Biopsy-proven residual cervical cancer at the end of combined chemoradiation predicts poor outcome-Retrospective single-center cohort study

Abstract

Introduction: Persistent tumor after combined chemoradiation for locally advanced cervical cancer is an established prognostic factor. Detection may include magnetic resonance imaging, positron emission tomography (PET) combined with CT scan, ultrasound, or biopsies; however, no agreement about the best method and time point has been reached. In our institution, a standardized biopsy protocol of at least four punch biopsies is routinely performed at the last brachytherapy with re-biopsies 6 weeks later in cases not showing histologic complete response (hCR). This study aims to assess the prognostic relevance of these biopsies, especially with respect to the time point of hCR.

Material and methods: This investigation was a retrospective single-center observational cohort study that included all patients treated for locally advanced or node-positive cervical cancer with combined chemoradiation at the University Hospital Innsbruck between 2008 and 2023. Patients with a hCR at the end of radiotherapy were classified as primary negative and otherwise as primary positive. Primary positive patients that achieved complete response at a control biopsy 6 weeks later were classified as secondary negative, and the remaining patients with residual tumor as secondary positive. Progression-free survival (PFS) and overall survival (OS) were compared between all these groups.

Results: We included 184 patients in this study, from which 46 (25%) were classified as primary positive. These patients experienced a significantly worse PFS compared to primary negative patients (p = 0.008, HR = 2.03, 95% CI [1.20, 3.45]). The difference in PFS was also evidenced when comparing primary negative patients to those who had a hCR 6 weeks after radiotherapy (secondary negative) (p = 0.018, HR = 2.00, 95% CI [1.13, 3.56]). However, in primary positive patients, OS was not significantly reduced (p = 0.29, HR = 1.45, 95% CI [0.73, 2.86]).

Conclusions: Early response evaluation using punch biopsies at the time of the last brachytherapy can identify patients with residual tumor, which exhibit a statistically significant and clinically meaningful risk of disease progression. This risk was not reversed even in the case of a delayed hCR 6 weeks after completion of chemoradiation.

Keywords: biopsy; cervical cancer; chemoradiation; follow‐up; persistence; radiotherapy.

FIGURE 1

Flow diagram showing patient inclusion process and biopsy results at the end of CRT and after 6 weeks (hCR, histologic complete response; CRT, chemoradiotherapy).

FIGURE 2

Kaplan–Meier curves showing PFS (A) and OS (B) comparing patients with primary negative vs. primary positive biopsy results after CRT.

FIGURE 3

Multivariate Cox proportional hazards regression for progression‐free survival (PFS). The plot shows adjusted hazard ratios (HR) with 95% confidence intervals for the risk of disease progression or recurrence. The reference group for each categorical variable is as follows: primary negative biopsy (vs. primary positive biopsy), squamous cell carcinoma (SCC) (vs. adenocarcinoma), no lymph node involvement, FIGO I, and tumor grade 1.

FIGURE 4

Kaplan–Meier curves showing PFS comparing patients with primary negative vs. secondary negative biopsy results (A) and PFS comparing patients with secondary negative vs. secondary positive biopsy results (B) 6 weeks after CRT.