Surgery of Penile and Urethral Carcinoma Campbell’s Urology Chapter 32 W. Britt Zimmerman April 15, 2009

Surgery of Penile & Urethral Carcinoma Penile Cancer Male Urethral Cancer Female Urethral Cancer

Penile Cancer Typically Squamous Involves: Glans penis Coronal Sulcus Inner preputial skin

Penile Cancer Biopsy Imperative to include area of question as well as adjacent normal tissue Allows for evaluation of depth of invasion May be punch or excisional Urethral meatus involvement Urethroscopy is mandatory

Penile Cancer Laser Therapy Carbon Dioxide (CO2) Neodymium:yttrium-aluminum-garnet (Nd:YAG) Potassium titanyl phosphate (KTP) Circumcision is usually recommended at the time of laser surgery if not already done

Laser Therapy CO2 Wavelength: 10,600 nm Skin depth: 0.01 mm Blood vessels: 0.5 mm 33% local recurrence Healing time: 5 – 8 weeks

Laser Therapy Nd:YAG Combination Most commonly reported Skin dept: 3 – 6 mm 20% recurrence Stage T1 Healing time: 8 – 12 weeks Combination Surgery and laser to the base 18% – 20% recurrence

Laser Therapy KTP Wavelength: 532 nm Intermediate depth Between CO2 and Nd:YAG Healing time: 8 – 12 weeks

Laser Therapy Technical improvements Final thoughts 5% Acetic acid wraps 5-aminolevulinic acid Final thoughts Reasonable for Tis and T1 SCC T2 patients refusing aggressive surgery

Mohs Micrographic Surgery Excision of penile cancer by thin tissue layers Frozen sectioning with immediate pathological evaluation Cure rates (5 years) < 1 cm: 100% 1 – 2 cm: 83% 2- 3 cm: 75% > 3 cm: 50%

Mohs Micrographic Surgery Best suited for small superficial cancers Comparable to partial penectomy In the right setting

Conservative Surgical Excision Local excision and Glansectomy In the setting of low stage penile cancer Traditionally, 2 cm margin Grade plays a central role Grade 1 & 2 Histologic extent 5 mm Location also plays a role Coronal Sulcus 50% recurrence

Conservative Surgical Excision Glanular tumors Difficult secondary inability to achieve adequate margin Preputial skin flap or split thickness skin graft (STSG) can assist in closure Recurrence: Traditionally 32 – 40% Contemporary studies 8 – 11%

Figure 32-1 Surgical glans defect covered with outer preputial flap as described by Ubrig and colleagues (2001). A, Superficial glans tumor. B, Outer preputial flap outlined. C, Tumor excised and circumcision performed. D, Glans defect filled with outer preputial flap.

Figure 32-2 Finely meshed extragenital split-thickness skin graft quilted to glans defect after superficial tumor excision.

Conservative Surgical Excision Total Glansectomy First described in 1996 Used in patients with stage T1 & T2 SCC of the glans, prepuce, and coronal sulcus Dissassembly of glans and distal corpus spongiosum Frozen section for margin evaluation STSG with urethrostomy formation Benefits Voiding Sexual function preservation

Partial Penectomy Most common surgical procedure for treatment of patients primary SCC Penile amputation 2 cm proximal to the tumor Goals Voiding Sexual function

Partial Penectomy Figure 32-3 Partial penectomy. A, Incision with ligation and division of dorsal penile vessels within Buck's fascia (inset). B, Corpora transected and urethra spatulated. C and D, Closure of corpora cavernosa. E, Final closure with construction of urethrostomy.

Partial Penectomy 1.0 to 1.5 cm distal to the cavernosal amputation site Urethrostomy is created by approximating the urethra to the surrounding penile skin Lengthening Suspensory ligament division

Partial Penectomy Skin coverage Glans reconstruction Scrotal flaps Z-plasty Glans reconstruction Skin grafts Pedicle flaps

Penectomy Local recurrence rates 0 – 8%

Total Penectomy At the level of the suspensory ligament Corpra cavernosa proximally remains Performed for large or proximal Lesions Patients void sitting down via a perineal urethrostomy

Total Penectomy Figure 32-5 Total penectomy. A, Incision. B, Transection of the corpora near the level of the pubis. C, Mobilization of the remaining urethra off of the proximal corporal bodies. D, Transposition of the urethra through a curvilinear perineal incision. E, Completion of perineal urethrostomy.

