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Ca penisEdmond Wong              1
Ca Penis•   Epidemiology•   Risk factor•   Pathology•   Premalignant lesion & Mx•   Investigation and dx•   Staging•   Mx ...
Epidemiology• What is the incidence of Ca penis?  – 1 case per 100 000  – ~ 0.5 % of all malignancies Western World (decre...
Risk factors• What are the risk factors?   1. Smoking   2. UV radiation   3. Foreskin: phimosis , poor hygiene       • neo...
Pathology•    SCC (95%)    1.   Usual type (60-70%)    2.   Papillary (7%)    3.   Condylomatous (7%)    4.   Verrucous (7...
What are the growth patterns anddifferentiation grading systems?                        6
What is Broders’ & Maiche                 classification?• Broders’ grading :Divided into 4 grade (1921)   – Define the le...
What is the distribution of Ca             penis?• Glans (50%)• Prepuce (21%)  – May be related to constant exposure to   ...
Risk factor for metastasis1. Growth pattern (Cubilla 1993)  – Superficiallly spreading, LN met in 42%  – Vertical growth, ...
How do they present ?Presentation:• a sore that has failed to heal• a subtle induration in the skin, to a large exophytic ...
Natural History• Begins as small lesion, papillary & exophytic or  flat & ulcerative.• Flat & ulcerative lesions >5cm and ...
Premalignant lesions                 12
What are the benign penile lesion?• Non cutaneous:  –   Congenital and acquire inclusion cyst  –   Retention cyst  –   Ang...
Zoon balanitisPPP      Lichen Planus                                       14
Viral related lesions1. Condyloma Acuminatum:   –   Genital warts related to HPV infection (16,18)   –   Asso with SCC   –...
What are the premalignant lesions?                         16
•       Cutaneous horn:    –      extreme hyperkeratosis with base malignant txn with wide local excision•       Pseudo-e...
Premalignant lesion: CIS•   Erythroplasia of Queyrat: [non keratinising CIS]    – CIS: as oppose to Bowen’s disease, occur...
Balanitis Xerotica Obliterans (BXO)– Lichen sclerosis et atrophicus– >10% asso with future Ca penis– Location: White patch...
Circumcision• Consent:  –   Bleeding (2%)  –   Infection (2%)  –   Altered sensitivity of glans  –   Meatal stenosis (10%)...
Q14      Diagnosis? EPQ      Premalignant? Yes      If occurs on the shaft, what is it called? Bowens disease             ...
Diagnostic schedule for penile           cancer                       22
What is diagnostic schedule for        penile cancer?                        23
What is 2009 Staging of Ca penis?      SCC penis invading prostate is T3   24
What is the shortcoming of the              staging?• Prognosis of patients with tumour invasion of the  corpus spongiosum...
What is the proposed modification to 2009 TNM                classification?                                    26
Jackson’s staging system,         1966.                    27
Case:•   Patient present with a penile mass•   Painless•   Not affecting urination•   P/E:    – 1.5cm solid growth at glan...
History•   Age•   Previous duration of phimosis•   LUTS•   Smoking history•   Sexual history: HPV infection•   Exposure to...
PE     30
Penile biopsy• The most important diagnostic test• Circumcision and excisional biopsy if the cancer  is small• Incisional ...
How would you stage theLocal staging                tumor?1. USG, 7.5 MHz   – Tumor appear as hypoechoic   – Adv : detect ...
LNs staging              33
What is the lymphatic drainage            of penis?• First to the inguinal LN and then to the pelvic LN• Bilateral drainag...
What is the accuracy of P/E of       lymadenopathy?• High (90%) sensitivity but a low specificity (20%)  of clinical exami...
What is the imaging        investigation for LN?• CT / MRI  – Predict LN involvement by size only  – Sensitivity : 35 %, s...
Treatment strategies for penile           cancer                       37
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What are options of organ             preserving therapy?• Circumcision   – Small tumors confined to the prepuce   – But w...
What is organ preserving therapy?• Mohs micrographic surgery (MMS)   – “ shaving “ the tumour mass by excising thin layers...
What is organ preserving therapy?•    Laser surgery    –   For local and limited invasive disease    –   Four types of las...
What are the problems of      conservative treatment?• Not be suitable in cases of multifocal  lesions• Mohs’ micrographic...
What is Partial penectomy?•   When the cancer involves the glans and distal shaft•   T1a to T2 (not for T3 !!!!)•   Tradit...
How to perform partial              penectomy?• Tourniquet control, cover tumor with glove finger• Deglove the penis• Mark...
What is total Penectomy ?• Total amputation of penis + excision of  scrotum and its content• Formation of perineal urethro...
• CIS, Ta-1 G1-2 (i.e T1a)   – Penis-preserving strategy for those guarantee regular FU (70%)       • local excision + rec...
• T2 (invasion to copora)   – Partial amputation   – Margin 5-10mm   – If no LN on presenstation  5yr survival 66%• T3 (i...
What are treatment strategies     for penile cancer?                      48
What are treatment strategies     for penile cancer?                      49
RT?•    Indications:    1. Organ-preserving treatment in young pt with T1-2 lesions < 4 cm         – EBRT: Response rate: ...
Radiotherapy?•   Adv     – Avoid the psychological trauma associated with partial or complete penectomy     – Potential to...
Mx of LNs in Ca Penis                  52
What is the draining LNs of Ca                penis?•   Femoral and inguinal lymph nodes are the earliest path for tumor  ...
LN spread in Ca Penis• Regional LN of penis are located in inguinal region :  superficial or deep• Then drain to 2nd line ...
Daseler region•   Inguinal region is divided into four sections by a horizontal and a vertical line drawn through the    f...
