Long-course chemoradiotherapy resulted in superior 12-month total mesorectal excision–free survival compared with short-course radiotherapy in the STAR-TREC trial. The interim analysis, led by Simon P. Bach, FRCS, and colleagues and published in The Lancet Oncology, included patients pursuing organ preservation for early- and intermediate-stage rectal cancer. At 12 months, 78.5% of patients treated with long-course chemoradiotherapy remained free of total mesorectal excision compared with 60.6% of those receiving short-course radiotherapy.
Total mesorectal excision (TME) remains the standard treatment for most patients with early- and intermediate-stage rectal cancer and can provide what the investigators described as “excellent local control,” but can also result in stoma formation, long-term bowel dysfunction, and reduced quality of life.
According to the investigators, STAR-TREC is the first randomized trial to directly compare long-course chemoradiotherapy and short-course radiotherapy as organ preservation strategies in this setting, and the first international trial to use a standardized, response-adapted framework.
Study Details
STAR-TREC is an international, multicenter, open-label, randomized phase II/III trial conducted at 37 hospitals in the United Kingdom, the Netherlands, Sweden, Denmark, and Belgium. Eligible patients had magnetic resonance imaging–staged T1 to T3b, node-negative rectal adenocarcinoma measuring no more than 40 mm and an Eastern Cooperative Oncology Group performance status of 0 or 1.
In phase II of the study, patients were randomly assigned to undergo long-course chemoradiotherapy–based organ preservation (LCCRT-OP), short-course radiotherapy–based organ preservation (SCRT-OP), or primary TME. In phase III, patients could choose organ preservation or TME, with those choosing organ preservation randomly assigned to LCCRT-OP or SCRT-OP.
LCCRT consisted of 50 Gy in 25 fractions plus oral capecitabine, whereas SCRT consisted of 25 Gy in 5 fractions. Treatment response determined whether patients entered nonoperative surveillance, underwent selective transanal local excision, or proceeded to TME.
The current interim analysis included 409 treated patients recruited before August 8, 2023: 163 assigned to LCCRT-OP, 168 to SCRT-OP, and 78 to primary TME. The prespecified phase III primary endpoint is successful organ preservation at 30 months, defined as the absence of TME, stoma, or local recurrence; that endpoint has not yet been reported.
Key Findings
At 12 months, estimated TME-free survival was 78.5% with LCCRT-OP compared with 60.6% with SCRT-OP (hazard ratio = 1.90); the probability that LCCRT-OP was superior exceeded 99.5%.
Clinical complete response was more frequent with LCCRT-OP than SCRT-OP (64% vs 36%), and fewer patients converted to TME before surveillance (17% vs 33%). Nonoperative management occurred in 57% vs 32%, respectively, whereas transanal local excision was required less often with LCCRT-OP (20% vs 31%).
No notable differences between strategies were observed at 12 months in pelvic tumor control, metastasis-free survival, disease-free survival, or overall survival.
Grade 3 or worse serious adverse events over 12 months were reported in 8% of patients allocated to organ preservation compared with 19% of those allocated to primary TME. One patient in the primary TME group died following an anastomotic leak; this was the only death during the 12-month reporting period.
Quality-of-life measures were generally stable through 12 months, and among patients without a stoma, bowel function was reported to be better with organ preservation than with TME.
The investigators cautioned that the current analysis is intentionally short term and cannot establish durable organ preservation or long-term oncologic safety. In addition, the phase III switch to a partially randomized patient-preference design introduced potential selection bias in comparisons with primary TME.
“These early results support a response-adapted organ-preservation approach, with LCCRT appearing more effective than SCRT at 12 months,” the investigators concluded. Longer follow-up will determine whether these early advantages translate into durable organ preservation without compromising oncologic safety.
Simon P. Bach, FRCS, of University College London, is the corresponding author of the article.
DISCLOSURE: The study was funded by Cancer Research UK, Stand Up to Cancer, the Dutch Cancer Society, the Danish Cancer Society, Kom Op Tegen Kanker, Cancerfonden, ALF Region Stockholm, and RCC Region Stockholm. Dr. Bach reported institutional funding from Cancer Research UK and Stand Up to Cancer for the current study and from Intuitive Surgical Sarl for unrelated work. Other authors reported relationships with industry and research organizations. For full disclosures of the study authors, visit thelancet.com.
