survival affected?

No difference, as long as recurrences are detected and treated.

Does lymph drainage follow an ipsilateral pattern from the penile lesion?

No, multiple cross connections exist at all nodal levels (drainage is bilateral to both inguinal areas)

Are FNA and sentinel node biopsies recommended anymore? What about DSNB?

No, poor sensitivity (high false negatives). DSNB has better sensitivity but still not ideal.

Do metastases occur commonly with CIS of the penis present?

No, very rare. Usually mets only with presence of actual penile carcinoma.

Should radiation be given as prophylaxis to patients with high risk penile tumors, and non-palp nodes?

No. ILND is still best option. Radiation does not alter natural history of inguinal mets.

Should unilateral ILND be done for unilateral palpable lymphadenopathy?

No. Penile lymphatics have a lot of crossover, so drainage is bilateral. Do contralateral SF ILND.

What is a cutaneous horn? How do you treat?

Overgrowth and hyperkeratosis of any pre-existing lesion, protrudes out. Associated with HPV-16. Treat: exise, negative margin around base, close f/u PIC: horn with underlying SCC

What is Kaposi sarcoma? How does one treat it?

Painful tumor commonly caused by either immunosuppression or HIV. Can also be idiopathic. Treat: excise if idiopathic. If immunosuppression, then reversing immunosuppression causes tumor to regress. Otherwise use radiation or local excision.

What is the gold standard for evaluating inguinal lymphadenopathy?

Physical exam. Do CT in obese patients on pts with prior inguinal surgery

What is bowenoid papulosis? How to treat? (HINT: this is not quite the same as Bowens disease)

Pigmented lesions, papules. Low malignant potential even though is technically a form of CIS. Treat: 5-FU, excision, or any other ablation (laser, cryo, etc).

What does Bowens disease look like?

Plaques (raised large lesions) of scaly erythema on penile shaft. Variants: crusted or ulcerated DDx: bowenoid papulosis, eczema, psoriasis, BCC

Describe the 4 stages of lymphatic drainage of the penis.

Prepucial/shaft skin lymphatics --> SF inguinal nodes (external to fascia lata) --> deep inguinal nodes (deep to fascia lata) --> pelvic nodes (external iliac, internal iliac, obturator)

What is the most important prognostic factor for survival in patients with SCC of penis?

Presence and extent of inguinal node metastases

What does erythroplasia of Queyrat look like? Microscopically?

Red, velvety, well demarcated lesions of glans or prepuce. Histologically, they are different from chronic balanitis in that there are atypical hyperplastic cells with hyperchromatic nuclei and mitotic figures.

What kinds of symptoms can large regional inguinal lymph nodes cause in distant spread of penile cancer?

Skin necrosis, infections, hemorrhage, sepsis

What is condylomata acuminata? What types of HPV are associated with penile cancer?

Soft papillary HPV lesions on glans, shaft, and prepuce. Keratinized tissue overlying papillary fronds. Themselves are benign, but have been associated with SCC. Types 16 and 18

If chemo achieves a good response in patients with advanced disease, what can be considered as the next step?

Surgical consolidation

Which stages and grades of penile cancer exhibit the lowest risk of mets and therefore should be considered for penile sparing procedures? (i.e.: not partial/total penectomy)

T1 and lower Grades 1 and 2

What is the T-staging of penile cancer?

Tx: cannot be assessed T0: no tumor Tis: CIS Ta: noninvasive verrucous carcinoma T1a: invades subepithelial connective tissue, no LVI, low grade (1-2) T1b: invades subepithelial connective tissue, with LVI OR high grade (3-4) T2: invades corpora T3: invades urethra T4: invades adjacent structures (ex: prostate)

What is BXO? How does it present?

White, indurated, sclerotic patches on glans, can involve meatus. Can cause erosions and stenosis. Etiology of BXO is unknown (maybe Borrelia burgdorferi?). Presents: pain, dyspareunia, painful erections

When do most patients with mets to the penis die?

Within 1 year, as mets to the penis usually indicates advanced primary disease.

Was there a big difference between doing early lymphadenectomy (for both non-palp and palpable nodes) and delayed lymphadenectomy (waiting until nodes are palpable)?

Yes! Significant reduction in 5-year survival in the delayed lymphadenectomy group (ie: difficult to salvage patients if you observe them until they are clinically palpable).

Does timing of circumcision affect risk of penile cancer?

Yes. Neonatal circ will bring risk to 0%, whereas adult circumcision (post-puberty) offers no protection.

Is radiation useful for inoperable nodes (bulky, fixed)?

Yes. Used with chemoradiation, may allow for nodal disease to be more amenable to resection.

What HPV types are associated with: a) non dysplastic lesions (genital warts, verrucous carcinomas) (2) b) CIS, invasive carcinoma (4)

a) HPV 6, 11 b) HPV 16, 18, 31, 33 HPV-16 = most common in met lesions

What is the treatment for the following non-squamous penile cancers: a) Basal cell carcinoma b) Melanoma c) Sarcoma d) EM Paget Disease e) Adenosquamous carcinoma f) Lymphoreticular malignant neoplasm

a) Local excision - highly curative b) Aggressive cancer. Partial/total penile amp, and ILND if melanoma is deep, possible radiation and chemo if advanced or palliative c) SF <2cm sarcoma = local excision; deep sarcoma (corporeal) = partial/total penile amp (no ILND needed) d) Resect skin and dermis, 3cm margin. Rarely invades deep, but need to amp if it does. e) Local excision/amp (exophytic mass), ILND if palp. f) Lymphomatous infiltration of penis, so look for other systemic signs of same disease. Treat with chemo, no surgery. May cause priapism.

What do you call CIS of the: a) glans penis/prepuce b) body of penis/remainder of genitalia

a) erythroplasia of Queyrat b) Bowens disease

What are 2 other names for Buschke-Lowenstein Tumor?

i) Verrucous carcinoma (verrucous = warty projections) ii) Giant Condyloma accuminatum