2. • A 65year old gentleman came with history of growth in the penis for
6 months, growth is not associated with bleeding , pain, discharge.
• h/o difficulty in passing urine
• h/o increased frequency of urine
• No h/o fever / haematuria / burning micturition.
• No h/o white discharge from urethra.
• No h/o trauma
• No h/o any swelling in the inguinal region.
• No h/o any scrotal swelling.
• Normal bowel habits.
• No known co morbidity
• h/o traumatic sigmoid perforation with colostomy 2 month back.
Reversal done 1 month back.
History
3. Examination
• External genitalia : 3x2 cm ulcerated growth over the glans
penis over ventral aspect. Erythema present, no discharge.
• B/L inguinal region: no palpable mass
• Abdomen : soft non tender, no mass palpable, midline scar
seen, scar seen in left lumbar region(s/p cholostomy closure)
• P/R: normal sphincter tone, no palpable mass, grade II
prostatomegaly.
• Vitals: stable
• Systemic examination: no abnormality detected.
6. Imaging and histopathology
• USG inguinal region – multiple enlarged superficial inguinal
lymph nodes in B/L inguinal region largest measuring
1.5x0.5cm on right side, and 1.32 x 0.4 cm on left side with
maintained fatty hilum.
• Biopsy of tumour – moderately differentiated squamous cell
carcinoma
• USG GUIDED FNAC B/L inguinal lymph node - non specific
reactive lymphadenitis and negative for metastasis.
7. Surgery
• PARTIAL PENECTOMY + (modified CATALONA PROCEDURE )
STAGING B/L INGUINAL LYMPH NODE DISSECTION under SA.
8. PROCEDURE:
• INTRAOPERATIVE FINDINGS: Ulcero proliferative growth
involving ventral aspect of glans penis up to frenulum, coronal
sulcus, encroaching urethral meatus.
• Partial penectomy done with proximal stump of 4 cm.
• B/L inguinal lymph node dissection done
• B/L staging inguinal lymph node dissection showed multiple
suspicious nodes in femoral triangle.
• FROZEN section:
• Penis – margins free of tumour.
• Right inguinal lymph nodes send of FROZEN section
intraoperatively showed 3/7 lymph nodes positive for
malignancy , Cloquets’s node negative of tumour.
• Sartorious muscle transposition flap done.
• B/L Inguinal region vacuum drain placed
9. POST OPERATIVE PERIOD:
• Uneventful
• Compression stockings applied on both lower limb upto groin.
• Inguinal region B/L Sutures removed on POD – 14
• Right inguinal drain removed on POD - 16
• Left inguinal drain removed on POD - 22
10. FROZEN
GROSS:
• Received partial
penectomy specimen
measuring 8cm in length
• One ulcero-proliferative
growth in seen in glans
penis measuring
2.5x2x0.8cm
• Growth is superficial and
appears not involving
corpora and urethra
• Growth is 4.5cm away
from surgical margin
11. MICROSCOPY - FROZEN
• Frozen section from resected surgical margins appear free of
tumor
• Skin surgical margins also appears free of tumor
12. FROZEN SECTION
REPORT:
• FR – 04/17: Container labeled B.
Cloquet’s Node (Right side
superomedial lymph node):
• Three lymph nodes submitted for
frozen section.
• All three lymph nodes are free of
tumor
• Histopathology report will follow
• FR – 03/17: Container labeled A.
Right side Inguinal Block
Dissection:
• Five lymph nodes submitted for
frozen section.
• Three lymph nodes are positive for
malignancy
• Histopathology report will follow
16. 253/17-Container labeled B. Cloquet’s node
(Right supero-medial lymph node):
• Received unfixed 3 lymph nodes, out of which 2 are all embedded
and submitted for frozen section. 1 lymph node bissected and
one half submitted to frozen and remaining half was routinely
processed
252/17-Container labeled A. Right Side Inguinal
Block Dissection:
• Received single soft tissue mass measuring 10x6.5x2.5cm.
• Identified 19 lymph nodes, largest measuring 2x1x0.5cm
17. 266/17-Container labelled Left inguinal
dissection:
• Received single soft tissue mass measuring 10x6x3cm.
• Identified 18 lymph nodes, largest measuring 2x0.8x0.2cm
23. MICROSCOPY
• 251/17- Section studied from skin and soft tissue surgical
margins (including urethral and corpora margins) are free of
tumor.
• Section studied from tumor proper shows sheets of atypical
squamous cells with surface papillomatous architecture and
ulceration with dense inflammation.