Incidence• Depends on:  – Tumor grade: 30% G1 vs 40% G3  – Local stage : 60% in pT2 & 75% in pT3-4  – T1G2: 50% [Naumann B...
Prognostic significant of LN met•   Presence and extent of inguinal LN metastasis    are the most important factors for th...
Predictor of LN met• Variable if only take primary tumor into  account (pT stage, grade , depth of  invasion & histologica...
What are the risk factors for LN                  metstasis ?•    Risk factors    1. Lymphovascular invasion & Perineural ...
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Molecular marker• HPV DNA status: conflicting results• Ki-67: conflicting result on LN met• Reduce KAI1/CD82 expression: p...
What is the approach for non-                palpable nodes?•   Explained :     – 25% risk of lymph node metastases     – ...
Non-palpable LN : by pT stage•   Low risk gp: pTis, pTaG1/2, pT1 G1 (LN met < 17%)     – Active surveillance     – Optiona...
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What is the approach for palpable LN ?•   Explained:     –   Palpable LN present at diagnosis in 58% patients     –   Trad...
Palpable mobile LN• If T1 & G1 & no vascular invasion, mobile LN   – Antibiotics for 4 weeks & reassess (50% inflammatory)...
Summary• Whenever there is palpable LN  RLND• Whenever FZ show LN +ve  RLND                              70
Pelvic LND•   Incase of uninvolved inguinal LN, pelvic LND not indicated•   Risk of +ve pelvic LN: Culkin J Urol 2003;170:...
Fixed inguinal LN• Neo-adjuvnat chemotherapy (response rate 20-60%)   –   [Pizzocaro’s series]   –   3-4 courses of cispla...
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Surgical LN staging• Direct histological examination of inguinal  LN is the most reliable method of  assessing their invol...
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SEV, superficial epigastric; SEPV, superficial external                                                           Deep ing...
What is the boundary of femoral               triangle?•   Superior: Inguinal ligament•   Lateral: Medial border of sartor...
Radical inguinal                                   Modified inguinal  lymphadenectomy                                    l...
Describe the difference between radical vs   modified inguinal lymphadenectomy1. Shorter skin incision2. Limitation of the...
Complications• Early minor complications :40%  – Hemorrhage  – Wound infection  – Flap necrosis• Major complications: 15% ...
How to decrease morbidity of LND?• Prevention:  –   Prophylatic antibiotic  –   Care and diligent tissue handling  –   Use...
Dynamic sentinel node biopsy                 (DSNB)•   Identification of the LN in pt which is the first drainage node•   ...
How was the FN rate of DSNB            improved?• Before : FN rate of DSNB is 25%• Now: 5%• This is achieved by combinatio...
Video endoscopic LND•   Recently described technique•   Lower risk of skin complication•   Higher risk of lymphocele (23%)...
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Treatment for local recurrence                       87
What is the treatment for local          recurrence?• For local recurrence after conservative therapy,  a second conservat...
Chemotherapy               89
How about chemotherapy?• For distant metastasis disease• Drugs :   – cisplatin, bleomycin, methotrexate (CBM), and fluorou...
Chemotherapy• cis platin +/- 5FU, VMB, CMB.• Adjuvant following RLND, 82% 5 yr survival.                                  ...
Neo-adj chemo• Neoadjuvant chemotherapy for high risk groups :  – extranodal extension  – pelvic LN  – bilateral metastasi...
Follow-up schedule for penile             cancer• Most relapses in first 2 years.• 0-7% chance of relapse after partial / ...
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Prognosis            95
What is the prognosis of Ca             penis?• 5 Yr Survival  – Localized disease           70-95%     • T2 – 70%  – LN m...
Primary urethral tumor                    97
•   SCC (80%) Bulbomembranous urethra (60%)•   Risk factors – HPV, UV, chronic inflammatory or stricture condition, STD•  ...
Ca scrotum• SCC, < 50yr• Chimmey worker: chronic exposure to  soot , tar or oil• Presentation: painless lump or ulcer in  ...
