These phase 3 study results support the use of sequential chemoradiation as a preferred adjuvant treatment following radical hysterectomy for patients with early-stage cervical cancer.
Sequential chemoradiation (SCRT) resulted in a higher disease-free survival (DFS) rate and lower risk of cancer death versus concurrent chemoradiation (CCRT) or radiation (RT) alone after surgery among women with early-stage cervical cancer, according to results from the randomized phase 3 STARS clinical trial (NCT00806117) which evaluated the 3 treatment modalities in a postoperative adjuvant treatment setting.
These study results, published in JAMA Oncology, support the use of SCRT as a preferred adjuvant treatment following radical hysterectomy for patients with early-stage cervical cancer.
“All of the findings together suggest that SCRT could be the most effective method among current adjuvant treatments for early-stage cervical cancer,” wrote the study authors, who were led by He Huang, MD.
In this multicenter, open-label trial, patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB to IIA cervical cancer with adverse pathological features following radical hysterectomy at 1 of 8 participating hospitals in China were enrolled. Participants were randomized 1:1:1 to receive either adjuvant RT, CCRT, or SCRT. The study’s primary end point was the rate of DFS at 3 years.
Overall, 1048 women were enrolled, including 350 in the RT group, 345 in the CCRT group, and 353 in the SCRT group. Importantly, baseline demographic and disease characteristics were well balanced across the treatment groups, with the exception of the rate of lymph node involvement being the lowest in the RT group (18.3%) compared with either the CCRT (30.1%) or the SCRT (29.7%) groups.
Among those in the intention-to-treat population, SCRT was found to be associated with a higher 3-year DFS rate (90.0%) when compared with both RT (82.0%; HR, 0.52; 95% CI, 0.35-0.76) and CCRT (85.0%; HR, 0.65; 95% CI, 0.44-0.96). Following adjustments for lymph node involvement, treatment with SCRT was also shown to have decreased cancer death risk compared with RT (5-year rate, 92.0% vs 88.0%; HR, 0.58; 95% CI, 0.35-0.95).
Importantly though, among patients treated with either CCRT or RT, there was no difference regarding DFS or cancer death risk.
“In the current study, median interval between surgery and adjuvant treatment in the SCRT group (8 days) was much shorter than the other 2 groups (32 days for RT and 33 days for CCRT),” the authors noted. “We believed that early initiation of adjuvant treatment after surgery would be beneficial for oncologic outcomes, as previously reported. Sequential chemoradiation could be an alternative and more applicable modality for adjuvant treatment in resource-limited countries where shortages of radiation resources are severe because chemotherapy can be easily administered while waiting for radiation.”
Regarding safety, a total of 921 patients were evaluable for toxicity. Ultimately, patients in the RT group presented with the lowest rate (12.9%) of grade 3 or 4 adverse events (AEs) compared with those receiving CCRT (28.5%) and SCRT groups (25.3%) (P < .001). No statistically significant differences were noted in the incidence of grade 3 or 4 hematological toxic effects between the CCRT and SCRT groups (18.8% vs 19.1%, respectively; P = .93). However, when compared with the SCRT patient cohort, those in the CCRT cohort experienced higher rates of grade 3 or 4 gastrointestinal toxic effects, such as nausea (6.4% vs 2.5%) and vomiting (5.4% vs 1.9%) (P = .02). Contrastingly, in the SCRT group, higher proportions of lymphocele and peripheral sensory neuropathy were observed.
The current study was not without limitations, including that surgical approach (laparotomy vs laparoscopy) was not used to stratify participants. When the trial was initiated, laparoscopic surgery was considered equally as safe as laparotomy for the treatment of cervical cancer; however, laparoscopic surgery has since been correlated with higher recurrence and worse prognosis. Importantly though, the majority of patients (92.3%) in the present study underwent laparotomy, and the number of participants who underwent laparoscopic surgery was evenly dispersed among the 3 study arms.
Huang H, Feng Y, Wan T, et al. Effectiveness of sequential chemoradiation vs concurrent chemoradiation or radiation alone in adjuvant treatment after hysterectomy for cervical cancer. JAMA Oncol. Published online January 14, 2021. doi: 10.1001/jamaoncol.2020.7168