Immunochemotherapy before surgery doubles pathologic response in advanced cervical cancer

Adding an immune checkpoint inhibitor to chemotherapy before surgery appears to dramatically improve how completely locally advanced cervical cancer responds to treatment, according to a new real-world study published in BMC Cancer. In the two-center cohort, 23.2 percent of patients who received neoadjuvant immunochemotherapy had no residual tumor in their surgical specimen, a pathologic complete response, compared with just 6.6 percent of patients who received conventional neoadjuvant chemotherapy alone. The advantage persisted across every statistical adjustment the researchers applied, and it came without any detectable increase in perioperative complications or toxicity. The findings are among the first to test this combination outside clinical trials, in the ordinary conditions of tertiary cancer centers.

Neoadjuvant chemotherapy followed by radical hysterectomy remains an option for selected patients with locally advanced cervical cancer, particularly in settings where access to definitive chemoradiotherapy is constrained. Whether pairing chemotherapy with an immune checkpoint inhibitor, an approach the researchers call neoadjuvant immunochemotherapy, could sharpen pathologic outcomes without raising surgical risk had been unknown outside trial populations. The team retrospectively analyzed consecutive patients with FIGO 2018 stage IB3, IIA2, or IIIC1 disease who received neoadjuvant therapy followed by radical surgery at two tertiary centers. Of 490 patients screened, 246 were eligible: 151 received chemotherapy alone and 95 received the immunochemotherapy combination. Because immune checkpoint inhibitors became available only in 2021, treatment assignment was almost perfectly entangled with calendar time, so the investigators interrogated this confounding with contemporaneous-period analyses, temporal falsification tests, restriction analyses, and quantitative bias assessment using E-values, alongside 1:1 propensity score matching and stabilized inverse probability of treatment weighting, with doubly robust models further adjusted for any covariates that remained imbalanced after matching.

The primary endpoints were pathologic complete response, major pathologic response, and optimal pathologic response, defined as the union of complete and major response. Complete response occurred in 22 of 95 patients receiving immunochemotherapy versus 10 of 151 receiving chemotherapy alone, an odds ratio of 4.25. After propensity score matching, the rates were 23.5 percent versus 8.8 percent, an odds ratio of 3.18, and after inverse probability weighting they were 20.6 percent versus 6.7 percent, an odds ratio of 3.60. Optimal pathologic response favored the combination in all three models, reaching 47.4 percent versus 13.9 percent in the crude cohort, with adjusted odds ratios of 4.61 after matching and 3.00 after weighting. Major pathologic response favored the combination in the crude and matched cohorts but was attenuated after weighting, losing statistical significance. Nodal metastasis in the surgical specimen was markedly less frequent with the combination after adjustment, 14.7 percent versus 38.2 percent after matching, while the use of adjuvant radiotherapy did not differ between groups.

Safety outcomes were closely scrutinized because a more intense preoperative regimen could theoretically complicate surgery. Operating time was longer with immunochemotherapy in the crude cohort, a median of 220 versus 190 minutes, but the difference disappeared after matching. Estimated blood loss, transfusion rates, and complications were comparable: any complication of Clavien-Dindo grade I or higher occurred in 48.4 percent versus 47.7 percent of patients, and severe complications in 6.3 percent versus 4.0 percent, neither statistically significant. Any-grade treatment-related adverse events were similar at 95.8 percent versus 94.0 percent, with no significant between-group difference in any individual hematologic or non-hematologic toxicity; thrombocytopenia was numerically less frequent with the combination. Immune-related adverse events were confined to the immunochemotherapy group and were uncommon, led by hypothyroidism in 13.7 percent, pneumonitis in 5.3 percent, enteritis in 4.2 percent, and adrenal insufficiency in 3.2 percent.

Survival data remain immature, with 28 progression events and 16 deaths overall. Twenty-four-month progression-free survival was 93.4 percent with immunochemotherapy versus 91.2 percent with chemotherapy alone, and no death occurred in the immunochemotherapy group, but all survival comparisons were underpowered and are reported descriptively. For the primary matched estimate of pathologic complete response, the E-value was 2.96, indicating that an unmeasured confounder would need to be associated with both treatment and outcome by nearly a threefold factor to explain away the finding. The researchers emphasize that because treatment assignment was almost perfectly confounded with calendar time, these results represent associations only; they are hypothesis-generating and require confirmation in prospective randomized trials before immunochemotherapy can be considered a standard preoperative strategy for locally advanced cervical cancer.

Subject of Research: Neoadjuvant immunochemotherapy and pathological response in locally advanced cervical cancer: a real-world bicenter cohort study

Article Title: Neoadjuvant immunochemotherapy and pathological response in locally advanced cervical cancer: a real-world bicenter cohort study

Article References: Zhao, L., Zhang, N., Fu, X., Li, L., Li, M., Wang, X., Hou, J., Zhang, W., Tu, Y., Zhai, Q., Xie, X., Wen, X., Meng, Y., Ye, M., & Gu, C. (2026). Neoadjuvant immunochemotherapy and pathological response in locally advanced cervical cancer: a real-world bicenter cohort study. BMC Cancer. https://doi.org/10.1186/s12885-026-17220-7

Image Credits: AI Generated

DOI: 10.1186/s12885-026-17220-7

Keywords: Neoadjuvant, immunochemotherapy, pathological, response, locally, advanced, cervical, cancer, real-world, bicenter, cohort, scientific research