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Ca penis [edmond]

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Penile Cancer

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Transcript of "Ca penis [edmond]"

  1. 1. Ca penisEdmond Wong 1
  2. 2. Ca Penis• Epidemiology• Risk factor• Pathology• Premalignant lesion & Mx• Investigation and dx• Staging• Mx of local tumor according to stage• Mx of LN• Metastasis 2
  3. 3. Epidemiology• What is the incidence of Ca penis? – 1 case per 100 000 – ~ 0.5 % of all malignancies Western World (decreasing) – Higher incidence in South America (Brazil), East Africa and South East Asia (10% of all male malignancy) – SEER database: no racial difference between black and white in US – But poor prognostic factor if African American ethnicity (Rippentrop et al, 2004) – Overall incidence is decreasing 3
  4. 4. Risk factors• What are the risk factors? 1. Smoking 2. UV radiation 3. Foreskin: phimosis , poor hygiene • neonatal circumcision eliminate risk by 5x [Daling 2005] • But not circumcision in adult (Maden 1993) 4. HPV infection (16, 18): asso in 50% • Sexual transmission causing genital warts, condyloma acuminate • HPV infects the basal epithelial cell that proliferates • Daling (2005) HPV DNA was detected in 80 % of tumor specimens • Carcinogenesis : interfering with p53 & pRB • Role in prognosis is unclear • Verrucous carcinoma is not related to HPV infection 5. Penile trauma• Prognostic makers: – p53, SCC antigen, P16, Ki-67m E-cadherin and MMP-2 4
  5. 5. Pathology• SCC (95%) 1. Usual type (60-70%) 2. Papillary (7%) 3. Condylomatous (7%) 4. Verrucous (7%) 5. Basaloid (4%) 6. Sarcomatoid (4%)• Malignant Melanoma (2%)• Basal cell carcinoma (2%)• Extra-mammary Paget’s disease (adenoCa from penile skin)• Sarcoma 5
  6. 6. What are the growth patterns anddifferentiation grading systems? 6
  7. 7. What is Broders’ & Maiche classification?• Broders’ grading :Divided into 4 grade (1921) – Define the level of differentiation based on • Keratinization • Nuclear pleomorphism • Number of mitosis • + other factors – 80 % of the Ca penis is low grade lesion ( Gd 1 and 2 ) – 20% Gd 3 and 4• Maiche grading : divided into 3 grade Maiche 1991 – Correlate with 5 year survival Grade 1 80% Grade 2,3 50% Grade 4 30% 7
  8. 8. What is the distribution of Ca penis?• Glans (50%)• Prepuce (21%) – May be related to constant exposure to irritants within the prepuce• Glans and prepuce (9%)• Coronal sulcus (6%)• Shaft (less than 2%) 8
  9. 9. Risk factor for metastasis1. Growth pattern (Cubilla 1993) – Superficiallly spreading, LN met in 42% – Vertical growth, LN met in 82%1. Basaloid and sarcomatous histologic pattern [MSKCC review (Cubilla 2001)]2. Stage3. Grade4. Status of vascular invasion (Slaton 2001) 9
  10. 10. How do they present ?Presentation:• a sore that has failed to heal• a subtle induration in the skin, to a large exophytic growth.• a phimosis may obscures the tumor and allows it to grow undetected.• Rarely, a mass, ulceration, suppuration, or hemorrhage may manifest in the inguinal area because of nodal metastases.• Pain is infrequent.• Buck fascia, which surrounds the corpora, acts as a temporary barrier.• Eventually, the cancer penetrates the Buck fascia and the tunica albuginea, where the cancer has access to the vasculature and systemic spread is possible• Delay presentation (50%) due to – Embarrassment, guilt, fear, ignorance, and neglect – Self treatment with various skin creams and lotions. – Doctor: confuse with other benign penile lesions• Metastasis : – Dehydration : hypecalcemia in 20% on presentation (PTH like) [MSKCC] – SOB 10
  11. 11. 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. 11
  12. 12. Premalignant lesions 12
  13. 13. What are the benign penile lesion?• Non cutaneous: – Congenital and acquire inclusion cyst – Retention cyst – Angioma , lipoma – Pyogenic granuloma – Peyronies plaque• Cutaneous: – Pearly Penile papules (PPP) • White, dome-shaped, closely spaced small papules at glans penis • Arranged circumferentially at corona • Histology : angiofibromas similar to lesion TS • 25% of young adults (uncircumcised) • NO association with HPV infection/ cervical CIN • Mx: Reassurance • Local destruction: CO2 laser, cryotherapy – Zoon balanitis: shinny , erythematous plaque on glans or prepuce – Lichen Planus :flat-topped violacious papule 13
  14. 14. Zoon balanitisPPP Lichen Planus 14
  15. 15. Viral related lesions1. Condyloma Acuminatum: – Genital warts related to HPV infection (16,18) – Asso with SCC – Soft, multiple lesion on glans, prepuce and shaft – Dx: biopsy – Txn: popdophyllin , diathermy if urethral involvement2. Bowenoid papulosis: – Resemble CIS , but with benign course – Muliple papules or flat glanular lesion – Dx: bx3. Kaposi’s sarcoma : – 2nd commonest penile tumor, reticulo-epithelial tumor – Raised , painful , bleeding, violacious papule urethral obstruction – Or bluish ulcer with local edema – Asso with HIV infection – Txn: palliative , intralesional chemo , – laser or cryo-ablation, RT 15
  16. 16. What are the premalignant lesions? 16
  17. 17. • Cutaneous horn: – extreme hyperkeratosis with base malignant txn with wide local excision• Pseudo-epitheliomatous micaceous and keratotic balanitis (PEMKB) – Unusual hyperkeratotic gorwth of the glans – Txn: Excision , may recur• Leukoplakia: – Whitish glanular plaque involve meatus – Asso with CIS – Txn: Excision and FU• Bowenoid papulosis have high risk of progression to SCC (90% long term)• Giant condyloma acuminata or Buschke-Löwenstein tumor – Displaces, invades, and destroys adjacent structures by compression, whereas the standard condyloma remains superficial and never invades – Does not metastasis – Treat with excision and recurrence is common 17
