A NEW COMBINATION of radiotherapy, chemotherapy and immunotherapy could offer more rectal cancer patients the chance of a complete tumour response before surgery, recent research shows.
The phase II trial in China showed that the addition of tislelizumab to pre-surgery radiotherapy and chemotherapy regiments nearly doubled the rate of major tumour regression, and showed a similar, though not statistically significant, trend toward complete tumour response, without increasing serious side effects
Total neoadjuvant therapy, which combines radiotherapy and chemotherapy before surgery, is now standard practice for locally advanced rectal cancer. The method has been shown to improve outcomes over older approaches.
However, the proportion of patients whose tumours disappear entirely under the microscope after treatment, known as a pathological complete response, has remained stuck at around 30% across multiple studies.
Researchers have increasingly looked to immune checkpoint inhibitors to push that figure higher, building on evidence that radiotherapy and immunotherapy can work in tandem to produce a stronger anti-tumour effect than either alone.
Several recent trials have suggested that short-course radiotherapy in particular may pair well with these types of drugs.
For this study, 118 patients with locally advanced rectal cancer were randomised into two categories, to receive short-course radiotherapy followed by chemotherapy with or without tislelizumab, before undergoing surgery.
Among the 111 patients who began treatment, 45.3% of those in the immunotherapy group achieved a complete pathological response, compared with 27.6% in the chemotherapy-only group.
While this difference fell just short of statistical significance, a broader measure of strong tumour regression, known as major pathological response, was significantly higher with the addition of tislelizumab, at 50.9% versus 31.0%.
Among patients who completed the full treatment protocol, those who received the immunotherapy combination were also more likely to undergo sphincter-sparing surgery, preserving normal bowel function, and showed deeper tumour regression on pathology review.
Rates of severe side effects during treatment were comparable between the two groups, with anaemia the most common in both.
Mild thyroid-related side effects, a known consequence of immunotherapy, were more frequent in the combination group but were manageable. No cases of severe immune-related lung or pituitary toxicity were recorded, and postoperative complications were similar across both arms.
Early signs on longer-term outcomes were encouraging, with three-year progression-free survival and overall survival both numerically higher in the immunotherapy group, though neither difference reached statistical significance.
Researchers noted that with a median follow-up of just under three years, survival differences between the groups may not yet have had time to fully emerge.
Subgroup analysis suggested that certain patients, including those aged 60 or younger, those with higher PD-L1 expression, and those with more advanced local tumour features, may benefit most from the combination approach, echoing patterns seen in similar international trials.
The findings as preliminary evidence that adding immunotherapy to short-course radiotherapy-based neoadjuvant treatment can meaningfully improve tumour regression in locally advanced rectal cancer.
The scientists stipulate that a larger, multi-centre phase III trial would be needed before the approach could shift standard practice.
Reference
Fengpeng W et al. Short-Course Radiotherapy-Based Total Neoadjuvant Therapy plus Tislelizumab for Locally Advanced Rectal Cancer (Neo-STAR): Early Outcomes of a Randomized Phase II Trial. Cancer Commun. 2026. 46:0041.DOI:10.34133/canc
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