DR. N. SRAVANTHI DR. NEHA DR. S. C. SAHA 8/8/2012
Pre- treatment work up A thorough pre- operative evaluation for coexisting medical problems Routine investigations and Chest radiograph PAP smear and colposcopy of cervix and vagina. Imaging : CT and MRI may help to determine resectability and treatment planning, and distant metastases Cystoscopy, intravenous pyelography, or proctoscopy (or all three) is indicated if it appears that locally advanced cancer
Standard treatment in the past : Radical vulvectomy and en bloc groin dissection ( Taussig and Way) Involves radical removal of the entire vulva, the mons pubis, the inguino-femoral lymph nodes, and often the pelvic lymph nodes.
ISSUES OF CONCERNS : High rate and the severity of wound complications Psychosexual effects of radical removal of the vulvar tissues Urinary or fecal incontinence Vaginal relaxation, Overtreatment of early cancer, Inadequate treatment of more advanced disease
During the past 20 years, a number of significant advances have been made in the management of vulvar cancer, reflecting a paradigm shift toward a more conservative surgical approach without compromised survival and with markedly decreased physical and psychological morbidity Individualization of treatment for all patients with invasive disease Vulvar conservation for patients with unifocal tumors and an otherwise normal vulva
Omission of the groin dissection for patients with T1 tumors and, <1 mm of stromal invasion . Elimination of routine pelvic lymphadenectomy. Investigation of role of sentinel lymph node procedure to eliminate requirement for complete inguino-femoral lymphadenectomy. The use of separate incisions for the groin dissection to improve wound healing
Omission of the contralateral groin dissection in patients with lateral T1 lesions and negative ipsilateral nodes The use of preoperative radiation therapy to obviate the need for exenteration in patients with advanced disease. The use of postoperative radiation therapy to decrease the incidence of groin recurrence in patients with multiple positive groin nodes
Prognostic factors Primary Tumor factors : depth of invasion or tumor thickness, tumor diameter, tumor differentiation, lymph-vascular space involvement, and Margin status : most powerful predictor of local recurrence ( At least 1cm grossly negative surgical margin) ( Closer than 0.8cm margins – almost 50% recurrence risk
Status of the inguino-femoral lymph nodes- single most important prognostic factor NODAL STATUS 5 YEAR SURVIVAL RATE NEGATIVE >80% POSITIVE <50% No. Of Nodes: No. of NODES Prognosis Single microscopically +ve Similar as negative nodes 3 or more +ve nodes 2year survival of 20%
Extra-capsular extension Clinical nodal status Size of the metastatic deposit inside the lymph node, Percentage of nodal replacement.
Modifications in Management of the VulvarPhase of Treatment Modified radical vulvectomy - generally refers to radical removal of the portion of the vulva containing the tumor AIM: to obtain 2cm skin margins while sparing of as much normal vulvar tissue as possible is less likely to produce sexual dysfunction and a sense of disfigurement Chief concerns : possibility of an increased risk of local recurrence and later an increased risk of a second primary vulvar cancer
A comparative study of radical vulvectomy and modified radical vulvectomy forthe treatment of invasive squamous cell carcinoma of the vulva SURGERY No. of Patients Local recurrence Modified Radical 45 1 (2.2%) Vulvectomy Radical vulvectomy 45 2 (4.4%) Hoffman MS, Roberts WS, Finan MA, Fiorica JV, Bryson SC, Ruffolo EH, Cavanagh D Gynecol Oncol 1992 May;45(2):192-7
The evolution of surgical techniques in vulvar cancer. (A) Radical vulvectomy with en bloc dissection;(B) radical vulvectomy with triple incision; (C) modified radical vulvectomy;(D) clitoral-sparing modified radical vulvectomy
STAGE I Vulvar cancer Radical vulvectomy (5-year survival rates ) >90%. Choice of treatment depends on various tumor and patient factors. Micro-invasive lesions (<1 mm Wide (5–10 mm) local excision invasion) Lesions >2cm with <5mm invasion “Radical local excision” with and clinically negative nodes complete unilateral lymphadenectomy “At least 1cm grossly negative margin, without putting the skin under tension, should be obtained and extended to the level of inferior fascia of the urogenital diaphragm .”
