Role of Intensification of Neoadjuvant Treatment of Patients with Locally Expanded Rectal Cancer
Authors: Polynovskiy A. , Kuz'michev D. , Mamedli Z. , Tkachev Sergey , Chernich M. , Suraeva Yu. , Madyarov J. , Aniskin A. , Kolobanov E. 
Published: November 2021

Purpose: To improve the effectiveness of treatment of patients with locally advanced rectal cancer (LARC) stage T3(MRF+)-4N0-2M0 by developing a new strategy of therapy.

Material and methods: The study included 414 patients with LARC. Control group I included 89 patients who underwent neoadjuvant CRT 52–56 Gy with capecitabine. Control group II included 160 patients, underwent neoadjuvant CRT 52–56 Gy with capecitabine and oxaliplatin once a week, during the course of RT. Study group III - 165 patients. This group combined neoadjuvant CRT 52–56 Gy with capecitabine and additional consecutive courses of chemotherapy (CT) in the CapOx mode. This group, depending on the variant of chemotherapy, was divided into 2 subgroups: subgroup IIIa included 106 patients with consolidating CT (after CRT); subgroup IIIb included 59 patients who underwent "sandwich" treatment. Therapy consists of conducting 1 or 2 courses of induction CT (up to CRT) in the CapOx mode and 1 or 2 courses of consolidating CT in the CapOx mode with an interval of 7 days. In the interval between the courses of drug therapy, prolonged CRT was performed. According to the results of the control examination, further treatment tactics were determined.

Results: IComplete therapeutic pathomorphosis in the tumor was significantly more frequently registered in patients in the study group III (17.5 %; p=0.021) compared to the control groups: in I – 8.0 % and II – 8.3 %. In total, relapses in the study were registered in 34 (8.3 %) of 410 patients. A comparative analysis of patients in the control groups (I and II) of treatment did not determine significant differences in the development of relapses (11.4 % vs. 10.8 %, respectively; p=0.884). When analyzing the subgroups (IIIa and IIIb) of the study group, there were also no significant differences in the development of relapses (4.8 % vs. 3.4 %; p=0.676). In the present study, long-term metastases at various times after treatment were diagnosed in 100 (24.4 %) of 410 patients. All metastases occurred at a median follow-up of 20.9 months (4 to 46 months). Metastases were significantly less frequent in patients in group III (18.3 %) compared to group I (31.8 %; p=0.015) and II (26.6 %; p=0.037). There were no significant differences between patients in group I and II (p=0.382). The analysis of the treatment subgroups of the study group (IIIa and IIIb) did not determine significant differences in the development of metastases (19.1 % vs. 17.0 %; p=0.456). The overall five-year survival rate in patients in group III was 90.5 %, in group I – 71.8% and in group II – 78.3%. Five-year relapse-free survival in patients in the study groups was: III – 71.5%, I – 56.9% and II – 65.6%, respectively.

Conclusion: The shift in the focus on strengthening the neoadjuvant effect on the tumor and the improvement of approaches to drug therapy regimens allowed to significantly increase the relapse-free survival in this category of patients.