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


Erken A. A., Dincer S. T.

Asia-Pacific Journal of Clinical Oncology, 2026 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1111/ajco.70119
  • Dergi Adı: Asia-Pacific Journal of Clinical Oncology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE, Academic Search Ultimate (EBSCO), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest)
  • Anahtar Kelimeler: complete or near-complete response, lymphovascular invasion, perineural invasion, rectal cancer, total neoadjuvant therapy, tumor regression grade
  • Sağlık Bilimleri Üniversitesi Adresli: Evet

Özet

Aims: 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. Methods: 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. Results: 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. Conclusion: 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. Trial Registration: Not applicable. This study is a retrospective observational study and does not require trial registration.