Vulva PPT

Seminar in oncology :carcinoma of the vulva : Seminar in oncology :carcinoma of the vulva Presented by Kanograt Tangsriwong,MD July 16th, 2010

anatomy : anatomy

Lymphatics drainage : Lymphatics drainage Superficial inguinal and femoral lymph nodes Deep femoral lymph nodes Pelvic lymph nodes ; Obturator and external iliac lymph nodes

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Epidemiology : Epidemiology Only 1-2% of all cancers diagnosed in women About 3-4% of all gynecologic neoplasm Higher incidence in woman 70 yrs of age or older Higher incidence of non-genital second primary cancers More common in immunosuppressed, leukoplakia, genital urinary cancer, lower socioeconomic class and history of employment in laundry and cleaning industies

Natural history : Natural history Arise in labia majora and labia minora (71%) > clitoris (14%) > perineum and fourchette (5%) Well-lateralized lesions metastasis to the contralateral inguinal or pelvic lymph nodes is unusual in absence of ipsilateral inguinofemoral node involvement Involvement of the pelvic nodes without involvement of the inguinal nodes is rare

Natural history : Frequency of inguinal lymph nodes metastasis in ranges from 6% to 50% Histologically positive inguinal nodes, the probability of having positive pelvic nodes is about 30% The most common metastatic sites are lungs, liver and bones Natural history

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Clinical presentation : Clinical presentation Pruritus Spotting or bleeding Pain Discharge Other; dysuria, difficulty with defecation and difficulty with intercourse

Pathology : About 85% are squamous cell type Melanomas Basolid adenocarcinoma Neuroendocrine carcinoma (Merkel cell) Sarcomas Pathology

Epidermoid carcinoma : Epidermoid carcinoma Arise within squamous epithelium but does not have a transitional zone 3 types of growth patterns; confluent, compact and fingerlike growth

Malignant melanoma : Malignant melanoma White woman Sixth to seventh decades 3 categories; Superficial, nodular and acral lentiginous

Merkel cell tumors : Merkel cell tumors Rare Poor prognosis

Adenocarcinomas : Adenocarcinomas Arise in Bartholin’s glands Older women Often present with more advanced at primary site and metastases to the inguinal-femoral lymph nodes

Vulva paget’s disease : Vulva paget’s disease Vary in appearance; eczematoid, red, weeping area, ulcerated or leukoplakia Contain carcinoembryonic antigen Most often in post menopausal, older white woman Mistaken diagnosed as eczema or contact dermatitis Analogous to patient with breast lesions and associated with invasive carcinoma about 20-30%

Verrucous carcinomas : Verrucous carcinomas Usually found in patients with fifth or sixth decade of life Low incidence of lymph nodes involvement Good prognosis

Slide 17 : “ Some dream of worthy accomplishments, while others stay awake and do them.”

Prognostic factors : Prognostic factors Inguinal node metastases result in about 50% reduction of long- term survival - Rutledge et al. ; Tumor thickness is nodal metas. 3. 1 % Tumor thickness is > or = 5 mm - > nodal metas. 33.3 %

Prognostic factors : Prognostic factors Inguinal node metastases result in about 50% reduction of long- term survival - Rutledge et al. ; Depth of invasion is 1 mm - > nodal metas. 4.3 % Depth of invasion is 2 mm - > nodal metas. 7.8 % Depth of invasion is 3 mm - > nodal metas. 17 %

Prognostic factors : Prognostic factors Inguinal node metastases result in about 50% reduction of long- term survival - Rutledge et al. ; Perineural invasion is strongly associated with lymph node metastasis

Prognostic factors : Prognostic factors Inguinal node metastases result in about 50% reduction of long- term survival GOG protocol ; Lesions is nodal metas. 18.9 % Lesions is > 2 cm in diameter- > nodal metas. 41.6%

Prognostic factors : Prognostic factors Inguinal node metastases result in about 50% reduction of long- term survival - Donaldson et al. ; Lesions is less than 3 cm - > nodal metas. 18.9 % Lesions is > or = 3 cm - > nodal metas. 72.4%