• Individual tumor cells are polygonal to round with eosinophilic
cytoplasm, increased N:C ratio and hyperchromatic nucleus,
places arranged in lobules separated by fibrous stroma with
dense neutrophilic infiltration, few keratin pearls and foreign
body giant cells seen, occasional atypical mitosis are seen.
• Adjacent skin shows dysplasia.
• Tumor infiltrating upto superficial sub-epithelial
fibrocollagenous tissue. No lympho-vascular invasion seen.
24. • 252/17-Section studied from Right side inguinal
block dissection nodes totally 19 lymph nodes, are
all free of tumor
• 253/17-Section studied from Cloquet’s node (3
lymph nodes were identified) are all free of tumor
• 266/17-Section studied from Left inguinal block
dissection nodes.
• Totally 18 lymph nodes dissected are all free of
tumor
25. • IMPRESSION:
• Features suggestive of conventional moderately
differentiated squamous cell carcinoma of penis,
Superficial spreading type (T1N0Mx)
• Skin, soft tissue surgical margins and 19 right side
inguinal nodes, are all free of tumor
• 3 Cloquet’s node and 18 left inguinal nodes are all free
of tumor
• No lympho-vascular invasion seen
29. Follow upFollow up for the patient
TREATMENT FOLLOW UP
1-2 YEARS
FOLLOW UP
YEAR 3-5
FOLLOW UP
YEAR >5
WORKUP
Penectomy 6 months 12 months Annually Regular physical
examination
pN0 6 months 12 months annually Regular physical
examination, usg and
fnac of abnormal node
32. Discussion
• Introduction:
• Penile carcinoma is mostly a squamous cell carcinoma (SCC)
but other types of carcinoma exist as well. It usually originates
from the epithelium of the inner prepuce or the glans. Also,
penile SCC occurs in several histological subtypes. Penile SCC
shares similar pathology with SCC of the oropharynx, the
female genitalia (cervix, vagina and vulva) and the anus.
33. •EPIDEMIOLOGY
• The annual age-adjusted incidence is 0.7-3.0 in 100,000 men
in India. 8.3 per 100,000 men in Brazil and even higher in
Uganda.
• Penile cancer is common in regions with a high prevalence of
human papilloma virus (HPV)
• According to race ; The highest incidence of penile cancer
found in white Hispanics (1.01 per 100,000), followed by a
lower incidence in Alaskan, Native American Indians (0.77 per
100,000), blacks (0.62 per 100,000) and white non-Hispanics
(0.51 per 100,000)
• Recently, an increased incidence has been reported from
Denmark and the UK. A longitudinal study from the UK has
confirmed a 21% increase in incidence over the period 1979-
2009 . The incidence of penile cancer increases with age, with
an age peak during the sixth decade of life. However, the
disease does occur in younger men.
34. RISK FACTORS
• Phimosis OR 11-16 versus no phimosis (2,3)
• chronic penile inflammation (balanoposthitis related to
phimosis)
• balanitis xerotica obliterans (lichen sclerosus)
• sporalene and UV-A phototherapy for various dermatologic
conditions such as psoriasis
• smoking 5-fold increased risk versus non smokers
• HPV infection condylomata acuminata
• Rural areas, low socio-economic status, unmarried
• multiple sexual partners early age of first intercourse
35. TNM CLASSIFICATION
Clinical classification
T - Primary Tumour
• TX Primary tumour cannot be assessed
• T0 No evidence of primary tumour
• Tis Carcinoma in situ Ta Non-invasive carcinoma
• T1 Tumour invades subepithelial connective tissue
• T1a Tumour invades subepithelial connective tissue without
lymphovascular invasion and is not poorly differentiated or
undifferentiated (T1G1-2)
• T1b Tumour invades subepithelial connective tissue with
lymphovascular invasion or is poorly differentiated or
undifferentiated (T1G3-4)
• T2 Tumour invades corpus spongiosum and/or corpora cavernosa
• T3 Tumour invades urethra
• T4 Tumour invades other adjacent structures
36. • N - Regional Lymph Nodes
• NX Regional lymph nodes cannot be assessed
• N0 No palpable or visibly enlarged inguinal lymph node
• N1 Palpable mobile unilateral inguinal lymph node
• N2 Palpable mobile multiple unilateral or bilateral inguinal
lymph nodes
• N3 Fixed inguinal nodal mass or pelvic lymphadenopathy,
unilateral or bilateral
• M - Distant Metastasis
• M0 No distant metastasis
• M1 Distant metastasis
37. Pathological classification
• The pT categories correspond to the clinical T categories. The pN categories are
based upon biopsy or surgical excision.
