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Survival outcomes and prognostic factors in high risk locally advanced rectal cancers (LARC) undergoing concurrent capecitabine and long course radiation (Cape – RT) – results of a large cohort study
Chemoradiation with Cape – RT is the standard of care in patients with LARC, though total neoadjuvant therapy might improve survival outcomes. Establishing baseline outcomes with Cape – RT in the Indian scenario is important before shifting treatment patterns. Chemoradiation with Cape – RT is the standard of care in patients with LARC, though total neoadjuvant therapy might improve survival outcomes. Establishing baseline outcomes with Cape – RT in the Indian scenario is important before shifting treatment patterns.
Treatment naïve patients with adenocarcinoma on histology and clinico-radiologically diagnosed LARC who received Cape-RT from June 2014 to December 2021 were evaluated for inclusion in the study. Patients received long course conventionally fractionated external beam radiotherapy with concurrent oral Capecitabine at a dose of 1250 mg/m2/day. Post approximately 6-8 weeks of completion of Cape – RT, patients were evaluated clinically and by MRI pelvis for total mesorectal excision (TME) in the multidisciplinary team meetings. The primary endpoint of the study was event free survival (EFS), calculated from diagnosis of LARC to the date of recurrence, disease progression, loss to follow-up or death, whichever was earlier. EFS and overall survival (OS) was calculated by Kaplan Meier method.
A total of 1197 patients with a median age of 49 years (range: 15-95) were included in the study. A significant proportion of patients had high risk characteristics like T3/T4 disease (94%), node positivity (90%) and involved circumferential margin (CRM) (51%) at baseline. Signet ring histology and mucinous histology were seen in 13% and 11% of patients. Two hundred and eighty patients (23%) required further consolidation chemotherapy (commonly CAPOX or modified FOLFIRINOX) post Cape – RT prior to attempting surgery, with the most common reasons for chemotherapy administration being persistent CRM positivity (239 patients, 85%; n=280) and interim chemotherapy due to delayed surgery (30 patients, 11%; n=280). Post Cape – RT, with or without chemotherapy, 939 patients (78%) underwent TME. Chemotherapy post TME was administered in 805 patients (78%). With a median follow-up of 54 months (range:51.2-57.2), the 3-year and 5-year EFS for the entire cohort was 73.2% (95% CI: 70.6-75.8) and 64.3% (95%CI: 61.1-67.5), respectively, while estimated 3-year and 5-year OS was 81.3% (95%CI: 78.9-83.7) and 73% (95% CI: 70-76) respectively. On Multivariate analysis of significant factors, presence of CRM positivity (p=0.012), extramesorectal nodes (p < 0.001) and signet ring histology (p < 0.001) predicted for inferior EFS in this cohort, while the receipt of adjuvant chemotherapy did not correlate with EFS (p=0.15).
In this large cohort study of locally advanced rectal adenocarcinomas with predominantly high-risk unfavourable characteristics like T3/T4 status, extramesorectal nodal involvement, CRM positivity and signet ring histology, concurrent chemoradiation and an increased use of induction chemotherapy resulted in favorable survival outcomes.
OIEC/4116/2023/00002.
The authors.
Has not received any funding.
V. Ostwal: Advisory / Consultancy: AstraZeneca ; Research grant / Funding (institution): Dr. Reddy's Lab Pvt limited, Zydus Cadilla Pvt Ltd; Travel / Accommodation / Expenses: AstraZeneca . P. Bhargava: Honoraria (Institution): Pfizer Ltd, Novartis Ltd, Intas Ltd; Advisory / Consultancy: Glenmark pharmaceutical Ltd; Research grant / Funding (institution): Dr. Reddy laboratory Pvt Ltd., Cadila health care pvt Ltd., Shilpa Medicare Pvt Ltd. All other authors have declared no conflicts of interest.
