Every patient enrolled in a groundbreaking rectal cancer trial has remained disease-free for more than three years after receiving immunotherapy alone, with none requiring surgery, radiation, or chemotherapy. The results, from a Memorial Sloan Kettering Cancer Center study led by oncologist Andrea Cercek, were registered as trial NCT04165772 and published in the New England Journal of Medicine. As of May 2026, the findings remain the most striking example of immunotherapy replacing conventional cancer treatment entirely.
What the trial showed and who it helps
The drug is dostarlimab, sold under the brand name Jemperli. It belongs to a class of treatments called immune checkpoint inhibitors, which work by removing molecular brakes that prevent the immune system from attacking cancer cells. In this phase 2 trial, patients with locally advanced rectal cancer received dostarlimab infusions every three weeks for six months. No chemotherapy. No radiation. No surgery. Those conventional treatments were held in reserve, available immediately if the immunotherapy failed to eliminate the tumor.
It never failed. Every patient in the study achieved what oncologists call a complete clinical response, meaning scans, endoscopy, and physical examination found no remaining cancer. Updated data presented by Cercek at the 2024 American Society of Clinical Oncology annual meeting (Abstract LBA1) confirmed that the responses held at a median follow-up exceeding three years. No patient experienced disease progression. No cancer-related deaths occurred. A peer-reviewed account of the outcomes, published in the New England Journal of Medicine (DOI: 10.1056/NEJMoa2404512), detailed the imaging protocols, response criteria, and safety data behind those numbers.
“We are seeing something that has never happened before in the history of cancer,” Cercek told reporters after the ASCO presentation. For patients facing the prospect of permanent colostomy bags and years of rehabilitation, the results carry a weight that statistics alone cannot capture. One participant, speaking publicly after completing the six-month course, described the experience as “getting my life handed back to me” after bracing for surgery that never came.
The patients who qualified share a specific molecular trait: mismatch repair deficiency, or dMMR. In healthy cells, mismatch repair genes act as proofreaders, catching and correcting errors during DNA replication. When those genes stop working, errors pile up, and the resulting tumors carry an unusually heavy load of mutations. That mutation burden, counterintuitively, makes the cancer more visible to the immune system and far more vulnerable to checkpoint inhibitors. The National Cancer Institute defines mismatch repair deficiency as a loss of the cell’s ability to fix certain DNA copying mistakes. Roughly 5 to 10 percent of rectal cancers carry this feature, meaning the trial’s approach applies to a meaningful but limited slice of patients.
Why organ-sparing matters for rectal cancer patients
Standard treatment for locally advanced rectal cancer is punishing. It typically involves weeks of combined chemotherapy and radiation, followed by major surgery to remove part or all of the rectum. For many patients, that surgery means a permanent colostomy bag. Even when surgeons can reconnect the bowel, the aftermath often includes chronic urgency, fecal incontinence, sexual dysfunction, and nerve damage. For younger patients, the consequences can stretch across decades, affecting fertility, careers, and relationships.
“When you tell a 30-year-old they may need a permanent bag, the conversation changes completely,” said Julio Garcia-Aguilar, chief of the colorectal surgery service at Memorial Sloan Kettering and a collaborator on the trial. “This study shows that for the right patients, we may be able to avoid that entirely.”
The dostarlimab trial offered a fundamentally different sequence. By leading with immunotherapy and holding surgery as a fallback, the study tested whether the immune system could do the work alone. In every case, it could. Each participant was spared radiation’s tissue damage and the life-altering reality of rectal surgery. The protocol’s built-in safety net meant no one was denied proven treatment if immunotherapy fell short. Instead, the trial inverted the traditional order, treating surgery as a backup rather than the default first step.
An editorial by Thierry Andre and Julien Taieb, published in April 2025 in Nature Reviews Clinical Oncology, called the durability of these results a key milestone. The authors noted that multi-year disease-free status across an entire treated cohort is an outcome rarely seen in oncology, especially when therapy is limited to a finite six-month course. The editorial distinguished this study from earlier immunotherapy experiments in gastrointestinal cancers, where responses were often partial and organ preservation inconsistent.
What remains uncertain
The trial enrolled roughly 30 patients, all treated at a single elite cancer center, all carrying the dMMR molecular profile. That is a small, highly selected group. Patients whose tumors are mismatch repair proficient, which accounts for the vast majority of rectal cancers, would not be expected to respond the same way based on prior immunotherapy research across colorectal and other solid tumors. The study’s remarkable success rate cannot be projected onto most people diagnosed with rectal cancer.
The single-arm design is another limitation. Without a comparison group receiving standard chemoradiation, it is impossible to quantify the precise advantage of immunotherapy in a head-to-head setting. Historical data show that many patients treated with conventional therapy still experience recurrences or lasting complications, but only a randomized trial could definitively prove that dostarlimab-first treatment improves survival, quality of life, or both.
Follow-up, while encouraging past three years, has not yet reached the five-year mark built into the trial protocol. Late recurrences in rectal cancer are not unheard of, particularly when patients are managed without surgery. The oncology community will need longer observation before these responses can be called permanent cures. Detailed event-free survival curves and patient-level data from the ASCO presentation have not been made publicly available in granular form, which limits independent analysis of subgroup outcomes or biomarker correlations.
Access and cost present practical hurdles. Dostarlimab carries a list price exceeding $11,000 per dose in the United States, and a six-month course involves multiple infusions. The drug already holds regulatory approval for certain other cancer indications, but as of early 2026, no specific approval pathway for this rectal cancer use has been publicly outlined by the U.S. Food and Drug Administration. Whether regulators pursue accelerated approval based on response rates or require larger confirmatory studies remains an open question. Until that process concludes, the regimen is investigational for rectal cancer, and access outside clinical trials depends on institutional policies and off-label prescribing decisions.
Why molecular testing at diagnosis now matters more than ever
Cercek and her colleagues at Memorial Sloan Kettering continue to follow the original cohort as the study approaches its five-year observation window. Meanwhile, other cancer centers have begun enrolling patients in similar immunotherapy-first protocols for dMMR rectal cancer, which will test whether the results hold outside a single institution and across more diverse patient populations. Larger, randomized trials comparing immunotherapy-first strategies against standard chemoradiation are in planning or early enrollment stages.
For patients newly diagnosed with rectal cancer, the immediate practical step is molecular testing. Identifying whether a tumor is mismatch repair deficient should now be considered essential, not optional, because it determines eligibility for a treatment approach that has so far spared every recipient from surgery. Oncologists increasingly recommend universal dMMR screening at diagnosis, a position supported by guidelines from the National Comprehensive Cancer Network.
The broader significance extends beyond rectal cancer. The trial is among the clearest demonstrations that immunotherapy, guided by precise molecular selection, can sometimes replace surgery and radiation entirely. That principle is being tested in bladder cancer, esophageal cancer, and other tumor types where organ preservation would dramatically improve patients’ lives. If the dostarlimab results hold at five years and replicate in larger studies, they will mark a turning point not just for rectal cancer care but for how oncology thinks about the sequence and necessity of its most invasive tools.
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*This article was researched with the help of AI, with human editors creating the final content.