  18. 18. Premalignant lesion: CIS• Erythroplasia of Queyrat: [non keratinising CIS] – CIS: as oppose to Bowen’s disease, occur in glans or inner part of prepuce – Red velvety circumscribed painless lesion , may ulcerate and painful – Histology: • Atypical hyperplastic mucosal cell with malignant features • Hyperchromatic nuclei & multi-level mitotic figures • Submucosa : proliferation of capillaries & inflammatory infiltrate of plasma cell – 10x more likely to progress then Bowen’s disease – Treatment – Penile preserving: • Topical 5-FU or imiquimod – 5-FU: block DNA synthesis (structure similar to thymine) SE: erythema , weeping – 5% Imiquimod (imidazoguinonin tetracyclicamine): induce IF-alfa • Laser (CO2) , photodynamic therapy , cryotherapy , Mohs MS • If affect large area or recurrence: Total glans resurfacing + skin graft + deep biopsy – High risk of local recurrence in penile preserving txn• Bowen’s disease: [Keratinising CIS ] – CIS in the genital and perineal skin – Txn : WLE , laser, cryoablation 18
  19. 19. Balanitis Xerotica Obliterans (BXO)– Lichen sclerosis et atrophicus– >10% asso with future Ca penis– Location: White patch on Glans and prepuce, may affect meatus or fossa navicularis– Aetiology: Infection/ chronic antigenic stimulation, phimosis– Histology : 1. epidermal atrophy, 2. loss of rete pegs, 3. chronic inflammatory change, 4. hyperkeratosis with collagenized dermis 5. perivascular infiltration of dermis– Treatment: • Steroid cream 4-6/52 for mild scarring and retractable foreskin • Surgical excision (circumcision), reconstruct if stricture. • Remember not to use genital skin for reconstruction (recurrence)– If still not responsive > biopsy to rule out other causes like erythroplasia of Queyrat– Koebner phenomenon: BXO recur on split skin graft 19
  20. 20. Circumcision• Consent: – Bleeding (2%) – Infection (2%) – Altered sensitivity of glans – Meatal stenosis (10%) – Need of further bx of suspicious lesion – Unsatisfactory cosmetic result (4%)• Procedure: – Penile block – Midline dorsal slit – Inspect meatus (no hypospadias) & look for lesion – Circumcoronal incision of inner prepuce and outer skin – Meticulous hemostasis (bipolar diathermy) – Skin closed with interrupted undyed absorbable suture 20
  21. 21. Q14 Diagnosis? EPQ Premalignant? Yes If occurs on the shaft, what is it called? Bowens disease 21
  22. 22. Diagnostic schedule for penile cancer 22
  23. 23. What is diagnostic schedule for penile cancer? 23
  24. 24. What is 2009 Staging of Ca penis? SCC penis invading prostate is T3 24
  25. 25. What is the shortcoming of the staging?• Prognosis of patients with tumour invasion of the corpus spongiosum is much better than invasion of the corpus cavernosum in terms of local recurrence and mortality – Rees et al• Authors proposed defining – T2a patients by spongiosum-only invasion – T2b patients by involvement of tunica or corpus cavernosum• No differences in long-term survival between T2 and T3• No differences between N1 and N2 25
  26. 26. What is the proposed modification to 2009 TNM classification? 26
  27. 27. Jackson’s staging system, 1966. 27
  28. 28. Case:• Patient present with a penile mass• Painless• Not affecting urination• P/E: – 1.5cm solid growth at glans of penis – 1cm Right groin LN• What is your approach? 28
  29. 29. History• Age• Previous duration of phimosis• LUTS• Smoking history• Sexual history: HPV infection• Exposure to UV radiation 29
  30. 30. PE 30
  31. 31. Penile biopsy• The most important diagnostic test• Circumcision and excisional biopsy if the cancer is small• Incisional biopsy should contain tissue beneath and beside the tumor in order to help stage the disease – Confirm histological diagnosis – Determine the depth of invasion – Detect the presence of vascular invasion – Evaluate the grading of the tumour ( Broders’ classification ) 31
  32. 32. How would you stage theLocal staging tumor?1. USG, 7.5 MHz – Tumor appear as hypoechoic – Adv : detect corpus cavernosal invasion with sensitivity of 100 % – Disadv: Could not differentiate Ta from T12. MRI penis with intracavernosal prostaglandin – Accurate in demonstrating invasion of the corpora, and the extent of the cancer3. CT: – Not useful in local tumour staging because of poor soft tissue resolution – For LN status 32
  33. 33. LNs staging 33
  34. 34. What is the lymphatic drainage of penis?• First to the inguinal LN and then to the pelvic LN• Bilateral drainage of the penis to the LN• The inguinal LN – Superficial group that lie deep to the Scarpa’s fascia but superficial to the fascia lata (8-25 LNs) – The deep group (deep to the fascia lata) is a smaller group that lie around the junction of the long saphenous and femoral veins• The commonest detected group of LN which include the LN of cloquet lies cranimedial to the junction between the long saphenous and femoral veins 34
  35. 35. What is the accuracy of P/E of lymadenopathy?• High (90%) sensitivity but a low specificity (20%) of clinical examination detecting pathologically positive inguinal lymphadenopathy• 50% of patients with penile cancer will have clinically palpable inguinal LN at presentation• 50% of patients with pathologically positive unilateral inguinal LN will have contralateral metastatic disease 35
  36. 36. What is the imaging investigation for LN?• CT / MRI – Predict LN involvement by size only – Sensitivity : 35 %, specificity : 100 %• Strongest predictor for survival is the presence or absence of nodal metastases 36
  37. 37. Treatment strategies for penile cancer 37
  38. 38. 38
