Comparison of outcome measures in patients with advanced squamous cell carcinoma of the vulva treated with surgery or primary chemoradiation. Chemoradiation with 5-fluorouracil and mitomycin C in the treatment of vulvar squamous cell carcinoma.
To review outcome measures including overall survival (OS), progression free survival (PFS), and patterns of recurrence in patients with advanced vulvar cancer managed by primary surgery (PS) or primary chemoradiation (PCRT) as well as population characteristics for the two groups.
                Patients diagnosed with stage III and IV squamous cell carcinoma of the vulva from 1990 to 2006 were identified for retrospective analysis at a single institution. Charts were abstracted for clinical and pathologic findings, treatment modalities, complications, recurrence, and follow-up. Kaplan-Meier method was used to determine PFS and OS.
                Sixty-three patients with stage III (n=47) and IV (n=16) carcinoma of the vulva were identified; 30 patients were treated with PS, and 33 patients had tumor that was unresectable by vulvectomy and underwent PCRT. Patients treated with PCRT were younger (61 vs. 72 years; p=0.09), had less metastasis to lymph nodes (54% vs. 83%, p=0.01), and larger tumors (6 vs. 3.5 cm, p=0.0001) compared to patients treated with PS. Despite these differences, OS for the PS and PCRT groups was 69% and 76% (NS), respectively, with median follow-up at 31 months. There were no differences in PFS or recurrence rates between the two groups. By multivariate analysis, age was the only significant predictor of OS or PFS.
                Patients with advanced vulvar cancer that are managed with PS tend to be older patients that have smaller lesions but positive lymph nodes, whereas patients requiring PCRT are younger and have larger volume disease but fewer lymph node metastases. Despite these differences, patients treated with PS and PCRT have no differences in OS, PFS, or recurrence rates. Age is the most powerful predictor of survival when size, lymph node status, stage and treatment are accounted for. To investigate the acute and late toxicities associated with the use of chemoradiation therapy (CRT) with 5-fluorouracil (5-FU) and mitomycin C or mitomycin C alone for primary, adjuvant, and salvage therapy for vulvar cancer.
                Medical charts of 17 patients who received CRT with this regimen were reviewed. Toxicity was scored by 1998 standardized common toxicity criteria, Version 2.0, for acute toxicity and the RTOG/EORT Late Radiation Morbidity Scoring Schema for late toxicity. Median follow-up was 20 months (range: 5-74 months).
                Six patients had grade 4 neutropenia. In three patients, life-threatening neutropenic sepsis developed after the second cycle of chemotherapy. Severe enterocolitis was a direct cause of death in two patients. In four patients, the second cycle of chemotherapy was cancelled because of severe toxicity associated with the first cycle. One patient had grade 4 skin toxicity in the vulvar-perineal area. Six patients had grade 3 and seven patients had grade 2 acute skin toxicity. Skin toxicity necessitated the interruption of CRT in nine patients at a median dose of 32.4 Gy (range: 16.2-48 Gy). One patient developed bowel perforation and colovaginal fistula 1.5 years after completion of CRT.
                Chemoradiation therapy utilizing 5-FU and mitomycin C or mitomycin C alone in the treatment of vulvar cancer can be associated with a high incidence of morbidity and mortality. Strict attention to indications for treatment interruptions or chemotherapy dose adjustments is obligatory for safe delivery of CRT to these patients.
Women with advanced vulval tumours showed no significant difference in overall survival or treatment-related adverse events when chemoradiation (primary or neoadjuvant) was compared with primary surgery.
The retrospective studies had a high risk of bias as the entry criteria for primary chemoradiation was based on inoperability or tumour requiring exenteration.The radiochemotherapy regimens varied widely. There was no data on QoL.
There is no standard terminology for 'operable and inoperable vulval cancer', and for 'primary and neoadjuvant chemoradiation'. Stratification according to unresectability of the primary tumour and/or lymph nodes is needed, for good quality comparison.