STAGE II Vulvar cancer Standard therapy : Modified radical vulvectomy with bilateral inguinal and femoral lymphadenectomy(Target : tumor free margins of at least 1 cm) Adjuvant local radiation therapy may be indicated for surgical margins less than 8 mm, and particularly if the patient also has positive nodes
STAGE III Vulvar cancer Modified radical vulvectomy with inguinal and femoral node dissection. Radical vulvectomy with inguinal and femoral node dissection followed by radiation therapy
STAGE IV Vulvar cancer Radical vulvectomy and pelvic exenteration (if resectable).
A phase II trial of radiation therapy and weekly cisplatin chemotherapy forthe treatment of locally-advanced squamous cell carcinoma of the vulva: agynecologic oncology group study.Moore DH, Ali S, Koh WJ, Michael H, Barnes MN, McCourt CK, Homesley HD, Walker JLGynecol Oncol. 2012 Mar;124(3):529-33. Epub 2011 Nov 9 OBJECTIVES: To determine the efficacy and toxicity of radiation therapy and concurrent weekly cisplatin chemotherapy in achieving a complete clinical and pathologic response when used for the primary treatment of locally-advanced vulvar carcinoma. METHODS: Patients with locally-advanced (T3 or T4 tumors not amenable to surgical resection via radical vulvectomy), previously untreated squamous cell carcinoma of the vulva were treated with radiation (1.8 Gy daily × 32 fractions=57.6 Gy) plus weekly cisplatin (40 mg/m(2)) followed by surgical resection of residual tumor (or biopsy to confirm complete clinical response). Management of the groin lymph nodes was standardized and was not a statistical endpoint. Primary endpoints were complete clinical and pathologic response rates of the primary vulvar tumor. RESULTS: A planned interim analysis indicated sufficient activity to reopen the study to a second stage of accrual. Among 58 evaluable patients, there were 40 (69%) who completed study treatment. Reasons for prematurely discontinuing treatment included: patient refusal (N=4), toxicity (N=9), death (N=2), other (N=3). There were 37 patients with a complete clinical response (37/58; 64%). Among these women there were 34 who underwent surgical biopsy and 29 (78%) who also had a complete pathological response. Common adverse effects included leukopenia, pain, radiation dermatitis, pain, or metabolic changes. CONCLUSIONS: This combination of radiation therapy plus weekly cisplatin successfully yielded high complete clinical and pathologic response rates with acceptable toxicity
Management of vulvar cancer with peri-urethralinvolvement Needs removal of outer urethra Foley’s catheter for one week postoperatively facilitate healing and splinting of the urethra If >1 cm of urethra removed or any preoperative stress urinary incontinence – consider surgical anti-incontinence procedure.
Management of vulvar cancer with perianalinvolvement Difficult to obtain adequate surgical margin on resection Difficult to decide b/w radical excision and colostomy or preoperative radiotherapy
Measures to minimize incontinence : ( rarely needed ) Sphincter approximation and levator muscle plication Bowel preparation, prophylactic antibiotics ,post-operative bowel management Use of cutaneous rhomboid flaps in reconstruction of perineum and perianal areas
MANAGEMENT OF REGIONAL LYMPH NODES Appropriate groin dissection – single most important factor in decreasing mortality in early vulvar cancer Virtually no risk of lymph node metastasis if stromal invasion < 1 mm therefore one can omit groin dissection if invasion < 1mm ,no lympho-vascular space invasion and no clinically suspicious groin lymph node Depending on laterality of vulvar lesion- ipsilateral or bilateral lymphadenectomy becomes necessary Recurrence in undissected groin > 90% mortality
All patient whose tumors demonstrate more than >1mm of stromal invasion Or whose tumors are >2cm (T1b and above ) Require inguinal- femoral lymphadenectomy
If Groin dissection is indicated in patients with vulvar cancer, it should be a thorough inguinal- femoral Lymphadenectomy. UNILATERAL GROIN DISSECTION: if the primary lesion is unilateral and ipsilateral nodes are negative. Recommended that patients with any bulky or multiple microscopically positive ipsilateral lymph nodes should undergo contralateral inguinal – femoral lymphadenectomy. Bilateral inguinal-femoral lymphadenectomy be performed for Midline lesions Those with in 2 cm from midline
If Pre-operative pelvic imaging reveals bulky pelvic lymph nodes Resection via extra-peritoneal approach prior to radiation( limited ability of external beam radiation therapy to sterilize bulky positive pelvic nodes)
