Concomitant chemoradiation should be standard for locally advanced cervical cancer
Neoadjuvant chemotherapy followed by radical surgery did not improve outcomes compared with cisplatin-based concurrent chemoradiation for women with locally advanced squamous carcinoma of the cervix, according to results of a randomized controlled trial presented at the European Society for Medical Oncology Congress.
An estimated 528,000 new cases of cervical cancer are diagnosed worldwide each year, and approximately 266,000 women die of the disease annually. Many patients — particularly those in less developed countries — present with locally advanced disease, meaning the cancer has invaded the tissue that surrounds the cervix.
“Giving radiotherapy and simultaneous chemotherapy using cisplatin has been the standard treatment for close to 20 years based on the results of several large high-quality trials,” Sudeep Gupta, MD, DM, professor of medical oncology at Tata Memorial Center in India, said during a press conference. “However, despite treatment, about 25% to 40% of patients relapse and die of their disease.”
An alternative treatment strategy that consists of neoadjuvant chemotherapy followed by radical surgery is practiced in many parts of the world — particularly in Europe and Asia — despite a lack of evidence about its efficacy, Gupta said.
Gupta and colleagues conducted a single-center trial at Tata Memorial Centre, the largest cancer hospital in India, to compare neoadjuvant chemotherapy followed by radical surgery with standard concomitant chemoradiation.
The trial, initiated in 2003, included 633 women with stage IB2 (17%), IIA (25%) or IIB (57.2%) squamous cell carcinoma of the cervix.
Researchers randomly assigned 316 women to neoadjuvant chemotherapy — comprised of three cycles of paclitaxel 175 mg/m2 and carboplatin area under the curve 5-6 every 3 weeks — followed by radical hysterectomy. The other 317 received concomitant chemoradiation, which included standard pelvic radiation plus five cycles of cisplatin 40 mg/m2 once per week for 5 weeks. Postoperative radiation was administered per protocol criteria.
Treatment arms were balanced with regard to disease stage, patient age, performance status, hemoglobin and radiological pelvic lymph node status.
DFS served as the primary endpoint. Secondary endpoints included OS and toxicity.
Median follow-up was 58.5 months. By that time, 30% of patients in the chemotherapy/surgery group and 23% in the chemoradiation group had relapsed or died. Researchers reported 5-year DFS rates of 69.3% in the chemotherapy/surgery group and 76.7% in the chemoradiation group (HR = 1.38; 95% CI, 1.02-1.87).
Results showed no significant difference in 5-year OS (74.8% vs. 74.7%; HR = 1.02; 95% CI, 0.75-1.39).
When researchers adjusted data to account for prognostic factors, they determined neoadjuvant chemotherapy followed by surgery was not superior for DFS or OS.
Gupta and colleagues measured acute and delayed toxicities of treatment in both groups.
At 2 years, results showed no significantly differences between the chemotherapy/surgery group and chemoradiation group with regard to rectal toxicity (2.2% vs. 3.5%) or bladder toxicity (1.6% vs. 3.5%). However, researchers reported double the incidence of vaginal toxicity in the chemoradiation group (25.6% vs. 12%; P < .001).
“This is a robust trial with 635 patients, and we believe these data are definitive,” Gupta said. “Chemotherapy followed by surgery is not superior to radiotherapy and simultaneous chemotherapy in locally advanced cervical cancer. Chemotherapy followed by surgery should not be routinely practiced. Concomitant chemoradiation therapy should be the standard treatment.” – by Mark Leiser.
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