Perineal Urethrostomy

Perineal Urethrostomy

Perineal Urethrostomy

Perineal Urethrostomy Foley left for 7 – 10 days

Radical Penectomy The corporal bodies are dissected to the tips of the crura, which are completely excised. Urethra is matured into a standard perineal urethrostomy.

Radical Penectomy

Regional Lymph Nodes SCC on the penis spreads regionally before it spreads distantly. No skip lesions. One midline structure can metastasize to either side or bilaterally. Metastatic lymph nodes confer a poorer prognosis Aggressive lymphadenectomy: cure in 30 – 60%

Inguinal Anatomy Lymph nodes Superficial lymph nodes (5 groups) Deep Superficial lymph nodes (5 groups) Central (saphenofemoral junction) Superolateral (superficial circumflex vein) Inferolateral (lateral femoral & superficial circumflex) Superomedial (superficial ext. pudendal & superficial epigastric veins Inferomedial (greater saphenous vein)

Superficial lymph nodes (5 groups) Figure 32-14 Superficial inguinal lymph nodes and the branches of the saphenous vein. SEV, superficial epigastric; SEPV, superficial external pudendal; MCV, medial cutaneous; LCV, lateral cutaneous; SCIV, superficial circumflex iliac.

Inguinal Anatomy Deep inguinal nodes Medial to femoral vein in the femoral canal Cloquet – most cephalad of the deep group Between the femoral vein and the lacunar ligament External iliac nodes Deep inguinal Obturator Hypogastric

Deep Inguinal Nodes

Inguinal Anatomy Skin blood supply Common femoral artery Superficial external pudendal Superficial circumflex iliac Superficial epigastric arteries Transverse skin incision compromises the least amount of blood supply

Inguinal Anatomy Femoral nerve Deep to iliacus fascia Motor Sensation Pectineus Quadriceps femoris Sartorius Sensation Anterior thigh

Inguinal Anatomy Femoral triangle: Inguinal ligament – superiorly Sartorius muscle – laterally Adductor longus muscle – medially Floor Pectineus (medially) and iliopsoas (laterally)

Sentinel Node Biopsy First describe by Cabanas in 1977 Results a have been variable

Modified Inguinal Lymphadenectomy Catalona 1988 Same therapeutic benefit Less morbidity Key aspects Shorter skin incision Excludes the area lateral to the femoral artery and caudal to the fossa ovalis Saphenous vein preservation Elimination of sartorius muscle transposition

Modified Inguinal Lymphadenectomy Figure 32-17 Limits of standard and modified groin dissection. (From Colberg JW, Andriole GL, Catalona WJ: Long-term follow-up of men undergoing modified inguinal lymphadenectomy for carcinoma of the penis. Br J Urol 1997;79:54-57.)

Modified Inguinal Lymphadenectomy Figure 32-18 Modified inguinal lymphadenectomy. Lymph node packet is medial to the femoral artery and includes superficial and deep inguinal nodes.

Modified Inguinal Lymphadenectomy Figure 32-19 Intraoperative photograph of right inguinal region after modified lymphadenectomy. SC, spermatic cord; V, femoral vein; S, saphenous vein; AL, adductor longus.

Radical Ilioinguinal Lymphadenectomy Indicated in patients with resectable metastatic adenopathy and may be curative when inguinal nodes disease only. May also be used in palliation

Radical Ilioinguinal Lymphadenectomy

Radical Ilioinguinal Lymphadenectomy Figure 32-21 Ilioinguinal lymph node dissection. A, Incisions for inguinofemoral lymph node dissection (1), unilateral pelvic lymph node dissection (2), and bilateral pelvic lymph node dissection (3). B, Single incision approach for ilioinguinal lymph node dissection.

Radical Ilioinguinal Lymphadenectomy Figure 32-22 A, Incision and area of dissection for left inguinofemoral lymph node dissection with excision of adherent skin overlying nodal mass. B, Single incision approach and area of dissection for right ilioinguinal lymph node dissection with excision of overlying skin.