Saphenous vein sparing during inguinal lymphadenectomy to reduce morbidity in patients withvulvar carcinoma.Gynecol Oncol. 2006 Apr;101(1):140-2. Epub 2005 Dec 20Dardarian TS, Gray HJ, Morgan MA, Rubin SC, Randall TC OBJECTIVES: To compare short- and long-term morbidity associated with saphenous vein sparing versus ligation during inguinal lymphadenectomy for vulvar carcinoma. METHODS: A retrospective evaluation of patients with carcinoma of the vulva that underwent inguinal lymphadenectomy was performed. Operative reports were evaluated and patients were divided into those who had sparing of the saphenous vein versus ligation. Postoperative short- and long-term complications were compared between the two groups using Pearson chi squared analysis. RESULTS: There were a total of 49 inguinal lymphadenectomies performed on 29 patients. The saphenous vein was spared in 18 (37%) groin dissections compared to 31(63%) in which the saphenous vein was ligated. The two groups were similar in regards to clinical characteristics. All patients received closed suction drains and prophylactic antibiotics. Median number of nodes dissected was similar. Cellulitis was more common in the vein-ligated group compared to the vein-spared group (45% vs. 0%; P < 0.001). Wound breakdown occurred in 25% of dissections where the saphenous vein was ligated versus 0% in dissections where the vein was spared (P = or < 0.02). Short-term edema (< or = 6 months) was similar between vein-ligated and vein- spared groups (67% vs. 72%, P < 1.0). Subsequently, chronic lymphedema (> 6 months) persisted in 38% of the vein-ligated group compared to 11% in the vein-spared group (P < 0.05). The incidence of recurrent disease was similar in both groups (19.3 % vs. 22.2% P < 0.1). CONCLUSIONS: Routine preservation of the saphenous vein during inguinal lymphadenectomy for vulvar carcinoma may reduce the incidence of wound cellulitis, wound breakdown, and chronic lymphedema.
Sparing of saphenous vein during inguinal lymphadenectomy for vulval malignancies.Zhang X, Sheng X, Niu J, Li H, Li D, Tang L, Li Q, Li Q.Gynecol Oncol. 2007 Jun;105(3):722-6. Epub 2007 Apr 3 Abstract OBJECTIVE: This work was set out to investigate the effect of saphenous vein preservation during inguinal lymphadenectomy for patients with vulval malignancies. METHODS: 64 patients with vulval malignancies were allocated into two groups depending on their clinical stages, with one of them (31 patients included) being subjected to sparing of saphenous vein and the other to saphenous vein ligated surgery while treated with inguinal lymphadenectomy. The operative time, blood loss, 5-year survival rate, short- and long-term postoperative complications, 5-year survival rate and groin recurrence were selected as the monitored parameters, through which the above two groups were compared with each other using t test, chi2 and life table analysis. RESULTS: (1) The median operative time for bilateral inguinal lymphadenectomy was 155 min (130-170 min) in the sparing group, compared to 140 min (120-170 min) in the excision group (P>0.05). The median intraoperative blood loss was 295 mL (100-450 mL) in the sparing group, and 270 mL (150-390 mL) in the excision group (P>0.05). (2) Short-term lower extremity lymphedema occurred with 27 patients (43.5%) in the sparing group and 44 patients (66.7%) in the excision group (P<0.01). Still, short-term lower extremity phlebitis was observed with 7 patients (11.3%) in the sparing group while 17 developed phlebitis (25.8%) in the excision group (P<0.05). However, there was no statistical difference in postoperative fever, acute cellulites, seroma, or lymphocyst formation. (3) Long-term complication occurrence rate decreased by about 50% in patients subjected to saphenous vein sparing surgery compared with those to ligated surgery, while there was no remarkable difference between two groups in the occurrence rates of phlebitis and deep venous thrombosis (P>0.05). (4) The overall 5-year survival rate was 67.3%, with 66.7% and 68.0% for the excision group and the sparing group, respectively (P>0.05). CONCLUSION: The application of saphenous vein preservation technique during inguinal lymphadenectomy for patients with vulval malignancies could significantly decrease the occurrence rate of postoperative complications without compromising outcomes and should be widely put into clinical practice.
