Neoadjuvant chemoradiation for advanced primary vulvar cancer

In advanced stage primary vulvar cancer, treatment is tailored to individual patient needs. Combined treatment modalities have been developed, using chemotherapy, radiotherapy and surgery.

To determine whether the combined treatment strategy using concurrent neoadjuvant chemoradiation therapy followed by surgery is effective and safe in vulvar cancer patients with advanced primary disease. Main outcomes of interest were: types of surgical intervention following chemoradiation and survival, recurrence and complication rates.

We searched the Cochrane Gynaecological Cancer Review Group Specialised Register. The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE (PubMed), EMBASE, CANCERLIT, other databases and reference lists of articles. The latest search was conducted on 12 March 2005.

Studies of curative treatment of patients with advanced, primary squamous cell carcinoma of the vulva were included. Treatment included concurrent radiotherapy and chemotherapy, followed by surgery.

Twenty-eight abstracts and papers were selected either by the search strategy or by checking the cross references. Randomised controlled trials (RCTs) were not available. Five studies met the inclusion criteria. (Eifel 1995; Landoni 1996; Montana 2000; Moore 1998; Scheistroen 1993). Two authors (HCvD, MV-L) independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials.

Chemotherapy was given uniformly within each of the five selected studies. However, four different chemoradiation schedules were applied. Radiotherapy dose fractionation techniques, fields and target definitions varied. Skin toxicity was observed in nearly all patients. Wound breakdown, infection, lymphedema, lymphorrhea and lymphoceles were also common. Operability was achieved in 63 to 92% of cases in the four studies using 5FU and CDDP or 5FU and MMC. In contrast, only 20% of the patients who received Bleomycin were operable after chemoradiation. After a follow up of 5 to 125 months, 26 to 63% of participants were alive and well. A total of 27 to 85% of participants died due to treatment related causes or disease. The five studies included in this review show that preoperative chemoradiotherapy reduces tumour size and improves operability. However, complications of treatment are considerable and information on the effects of quality of life (QOL) is not available. Furthermore, treatment results of the respective studies diverge considerably.

Patients with inoperable primary tumours or lymph nodes benefit from chemoradiation if an operation can be performed. In patients with large tumours that can only be treated with anterior and/or posterior exenteration complications of neoadjuvant therapy might outweigh complications of exenterative surgery. With the current knowledge neoadjuvant therapy is not justified in patients with tumours that can be adequately treated with radical vulvectomy and bilateral groin node dissection alone.