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Prolonging the interval between short course radiotherapy (SCRT) and total mesorectal excision (TME) for rectal cancer increases tumor downsizing and the probability of organ-preservation. A prolonged interval has been reported to decrease postoperative complications compared to immediate surgery. It might however increase radiation-induced toxicity. This study systematically evaluated patient-reported bowel dysfunction and physician-reported radiation toxicity during a prolonged interval between SCRT and TME for rectal cancer.

Consecutive patients treated with SCRT and prolonged interval (> 4 weeks) to TME for intermediate risk rectal cancer (T1-3(MRF-)N1M0 or T3(MRF-)N0M0), locally advanced rectal cancer (LARC; T3-4(CRM+)N0-2M0 or T1-4N2M0) and contra-indication for chemoradiation, or M1 rectal cancer were included. Repeated measurements of patient-reported bowel dysfunction (measured by the low anterior resection syndrome (LARS)-score) and physician-reported toxicity (diarrhea, fatigue, cystitis non-infective, dermatitis and urine-incontinence according to CTCAE) were done before start of SCRT (baseline), at completion of SCRT and (bi-)weekly until TME or 8 weeks after completion of SCRT.

Fifty-one patients were included, of whom 31 (61%) were male and the median age was 67 (range: 44-91). The indication for SCRT with prolonged interval to TME was intermediate risk in 32 (63%), LARC in 5 (10%) and M1 in 14 (28%) patients. Median interval to TME was 68 days (IQR 52-93).

Both patient-reported bowel dysfunction and physician-reported radiation toxicity peaked at week 1-2 after completion of SCRT and gradually declined thereafter. Thirty-seven (79%) patients self-reported major bowel dysfunction at week 2 after completion of SCRT, declining to 8 (25%) patients at week 8. Physicians reported diarrhea grade 1-3 in 35 (74%) patients at week 2 (of whom 11 (23%) grade 3), declining to 9 (27%) grade 1-2 at week 8. One patient had his TME scheduled earlier due to persisting grade 3 diarrhea. Physicians reported fatigue grade 1-2 in 30 (64%) patients at week 2, cystitis grade 1-2 in 19 (43%) patients at week 1, dermatitis grade 1 in 8 (18%) patients at week 1 and urine-incontinence grade 1 in 2 (7%) patients at baseline.

No grade 4-5 radiation toxicity occurred during a prolonged interval between SCRT and TME for rectal cancer. Patient-reported major bowel dysfunction and physician-reported grade 1-3 diarrhea, grade 1-2 fatigue, grade 1 cystitis and grade 1 dermatitis were prevalent during 1-2 weeks after SCRT and gradually restored thereafter. Patients reported major bowel dysfunction with a higher incidence than physicians reported diarrhea.