“Chemotherapy followed by surgery is not superior to radiotherapy and simultaneous chemotherapy in patients with locally advanced cervical cancer...and should not be routinely practiced.”

— Sudeep Gupta, MD, DM

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THE FIRST FORMAL comparison of two acceptable approaches to locally advanced cervical cancer has concluded that standard chemoradiotherapy is preferable to neoadjuvant chemotherapy plus surgery. The findings confirm what most specialists have believed to be the optimal treatment. 

The results came from a randomized trial of 633 patients (median age 49) with stage Ib2–IIb squamous cell carcinoma of the cervix, presented at the European Society for Medical Oncology (ESMO) 2017 Congress Presidential Symposium II by Indian investigators.¹ Principal investigator Sudeep Gupta, MD, DM, of Tata Memorial Centre in Mumbai, called the study “robust” and the data “definitive,” indicating the trial “answers a long-standing treatment question.” 

“Chemotherapy followed by surgery is not superior to radiotherapy and simultaneous chemotherapy in patients with locally advanced cervical cancer...and should not be routinely practiced,” Dr. Gupta concluded. “Concomitant chemoradiation should be the standard of care in locally advanced cervical cancer.” 

For almost 20 years, the standard of care in locally advanced cervical cancer has been radiotherapy plus cisplatin-based chemotherapy; however, the fact that up to 40% of patients relapse has prompted interest in neoadjuvant chemotherapy followed by radical surgery. In older studies, neoadjuvant chemotherapy followed by radical surgery was shown to improve survival compared with radiotherapy alone—but radiotherapy alone “is now an obsolete standard,” he pointed out. 

The study’s hypothesis was that neoadjuvant chemotherapy with paclitaxel plus carboplatin followed by surgery would improve outcomes over concomitant chemoradiation because of its ability to downstage local disease and eradicate systemic metastases. The hypothesis, however, was not proven in this study, as neoadjuvant chemotherapy followed by surgery was associated with a significant increase of almost 40% in the rates of relapse or death over 5 years, Dr. Gupta reported. The difference in outcome was primarily seen in stage IIb patients. 

Study Details 

THE NEOADJUVANT chemotherapy arm received three cycles of paclitaxel plus carboplatin, and the chemoradiotherapy arm received cisplatin once a week for 5 weeks in conjunction with external-beam radiotherapy plus high-dose–rate brachytherapy. Crossover was allowed; 71.8% of those assigned to neoadjuvant chemotherapy followed by surgery went on to have radical surgery. 

After a median follow-up of about 5 years, analysis of the intent-to-treat population showed disease-free survival rates to be 76.7% for chemoradiotherapy, vs 69.3% with neoadjuvant chemotherapy followed by surgery (hazard ratio [HR] = 1.38; P = .038). Approximately 76% of the patients in each arm were alive at 5 years (HR = 1.03). 

A subgroup analysis suggested that women with stage IIb disease, in particular, experienced a significant benefit in disease-free survival with chemoradiotherapy compared with neoadjuvant chemotherapy followed by surgery, and this benefit drove much of the difference in outcomes between the arms. 

Chemoradiotherapy was associated with higher 90-day rates of adverse events than neoadjuvant chemotherapy followed by surgery, but 2-year rates of any-grade toxicity were similar for rectal sites (P = .474), bladder sites (P = .204), and other sites (P = .334). Chemoradiotherapy did increase the risk of vaginal toxicity, which at 2 years remained 25.6% with chemoradiotherapy vs 12.0% with neoadjuvant chemotherapy followed by surgery (P < .001). 

With a slightly different chemotherapy backbone, these approaches are now being compared in a study of 629 patients by the European Organisation for Research and Treatment of Cancer (EORTC). The results of EORTC 55994, whose primary endpoint is overall survival, are expected in 2019. ■

DISCLOSURE: Dr. Gupta reported no conflicts of interest. 

REFERENCE 

1. Gupta S, Parab P, Kerkar R, et al: Neoadjuvant chemotherapy followed by surgery versus concurrent cisplatin and radiation therapy in patients with stage IB2 to IIB squamous carcinoma of the cervix: A randomized controlled trial. ESMO 2017 Congress. Abstract 928O_PR. Presented September 10, 2017.