  39. 39. What are options of organ preserving therapy?• Circumcision – Small tumors confined to the prepuce – But with recurrence 40%• Local wedge excision – Margin of 5 mm – 50% recurrence rate• Glansectomy : T1 (not involving the CC) – Tourniquet control – subcoronal incision down to Buck’s fascia – proximal margin at least 5mm – the glans cap is mobilized off the head of the corpora cavernosa – Urethra is transected and split and fixed – Shaft skin is anchored to the new corona – Raw surface is covered with partial thickness skin graft – T1G3 - lowest recurrence rate of 2% 39
  40. 40. What is organ preserving therapy?• Mohs micrographic surgery (MMS) – “ shaving “ the tumour mass by excising thin layers of tissue and examining them microscopically till clear deep resection margin is confirmed by frozen section – Adv : • With a surgeon experienced in MMS, it is able to remove the cancerous tissue while preserving normal structures – Disadv : • Messy and bloody and time consuming • Required expert technique • Experienced pathologist is needed to confirm clear margin by frozen section • Wound may healed with scarring result in disfiguration • Urethra is sometime involved and required urethroplasty • Recurrence rate was high at 30% 40
  41. 41. What is organ preserving therapy?• Laser surgery – For local and limited invasive disease – Four types of lasers have been used 1. Carbon dioxide 2. Neodymium:yttrium-aluminum-garnet (ND:YAG) 3. Argon 4. Potassium-titanyl-phosphate (KTP) lasers – The carbon dioxide laser • vaporizes tissue • penetrates only to a depth of 1mm • coagulate blood vessels less than 0.5 mm – The ND:YAG laser • penetrate 5 mm depending on the power • Can coagulate vessels up to 5 mm – The argon and KTP lasers have less tissue penetration than the carbon dioxide laser and are rarely used – Result : 7% recurrence in 4yr FU [Frimberger 2002] 41
  42. 42. What are the problems of conservative treatment?• Not be suitable in cases of multifocal lesions• Mohs’ micrographic surgery, photodynamic and topical therapy with 5- fluorouracil ( 5-FU) or 5% imiquimod cream have been reported for superficial lesions with relatively high recurrence rate• Best results are achieved with laser surgery 42
  43. 43. What is Partial penectomy?• When the cancer involves the glans and distal shaft• T1a to T2 (not for T3 !!!!)• Traditionally, partial amputation has required removal of 2-cm tumour-free margins, to lower risk of local recurrence T (50% reduced to 6%)• Pathological confirmation a surgical margin of 5-10 mm is safe• Frozen sections at the time of surgery are often helpful, and a careful review of the specimen and permanent sections with the pathologist help to determine if the resection has been adequate• If margin + ve: local recurrence in 10%• Patient should be counsell about poor cosmetic and functional result – He will need to sit to void – He cannot have sexual intercourse• If surgical resection by either wedge or partial penectomy does not provide an adequate margin, a total penectomy should be considered• If the amount of residual penis and urethra is inadequate to allow the patient to urinate while standing, a perineal urethrostomy can be performed• Berry suggested to have 3cm penile functioning length and 2cm clear margin before consideration of partial penectomy• Recurrence of partial or total penectomy: 0-8% 43
  44. 44. How to perform partial penectomy?• Tourniquet control, cover tumor with glove finger• Deglove the penis• Mark the extent of tumor free margin• Mobolise the neurovascular bundle and ligated• Mobolise the urethra• Send the proximal margin for frozen-section• Oversew the corpora and Buck’s fascia and cover the corpora with penile skin or skin graft• Spatulate the urethra, creation of neoglan with split skin graft• Further lengthening can be achieved by dividing suspensory ligament +/- full thickness SG• Foley to BSB 44
  45. 45. What is total Penectomy ?• Total amputation of penis + excision of scrotum and its content• Formation of perineal urethrostomy• Complication: – Urethral meatal stenosis 45
  46. 46. • CIS, Ta-1 G1-2 (i.e T1a) – Penis-preserving strategy for those guarantee regular FU (70%) • local excision + reconstructive syrgery / glansectomy (depend on size and location of tumor) • Laser , cryoablation, RT & brachytherapy • Moh’s MS or photodynamic therapy for (CIS, TaG1) • Local 5-FU (for CIS only) – No difference in local recurrence rate between micrographic surgery, EBRT, insterstitial brachy and laser – Overall recurrence 15-20% – Partial amputation for those who don’t comply with regular FU.• T1b G3, T2 (glans only) – V. carefully selected patients with tumour less than half of glans & close FU can be carried out → conservative strategy – Glansectomy +/- Tip amputation or reconstruction – Margin 3mm is consider safe 46
  47. 47. • T2 (invasion to copora) – Partial amputation – Margin 5-10mm – If no LN on presenstation  5yr survival 66%• T3 (invasion to urethra) – Total amputation with perineal urethrostomy• T4 (invasion to other structure) – Neo-adj chemo + surgery in responsive patient (selected) – Others: RT• Local disease recurrence – 2nd conservative procedure if < T2 – If large or deep infiltrating recurrence → partial / total amputation – External beam radiotherapy / brachytherapy for lesions < 4cm diameter 47
  48. 48. What are treatment strategies for penile cancer? 48
  49. 49. What are treatment strategies for penile cancer? 49
