Penile Cancer
Kashif Siddiqui, T. McDermott
RCSI, March 29, 2004.
Benign Lesions
Non cutaneous
• Inclusion/Retention cysts
• Syringoma
• Neurilemmoma
• Angioma, Fibroma,
Neuroma, Lipoma,
Myoma
• Pseudotumors
Cutaneous
• Penile papules
• Hirsute papillomas
• Coronal papillae
• Zoons erythroplasia
• Rashes & ulcerations
secondary to irritation, allergy
and infections
Premalignant lesions
• 42% of pts with SCC
had hx of pre existing
penile lesions.
(Bouchot etal 1989)
• Cutaneous Horn
• Pseudoepitheliomatous
Micaceous & Keratotic
Balanitis
• Balanitis Xerotica
Obliterans
• Leukoplakia
Viral related conditions
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Human Papilloma virus
(HPV)
Types 6,11,42,43 & 44
associated with low grade
dysplasia.
Types 16,18,31,33,35 & 39 have
higher association with
malignancy.
• Human Herpesvirus 8
(HHV 8)
• Condylomata Acuminatum
• Bowenoid Papulosis
• Kaposi’s Sarcoma
Buschke-Lowenstein Tumor
(Verrucous Carcinoma, Giant Condyloma
Acuminatum)
• initially described in 1925.
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true incidence is unknown.
Does not metastasize rather invades locally.
Treatment is excision.
Recurrence is common.
Topical therapy with Podophyllin, 5FU, radiation
and chemotherapy have all been tried with no
great success.
Penile Cancer
• Squamous cell carcinoma. > 95%
• Mesenchymal tumors.
< 3%
e.g Kaposi sarcoma, angiosarcoma etc
• Maligannt Melanoma.
• Basal cell carcinoma.
• Metastasis.
Sufrin & Huben 1991
Carcinoma in situ
Penile intraepithelial neoplasia, Erythroplasia of
Queyrat, Bowen’s disease
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can progress to invasive carcinoma.
Histological confirmation with proper determination of
invasion.
• Treatment
Circumcission------------Preputial lesions
Local excision------------small & non invasive
Radiotherapy
Topical 5FU as 5% base
Nd:YAG & CO2 laser, liquid nitrogen
Kelley etal 1974, Graham & Helwig 1973, Mortimer etal 1983
Invasive carcinoma
• Uncommon.
• 0.1 – 0.9 per 100,000 in USA, Europe.
• Upto 10% in some asian, african and south
american countries, (Vatamasapt etal 1995)
• Disease of older men, 6th decade, reported in
younger men & children. (Narsimharao 1985)
• Primary tumor localized to glans (48%), prepuce
(21%), both glans & prepuce (9%), coronal (6%),
shaft (<2%). (Sufrin & Huben 1991)
Etiology
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Circumcission practice.
Hygiene standards.
Phimosis.
No. of sexual partners.
HPV infection.
Exposure to tobacco products.
No convincing association with occupation, gonorrhea,
syphillis & alcohol intake.
Barrasso etal 1987, Maiche 1992, Maden etal 1993
Prevention
• Routine neonatal circumcission.
AAP Paediatric guidelines 1999.
• Good hygiene practice.
• Avoid HPV infection and tobacco.
Natural History
• Begins as small lesion, papillary & exophytic or
flat & ulcerative.
• Flat & ulcerative lesions >5cm and extending
>75% of the shaft have higher incidence of
metastasis and poor survival.
• Pattern in lymphatic spread.
• Metastatic nodes cause erosion into vessels, skin
necrosis & chronic infection.
• Distant metastasis uncommon 1 – 10%
• Death within 2 years for most untreated cases.
Presentation
• Symptoms
malaise, wt loss, fatigue, weakness,
hemorrhage, pain.
• Signs
penile lesion.
rarely nodal mass, ulceration, suppuration.
Diagnosis
• Primary lesion.
• Regional lymph
nodes.
• Distant metastasis.
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Physical examination.
Ultrasound.
MRI.
CT.
Cavernosography.
Lymphangiography.
Diagnosis
• Histological diagnosis is absolutely necessary
prior to treatment decision.
• Growth pattern of SCC
superficial spreading.
vertical growth.
multicentric.
verrucous.