First draining lymph-node in the lymphatic basin that recieves primary lymph flow from the tumor. Use of comprehensive serial sectioning, Immunohistochemistry (IHC), and reverse transcription-polymerase chain reaction have been investigated as potential methods to detect the earliest signs of metastatic disease.
PROCEDURE 1-2mlof isosulfan blue dye or 400mCi of technetium labeled sulfur colloid injected circumferentially intradermally around the tumor, and lymphoscintigraphy was performed. The sites of the SLNs marked on the skin with a pencil. SLNs identified using a handheld probe and the dissection of blue- stained lymph vessels and lymph nodes.
Intra operative gamma counter to identify for identification of the nodes and lymphatics. The removed SLNs sent to the pathologist separately. Ultrastaging consisted of performing serial sectioning and IHC analysis with cytokeratins.
Studies in vulvar cancer in which SLN detection wasfollowed by a completion inguino-femoral lymphadenectomy suggest that the SLN procedure is highly accurate inidentifying lymph node metastases with an NPV approaching 100%
STUDIES Details GROINSS-V 403patients 3% groin recurrences 26% metastatic sentinel nodes GOG-173 452 women underwent the 132 node-positive women planned procedures, 11 (8.3%) with false- 418 had at least one negative sentinel lymph 23% true positive detected by IHC sensitivity was 91.7% False-negative predictive value 3.7%Sentinel lymph node biopsy is a reasonable alternative to inguinal femorallymphadenectomy inselected women with squamous cell carcinoma of the vulva.
Reliance on the SLN is dependent on accurate injection of the blue dye and/or radioisotope, interpretation of the preoperative lymphoscintigraphy, and proper handling of the node by the pathologist, including serial sectioning and IHC analysis. Implementation in the routine treatment of early-stage vulvar cancer requires quality control at each step of this multidisciplinary procedure. Learning curve associated with the SLN procedure Success of the procedure is surgeon dependent (requires a surgeon with successful experience SLN procedure followed by full lymphadenectomy in at least 10 patients.) Finally, to keep the experience at a high level, an exposure of at least 5–10 SLN procedures per year per surgeon is likely necessary. In a rare tumor such as vulvar cancer, this requires centralization of early stage vulvar cancer treatment in oncology centers
Reconstruction of surgical defects Gluteus maximus myocutaneous flaps Rectus abdominis myocutaneous flap
Tensor fascia lata myocutaneous graft – for extensive defect in groin and vulva.
Rhomboid flap – best suited for posterior vulva.
Mons pubis pedicle flap – for lateral defects. Unilateral or bilateral Gracilis myocutaneous grafts - when extensive resection done from mons to perianal region.