Prognostic factors : Prognostic factors Inguinal node metastases result in worsening of prognosis - Donaldson et al. ; Extension of the primary tumor to urethra, vagina and anal area is associated with lymph nodal involvement

Prognostic factors : Prognostic factors Wharton; - Lymph nodes dissection can be avoided in patients with tumors with < 1 mm invasion (stage IA)

Prognostic factors : Prognostic factors Heaps et al ; - Sharp rise in incidence of local recurrence with microscopic, surgical margins < 8mm -> minimum adequacy of margins is 1cm

Prognostic factors : Prognostic factors Hacker et al; - Pelvic lymph nodes need not to be treated in patients without inguinal node involvement

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Slide 30 : “ There is nothing either good or bad but thinking makes it so.”

Staging : Staging

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Slide 40 : Midline or involves both sides -> both inguinal lymph nodes need to be evaluated Lateralized lesions with positive inguinal nodes -> contralateral side is recommended to evaluate Surgical treatment of nodes when combined with radiation cause morbidity should be avoided if it is determined that the nodes are not involved

General management : General management Further complicated by the major psychosexual impact that the treatment can have on the patients Now multimodality therapy with the surgery being more tailored to the extent of the disease Due to radical surgery results in recognition of morbidity and negative impact on sexual function and body-self image

General management : General management Controlling primary tumor with surgery largely depends on the margins of resection; clear margins is about 1 cm.

General management : General management Early invasive disease Advanced disease Histologic variants

Early invasive disease : Early invasive disease Surgery: Small favorable lesions (

Early invasive disease : Early invasive disease Surgery: Lesions with >5mm invasion or with vascular space involvement or poorly diff. or centrally located lesions should undergo bilateral groin dissections; those are indicating of higher risk for inguinal node metastasis. - Deep node dissection is recommended if the superficial nodes are involved.

Early invasive disease : Early invasive disease Radiation therapy : - Post op. RT to the vulva can improve survival and decreased local recurrence - Prevent local recurrence in the higher risk groups : LVSI : Depth of invasion > 5 cm : margins < 8 mm : microscopically positive margins

Early invasive disease : Early invasive disease Radiation therapy : Pre op. RT to the vulva should be offered to patients with tumors close to the urethra, clitoris or rectum.

Early invasive disease : Early invasive disease Radiation therapy : Post op. RT to the pelvis and groins is recommended for patients with pathologically involved groin nodes: extracapsular extension, residual disease in the inguinal areas

Advanced disease : Advanced disease Extensive, radical surgery should be reserved for patients who fail initial therapy, who have no evidence of distant metastasis, good general condition and withstand this type of surgery

Histological variants : Histological variants Melanoma Bartholin’s gland carcinoma Verrucous carcinoma

Histological variants : Histological variants Melanoma Surgery if possible RT plays a secondary role, sometimes used for palliation Worsening prognosis in deep invasion, ulceration, nodular growth patterns c superficially spreading ,epitheloid cell type as opposed to spindle cell or mixed, high mitotic rate, older patients

Histological variants : Histological variants Bartholin’s gland carcinoma - Wide local excision and ipsilateral lymph node dissection - Adjuvant radiation to the vulva and regional nodes, following conservative surgery, may decrease local recurrence Contralateral groin nodes dissection reserved for patients with clinically suspicious nodes or involvement of ipsilateral nodes

Histological variants : Verrucous carcinoma - Usually treated with wide local excision - Node dissections are usually not performed - No evidence that radiation is useful in the treatment for verrucous carcinoma Histological variants

Slide 54 : “We write our own destiny. We become what we do.”

