A systematic study on local failure events post chemoradiotherapy for cervical cancer: understanding the impact of baseline lateral anatomical compartment involvement.

Purpose: To dissect the local failure (LF) events, including specific rates by anatomical compartments, after definitive chemoradiotherapy for locally advanced cervical cancer (LACC).

Methods: Records of all consecutive women with LACC treated with definitive chemoradiotherapy and image-guided adaptive brachytherapy (IGABT) were reviewed, focusing on the local disease status. No patient received external-beam radiotherapy (EBRT) parametrial boost. Incidence estimations, timing analysis (true persistent disease [TP]) versus new recurrence [NR]), calculations of LF rates by anatomical compartments (at the time of LF detection), and test of association of compartment-specific LF with baseline (at diagnosis) involvement (adjusted odds ratio [aOR]), were performed.

Results: Among the 225 patients included (75% FIGO III-IV; 32% IC/IS BT use; median FU 46.2 months), 34 LFs occurred (24 TP; 10 NR), involving 92 anatomical compartments. Isolated LF was the first relapse in 55.9% (19/34), with no events after 3 years, resulting in 6.2% 3-year/5-year overall NR and 16.3% 3-year/5-year overall LF (NR + TP) rates. TP had worse survival compared to NR (2y-OS: 19.1% vs. 72.9%, p=0.04). The most involved compartments were the cervix (79.4%), parametrium (PMT) (61.8%), uterine corpus (33.3%), bladder (14.7%), vagina (11.8%), and mesorectum (2.9%). Recurrence followed the cardinal (CL), uterosacral (USL), and pubocervical (PCL) directions in 58.8%, 35.3%, and 23.5% of cases, respectively. Only two intact PMT at diagnosis developed ipsilateral LF (1.1%, 2/181, CL only), while baseline ipsilateral PMT involvement with hydronephrosis was associated with ipsilateral LF (aOR 22.2, p<0.01, rate: 21.3%, 10/47, involving CL±PCL±USL), but not with contralateral LF (aOR 0.4, p=0.28).

Conclusion: In the non-operative setting, the lateral PMT is the second most involved anatomical compartment by LF (>60%) after the cervix (80%). An intact baseline PMT has low frequency (1%) and limited extension (CL only) of ipsilateral failure. In contrast, baseline hydronephrosis is strongly associated with extensive ipsilateral PMT relapse, requiring side-specific treatment intensification.