The RAPIDO trial investigated a new treatment strategy for locally advanced rectal cancer (LARC), which is cancer that has grown through the rectal wall and may have spread to nearby lymph nodes or tissues but not to distant organs. The trial aimed to improve patient outcomes by exploring if an altered pre-surgical treatment sequence could reduce cancer recurrence or spread.
The Established Treatment Approach
Before the RAPIDO protocol, standard treatment for locally advanced rectal cancer involved a multi-step process. Patients typically underwent long-course chemoradiotherapy, combining radiation and chemotherapy over several weeks, usually five to six weeks. This preoperative treatment aimed to shrink the tumor and address microscopic spread in the pelvic area before surgery.
Following chemoradiotherapy, patients underwent total mesorectal excision (TME) surgery to remove the tumor and surrounding lymph nodes. After recovery, many also received adjuvant chemotherapy to further reduce recurrence risk. This entire sequence often extended for many months, sometimes lasting up to 44 weeks.
The RAPIDO Protocol Explained
The RAPIDO trial introduced an experimental treatment sequence that shifted the timing of systemic chemotherapy. This protocol began with short-course radiotherapy, delivering a higher dose of radiation over five days for a rapid anti-tumor effect.
After this, patients had a waiting period followed by several cycles of “consolidation” chemotherapy. This systemic chemotherapy, often regimens like CAPOX or FOLFOX4, was administered before surgery. The choice of chemotherapy regimen was determined by physician discretion or hospital policy. The key distinction of the RAPIDO protocol was moving the bulk of chemotherapy to the preoperative phase, aiming to address potential microscopic distant disease earlier.
Key Findings and Results
The RAPIDO trial enrolled 912 patients with a median follow-up of 4.6 years. At three years, the study found a significant reduction in “disease-related treatment failure” in the experimental group (23.7%) compared to the standard care group (30.4%). This difference, represented by a hazard ratio of 0.76, indicated a benefit for the experimental approach.
This reduction was primarily driven by lower rates of distant metastases, meaning cancer spreading to other organs. The probability of distant metastasis at three years was 19.8% in the RAPIDO group versus 26.6% in the standard group. The RAPIDO protocol also led to a higher rate of “pathological complete response” (pCR), defined as the complete absence of cancer cells in surgical tissue, observed in 27.7% of experimental patients versus 13.8% in the standard arm. While the experimental arm showed a higher rate of locoregional recurrence (10% vs 6%), the overall reduction in disease-related treatment failure and distant metastases was maintained.
Side effects of grade 3 or higher toxicity were comparable. Diarrhea was a common side effect during preoperative therapy, occurring in 18% of the experimental group and 9% of the standard group. Neurotoxicity, particularly grades 1-2, was more frequently observed in the experimental arm and in standard arm patients who received adjuvant chemotherapy. The trial found no significant differences in surgical complications between the two treatment approaches.
Clinical Significance for Patients
The RAPIDO trial findings have significantly shifted how locally advanced rectal cancer is treated. The trial demonstrated that moving systemic chemotherapy to before surgery effectively reduces the risk of cancer spreading to distant parts of the body. This is a major improvement, as distant spread is a primary concern and a leading cause of treatment failure.
The increased rate of pathological complete response also means more patients may achieve complete cancer eradication in the rectum before surgery. This outcome can potentially open doors for organ preservation strategies in some patients. The RAPIDO approach offers a new option oncologists now consider for eligible patients, particularly those with high-risk features on imaging, aiming to improve long-term survival and overall outcomes for individuals diagnosed with locally advanced rectal cancer.