  50. 50. RT?• Indications: 1. Organ-preserving treatment in young pt with T1-2 lesions < 4 cm – EBRT: Response rate: 50% Local failure rate: 40% – Brachytherapy: response rate 70%, failure 16%. 2. Alternative to chemo + surgery in T4 diseas 3. Those who have metastatic disease and need some form of palliative therapy• Procedure: – High dose: 60cGy during 3 weeks – Circumcision prior to initiating radiation therapy • Prepuce will fuse with the glan • Allows better evaluation of the tumor stage • Minimizes the morbidity associated with the therapy, includes swelling, irritation, moist desquamation, phimosis, and infection• 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. 50
  51. 51. Radiotherapy?• Adv – Avoid the psychological trauma associated with partial or complete penectomy – Potential to maintain potency – Local control rate 60-90%• Disadv – Squamous cell carcinomas tend to be resistant – High tumor dose (ie, 60 cGy) required – Complication: 1. Meatal stenosis + urethral stricture (30%) 2. glans necrosis 3. Telangiectasia (90%) 4. Late fibrosis of the corpora cavernosa 5. Late fistula and pain 6. Testicular damage 7. Secondary neoplasia – Disfiguration and associated pain may in fact make the phallus practically useless – Close FU is necessary – Difficulty in distinguishing tumour recurrence and post – RT fibrosis / scarring making multiple Bx necessary – Local recurrence rate – 40% (EBRT), 16% (Brachytherapy) 51
  52. 52. Mx of LNs in Ca Penis 52
  53. 53. What is the draining LNs of Ca penis?• Femoral and inguinal lymph nodes are the earliest path for tumor dissemination• The lymphatics of the prepuce join with those from the shaft. These drain into the   sentinal LN ( superomedial to the saphenofemoral junction )   other superficial inguinal nodes. ( superficial to the fascia lata )   deep inguinal nodes, which are beneath the fascia lata.   to the pelvic nodes• Multiple cross connections exist at all levels, permitting penile lymphatic drainage to proceed bilaterally (80%)• Untreated, metastatic enlargement of the regional nodes leads to skin necrosis, chronic infection, and, eventually, death from sepsis or hemorrhage secondary to erosion into the femoral vessels• No lymphatic drainage was observed from the penis to the inferior two regions of the groin and no direct drainage to the pelvic nodes 53
  54. 54. LN spread in Ca Penis• Regional LN of penis are located in inguinal region : superficial or deep• Then drain to 2nd line LN: Iliac & obturator fossa• Most constant node: – Cloquet’s (or Rosenmuller’s) – Medial side of the femoral vein – Mark the transition btw inguinal and pelvic region• Superficial: under subcutaneous fascia and above fascia lata, 25 LN on the muscle of the upper thigh in Scarpa’s triangle• Deep: region of fossa ovalis where greater saphenous vein drain into femoral vein through an opening of the fascia lata• Most met found in medial superior Daseler group• Sentinel LN of Ca penis only found in superior and central zones of the inguinal region (by SPECT-CT) 54
  55. 55. Daseler region• Inguinal region is divided into four sections by a horizontal and a vertical line drawn through the fossa ovalis• Five anatomical subgroups with the central zone being located at the confluence of the greater saphenous vein and the femoral vein. The four other zones are described as lateral superior, lateral inferior, medial superior, and medial inferior 55
  56. 56. Incidence• Depends on: – Tumor grade: 30% G1 vs 40% G3 – Local stage : 60% in pT2 & 75% in pT3-4 – T1G2: 50% [Naumann BJU 2008] – Type of local tumor: Basoloid vs Classic 56
  57. 57. Prognostic significant of LN met• Presence and extent of inguinal LN metastasis are the most important factors for the prognosis of the pt• Pelvic LN worse then inguinal LN• Predictor of DFS: – Extra capsular growth in met node – Bilateral inguinal LN met – Pelvic nodal disease• 3yr Cancer specific survival: – Inguinal LN –ve or pN1: ~ 100% – pN2 : 70% 57
  58. 58. Predictor of LN met• Variable if only take primary tumor into account (pT stage, grade , depth of invasion & histological subtype)• Lymphovascular and vascular invasion was reported to predict LN met• Risk scoring system: Solsona• Ficarra nomogram (2006) 58
  59. 59. What are the risk factors for LN metstasis ?• Risk factors 1. Lymphovascular invasion & Perineural invasion(5x risk, Ficarra) 2. Histology Grade 3 (75% LN+, EAU) 3. ≥ pT2 (75% LN+, EAU) 4. Histological subtypes : – Sarcomatoid (75% LN+), adenosquamous (50%), basaloid (50%) 5. Tumour thickness >5mm (2x risk, Ficarra) 6. Infiltrating growth pattern (4x risk) 7. Molecular markers: p53, E-cadherin 8. Nomograms to predict pathological inguinal LN involvement• Ficarra (accuracy 88%)• Bhagat (accuracy 75%) 59
  60. 60. 60
  61. 61. 61
  62. 62. 62
  63. 63. 63
  64. 64. Molecular marker• HPV DNA status: conflicting results• Ki-67: conflicting result on LN met• Reduce KAI1/CD82 expression: predictive on LN involvement in one study• P53 –ve: better survival & less LN +ve• Conclusion: no tissue parameter is sufficiently validated as a prognostic marker for LN involvement to be used as a bssis for clinical decisions 64
  65. 65. What is the approach for non- palpable nodes?• Explained : – 25% risk of lymph node metastases – Radical LND for all will result in > 75% of over treatment• Any investigation suitable ? – No value in dx of inguinal LN met – Ultrasound + FNAC • may reveal abnormal nodes & guide for fine-needle aspiration biopsy • Non palpable LN: SV 40% , SP 100% – Sentinel node Bx not recommended due to high false –ve rate (25%) – Dynamic SNB - 100% specificity and 95% sensitivity, false negative rate 5% – CT/MRI groin cannot detect micrometastasis – Pelvic CT/MRI scan is not necessary in patients with no inguinal node metastases (SV 40%) – Nanoparticle-enhance MRI :SV 100%, SP 97% , PPV 80% – 18FDG PET/CT: SV 80% , SP 100%• Thus: risk adapted approach is more appropriate 65