Radical Ilioinguinal Lymphadenectomy

Radical Ilioinguinal Lymphadenectomy Figure 32-25 Inferior dissection during radical inguinofemoral lymph node dissection with removal of lymph node packet from the inferior border of the femoral triangle. After further lateral and medial dissection, the packet will remain in continuity with the pelvic dissection in the area of the femoral canal.

Radical Ilioinguinal Lymphadenectomy Figure 32-26 Intraoperative photograph after right radical inguinofemoral lymph node dissection in an obese patient. S, sartorius muscle; A, femoral artery; V, femoral vein; IL, inguinal ligament. Figure 32-27 Sartorius muscle after detachment from the anterior superior iliac spine and 180-degree rotation medially, with suture fixation to the fascia of the inguinal ligament and the adductor longus. S, sartorius muscle; SC, spermatic cord.

Key Points of Penile Cancer Early meticulous surgical management with close follow-up generally provides the best opportunity for cure of penile SCC. Include some adjacent normal tissue with the specimen to allow optimal evaluation of the depth of invasion of the cancer during biopsy.

Key Points of Penile Cancer Conservative surgical approaches may be reasonable for patients with stage Tis and small T1 SCC of the penis and for patients with manageable T2 tumors who refuse more aggressive surgical treatment. Partial penectomy with a 2-cm surgical margin remains the most common surgical procedure for treatment of the primary tumor in patients with invasive SCC and affords excellent local control in most instances.

Key Points of Penile Cancer In patients at risk for the development of inguinal metastatic disease and with no palpable adenopathy, modified inguinal lymphadenectomy provides excellent assessment of the regional nodes and may be converted to a full lymphadenectomy if metastatic disease is detected. Penile cancer metastases to the pelvic lymph nodes do not occur in the setting of negative ipsilateral inguinal nodes.

Male Urethral Cancer

Male Urethral Carcinoma Rare and presents in the 5th decade of life. Etiology is typically secondary to chronic inflammation. STDs Urethritis Urethral stricture HPV 16

Male Urethral Carcinoma Insidious onset 50% have stricture 25% have STD history 96% symptomatic Palpable urethral mass Obstructive voiding symptoms

Male Urethral Carcinoma

Pathology Bulbomembranous – 60% Penile – 30% Prostatic – 10% SCC – 80% TCC – 15% Adenocarcinoma – 5%

Pathology Direct extension Lymphatic invasion Anterior – superficial and deep inguinal, and occasionally external iliac nodes Posterior – pelvic lymph nodes Palpable lymph nodes are present 20% of the time and usually represent metastatic disease

Evaluation & Staging Primary tumor (T) (male and female) TX Primary tumor cannot be assessed T0 No evidence of primary tumor Ta Noninvasive papillary, polypoid, or verrucous carcinoma TisCarcinoma in situ T1 Tumor invades subepithelial connective tissue T2 Tumor invades any of the following: corpus spongiosum, prostate, periurethral muscle T3 Tumor invades any of the following: corpus cavernosum, beyond prostatic capsule, anterior vagina, bladder neck T4 Tumor invades other adjacent organs Transitional cell carcinoma of the prostate Tis-pu Carcinoma in situ, involvement of the prostatic urethra Tis-pd Carcinoma in situ, involvement of the prostatic ducts T2 Tumor invades any of the following: prostatic stroma, corpus spongiosum, periurethral muscle T3 Tumor invades any of the following: corpus cavernosum, beyond prostatic capsule, bladder neck (extraprostatic extension) T4 Tumor invades other adjacent organs (invasion of the bladder)

Evaluation & Staging Regional lymph nodes (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis in a single lymph node, 2 cm or less in greatest dimension N2 Metastasis in a single lymph node, more than 2 cm but less than 5 cm in greatest dimension; or in multiple nodes, none greater than 5 cm N3 Metastasis in a lymph node greater than 5 cm in greatest dimension Distant metastasis (M) MX Presence of distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis

Treatment Primarily a surgically treated disease process Anterior urethral lesion is more amendable to surgical control Posterior disease Associated with extensive local invasion Distant mets

Carcinoma of the Penile Urethra Superficial, papillary, low-grade tumors TUR Local excision Infiltrating Lesions located to distal half of penis Partial penectomy with 2 cm margin Lesions proximal Total penectomy

Carcinoma of the Penile Urethra

Carcinoma of the Penile Urethra Prophylactic inguinal lymph node dissection (LND) offers no benefit