Post-operative Management Prophylactic antibiotics for 24 hrs Ambulation delayed - If wounds are closed under tension Meticulous perineal hygiene Measures to keep the area dry and clean Continue suction drainage of groin till output is minimal to avoid groin seromas Heparin thrombo-prophylaxis until ambulatory Pneumatic calf compressions
A compression dressing (rolled gauze and an abdominal binder) is maintained on the groins for an additional 24 to 48 hours to prevent lymphocyst formation Foley’s catheter till patient ambulatory ( may be required for prolonged periods if significant peri-urethral swelling ) Bowel rest - depending on the degree of perineal or perianal resection
Early complications Wound infection Wound breakdown Major break down occurs in about 14% patients With separate incision approach – reduced to 44% Lymphocysts or groin seromas ( 10 – 15% cases) small and asymptomatic - be left alone Repeated aspirations until resolution is most commonly recommended
Late complications Depression, altered body image, sexual dysfunction major long term treatment complication Associated with the extent of vulvar surgery RX : modification of radical extent of surgery and preoperative and post operative counselling Chronic lymphedema (30%) reported in 10-20% of women after groin node dissection Can be a disabling problem More common if radiation is required after groin dissection Limiting groin node dissection in women with early cancers and preserving the saphenous vein decreases the incidence of this problem
Use of graduated compression stockings after lymphadenectomy can help prevent lymphedemaMx : Intermittent limb elevation Manual lymphatic drainage(massage combined with bandaging ) moderate exercise program carefully fitting compression stockings pneumatic compression devices
Recurrent lymphangitis and cellulitis of leg (10%) Dyspareunia – due to Introital stenosis Urinary stress incontinence (with or without genital prolapse) Femoral hernia Pubic osteomyelitis Recto vaginal or recto perineal fistulas
Survival Five – Year Survival with Vulvar carcinoma FIGO Stage 5- Year survival ( % ) I 79 II 59 III 43 IV 13 Modified from FIGO Annual report on the results of treatment in Gynecological Cancer using 1994 FIGO staging classification
RADIOTHERAPY Alone has a little role in the primary management, generally indicated in conjunction with surgery PRE- OPERATIVELY : patients with advanced disease who would otherwise require pelvic exenteration or suffer loss of anal or urethral sphincteric function POST- OPERATIVELY : to treat the pelvic lymph nodes and groin of patients with two or more microscopically positive or one grossly positive groin node.
Possible roles To prevent local recurrences in patients with involved or close surgical margins Primary therapy for patients with small primary tumors, particularly clitoral or peri-clitoral lesions in young and middle-aged women
The benefit of adjuvant postoperative radiotherapy is much more evident if there is gross replacement or extra-capsular involvement of a lymph node, or involvement of three or more lymph nodes, (the risk of groin recurrence and pelvic nodal metastases is substantial)
CHEMOTHERAPY The likely uses of chemotherapy in vulval cancer as a neo-adjuvant to shrink tumour initially considered unresectable as a concomitant to radiation for primary management of unresectable tumours as a postoperative adjuvant treatment either alone or concomitant to radiation for the management of relapsed disease.
Most extensively studied regimens : Bleomycin, methotrexate and cisplatin Others – 5FU, mitomycin-C A trial from European Organization for Research and Treatment of Cancer (EORTC)in the late 1980s evaluated the use of lomustine (CCNU), methotrexate and bleomycin in locally advanced cases with a surprisingly high activity
RECURRENCES 15 – 40% have recurrences 70% have local component 55 – 90% isolated local recurrences Isolated local recurrences commonest with neg. lymph nodes in groins Recurrence site – strongest predictor of outcome Groin recurrence occur sooner than vulvar recurrence ( median time : 6 months / 3 yrs )
Margin status at the time of radical resection : most powerful indicator of local recurrence ; however it doesn’t predict survival The long-term survival rate after radical excision of a vulvar recurrence has been reported as 50-60% Disease at sites other than the vulva and a short interval from initial treatment to recurrence diminish the cure rate after local recurrence . For a large recurrence, an exenterative procedure can be attempted
Resection of a groin recurrence is not usually recommended. Often, this area heals slowly if radiation has already been used. The only situation in which resection of a groin node recurrence should be attempted is if the groin node is an isolated recurrence and the patient has not been previously irradiated
“JUST TO SUMMARIZE” Vulvar cancer is surgically staged. Imaging such as CT of the abdomen and pelvis should be performed for women with tumors 2 cm or larger or to detect lymph node or other metastases. Staging should include evaluation of factors related to prognosis: tumor size, depth of invasion, lymph node involvement, and presence of distant metastases.
Inguino-femoral lymph node metastasis is the most important predictor of overall prognosis. Inguino-femoral lymphadenectomy or sentinel lymph node evaluation can be omitted for lesions 2 cm or smaller and depth of invasion less than 1 mm. Sentinel node biopsy seems to be a reliable means to pathologically assess inguino-femoral lymph node metastasis
All tumors larger than 2 cm require pathologic inguino-femoral lymph node evaluation. Radical local excision or modified radical vulvectomy is appropriate for most stage I and II lesions located on the lateral or posterior aspects of the vulva. A tumor-free surgical margin of at least 1 cm decreases the risk of local recurrence. Chemo-radiation therapy is the preferred approach for most patients with very advanced vulvar cancer