Neoadjuvant Chemo/Surgery Appears Non-Superior to CRT in Cervical Cancer


Investigators report acceptable morbidity and health-related quality of life with neoadjuvant chemotherapy plus surgery and concomitant chemoradiotherapy in those with cervical cancer.

"This [randomized clinical trial] comparing NACT-S with CCRT in FIGO stage IB2 to IIB [cervical carcinoma] failed to demonstrate a superiority of NACT-S over CCRT, but demonstrated acceptable morbidity and QOL in both arms," according to the study authors.

"This [randomized clinical trial] comparing NACT-S with CCRT in FIGO stage IB2 to IIB [cervical carcinoma] failed to demonstrate a superiority of NACT-S over CCRT, but demonstrated acceptable morbidity and QOL in both arms," according to the study authors.

Data from the European Organisation for Research and Treatment of Cancer trial 55994 (NCT00039338) did not demonstrate the superiority of neoadjuvant chemotherapy plus surgery (NACT-S) compared with concomitant chemoradiotherapy (CCRT) in patients with stage IB2 to IIB cervical carcinoma, according to findings published in Journal of Clinical Oncology.

Across the intent-to-treat population, the 5-year overall survival (OS) rate was 72% in patients receiving NACT-S vs 76% in those receiving CCRT (P = .291). Additionally, the median OS was not reached with either treatment (HR, 0.84; 95% CI, 0.64-1.12; P = .240). Investigators reported that 5-year OS rates were comparable in the per-protocol and safety populations. At 5 years, the progression-free survival (PFS) rate was 57% in the NACT-S arm vs 66% in the CCRT arm (HR, 0.73; 95% CI, 0.57-0.93; P = .011).

Investigators reported that there were no differences in OS between treatment arms in a subgroup based on International Federation of Gynecology and Obstetrics (FIGO) disease staging. At 5 years, there was a trend towards improved OS with CCRT (78%) compared with NACT-S (69%) observed in patients older than 50 years (HR, 0.66; 95% CI, 0.42-1.03). Five-year OS rates also appeared to be higher with CCRT (81%) vs NACT-S (71%) in patients with a body mass index of 25 or lower (HR, 0.59; 95% CI, 0.37-0.96).

At 2 years, investigators reported a health-related quality of life (HRQOL) survey completion rate of 69% at baseline, which fell to 27% by 2 years. An analysis highlighted no relevant differences in HRQOL between patients who received NACT-S and those who received CCRT.

“The strength of the current trial is that this is a multinational study with a very long follow-up. However, the long duration because of low accrual, [radiotherapy] technique improvements over time, and the different NACT regimens are limitations of our study,” the study authors stated. “This [randomized clinical trial] comparing NACT-S with CCRT in FIGO stage IB2 to IIB [cervical carcinoma] failed to demonstrate a superiority of NACT-S over CCRT, but demonstrated acceptable morbidity and QOL in both arms.”

Investigators assessed 626 patients from May 2002 to January 2014, of whom 314 were assigned to receive NACT-S and 312 were assigned to receive standard CCRT. Patients in the NACT-S arm received a minimum cumulative dose of a cisplatin at 225 mg/m2 and a cisplatin dose equivalent of 75 mg/m2 every 3 weeks. Those in the CCRT arm received cisplatin once with 5 to 6 weekly doses of 40 mg/m2 while they underwent radiotherapy.

The study’s primary end point was OS at 5 years. Secondary end points included PFS, toxicity, and HRQOL.

Patients eligible for enrollment were those who had stage IB2, IIA2, or IIB disease, a World Health Organization performance status of 0 to 2, and were between 18 and 75 years old.

The median patient age was 46 years (range, 23-73) in the NACT-S cohort and 47 years (range, 23-75) in the CCRT cohort. Additionally, most patients in each respective cohort had stage IIB disease (57% vs 57%) and squamous cell histology (85% vs 85%).

Overall, 76% of patients in the NACT-S arm proceeded with surgery per protocol. Of those who did not continue with surgery, 34% did so due to chemotherapy-related toxicity, and 24% due to progressive disease.

Among those receiving CCRT, 6% did not receive radiotherapy. Of these patients, 55% refused to receive radiation, and 25% did not receive it due to protocol violations.

With respect to safety, grade 3/4 AEs occurred in 41% of patients in the NACT-S arm compared with 23% of those in the CCRT arm. Grade 3 or higher instances of Chassagne occurred in 15% and 21% of patients in each respective treatment arm. Investigators reported 2 deaths in the CCRT arm following complications; one was attributed to chronic small bowel obstruction/malabsorption, and the other resulted from sepsis after surgery for a rectal stricture.


Kenter GG, Greggi S, Vergote I, et al. Randomized phase III study comparing neoadjuvant chemotherapy followed by surgery versus chemoradiation in stage IB2-IIB cervical cancer: EORTC-55994. J Clin Oncol. Published online September 1, 2023. doi:10.1200/JCO.22.02852

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