• pN - Regional Lymph Nodes
• pNX Regional lymph nodes cannot be assessed
• pN0 No regional lymph node metastasis
• pN1 Intranodal metastasis in a single inguinal lymph node
• pN2 Metastasis in multiple or bilateral inguinal lymph nodes
• pN3 Metastasis in pelvic lymph node(s), unilateral or bilateral or extranodal
extension of any regional lymph node metastasis
• pM - Distant Metastasis
• pM0 No distant metastasis
• pM1 Distant metastasis
• G - Histopathological Grading
• GX Grade of differentiation cannot be assessed
• G1 Well differentiated
• G2 Moderately differentiated
• G3-4 Poorly differentiated/undifferentiated
38. Stage
• 0 - Tis or Ta, N0, M0
• 1 - T1a, N0, M0
• 2 - T1b or T2 or T3, N0, M0
• 3 - T1-3, N1, M0 or T1-3, N2, M0
• 4 - T4, any N, M0 or any T, N3, M0 or any T, any N, M1
39. Investigations
• Primary tumour
• Physical examination, recording morphology, extent and invasion of penile
structures.
• MRI with artificial erection in selected cases with intended organ preserving
surgery.
• Inguinal lymph nodes
• Physical examination of both groins, recording number, laterality and
characteristics of inguinal nodes
• • If nodes are not palpable, invasive lymph node staging in high-risk patients.
• • If nodes are palpable, a pelvic CT may be indicated, PET/CT is an option.
• Distant metastases
• In N+ patients, abdomino-pelvic CT scan and chest X-ray are required for
systemic staging. PET/CT scan is an option.
• In patients with systemic disease or with relevant symptoms, a bone scan may
be indicated.
41. T3 with invasion of the urethra
• Partial penectomy or total penectomy with perineal urethrostomy.
T4 with invasion of other adjacent structures
• Neoadjuvant chemotherapy followed by surgery in responders.
Alternative: palliative external beam radiation.
Local recurrence after conservative treatment
• Salvage surgery with penis-sparing treatment in small recurrences or
partial amputation.
• Large or high stage recurrence: partial or total amputation.
Metastatic spread
• Treatment options include systemic chemotherapy or radiotherapy
or radiotherapy with concurrent chemotherapy [58]
• a) Responders receive consolidation ILND
• b) For those with no response/ disease progression, consider salvage
systemic chemotherapy or radiotherapy for local control and/or best
supportive care/ clinical trial
43. Chemotherapy
Neoadjuvant
• Neoadjuvant, cisplatin-based chemotherapy should be considered
the standard (prior to ILND) in patients with ≥4 cm inguinal lymph
nodes (fixed or mobile), if FNA is positive for metastatic penile
cancer. Patients with initially unresectable (T4) primary tumors may
be downstaged by response to chemotherapy.
• A Tx, N2-3, M0 penile cancer can receive 4 courses of neoadjuvant
paclitaxel, ifosfamide, and cisplatin (TIP). Stable or responding
disease should then undergo consolidative surgery with curative
intent.
The phase II response rate was 50% in the neoadjuvant setting.
The estimated rate of long-term progression-free survival for intent
to treat was 36.7%.
Improved progression-free and overall survival times were associated
with objective response to chemotherapy.
44. Adjuvant
• There are no sufficient data to form conclusions about the
use of adjuvant chemotherapy. By extrapolation from the
neoadjuvant data, it is reasonable to give 4 courses of TIP in
the adjuvant setting if it was not given preoperatively and the
pathology shows high-risk features.
Adjuvant EBRT or chemoradiotherapy can also be considered
for patients with high-risk features, which include any of the
following:
• Pelvic lymph node metastases
• Extranodal extension
• Bilateral inguinal lymph nodes involved
• 4 cm tumor in lymph nodes
45. Metastatic/Recurrent
• TIP is a reasonable first-line treatment for patients with metastatic
penile cancer, including palliative treatment of patients with distant
metastases.
• 5-FU + cisplatin has been used historically for metastatic penile cancer
and can be considered as an alternative to TIP. It appears to be effective
for some patients, although the toxicities may be limiting and require
dose reductions.
• Bleomycin-containing regimens are associated with unacceptable
toxicity and are no longer recommended.
• There are no randomized clinical trials due to the rarity of penile
cancer in industrialized countries.
Second-line
• No standard second-line systemic therapy exists.
• A clinical trial is preferred. The evidence to support the palliative use of
second-line therapy is limited.6 In select patients, paclitaxel7or
cetuximab8 may be considered, especially if not previously treated with
a similar class of agent.