Slide 55 : Surgery

Surgery : Surgery Primary tumor Inguinofemoral lymph nodes Pelvic lymph nodes

Primary tumor : Primary tumor Wide local excision, radical wide excision, and modified radical vulvectomy are recommended, if possible, instead of radical vulvectomy To lower the risk of local recurrence -> minimum margin of 1 cm on the periphery of tumor and to carry the depth of resection the perineal fascia

Primary tumor : Multifocal lesions require a radical vulvectomy The rectum, vagina or urethra are involved, extended radical vulvectomy and bilateral groin dissection or pelvic exenteration may be required Primary tumor

Inguinofemoral lymph nodes : Omitted in low risk of nodal involvement : Depth of invasion < or = 1 mm Small T1-T2, superficial (< 5mm deep) : treated with selective inguinal lymphadenectomy , sparing the deep lymph nodes if superficial nodes are pathological negative Inguinofemoral lymph nodes

Inguinofemoral lymph nodes : Inguinofemoral lymph nodes Main complications of groin surgery are wound breakdown and lower extremity lymphadema Bilateral superficial and deep inguinal node dissection are performed, the potential for wound breakdown and lower extremity lymphadema is increased

Inguinofemoral lymph nodes : Fixed or ulcerated inguinal nodes should be treated with combined radiation and chemotherapy, followed by surgery for the primary and nodes Inguinofemoral lymph nodes

Pelvic lymph nodes : Pelvic lymph nodes GOG trial ; - Pelvic node dissection and pelvic node radiation achieved control of the disease - Radiation to the pelvic nodes may be preferred over surgery -> Rx groins and pelvis at the same time

Slide 63 : Radiation therapy

Radiation therapy : Treatment volume and technique Preoperative radiation therapy Definitive chemoradiation Postoperative radiation therapy Radiation therapy

Radiation therapy : Patients treated with brachytherapy and/or external beam radiation therapy ;5-yr survival rate was 23% and local control rate was 40% Brachytherapy has been used for inoperable vulvular cancer and as a boost to the primary tumor and/or to the lymph nodes Radiation therapy

Treatment volume and technique : Treatment volume and technique Target volume: - vulva, both groins and the lower pelvic nodes - CT or MRI of the pelvis is essential to obtain the depth of inguinal nodes - Pelvic nodes should be treated in patients with positive inguinal nodes (28% incidence of pelvic node involvement)

Treatment volume and technique : Treatment volume and technique Technique: - medium or high energy photon beam (6 or 18MV) - AP/PA fields - supine or frog leg position with custom immobilization “ Frog leg “ has been used to minimize the bolus effect from skin folds - wire LN, vulvar, anus, scar

Frog leg position : Frog leg position

Treatment volume and technique : Treatment volume and technique Technique: Border Superior -L5/S1 or mid SI joints if no pelvic nodes L4/L5 if pelvic nodes +ve Inferior - entire vulva and 3cm inferior to bottom of ischium

Treatment volume and technique : Treatment volume and technique Technique: Border Lateral -2 cm beyond pelvic rim and greater trochanter (ASIS) to include inguinal lymph nodes Bolus should be used to ensure adequate dose to the superficial portions of the groin

Treatment volume and technique : Treatment volume and technique Reduce dose to femoral heads : Wide AP field with a narrow posterior field covering only the pelvis and sparing the femoral heads (fig 72.6) : matched AP/PA fields to include the primary and the pelvic nodes and treating the groins through separate anterior electron fields : modified segmental boost technique using MLC with a single isocenter technique and wide AP field, narrow PA field (fig 72.7)

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Treatment volume and technique : Treatment volume and technique Technique: May need to boost groins with en face electrons Consider IMRT to reduce dose to normal structures

Treatment volume and technique : Treatment volume and technique IMRT CTV: 1-2 cm margin around bilateral external iliac, internal iliac and inguinofemoral nodes : 1cm margin around the entire vulvar region PTV : 1cm margin beyond CTV Normal tissue constraints included the small bowel, bladder and rectum

Treatment volume and technique : Treatment volume and technique Dose prescriptions 1.8 Gy/F 45-50 Gy to vulva and pelvic LN 45-50 Gy for cN0 inguinal nodes and boost to 60 Gy for LN +ve or ECE For residual disease, boost to 65-70 Gy (may require brachytherapy)

