Concomitant Chemoradiation Remains Standard in Locally Advanced Cervical Cancer

Sudeep Gupta, MD

Standard cisplatin-based concomitant chemoradiation induced superior disease-free survival (DFS) compared with neoadjuvant chemotherapy followed by radical surgery in women with locally advanced squamous cervical cancer, according to findings from a phase III trial published online in the Journal of Clinical Oncology.

Five-year DFS was 76.7% in the concomitant chemoradiation group versus 69.3% in the neoadjuvant chemotherapy plus surgery group (HR, 1.38; 95% CI, 1.02-1.87; P = .038). DFS was also significantly better in the concomitant chemoradiation group after adjusting for stage, pelvic lymph node status, age, hemoglobin level, and performance status (adjusted HR, 1.46; 95% CI, 1.08-1.99; P = .015).

When the definition of a DFS event included death as a result of any cause, analysis of the entire patient population (N = 635) showed a trend demonstrating that 5-year DFS remained superior in the concomitant chemoradiation group (72.0% vs 67.6%), although the result did not reach statistical significance (unadjusted HR in the neoadjuvant chemotherapy plus surgery group, 1.28; 95% CI, 0.97-1.70; P = .086).

“Concomitant chemoradiation using single-agent weekly cisplatin results in a significantly increased DFS rate compared with neoadjuvant chemotherapy followed by radical surgery in this patient population,” corresponding author Sudeep Gupta, MD, Department of Medical Oncology, Tata Memorial Centre, Parel, Mumbai, and colleagues wrote.

“Concomitant chemoradiation resulted in an increased 5-year DFS rate compared with neoadjuvant chemotherapy and surgery, with an absolute difference of 7.4 percentage points between the groups. Subgroup analysis suggests that the main benefit of concomitant chemoradiation was in patients with stage IIb disease,” added Gupta et al.

Investigators enrolled women treated at Tata Memorial Centre in Mumbai, India, into this single-center, phase III, randomized controlled trial from September 2003 through February 2015. Eligible patients aged 18 to 65 years had been diagnosed stage Ib2, IIa, or IIb squamous cervical cancer.

Patients were stratified by stage, 57.2% had FIGO stage IIb disease, and randomly assigned to either 3 cycles of neoadjuvant chemotherapy using paclitaxel and carboplatin once every 3 weeks followed by radical hysterectomy (n = 316) or standard radiotherapy with concomitant cisplatin once every week for 5 weeks (n = 317). Patients in the neoadjuvant group received postoperative adjuvant radiation or concomitant chemotherapy and radiotherapy if indicated.

The median follow-up time in surviving patients was 58.5 months (IQR, 39.3-79.7) at the March 2017 data cutoff point.

In subgroup analyses, investigators found that the 5-year DFS detriment in the neoadjuvant chemotherapy plus surgery group was statistically significant in patients with FIGO stage IIb disease (79.3% vs 67.2%; HR, 1.90; 95% CI, 1.25-2.89; P = .003).

Rates of 5-year overall survival (OS) slightly favored the chemoradiation group, 75.4% versus 74.7%, but the difference was not significant (HR, 1.025; 95% CI, 0.752-1.398; P = .87). There was no difference in OS between the 2 groups after adjusting for stage, pelvic lymph node status, age, hemoglobin level, and performance status (HR, 1.06; 95% CI, 0.77-1.44).

In the neoadjuvant chemotherapy plus surgery group, grade 3/4 thrombocytopenia was more common than in the concomitant chemoradiation group (3.5% vs 0.3%; P = .003), but there was no significant difference between the 2 study groups for grade 3/4 gastrointestinal and bladder toxicities. In the neoadjuvant chemotherapy plus surgery group, perioperative hemorrhage with >1000 mL of blood loss occurred in 7.9% of patients.

There was a lower incidence of toxicity occurring or persisting 90 days after treatment completion in the rectum (5.7% vs 13.3%; P = .002), bladder (2.8% vs 7.3%; P = .017), and vagina (19.9% vs 36.9%; P <.001) in the neoadjuvant chemotherapy plus surgery group. However, there was no difference in rectal and bladder toxicities between the 2 groups 24 months after treatment completion, while vaginal toxicity remained more prevalent in the concomitant chemoradiation group (25.6% vs 12.0%; P <.001).

Gupta S, Maheshwari Am, Parab P, et al. Neoadjuvant chemotherapy followed by radical surgery versus concomitant chemotherapy and radiotherapy in patients with stage IB2, IIA, or IIB squamous cervical cancer: a randomized controlled trial [published online February 12, 2018]. J Clin Oncol. doi: 10.1200/JCO.2017.75.9985.