  66. 66. Non-palpable LN : by pT stage• Low risk gp: pTis, pTaG1/2, pT1 G1 (LN met < 17%) – Active surveillance – Optional: modified inguinal LND• Intermediate risk gp: pT1G2 or higher (LN met 50%) – DSNB , follow by complete LND if tumor +ve – If DSNB not available  base on risk factor + nomogram • Superficial growth + no vascular invasion: Active surveillance • vascular or lymphatic invasion OR infiltrating growth pattern: modified LND  radical if tumor +ve• High risk gp: pT2-4 , any G3 (LN met 70%) – Active surveillance is not appropriate: • Higher risk of recurrence [Leijte] – Immediate LN staging • DSN  then LND if +ve • 3 yr DSS: 91% vs 80% (surveillance) [Lont] – Modified  radical inguinal LND (if FZ +ve in MILND) – Immediate vs delay LND: • 3yr survival: 84% vs 35%• Which side? Both side 66
  67. 67. 67
  68. 68. What is the approach for palpable LN ?• Explained: – Palpable LN present at diagnosis in 58% patients – Traditional : 50% +ve for metastasis, 50% inflammatory [Brazil] – Today’s thinking: > 90% palpable LN are met – If LN +ve on one side there is 50% chance to be +ve on the other side• Any investigation suitable ? – No value in dx of inguinal LN met – Ultrasound + FNAC • may reveal abnormal nodes & guide for fine-needle aspiration biopsy • Palpable LN: SV 93% , SP 91% • If negative  repeat biopxy – Dynamic SNB – No role is palpable LN – Pelvic CT/MRI scan are widely done but with low SV/SP – Nanoparticle-enhance MRI :SV 100%, SP 97% , PPV 80% – 18FDG PET/CT: SV 80% , SP 100%• But since LND is going to be perform irrespective of FNA result , FNA may not be useful• Thus early & bilateral radical LND is the standard procedure 68
  69. 69. Palpable mobile LN• If T1 & G1 & no vascular invasion, mobile LN – Antibiotics for 4 weeks & reassess (50% inflammatory)• USG guide FNAC: may not be necessary• +ve  – Ipsilateral radical inguinal LN dissection – Contralateral superficial inguinal LN dissection & frozen section-> proceed to radical LN dissection if FZ +ve (Pompeo) – Pelvic LND if • Cloquet LN+, or ≥2 inguinal LN+, or extracapsular involvement • To be done on the side (uni or bi) whenever the above criteria is reach• -ve : – Repeat bx – Excised suspicious LN – Proceed to LND 69
  70. 70. Summary• Whenever there is palpable LN  RLND• Whenever FZ show LN +ve  RLND 70
  71. 71. Pelvic LND• Incase of uninvolved inguinal LN, pelvic LND not indicated• Risk of +ve pelvic LN: Culkin J Urol 2003;170:359-365 – 23% if < 2 inguinal LN involved – 56% if > 3 inguinal LN involved or 1 with extracapsular spread• Indication of pelvic LND: – Extracapsular spread – Cloquet node invovled – > 2 inguinal LN metastases• Consider if basaloid subtype or strong expresssion of p53• Approach: Extraperitoneal , midline incision• Includes external iliac lymphatic chain and ilio-obturator chain with the following borders: – proximal boundary: iliac bifurcation – lateral boundary: ilio-inguinal nerve – medial boundary: obturator nerve• Provide cure rate: 14-54%• Unanswered questions: – If extensive unilateral inguinal LN involvement , should pelvic LND be unilateral or bilateral? – When is the most suitable timing of pelvic LND? 71
  72. 72. Fixed inguinal LN• Neo-adjuvnat chemotherapy (response rate 20-60%) – [Pizzocaro’s series] – 3-4 courses of cisplatin & 5FU in 16 patients for fixed LN – 60% could be radically resected following primary chemoTx – 30% have probably cured – Survival rate 25%• Subsequent radical ilio-inguinal LNectomy strongly recommended• Should be used as part of a clinical trial• Or Radiotherapy followed by lymphadenectomy but higher morbidity• Problem: high toxicity + high number of non responder 72
  73. 73. 73
  74. 74. Surgical LN staging• Direct histological examination of inguinal LN is the most reliable method of assessing their involvement by metastses• Approach: – Radical inguinal LND – Modified inguinal LND – Sentinel node biopsy – Video endoscopic LND 74
  75. 75. 75
  76. 76. 76
  77. 77. SEV, superficial epigastric; SEPV, superficial external Deep inguinal lymph nodespudendal; MCV, medial cutaneous; LCV, lateral cutaneous; 77SCIV, superficial circumflex iliac.
  78. 78. What is the boundary of femoral triangle?• Superior: Inguinal ligament• Lateral: Medial border of sartorius• Medial: lateral border of adductor longus• Floor: – Medial: Pectineus muscle – Lateral: iliopsoas muscle – Femoral A & V 78
  79. 79. Radical inguinal Modified inguinal lymphadenectomy lymphadenectomyMargin : • Proposed by Catalona• Upper : anterior superior iliac spine to • Exclusion of area lateral to femoral artery & superior margin of external iliac ring caudal to fossa ovalis• Lateral : a vertical line of 20 cm from the • Boundary reduced by 1-2cm anterior superior spine• Medial : a vertical line of 15 cm from the pubic tubercle Margin :• Lower : joining the lateral and medial border • Upper : inguinal ligamentContent : • Medial : margin of adductor longus muscle• Superficiall inguinal LN deep to the Scarpa • Lateral : lateral border of the femoral artery fascia • Lower : apex of the femoral triangle• Deep inguinal LN deep to the fascia lata• LN remove: all 5 Daseler region + deep inguinal LN Content :• Saphenous vein is ligated and divided • The superficial LN deep to the Scarpa fascia,• Femoral artery and vein are skeletonized superficial to the fascia lata• dissection posterior to the femoral vessel is • But should dissect central and superior zones not required • If + ve LN is identified on modified approach,• Sartorius is divided at the origin and formal radical lymphadenectomy is transposed to cover the femoral vessel proceeded.• Skin rotation flaps + MC flaps for primary • Complications: early (7%) , late (3.4%) wound closure • Morbidity reduced : Skin necrosis (2.5% vsMorbidity: 8%) , lymphoedema (3% vs 20%) , DVT• wound infection , skin necrosis , wound (none vs 12%) dehiscence , lymph edema, lymphocele • False –ve rate increase 79
