P304 - Effect of Interval between Neoadjuvant Radiotherapy and Surgery on circumferential resection margin positivity and survival in low Rectal Cancer.

Purpose/Background: With growing enthusiasm for organ preservation and use of SCRT owing to logistic reasons, the TNT approach followed by surgery has risen leading to increase in the interval between end of RT to surgery.

Recent trials show that delay in surgery is associated with higher rate of mesorectal breach and CRM positivity, leading to higher loco-regional recurrence.

Methods/Interventions: Aim- To look for association between the duration of gap between end of RT to surgery with CRM positivity rate and survival

Primary end point- CRM positivity rate

Secondary end point- TRG, LRR, DFS and OS

Study design - Retrospective analysis from Jan 2019 to Dec 2023 at Tata Memorial hospital

Inclusion criteria-Low rectal cancers < 5 cm from AV with NACRT f/b surgery as treatment plan

Exclusion criteria- Upfront surgery, Other histology, M1

Study groups- Patients were categorized into three groups based on gap between RT and surgery

< 12, 12-24 and >24 weeks from end of RT to surgery

Statistical analysis - Propensity matching 1:1:1 to look for association between groups.

KM and log rank for survival.

Results/Outcomes: The baseline characteristics of patients were equally distributed among the three groups. In the matched analysis, the proportion of patients having CRM positivity on final HPR was 8% in >24 week category with RR 2.09 (95% CI 0.60-7.2; p 0.241). Risk of locoregional recurrence was greater in >24 week category i.e 38 %, RR 4.8 (95% CI 1.02-23; p 0.047).

A tumour regression grade score of 4/5 was higher in > 24 week category with RR of 3.9 (CI 2.01-7.7; p < 0.05)

When comparing surgical morbidity, the Clavien-dindo grades did not show significant variation across all groups, but blood loss was higher in patients undergoing delayed surgery implying technical difficulty.

On comparison of survival analysis, the 5yr DFS was 60% in > 24 week group vs 70% in < 12 weeks with HR of 1.54 (95% CI 1.00-2.35; p 0.045), although distant metastasis in these patients was low HR 0.67 ( CI 0.31-1.47; p 0.32)

OS showed similar trends 73% vs 79%, HR 1.42 (95% CI 0.82-2.46; p 0.204)

Conclusion/Discussion: In GRECCAR 6 trial, extending the interval to 11 weeks was found to have higher pelvic fibrosis and difficult dissection. This may explain higher rate of loco-regional recurrence (LRR) in the experimental arm of the RAPIDO trial with an intraoperative breach of the mesorectum of 11%.

In our study also the CRM positivity rate was more with increase in gap from RT with 2 times higher risk compared to patients who underwent standard therapeutic approach. LRR was also found to be higher although distant metastasis was lower in the >24 week category. Even though the incidence of distant metastasis was low in these patients, overall DFS was poor.

In the PRODIGE 23 protocol, where neo-adjuvant chemotherapy was given first, this trend of increased LRR has not been observed and with good TME quality.

Limitations of this study - The overall number of CRM positive patients was low, which may be credited to the surgical expertise at our high volume centre. Second, this is a retrospective analysis.

Conclusion- Increase in gap between RT and surgery seems to have an adverse outcome with regard to TME quality and may increase the risk of loco-regional failure (LRF). But distant metastasis is the most common cause of failure and shifting chemotherapy to earlier in the treatment sequence might improve distant metastases control without increasing the likelihood of locoregional failure.

BASELINE CHARACTERISTICS
Table shows the study population was equally distributed across all 3 groups with age, sex, clinical tumour (cT) and clinical node (cN) status. Standard mean difference (SMD) was used to analyse and propensity matching done 1:1:1
SURVIVAL CURVES
The left side shows the Kaplan Meir curve for DFS, 5 yr DFS in <12 week, 12-24 and > 24 weeks being 70%, 64% and 60%.

The right side shows Kaplan Meir curve for OS, 5 yr OS in 3 groups being 79%, 75% and 73 % respectively