Preoperative radiation therapy : Preoperative radiation therapy Preoperative radiation therapy in addition to chemotherapy is now used more frequently In general it is recommended to carry out the inguinal node dissection whether or not there has been complete response of the lymph node as residual disease is often found in the lymph nodes Dose 45-55 Gy Most common chemotherapeutic agents : 5-FU, cisplatin and mitomycin-C

Definitive chemoradiation therapy : Definitive chemoradiation therapy Chemotherapy should be continued throughout the course of radiation for purpose of radiosensitization Dose 60-70 Gy Total dose depends on the location and extent or bulk of the disease, the response to the therapy, and the estimated tolerance of the area requiring the high radiation dose

Postoperative radiation therapy : Postoperative radiation therapy Patients with close margins may be considered for repeat resection prior to radiation, particularly if the area in question is not in close proximity to the urethra, clitoris or anus Adjuvant radiation to both groins and the pelvis: involved more than 1 inguinal node, extracapsular extension, gross or residual nodal disease Surgical margins are clear, no indication to treat the vulva, a midline block can be used

Postoperative radiation therapy : Postoperative radiation therapy Possible residual microscopic disease , a dose of 50 Gy is recommended Extracapsular extension of tumor in lymph nodes, the dose to groins should be carried to 50-60 Gy Gross residual disease post surgery, the dose to area should be brought to 65 to 70 Gy

Slide 81 : Chemotherapy

Chemotherapy : Chemotherapy Single-agent chemotherapy is ineffective for advanced vulvar cancer except for bleomycin, but this agent causes significant toxicity Combination chemotherapy regimens, particularly those including cisplatin and 5-fluorouracil, yield improved response rates, but they are associated with significant toxicity.

Preoperative Chemotherapy : Preoperative Chemotherapy With recent studies using combined radiation and chemotherapy showing satisfactory response rates (97), preoperative chemotherapy alone is not recommended for patients with advanced vulvar cancer.

Adjuvant chemotherapy : Adjuvant chemotherapy If chemotherapy is given, it should be given concurrently with radiation to take advantage of the synergistic effect of the two modalities, although the morbidity of the treatment is enhanced.

Treatment sequelae : : Treatment sequelae : surgical complications Acute: wound infection, seromas, hemorrhage, deep vein thrombosis, pulmonary embolism, osteitis pubis, and anesthesia of the anterior aspect of the thigh secondary to femoral nerve injury.

Treatment sequelae : : surgical complications Chronic: edema of the lower extremities. “Lymphedema” is related to the extent of the lymphadenectomy and it is more likely to occur when a deep inguinal node dissection has been performed. The incidence of lymphedema may be as high as 69% Treatment sequelae :

Treatment sequelae : : Surgical complications: - Other chronic complications reported are chronic cellulitis of the inguinal areas, stenosis of the introitus, femoral hernias, and rectovaginal or rectoperineal fistulas. Treatment sequelae :

Treatment sequelae : : Treatment sequelae : Radiation - Acute morbidity of radiation alone or in combination with chemotherapy is the mucocutaneous reaction in the vulvar-perineal region and inguinal folds regions that can develop early during the course of the treatment.

Treatment sequelae : : Radiation - The most significant The severity of the reaction depends on the radiation fractionation schema used and the type of chemotherapy employed. - Often the degree of reaction is such that a treatment interruption is advised if not mandatory. Treatment sequelae :

Treatment sequelae : : Radiation: - Acute hematologic toxicity is not uncommon and depends on the type and intensity of the chemotherapy used. Treatment sequelae :

Treatment sequelae : : The late complications of chemotherapy/radiation and surgery combined, trimodality therapy, include telangiectasis and atrophy of the skin and mucosa of the vulva, dryness of the mucosa of the vagina and vulva, and narrowing of the vaginal introitus aggravated by the inclusion of the vulvar area in the radiation field. Avascular necrosis of the femoral head has been reported in patients treated to the pelvis with radiation alone or radiation in combination with chemotherapy. Treatment sequelae :

Slide 92 : “We write our own destiny. We become what we do.”

Slide 93 : Thank you for your attention

Treatment recommendations : Treatment recommendations