  80. 80. Describe the difference between radical vs modified inguinal lymphadenectomy1. Shorter skin incision2. Limitation of the dissection by excluding the area lateral to the femoral artery and caudal to the fossa ovalis3. Femoral vessel need not skeletonised deep to fascia lata4. Preservation of the saphenous vein (less edema)5. Elimination of the need to transpose the sartorius muscle 80
  81. 81. Complications• Early minor complications :40% – Hemorrhage – Wound infection – Flap necrosis• Major complications: 15% – Debilitating lymphedema – Lymphocele – Prolong lymph drainage – Patchy sensory loss of thigh 81
  82. 82. How to decrease morbidity of LND?• Prevention: – Prophylatic antibiotic – Care and diligent tissue handling – Use of vacuum drain – Elastic stocking +/- pneumatic stocking – Early ambulation & anticoagulant (controversial)• Treatment of lymphedema: – Supporting underwear – Avoid trauma to skin – Scrotoplasty 82
  83. 83. Dynamic sentinel node biopsy (DSNB)• Identification of the LN in pt which is the first drainage node• Assumption: there is stepwise and orderly progression of lymphatic metastatic spread from the sentinel node to secondary LN• Usage: in non palpable LN met (> pT1G2)• Method: – Technetium-99m nanocolloid injection around the penile tumor intradermally 1d before surgery – Shortly before OT: 1ml of patent blue dye injection intradermally – Sentinel LN indentify by lymphoscintigraphy , & area marked on skin – Dissection: sentinel LN identify by intra-op gamma-ray detection probe + patent blue dye staining – LN then isolated and removed for FZ – If FZ +ve  formal inguinal LND perform• Result: – With improved technique (combine with USG FNAC): false negative rate of 5% achieved (vs 25%) – Specificity : 95%, sensitivity : 95% – Netherlands Cancer Institute 83
  84. 84. How was the FN rate of DSNB improved?• Before : FN rate of DSNB is 25%• Now: 5%• This is achieved by combination of USG guided FNAC before OT• Reasons: – LN with extensive tumor does not have normal lymph drainage and TF not detect by DSNB – However, they are shown by USG + FNAC – Thus USG improved detection of extensive tumor involved LN which are clinical not palpable and not detected by DSNB• Thus reduced the FN rate of DSNB 84
  85. 85. Video endoscopic LND• Recently described technique• Lower risk of skin complication• Higher risk of lymphocele (23%)• Reliability is not yet possible 85
  86. 86. 86
  87. 87. Treatment for local recurrence 87
  88. 88. What is the treatment for local recurrence?• For local recurrence after conservative therapy, a second conservative procedure is strongly advised if there is no corpora cavernosa invasion• Palpable inguinal nodes on FU - Nearly 100% is metastatic• Local recurrence at groin after penile amputation – Poor prognosis – Bilateral inguinal LND – If more then 2 node  combined chemotherapy and radiotherapy 88
  89. 89. Chemotherapy 89
  90. 90. How about chemotherapy?• For distant metastasis disease• Drugs : – cisplatin, bleomycin, methotrexate (CBM), and fluorouracil – Cisplatin monotherapy • Partial short duration response rate15-23%, – Bleomycin +/- radiation or vincristine and methotrexate • Partial and/or complete response rate of 45% – Overall response is partial and short live (20-60%)• Adjuvant setting in high risk gp – 3 course Cipslatin + 5-FU in pN2-N3 patients with relapses (<10%) & survival benefit 90
  91. 91. 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 91
  92. 92. Neo-adj chemo• Neoadjuvant chemotherapy for high risk groups : – extranodal extension – pelvic LN – bilateral metastasis• combination regimen : – vincristine – bleomycin – methotrexate ( VBM )• improve 5- years survival of the high risk group from 40 % to 80 %• ( Milan National Tumour Institute ) 92
  93. 93. Follow-up schedule for penile cancer• 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. 93
  94. 94. 94
  95. 95. Prognosis 95
  96. 96. What is the prognosis of Ca penis?• 5 Yr Survival – Localized disease 70-95% • T2 – 70% – LN met 50% – Metastasis SCC <10%• Poor prognostic factors to survival: – presence of +ve LN – no. & site of +ve nodes – extracapsular nodal involvement 96
  97. 97. Primary urethral tumor 97
  98. 98. • SCC (80%) Bulbomembranous urethra (60%)• Risk factors – HPV, UV, chronic inflammatory or stricture condition, STD• Presentation – Late with metastasis – Bloody urethral discharge or painless hematuria (initial/end) – LUTS or perineal pain – Peri-urethral abscess or UC fistula• P/E: – Palpable mass at female urethral meatus or along course of male urethra – LN: pelvic LN (posterior) , inguinal LN (ant)• Ix – FC + biopsy first – EUA – MRI scan for local staging – CT abdomen and pelvis for LN• Tx – Localized anterior urethral Ca • Wide local excision with adjacent tunica albuginea, • Urethral recontstruction either perineal urethrostomy or hypospadiac urethra if adequate length • Total penectomy if advanced disease – Posterior or prostatic urethral Ca • Cystogrostatourethrectomy in men • Anterior pelvic exenteration in women (PLND, bladder , urethra, ureterus , ovaries, vagina) – For LN > same as CA penis – Locally advance: RT + surgery – Met : Chemo• 5-yr survival: – Surgery ant urethra 50% – Surgery post urethra 15% RT 30% – RT + surgery 50% 98
  99. 99. Ca scrotum• SCC, < 50yr• Chimmey worker: chronic exposure to soot , tar or oil• Presentation: painless lump or ulcer in scrotal wall, inguinal LN• Txn: Wide local excision +/- LND• Adj chemo• Poor prognosis in metastatic disease 99
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