Short-Course Radiation May Be Feasible in Older Rectal Cancer Population

"...SCRT represents a valuable tool in the treatment armamentarium for older patients with LARC," according to the study authors.

Short-course radiotherapy (SCRT) may provide a viable alternative to standard long-term radiation among older patients with locally advanced rectal cancer (LARC) who are unsuitable to receive chemotherapy, according to findings from the SOFT study (Protocol number 20240025859) published in Radiotherapy and Oncology.1

Data showed an objective response rate (ORR) of 61.7% (95% CI, 53.2%-69.8%), with 7.1% (95% CI, 3.5%-12.7%) experiencing a clinical complete response (CR) and 54.6% (95% CI, 46.0%-53.0%) achieving a partial response (PR). Investigators noted a disease control rate (DCR) of 96.4% (95% CI, 91.9%-98.8%).

A pathological CR (pCR) occurred in 5.7% of patients, with 56.9% having a histological specimen demonstrating a downstaging of their disease. Investigators highlighted an R0 resection rate of 93.6%.

The study treatment produced a median relapse-free survival (RFS) of 31.5 months (95% CI, 16.0-46.9), a median overall survival (OS) of 40.5 months (95% CI, 31.0-49.9), and a median cancer-specific survival (CSS) of 41.5 months (95% CI, 31.3-51.7). Overall, 21 patients died during the observation period, including 9.9% due to tumor-related causes and 5.0% due to other causes. The OS rates were 78% at 1 year, 50% at 2 years, 30% at 3 years, and 5% at 5 years.

“Although our study included only [patients] who had undergone surgery, a sample that is not necessarily representative of overall cases, SCRT appears to be an effective and feasible alternative for older patients, particularly those with comorbidities who may find prolonged treatment regimens challenging, providing similar oncological outcomes to long-course therapy with the added benefits of reduced treatment time and better tolerability,” lead study author Gerardo Rosati, from the Medical Oncology Unit of S. Carlo Hospital in Potenza, Italy, wrote with coauthors in the publication.1 “Further studies, particularly randomized controlled trials with longer follow-up periods, are needed to assess the long-term safety and efficacy of SCRT in this demographic. Nonetheless, SCRT represents a valuable tool in the treatment armamentarium for older patients with LARC.”

The study authors noted that SCRT has appeared as a potential strategy that may provide a condensed treatment regimen minimizing the burden of prolonged therapy among older patients with LARC, although the modality raised questions based on conflicting data in the literature.2 Investigators retrospectively assessed 141 older patients with LARC who were unsuitable to receive chemotherapy and assigned to undergo SCRT followed by delayed surgery across 11 Italian treatment centers. Radiotherapy included a total of 25 Gy across 5 daily fractions of 5 Gy each.

The study’s primary end points were the safety and efficacy of SCRT in this LARC population. Efficacy end points included ORR and downstaging of disease after completing radiotherapy, while safety outcomes included the incidence and severity of adverse effects. Secondary end points included the pCR rate, R0 resection rate, RFS, CSS, and OS.

Patients with histologically confirmed adenocarcinoma of the rectum within 12 cm of the anal verge, resectable T3 or T4 disease without lymph node involvement, and no susceptibility to chemotherapy were eligible for inclusion. Eligible patients also needed to have an ECOG performance status of 0 to 2.

The median patient age was 79 years, and most were 70 to 80 years old (54.6%) and male (60.2%). A majority of the population had an ECOG performance status of 1 (50.3%), differentiated disease (80.1%), stage III disease (68.8), and surgery via low anterior resection (73.7%).

Complications occurred in 23.4% of patients, with 8.5% experiencing anastomosis dehiscence, 5.7% developing an abdominal infection, 3.5% having problems with healing wounds, 2.8% experiencing bleeding, and 2.8% having intestinal sub-occlusions. Deaths following surgery occurred in 2.8% of patients, including 3 from sepsis and 1 due to hydronephrosis and renal failure.

References

1. Rosati G, De Stefano A, Restivo A, et al. Short-course radiotherapy for older patients with locally advanced rectal cancer and unfit for chemotherapy: the SOFT study. Radiotherapy and Oncology. 2026;214:111218. doi:10.1016/j.radonc.2025.111218
2. Donnelly SM, Wyatt J, Powell SG, Jones N, Altaf K, Ahmed S. What is the optimal timing of surgery after short-course radiotherapy for rectal cancer? Surg Oncol. 2023;51:101992. doi:10.1016/j.suronc.2023.101992.