Management of Vulvar Cancer Tevfik GUVENAL, Prof. Dr Celal Bayar University, Manisa

Vulvar Cancer Vulvar cancer is a rare disease Vulvar cancer accounts for 5% of all gynecologic malignancies Incidence of 0.5–1.5 in 100,000 women It primarily affect women older than 65 years There is an increasing incidence, particularly among younger women (increased HPV-exposure. De Sanjose S Eur. J. Cancer 2013 Siegel RL, Cancer J Clin. 2016 Howlader N, http://seer.cancer.gov 2016 Meltzer-Gunnes CJ, Gynecol Oncol 2017

Incidence Over the last five decades, the incidence rate of vulvar SCC has increased >2.5 fold Meltzer-Gunnes CJ, Gynecol Oncol 2017

Histolojik doğrulama Olgu sayısı

2 Types / Variants (15%) (85%)

Histopathologic Types Squamous Cell Carcinoma (85%) Keratinizing SCC 80%, older, related to LS and other vulvar dystrophy Basaloid SCC 20%, younger, HPV infection, other anogenital lesions, VIN, multifocality Melanoma (10%) Adenocarcinoma (5%)

Vulvar Adenocarcinoma

Vulvar Cancer Management Standart treatment in the past: Radical vulvectomy and en bloc groin dissection

Vulvar Cancer Management In last 30 years, a number of significant advances have made in the management of vulvar cancer, reflecting a paradigm shift toward a more conservative surgical approach without compromised survival with markedly decreased physical and psychological morbidity Individualization of the treatment for all patients with invasive disease Vulvar conservation for patient with unifocal tumors an otherwise normal vulva

The proportion of patients receiving surgery as the only treatment decreased by 25% (from 81 to 61%). The use of radiation alone and combination therapy increased >3-fold and almost 3.5-fold, respectively (from 3 to 11% and 6 to 20%, respectively)

(Int J Gynecol Cancer 2017;27: 832- 837)

Diagnosis and Referral The localization of the primary tumor is important SLN procedure: yes/no, expected unilateral or bilateral lymph drainage, visibility of scar, etc In any patient suspected for vulvar cancer, diagnosis should be established by a punch/incision biopsy. Excision biopsy should be avoided for initial diagnosis (may obstruct treatment planning)

Diagnosis and Referral In patients with multiple vulvar lesions, all lesions should be biopsied separately (with clear documentation of mapping) All patients with vulvar cancer should be referred to a gynecologic oncology center and treated by a multidisciplinary gynecologic oncology team

Ontogenetic Staging oT1 Vulvar subcompartment oT2 Vulvar compartment oT3 Extraembriyonic ectosurface metacompartment oT4 Ectosurface metacompartment Michael Höckel

Preoperative Investigations Clinical examination Size of lesion Distance to the midline, Palpation of the lymph nodes Involvement of clitoris, anus/vagina/urethra Evaluation of cervix Picture or clinical drawing is advised

Preoperative Investigations (Imaging) Ultrasound, CT or PET/CT, or MRI Involvement groin and pelvic nodes Distant metastases Suspicious nodes (at palpation and/or imaging) should be analyzed by… fine-needle aspiration or core biopsy

Surgical Management Local Treatment Wide or Radical local excision is recommended. In multifocal invasive disease, radical excision of each lesion as a separate entity may be considered. Vulvectomy may be required in cases with multifocal invasion arising on a background of extensive vulvar dermatosis.

Surgical Management Local Treatment The goal of excision is to obtain tumour-free pathological margins. Surgical excision margins of at least 1 cm are advised. It is acceptable to consider narrower margins where the tumour lies close to midline structures (clitoris, urethra, anus) When invasive disease extends to the pathological excision margins of the primary tumour, re-excision is the treatment of choice.

Surgical Management Groin Treatment Groin treatment should be performed for tumours >pT1a. no more than 1 mm stromal invasion and is 2 cm or smaller in size. For unifocal tumours < 4 cm without suspicious groin nodes on clinical examination and imaging (any modality) the sentinel lymph node procedure is recommended. For tumours ≥ 4 cm and/or in case of multifocal invasive disease, inguinofemoral lymphadenectomy by separate incisions is recommended.

