Long-term outcomes of total neoadjuvant treatment (TNT) for locally advanced rectal cancer: Maria Sklodowska Curie National Cancer Research Institute (MSCNCRI) cohort from Polish-II study.

84 Background: The data on long-term outcomes of TNT for locally advanced rectal cancer are still limited. The Polish-II study randomized 515 cT4/fixed cT3 rectal cancer to pre-operative chemoradiation (CRT) with 5fu/oxaliplatin or 5x5 Gy radiotherapy with consolidating chemotherapy (TNT). Despite the early separation of survival curves with benefit for TNT, the outcomes at the longer observation were similar reaching 49% in both arms surviving at 8 years. Here, we present the long-term oncological and functional outcomes of patients recruited to the study in MSCNCRI along with the quality of life in survivors at >10 years of observation. Methods: Of 180 patients treated in the study in MSCNCRI 88 and 92 pts were randomized to TNT and CRT arms, respectively. The long-term follow-up was performed according to the standard protocol, FACT-C and EORTC QLQ-C30 scales were used to assess the functional outcomes. Results: Median survival in the TNT group and CRT was 115 and 61 months (p=0.191). At the cut-off in March 2023, 53.4% and 61.1% of pts died in the TNT and CRT group (p = 0.375). In the TNT group, 73.9% of deaths were attributed to cancer corresponding to 81.8% in CRT (p = 0.725). Late relapses diagnosed over 5 years from the end of the active treatment were identified in 5 of 94 patients in the follow-up (1 local recurrence in the TNT group, 4 patients with lung metastasis – 3 in TNT with one having also CNS relapse - and 1 in CRT). All late relapses in the TNT group could be salvaged with local therapies. Regarding long-term quality of life, no differences were observed in FACT-C and EORTC QLQ C30 in patients treated with either arm: QLQ C30 – TNT: 50.68 ± 12.74 in the range 34.00- 79.00; CRT: 48.61 ± 11.39 in the range 34.00-70.00 (p = 0.507); FACT-C - TNT: 113.00 in the range 42.00-136.00; CRT: 118.00 in the range 74.00-136.00; p=0.252). No difference in physical, family, and emotional status was observed. At the ultimate observation, stoma was present in 40.5% and 40.6% of TNT and CRT groups, respectively (p>0.999). Conclusions: In this randomized cohort, after more than 10 years of observation TNT led to numerically longer OS than CRT, although this was not statistically significant. The functional outcomes of the long-term survivors are similar in both cohorts. Late relapses are rare but could be salvaged in most cases. This study further supports the use of TNT in patients with locally advanced rectal cancer. Clinical trial information: NCT00833131 .