Carcinoma of the Bulbomemebranous Urethra Poor survival figures for all recorded forms of treatment Radical surgery offers best longer-term prognosis Radical cystoprostatectomy Pelvic lymphadenectomy Total penectomy Pubic rami resection GU diaphragm excision

Carcinoma of the Bulbomemebranous Urethra

Radiation Therapy & Chemotherapy XRT Early-stage lesions of the anterior urethra Preserves skin Results are undetermined Chemo MVAC good for TCC lesions Platinum based therapy Results poor Combo therapy XRT and Chemo Surgery and Chemo

Management of the Urethra after Cystectomy General Considerations Cancer recurrence following cystoprostatectomy 2.1 – 11.1% recurrence (cutaneous diverison) 0.5 – 4% recurrence (orthotopic neobladder) Frozen section of apical margins of prostatic urethra during surgery should be NEGATIVE. 40% of recurrence within 1 year 18 months median

Management of the Urethra after Cystectomy Traditionally urethral wash was acceptable Survival benefit has been questioned Patients who have positive voided cytology or symptoms: Urethral bleeding Discharge Palpable mass Cystoscopy and Biopsy Superficial recurrence can be treated with BCG via urethral perfusion

Total Urethrectomy after Cutaneous Diversion Care must be exercised in completing the proximal dissection, in view of the possible postcystectomy adherence of intestine to the superior surface of the urogenital diaphragm.

Total Urethrectomy after Orthotopic Diversion Abdominal perineal approach Can use previous bowel for diversion Careful dissection to preserve blood supply Commonly perform ileal conduit, but carefully selected patient may undergo a continent reservoir creation

Urethrectomy after Cystoprostatectomy

Key Points: Male Urethral Cancer 80% of male urethral cancers are SCC Bulbomembranous urethra most common site Anterior urethral carcinoma More amenable to surgical control Better prognosis Posterior urethral carcinoma Extensive local invasion Distant metastasis

Key Points: Male Urethral Cancer Prophylactic inguinal lymph node dissection has no benefit Low incidence of urethral recurrence after orthotopic bladder replacement Negative frozen-section biopsy of the distal prostatic urethral margin during surgery

Key Points: Male Urethral Cancer Converting a patient to cutaneous conduit urinary diversion, bowel from the existing orthotopic neobladder can often be reconfigured with its blood supply intact and used for this purpose.

Female Urethral Cancer

Epidemiology, Etiology, & Clinical Presentation more in women, 4:1 Only urological malignancy with female predominance 0.2% of all GU malignancies <1% of CA of female GU tract 85% occurs in white women ( of 1200 cases reported)

Epidemiology, Etiology, & Clinical Presentation Leukoplakia, chronic irritation, caruncles, polyps, partuition, HPV, other viral infection Urethral diverticula 5% of CA Predisposition?

Epidemiology, Etiology, & Clinical Presentation 98% have symptoms Most common obstructive Dysuria, urethral bleeding, frequency, palpable, urethral mass, induration Otherwise healthy middle-aged woman with new-onset UR? Think urethral tumor (and neurolgic disease…..)

Epidemiology, Etiology, & Clinical Presentation Patterns of Spread Local Direct extension, may ulcerate @ skin/vulva If proximal may extend: Posteriorly into vagina Proximally into bladder Lymphatic involvement: 1/3 @ presentation (palpable nodes) ½ of pts with advanced/proximal tumors Hematogenous Lung, liver, bone, brain

Anatomy & Physiology Anterior (distal 1/3) Posterior (proximal 2/3) Can maintain continence with excision Posterior (proximal 2/3)

Anatomy & Physiology Histology of urethra Epithelium Proximal 1/3 Transitional urothelium Distal 2/3 Stratified squamous Glands Columnar epithelium Lymphatics Post urethra External/internal illiac, obturator Ant urethra/ labia Superficial/deep inguinal

Anatomy & Physiology Histology of Neoplasm SCC 50-70% TCC 10% Adenocarcinoma 25% Glandular origin Associated with diverticula Rare: lymphoma, neuroendocrine, sarcoma, paragangliomas, melanoma, metastasis