SLN Procedure In SLN Procedure Radioactive tracer is mandatory blue dye is optional Intraoperative evaluation and/or frozen sectioning of the SLN Multiple sectioning (micrometastases) Immunohistochemistry When an SLN is not found (method failure), inguinofemoral lymphadenectomy should be performed

SLN Procedure Where metastatic disease is identified in the SLN (any size) inguinofemoral lymphadenectomy in the groin with the metastatic sentinel lymph node. For tumors involving the midline, bilateral SLN detection is mandatory. When only unilateral SLN detection is achieved, an inguinofemoral lymphadenectomy in the contralateral groin should be performed

Surgical Management (Groin Treatment) In lateral tumours (medial border > 1 cm from midline), ipsilateral inguinofemoral lymphadenectomy is recommended. Contralateral inguinofemoral lymphadenectomy may be performed when ipsilateral nodes show metastatic disease. When lymphadenectomy is indicated, superficial and deep femoral nodes should be removed. Preservation of the saphenous vein is recommended. Where enlarged (> 2 cm) pelvic nodes are identified, their removal should be considered.

Surgical Management (Groin Treatment) In enlarged groin nodes inguinofemoral lymphadenectomy + RT groin node debulking + RT In enlarged pelvic nodes, debulking of lymph nodes +RT Radiotherapy alone will probably not sterilize large nodal pelvic disease.

Advanced stage vulva cancer Multiple treatment modalities. Treatment planning is often individualized.. primary tumor characteristics presence of regional and/or distant metastases. Comorbidity and/or frailty of the patient influences treatment planning. A multidisciplinary setting is needed to optimize treatment planning.

Surgical margin Re-excision is preferred in case of positive margins When possible without damaging structures such as anus, urethra, and clitoris, Re-excision is not possible, postoperative radiotherapy should be performed Addition of concomitant, radiosensitizing chemotherapy to adjuvant radiotherapy should be considered

Radiation Therapy Alone has a little role in the primary management, generally indicated in conjuction with surgery Pre-operatively: in advanced disease Post-operatively: to treat the pelvic and groin lymph nodes and/or to prevent local recurrences in patients involved or close surgical margin Adjuvant radiotherapy should start as soon as possible, preferably within 6 weeks of surgical treatment Radiosensitizing chemotherapy, preferably with weekly cisplatin, is recommended

Bilateral groin dissection, RT if positive Bilateral groin irradiation

Bilateral groin dissection, RT if positive Bilateral groin irradiation

Treatment of Recurrent Disease Local recurrences (vulva or groin) Wide local excision and inguinofemoral lymphadenectomy (invasion of more than 1 mm and not previously performed groin dissection) postoperative radiation in radiotherapy-naïve patients Computed tomography of the thorax/abdomen or PET/CT thorax/abdomen to examine the presence of additional metastases.

Recurrent Disease Journal of Obstetrics and Gynaecology, 2016

Groin recurrence

Follow-up There is no evidence for best follow-up schedule. Local recurrences may occur many years after primary treatment, lifelong follow-up is advised. Patients with associated VIN or lichen sclerosus/planus have a higher risk of local recurrence, more intensive follow-up may be indicated.

Follow-up (After primary surgical treatment) First follow-up 6 to 8 weeks postoperatively First 2 years every 3 to 4 months Third and fourth year biannually Follow-up should include clinical examination of the vulva and groins Data do not support routine use of imaging of the groins in follow-up

Follow-up (After definitive (chemo)radiation) First follow-up visit 10 to 12 weeks after completion of definitive (chemo)radiation First 2 years every 3 to 4 months Third and fourth year biannually At first follow-up visit 10 to 12 weeks after definitive (chemo)radiation, CT or PET/CT is recommended to document complete remission

Survival Meltzer-Gunnes CJ, Gynecol Oncol 2017

Conclusions The incidence of vulva cancer has increased in recent years The treatment of vulval cancer is primarily by surgery. The treatment of vulvar cancer has become more individualised and conservative (wide local excision) A tumor-free surgical margin of at least 1 cm decreases the risk of local recurrence

Conclusions Lymph node status is the most important determinant of survival All tumors larger than 2 cm require pathologic inguinofemoral lymph node evaluation When lymphadenectomy is indicated, superficial and deep femoral nodes should be removed. Sentinel node biopsy is a reliable method Chemoradiation is the treatment of choice in patients with unresectable disease.

BAYRAMIMIZ KUTLU OLSUN.