Cubilla etal 1993
Grading systems
• Broders grading
system (Ann Surg 1921;73:141)
divided into 4 grades
depends on differentiation
based on keratinization,
nuclear pleomorphism, no.
of mitosis
• Maiche system score
(Br J Urol 1991;67:522-526)
modified into 3 grades
5 year survival
Grade 1
80%
Grade 2,3
50%
Grade 4
30%
Maiche etal 1991
Staging
• Jackson’s staging system, 1966.
TNM staging system
Treatment of Penile lesion
Penile intraepithelial neoplasia
Penis preserving strategy
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Laser therapy.
Local excision.
5 FU cream.
Cryotherapy.
Photodynamic therapy.
5% topical imiquimod.
Treatment of Penile lesion
Ta-1 G1-2
Penis preserving strategy with regular follow up.
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Local excision plus reconstruction, recurrence 11-30%
Laser therapy, recurrence 15-25%.
Radiotherapy / Brachytherapy, recurrence 15-25%.
Glansectomy.
Treatment of Penile lesion
T1 G3, T ≥ 2
• Partial / total amputation.
• Conservative strategy is an alternative in very
carefully selected patients.
Treatment of Penile lesion
Local recurrence
• Second conservative procedure.
• Partial / total amputation.
• External beam radiotherapy / brachytherapy for
lesions < 4cm diameter.
Treatment of regional nodes
Non palpable nodes
20% harbour micrometastasis.
Low risk pTis, pTaG1-2, pT1G1
• Surveillance.
• Occult micrometastasis in < 16.5%.
Solsona J Urol 2001;165:1506-1509, Horenblas J Urol 1994;151:1239-1243, Theodoreson
1996 J Urol;155:1626-1631
Treatment of regional nodes
Non palpable nodes
Intermediate risk T1G2
• Vascular / lymphatic invasion & growth pattern.
• Surveillance for superficial pattern & no invasion.
• Modified lymphadenectomy in infiltrating growth pattern
or invasion.
• ? Role of sentinnel node biopsy.
Solsona J Urol 2001;165:1506-1509, Horenblas J Urol 1994;151:1239-1243, Theodoreson 1996 J
Urol;155:1626-1631
Treatment of regional nodes
Non palpable nodes
High risk T (2 or G3)
• Modified or radical lymphadenectomy.
• 70% may have occult metastasis.
Solsona J Urol 2001;165:1506-1509, Horenblas J Urol 1994;151:1239-1243, Theodoreson
1996 J Urol;155:1626-1631
Treatment of regional nodes
Palpable nodes
• Present at diagnosis in 58% patients.
• Of these 17-45% have nodal metastasis while
remaining have iflammatory disease.
Horenblas J Urol 1993;149:492-497, Ornellas J Urol 1994;151:1244-1249
Treatment of regional nodes
Positive palpable nodes
• Bilateral radical inguinal lymphadenectomy.
• Probability of pelvic node involvement
23% , 2-3 nodes +ve & 56%, >3 nodes +ve
Culkin J Urol 2003;170:359-365
• Incidence of pelvic nodes ↑ to 30% in 2-3 node
group with delayed pelvic lymphadenectomy.
Ornellas J Urol 1994;151:1244-1249
Treatment of regional nodes
Fixed inguinal mass / clinically +ve pelvic nodes
• Chemotherapy, partial / complete clinical response
in 21-60%. (Ficarra Int Urol Nephrol 2002;34:245-250, Culkin J Urol
2003;170:359-365, Pizzocaro J Urol 1995;153:246)
• Subsequent radical ilioinguinal lymphadenectomy.
• Radiotherapy followed by lymphadenectomy but
higher morbidity.
Treatment of regional nodes
Inguinal palpable nodes during surveillance
• Bilateral radical inguinal lymphadenectomy
• Inguinal lymphadenectomy at site of +ve
nodes in cases of long disease free interval.
Treatment
Integrated therapy
• In pts presenting with primary tumor and +ve
nodes, both issues should be managed
simultaneously.
• In pts presenting initially with +ve pelvic nodes,
induction chemotherapy followed by radical /
palliative surgery or DTx is administered
according to tumor response.
Treatment
Distant metastasis
• Chemotherapy.
• Palliative therapy.
Treatment
Technical aspects
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Surgeons experience.
Formal circumcission before radiotherapy.
~ 2 cm tumor free margin.
Landmarks for RIL include inguinal lig, adductor &
sartorius muscle, femoral vessels.
• MIL, saphenous vein should be preserved, boundaries 1-2
cm less than radical surgery.
• PL includes external iliac & ilio obturator chains with
boundaries of iliac bifurcation, ilioinguinal & obturator
nerve.