46. Preferred combination chemotherapy regimens
• Paclitaxel 175 mg/m2 IV over 3 hours on Day 1
• Ifosfamide 1200 mg/m2 IV over 2 hours on Days 1–3
• Cisplatin 25 mg/m2 IV over 2 hours on Days 1–3
• Repeat every 3 to 4 weeks
• 5-FU + cisplatin4 (category 2B)
• Continuous infusion 5-FU 1000 mg/m2/d IV on Days 1–5
• Cisplatin 100 mg/m2 IV on Day 1
• Repeat every 3 to 4 weeks
Radiosensitizing agents and combinations (Chemoradiotherapy)
• Preferred
• Cisplatin alone, or in combination with 5-FU
• Alternate options
• Mitomycin C in combination with 5-FU
• Capecitabine (for palliation)
47. Radiotherapy
Primary Radiation Therapy (Penile Preservation)
T1-2, N0
If tumor <4 cm
• • Circumcision followed by either:
• Brachytherapy alone (preferred approach) (should be performed with interstitial implant);
or
• EBRT with or without concurrent chemotherapy:Total dose 65–70 Gy with conventional
fractionation using appropriate bolus to primary
• penile lesion with 2-cm margins. Consider prophylactic EBRT to inguinal lymph nodes in
patients who are not surgical candidates or who decline surgical management.
If tumor ≥4 cm
• • Circumcision followed by either:
• EBRT with concurrent chemotherapy:45–50.4 Gy to a portion of or whole penile shaft
depending on bulk and extent of lesion plus pelvic/ inguinal nodes, then boost primary
lesion with 2-cm margins (total dose 60–70 Gy);
or
• Brachytherapy (in select cases and with careful post-treatment surveillance)
48. T3-4 or N+ (surgically unresectable)
Circumcision followed by:
• EBRT with concurrent chemotherapy: 45–50.4 Gy to whole penile
shaft, pelvic lymph nodes, and bilateral inguinal lymph nodes, then
• boost primary lesion with 2-cm margins and gross lymph nodes (total
dose 60–70 Gy).
Postoperative Adjuvant Radiotherapy
• Inguinal Lymph Node Positive
• Inguinal and pelvic lymph node EBRT to 45–50.4 Gy (strongly consider
concurrent chemotherapy).
• Boost gross nodes and areas of extracapsular extension to a total dose
of 60–70 Gy.
• Treat primary site of disease if positive margin.
• Primary Site Margin Positive
• Primary site of disease and surgical scar EBRT to 60–70 Gy (for close
margin consider radiation treatment vs. observation).
• Treat bilateral inguinal lymph nodes and pelvic lymph nodes if no or
inadequate lymph node dissection.
• Brachytherapy
49. Follow up
TREATMENT FOLLOW UP
1-2 YEARS
FOLLOW UP
YEAR 3-5
FOLLOW UP
YEAR >5
WORKUP
Penile
preserving
3 months 6 months annually Regular physical
examination
Penectomy 6 months 12 months Annually Regular physical
examination
Surveillance 3 months 6 months Annually Regular physical
examination, usg and
fnac of abnormal node
pN0 6 months 12 months annually Regular physical
examination, usg and
fnac of abnormal node
PN+ 3 months 6 months annually Regular physical
examination, usg and
fnac of abnormal node
50. Reference
• Mehren, Margaret von, R. Lor Randall, Robert S. Benjamin, Sarah Boles, Marilyn
M. Bui, Ernest U. Conrad, Kristen N. Ganjoo, et al. “Soft Tissue Sarcoma, Version
2.2016, NCCN Clinical Practice Guidelines in Oncology.” Journal of the National
Comprehensive Cancer Network 14, no. 6 (2016): 758–786.
• Merseburger, Axel S., Peter Hammerer, Francois Rozet, Thierry Roumeguère,
Orazio Caffo, Fernando Calais Da Silva, and Antonio Alcaraz. “Androgen
Deprivation Therapy in Castrate-Resistant Prostate Cancer: How Important Is
GnRH Agonist Backbone Therapy?” World Journal of Urology 33, no. 8 (2015):
1079–1085.
• Richter, Suzanne, J. Dean Ruether, Lori Wood, Christina Canil, Patricia Moretto,
Peter Venner, Joel Gingerich, et al. “Management of Carcinoma of the Penis:
Consensus Statement from the Canadian Association of Genitourinary Medical
Oncologists (CAGMO).” Canadian Urological Association Journal 7, no. 11–12
(December 5, 2013): 797. doi:10.5489/cuaj.1794.
• Van Poppel, H., N. A. Watkin, S. Osanto, L. Moonen, A. Horwich, V. Kataja, and on
behalf of the ESMO Guidelines Working Group. “Penile Cancer: ESMO Clinical
Practice Guidelines for Diagnosis, Treatment and Follow-Up.” Annals of Oncology
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