Clinical-Pathologic Response Discordance After Neoadjuvant Therapy in Rectal Cancer and Its Prognostic Implications

The prognostic value of clinical complete/near-complete response (cCR/near-cCR) relative to pathologic complete/near-complete response (pCR/near-pCR) after neoadjuvant therapy for locally advanced rectal cancer (LARC) remains incompletely defined.

We retrospectively analyzed 180 non-metastatic LARC patients treated with total neoadjuvant therapy (TNT) or standard neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision. Agreement between cCR/near-cCR and pCR/near-pCR was assessed using Cohen's κ, and associations with survival outcomes were evaluated using Kaplan-Meier and Cox models.

Preoperative cCR/near-cCR was observed in 89 patients (49.4%), whereas pCR/near-pCR occurred in 63 (35.0%), with moderate concordance (κ = 0.53, p < 0.001). Discordance between clinical and pathologic response classification was observed in 42 patients (23.3%). Compared with patients who achieved pCR/near-pCR, those without pCR/near-pCR had inferior 5-year distant metastasis-free survival (DMFS) (66.7% vs. 87.3%; hazard ratio [HR] 2.98, 95% confidence interval [CI] 1.44-6.09; p = 0.003) and locoregional recurrence-free survival (LRFS) (81.0% vs. 95.0%; HR 4.32, 95% CI 1.28-12.23; p = 0.02), while Overall survival (OS) did not differ significantly between groups (63.8% vs. 78.4%; HR 1.42, 95% CI 0.75-3.11; p = 0.06). cCR/near-cCR was associated with improved DMFS on univariable analysis; however, this association was attenuated after multivariable adjustment and did not remain independently significant. Prognostic separation by response was more pronounced in the TNT cohort. Among patients with pCR/near-pCR, baseline biopsy-derived lymphovascular invasion/perineural invasion was associated with numerically poorer outcomes, although these differences were not statistically significant.

pCR/near-pCR provides more consistent prognostic discrimination than cCR/near-cCR, and clinically relevant discordance persists in routine practice. Integrating baseline tumor biology with response assessment may refine post-treatment risk stratification, particularly after TNT.

Not applicable. This study is a retrospective observational study and does not require trial registration.