Treatment
Technical aspects
• Complications of LND.
• Sentinnel node biopsy & its limitations.
92% identified, 23 % +ve for tumor.
• Various lasers, CO2 0.1cm & NdYAG 0.4cm
absorption, local recurrence +/- 25%.
Treatment
Quality of Life
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Age, performance status.
Socioeconomic factors.
Sexual function.
Patient motivation.
Psychological aspects.
Morbidity of various procedures.
Tumor biology.
Chemotherapy
• cis platin +/- 5FU, VMB, CMB.
• Adjuvant following RLND, 82% 5 yr survival.
Pizzocaro Acta Oncol 1988;27:823-4
• Neo adjuvant, fixed inguinal nodes, 56%
resectable & 31% cured. Pizzocaro J Urol 1995;153:246
• Advanced disease, 32% response rate, 12% Rx
related deaths.
Haas J Urol 1999;161:1823-1825, Kattan Urol 1993;42:559-62
Radiotherapy
Primary tumor
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EBR, response rate 56%, failure 40%.
Brachytherapy, response rate 70%, failure 16%.
Tumor size < 4 cm.
Complications
telengiectasia >90%, meatal stenosis 30%, urethral
strictures / fistula 35%, penile necrosis.
Radiotherapy
Prophylaxis
• NOT recommended. (fails to prevent mets, morbidity, difficult to
follow)
Neo adjuvant
• can render fixed nodes operable.
Adjuvant
• may be used to reduce local recurrence.
Follow up
• Most relapses in first 2 years.
• 0-7% chance of relapse after partial / total
penectomy.
• Development of palpable nodes with non palpable
nodes initially means metastasis ~ 100%.
• Physical exam, CT & CXR.
EAU guidelines on diagnosis
Primary tumor
PE mandatory, recording morphology & characteristics of lesion.
Histological diagnosis or cytology is mandatory.
Penile US advisable, if inconclusive MRI optional.
Regional lymph nodes
PE mandatory.
Impalpable nodes, no indication for imaging or histology, DSNB adviable
in intermediate & high risk pts.
Palpable nodes, record morphology and characteristics, histology reqd
EAU guidelines on diagnosis
Distant metastasis (only in pts with inguinal nodes)
Pelvic / abdominal CT (pelvic nodes)
Chest xray
Bone scan only if symptomatic
Laboratory determinations for specific conditions optional
EAU guidelines on treatment
Primary Lesion
Penile intraepithelial neoplasia
Penis preserving strategy.
Ta-1 G1-2
Penis conservation, partial amputation in non compliance to follow up.
T1G3, T ≥ 2
Partial / total amputation standard, conservative option in selected pts
Local recurrence following conservative therapy
Second conservative procedure in no invasion cases
Partial / total amputation in infiltrating recurrences.
EAU guidelines on treatment
RN therapy in non palpable nodes
Low risk of occult mets (pTis, pTaG1-2, pT1G1)
Surveillance, MLND is optional in unreliable to follow pts.
Intermediate risk (pT1G2)
Strict surveillance is an option in cases with no lymphovas invasion &
favourable growth pattern
MLND is an option with poor histology, role of DSLNB
MLND enlarged to RLND in presence of + ve nodes
High risk (pT≥2 or G3)
MLND or RLND recommended.
EAU guidelines on treatment
Palpable positive RLN
Bilateral radical inguinal LND is standard recommendation.
PLND can be performed in cases with at least 2 +ve LNs or extracapsular
invasion.
MLND can be considered on contralateral groin with no palpable nodes.
Induction chemo followed by RLND for fixed inguinal mass or clinically
+ve pelvic nodes, alternative is neo adjuvant DTx.
Bilat RLND or LND at site of palpable nodes during surveillance,
adjuvant chemo & DTx are options.
EAU guidelines for follow up
Primary tumor
Conservative therapy, every 2/12 for 2 yrs, 3/12 for 1yr, 6/12 long term.
Partial / total penectomy, every 4/12 for 2 yrs, twice during third yr, then
annually long term.
Regional nodes & distant metastasis
Primary tumor removed, 2/12 for 2 yrs, 3/12 for 1 yr, 6/12 for 2 yrs
Lymphadenectomy (pN0), 4/12 for 2 yrs, 3/12 for 1 more yr
Lymphadenectomy (pN1-3), PE, CT & CXR at regular intervals
Bone scan if symptomatic
Thank you all
Discussion & Questions