A new multicenter randomized phase II trial aims to compare two neoadjuvant treatment approaches for locally advanced rectal cancer (LARC). The SOLAR trial, published in BMC Cancer on September 4, 2023, will evaluate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared to traditional long-course chemoradiotherapy (CRT).
The study is set to take place across nine tertiary academic hospitals in South Korea. It is funded by the National R&D Program for Cancer Control through the National Cancer Center, which is supported by the Ministry of Health & Welfare of the Republic of Korea.
The primary purpose of the SOLAR trial is to investigate if SCRT followed by four cycles of FOLFOX chemotherapy can improve 3-year disease-free survival (DFS) compared to conventional CRT in patients with LARC. The study aims to enroll 364 patients with LARC, defined as cT3-4, cN+, or presence of extramural vascular invasion.
Inclusion criteria specify patients aged 20-75 years with histologically confirmed rectal adenocarcinoma located within 10 cm of the anal verge. Key exclusion criteria include stage I rectal cancer, distant metastases, and history of chemotherapy or radiotherapy within 6 months. Patients will be randomized 1:1 to either the experimental arm (SCRT plus mFOLFOX6) or control arm (CRT).
In the experimental arm, patients will receive SCRT (25 Gy in 5 fractions) followed by four cycles of mFOLFOX6 chemotherapy. The control arm will undergo conventional CRT with 45-50.4 Gy in 25-28 fractions concurrent with capecitabine or 5-fluorouracil. All patients will then undergo total mesorectal excision surgery followed by adjuvant chemotherapy.
The primary endpoint is 3-year DFS. Secondary endpoints include pathological complete response rate, R0 resection rate, surgical morbidity and mortality, treatment-related toxicity, quality of life measures, and cost-effectiveness analysis.
A key strength of this trial is the emphasis on surgical quality control. Only experienced colorectal surgeons who have completed fellowships and met minimum case volume criteria are participating. Unedited surgical videos will be reviewed by the steering committee to ensure standardization of technique.
As of July 2023, 182 patients have been recruited. The trial is ongoing and final results are eagerly anticipated. If positive, this study could potentially shift the standard of care for LARC towards a short-course radiotherapy approach followed by more intensive systemic therapy.
The authors note some limitations, including the lack of a non-operative management arm, which has gained interest recently for select patients achieving clinical complete response. However, they argue their protocol offers a practical alternative that balances concerns of overtreatment with TNT against missed treatment opportunities with watch-and-wait approaches.
In their discussion, the investigators highlight how this trial differs from other recent studies evaluating total neoadjuvant therapy (TNT) for LARC. The SOLAR trial focuses specifically on mid-to-low rectal tumors and utilizes four cycles of FOLFOX, which may offer improved tumor response compared to prior studies using fewer chemotherapy cycles.
The authors conclude that if SCRT followed by FOLFOX chemotherapy demonstrates superior DFS compared to CRT, it could provide several potential advantages. These include improved systemic control of micrometastases, a shorter overall treatment duration, enhanced patient convenience, and possible cost savings.
For clinicians, the results of this trial could impact how LARC is managed, potentially shifting practice towards short-course radiation followed by more intensive chemotherapy before surgery. The rigorous surgical quality control measures may also help set new standards for assessing and reporting surgical outcomes in rectal cancer trials.
Additionally, the planned cost-effectiveness analysis will provide valuable data to inform health economic considerations around different neoadjuvant approaches. This is particularly relevant given the increasing costs associated with cancer care.
While final results are still pending, the SOLAR trial represents an important contribution to the evolving landscape of LARC management. It addresses key questions about optimizing the sequence and intensity of multimodality therapy while maintaining a focus on surgical quality. The findings have the potential to refine treatment algorithms and improve outcomes for patients with this challenging disease.
References
Kang MK, Park SY, Park JS, et al. Preoperative sequential short-course radiation therapy and FOLFOX chemotherapy versus long-course chemoradiotherapy for locally advanced rectal cancer: a multicenter, randomized controlled trial (SOLAR trial). BMC Cancer. 2023;23(1):1059. Published 2023 Nov 3. doi:10.1186/s12885-023-11363-7