Diagnosis & Staging Evaluation Staging Cysto, EUA, CT A/P, CXR +/- MRI for extension Staging TNM (see male) Pelvic LN mets: 20% Distant LN mets: 15% Palpable nodes: 30% overall Confirmed malignancy: 90% 50% of proximal or advanced CA

Treatment & Prognosis Prognosis Treatment No survival difference based on histological subtype Treatment Tumor location Clinical stage

Treatment Local excision vs extensive surgery Survival facts Small, distal urethral tumors, superficial Survival facts 5 yr DSS (disease specific survival) 71% (distal) 48% (proximal) 24% (large urethral lesions) Overall survival (Surgery, XRT) 30-40% Unchanged in 50yrs

Treatment Options Surgery, XRT, chemo, combo Multimodality preferred Survival @ 5-6 yrs: (Early urethral CA in women, Table 32-2) XRT (42 pts) 30% Surgery (14 pts) 10% Combo (3 pts) 2%

Treatment Distal Urethral CA Small, exophytic, superficial tumor from urethral meatus: Options: Circumferential excision of distal urethra & portion of anterior vaginal wall Laser coag described (small, distal tumors) Urethrectomy & diversion Anterior vaginal wall, periurethral tissues to bladder neck Ileovesicostomy, appendicovesicostomy to native bladder

Treatment Facts, surgical data: Distal tumor Low stage Cure rate 70-90% with local excision 21 % with < T2 treated with partial urethrectomy had a local recurrence (Dimarco et al 2004) 0-50% recurrence with partial urethrectomy +/- rads (Hahn 1991, Ghelier 1998)

Treatment Complications Meatal stenosis SUI (DiMarco 2004)

Treatment Radiation Low stage distal urethral CA 5 yr DSS 41% (Gordon 1993) 74% (part of urethra involved) 55% (entire urethra involved)

Treatment Delivery XRT, Brachy, Combination Results Complications Combo Fewer failures (14%) than all radiation Rx patients (36%) & surgery alone (60%) (University of Iowa) Complications 20-40% UI, strictures, necrosis, fistulas, cystitis, cellulitis Prognosis 5 yr survival: surgery, radiation “similar” (Foens, 1991)

Treatment Various Rx: Advanced stage urethral CA (Table 32-3) Radiation: 25 people, 28% survival, 5-6 yrs Surgery: 13 people, 15% survival, 5-6 yrs XRT + Surgery: 20 people, 5% survival, 5-6 yrs XRT+Chemo+Surg: 6 people, 50% survival, 2 yrs

Treatment Ilioinguinal lymphadenectomy Significant morbidity Systemic spread without regional LN involve No improved survival after pelvic, inguinal LADN Can’t predict micrometastatic LN involvement Recommend: no prophylactic or diagnostic LND Candidates for LND (+) inguinal, pelvic LAD on presentation without distant mets Pts who develop regional LAD during surveillance

Treatment Proximal female urethral CA Facts More likely high stage Advanced female urethral CA involves: Proximal location, entire urethra Locally invasive lesion: external genitalia, vagina or bladder Multimodal Rx is the rule Prognosis With anterior exenteration: 10-17% (5 yrs) Local recurrence 67%

Treatment Proximal female urethral CA Anterior exenteration, pelvic LN dissection (standard bladder + Cloquet’s node), wide vaginal or complete vaginal excision for (-) margins PRN: partial vulvectomy, labial excision PRN: pubis resection

Treatment Prognosis Radiotherapy alone Combo (XRT + surgery) 0-57% survival (5 yrs) Combo (XRT + surgery) Mean survival 54% (5 yrs) Chemo + XRT + surgery Local, distant control in advanced CA SCC 5 FU + Mitomycin C TCC MVAC or Gemcitabine

Urethral recurrence after Cystectomy in women Facts Incidence of CA involving urethra in females undergoing cystectomy for CaB 1-13% Bladder neck involvement and urethral sparing surgery (controversial) Few reported cases of urethral CA despite increasing # of orthotopic neobladders (urethral preservation)

Urethral recurrence after Cystectomy in women Limited data No conclusive treatment Rec. Options (in the absence of mets): Urethrectomy, resection of anastomosis with conversion to continent cutaneous diversion Conversion to cutaneous urinary conduit with bowel from orthotopic diversion

Surgery of Penile and Urethral Carcinoma Campbell’s Urology Chapter 32 W. Britt Zimmerman April 15, 2009