Preoperative Radiochemotherapy in Rectal Cancer: Is There an Impact of Oxaliplatin on Pathologic Complete Response and Survival Rates under “Real World“ Conditions?

Abstract

This study aimed to evaluate the benefit of additional administration of oxaliplatin during fluorouracil-based neoadjuvant radiochemotherapy (nRCT) in terms of pathologic complete remission (pCR), disease-free survival (DFS), and overall survival (OS) in patients with advanced rectal cancer. Between 2006 and 2021, 669 patients (pts) were diagnosed with locally advanced rectal cancer, of whom a total of 414 pts with nRCT were identified and included in the study. A total of 283 pts were treated by nRCT using concurrent chemotherapy with fluorouracil or capecitabine; 131 pts were treated using a combination of fluorouracil or capecitabine and oxaliplatin. Propensity score matching analyses (PSM) with 114 pts in each group were used to balance the patients’ characteristics. OS, DFS, pCR-rate, and potential prognostic factors were compared between the two groups. The median follow-up time was 59.5 weeks in the fluorouracil-group and 43 weeks in the fluorouracil/oxaliplatin group (p = 0.003). After PSM, the pCR-rate (including sustained clinical complete remission) was 27% (31/114 pts) in the fluorouracil/oxaliplatin group and 16% (18/114 pts) in the fluorouracil-group (p = 0.033). There was no difference between these two groups for both 10-year OS and DFS neither before nor after PSM, respectively (OS: 72.6% vs. 55.4%, p = 0.066, and 67.8% vs. 55.1%, p = 0.703, and DFS: 44.8% vs. 46.8%, p = 0.134, and 44.7% vs. 42.3%, p = 0.184). Multivariate analysis identified regression grading according to Dworak grade 4 (HR: 0.659; CI: 0.471–0.921; p = 0.015) and age over 60 years (HR: 2.231; CI: 1.245–4.001; p = 0.007) as independent predictors for OS. In conclusion, the addition of oxaliplatin to fluorouracil during nRCT significantly improved pCR-rate without having an impact on survival.

Recent advances in rectal cancer treatment – are we on the right track?

“…They should, based on present knowledge, obtain a combination of RT and chemotherapy, such as standard CRT (most patients have so far been treated with this) or a more intensified scheduled with higher radiation doses, addition of local RT [e.g. using brachytherapy ( 78 ) or contact therapy as in the OPERA trial ( 79 )], more intense chemotherapy than a fluoropyrimidine alone concomitant with the RT [although this has not markedly increased pCR-rates albeit seen in a meta-analysis ( 80 ), operated with a transanal local procedure rather than TME ( 60 ) or providing TNT (to be discussed below)]. In early stage tumours, chemotherapy alone followed by a local procedure has also resulted in favourable outcomes in small series ( 81 ).…”

Watch and Wait Approach for Rectal Cancer

“…Originally, the earliest experiences with cCR and W&W were derived from series using neoadjuvant chemoradiation (nCRT) with long-course radiation (RT) and concomitant 5FU-based chemotherapy [5]. While oxaliplatin has been associated with slightly higher pCR rates when used in combination with 5FU during RT, the significantly higher toxicity rates have limited its use in clinical practice [40,41]. As mentioned previously, response to treatment in rectal cancer after nCRT is a time-dependent phenomenon.…”