Some patient cases stay with you—both for their complexity and for the way they challenge your thinking as a clinician. I recently found myself reflecting on one such case after reading a fascinating new study published in the New England Journal of Medicine (April 2025… yes I know.. Im just catching up) on immune therapy for mismatch repair-deficient (dMMR) and microsatellite instability-high (MSI-H) tumors.
A Memorable Case of MSI-High Cancer in a Unique Setting
Some time ago, I cared for a patient with a particularly unusual medical history. This individual had suffered a chemical injury to the esophagus decades earlier and underwent a colonic interposition procedure—a complex surgery where a section of colon is used to reconstruct the esophagus. Years later, the patient began experiencing obstructive dysphagia symptoms. An endoscopy revealed something striking: a colon-type adenocarcinoma had developed within the colonic interposition segment, now serving as the esophagus.
Initially, there was discussion around the traditional treatment algorithm: chemotherapy and/or chemoradiation followed by surgery. If MSS, I had favored Total Neoadjuvant Approach along the lines of what we do in the rectal space and hoped perhaps we can consider a nonoperative approach if he had a complete response.
Further testing revealed that this tumor was MSI-High—a key molecular finding that immediately changed the treatment conversation. Given the tumor’s MSI-High status, immune checkpoint blockade with immunotherapy was introduced as a neoadjuvant (preoperative) option. However, there was this assumption was that surgery would follow once immune therapy had its effect.
I recall another case this time of a local recurrent malignant melanoma of the face where the patient had an excellent complete response to neoadjuvant immunotherapy yet still quite literally facing the need to have half his face come off replaced with his “butt cheek” as he affectionately called it. Was this really necessary? Post-operatively, he had no residual disease on pathology.
I found myself pausing… contemplating this idea of who needs “adjuvant surgery” or perhaps avoiding it altogether in these exceptional responders?
The Question That Lingers: Do We Always Need Surgery?
After 14 years of oncology practice, and having served on a GI and colorectal tumor board for much of that time, this case made me ask a question that seems simple but is becoming more relevant: If immune therapy works so well that a patient achieves a complete clinical response, do we still need to operate?
We’ve already seen this dilemma play out in the rectal cancer world. Multiple studies in recent years have shown that even patients with operable, locally advanced MSI-High rectal cancer can have dramatic, near-complete, or complete responses to immune checkpoint inhibitors. In some cases, they’ve been managed successfully with a “watch-and-wait” strategy, avoiding the morbidity of surgery altogether.
This patient wasn’t a rectal cancer case—it was technically a colonic cancer in the esophagus—but the principle felt the same. If the immune system, with some therapeutic help, can eradicate all visible disease, what role does surgery still play? What about other immune-sensitive cancer types?
The Study That Validated This Thinking
That’s why the recently published April 2025 NEJM study caught my attention. The researchers examined 117 patients with a variety of MSI-H/dMMR solid tumors—including rectal, colon, bladder, gastric, endometrial, prostate, and small bowel cancers—who were treated with PD-1 blockade (immune checkpoint therapy) with curative intent.
Here’s what stood out:
- Clinical complete response rate: Out of the 117 patients treated, 84 achieved a clinical complete response (meaning no detectable tumor on imaging, endoscopy, and/or biopsies after treatment).
- Organ preservation: Of the 84 complete responders, 82 avoided surgery entirely, maintaining organ function and avoiding surgical morbidity.
- Durable results: At two years, recurrence-free survival stood at an impressive 92%.
- Manageable toxicity: As expected with immune therapy, most adverse events were grade 1 or 2—generally mild and manageable.
One especially fascinating aspect of the study was their use of circulating tumor DNA (ctDNA) to help monitor treatment response. The majority of patients had detectable ctDNA at baseline, but in those achieving a complete response, ctDNA levels dropped to undetectable during therapy—adding another layer of evidence that immune therapy was clearing disease at a molecular level beyond our just clinical, endoscopic, and radiographic assessment tools.
Beyond Rectal Cancer: A New Paradigm Across Tumor Types?
This study didn’t just focus on rectal cancer. It included patients with bladder cancer (all five patients in that subgroup had complete responses), gastric cancer (where about half of the patients had a complete response), and smaller numbers of endometrial, prostate, and esophagogastric junction cancers. Even though not all tumor types had high complete response rates, the trend is clear: when immune therapy works, it can work remarkably well—even in tumors previously considered only treatable with major surgery without compromising the operative option.
Patient Autonomy and the “Parachute Argument”
Some may argue that we still need randomized phase 3 trials before changing standard practice, and I get that. But this reminds me of an infamous moment almost a decade ago, during one of the early studies of immune checkpoint inhibitors in MSI-H metastatic colorectal cancer… when nothing else worked and these patients were dying. After seeing unprecedented survival gains in chemo-refractory patients, a skeptical out-of-touch audience physician-member stood up and said, “We need a randomized trial to prove this works”?!
It felt like asking for a randomized trial to prove that parachutes save lives when jumping out of planes.
In oncology, when response rates are overwhelmingly high, and when the clinical effect is both dramatic and durable, sometimes we don’t need to wait for years of randomized data before thoughtfully evolving our approach—especially when we have real-time tools like imaging, endoscopy, and ctDNA to help us monitor patients closely. More so with the informed patient who understands the pros, cons, risk, benefits… the uncertainty.
Moving Forward: Shared Decision-Making Matters
Of course, non-operative management isn’t for everyone but I think it can start to be part of the conversation in the informed patient. Not all patients will achieve a complete response. Some will understandably prefer the reassurance of surgery despite a complete response, and others may not tolerate immune therapy well. But the point is that we now have evidence-based justification to consider non-operative strategies for exceptional responders, especially when the morbidity of surgery is high. And perhaps spare the butt-cheek.
For my patient with the colonic interposition tumor, this evolving data strengthens the conversation I had at the time: considering a non-operative path wasn’t just a gut feeling—it was a reasonable, emerging option supported by both biology and now, by high-quality prospective data. Especially given the significantly high morbidity of surgery in his situation.
This is a fascinating and hopeful time in oncology. Immune therapy continues to change the treatment landscape, challenging old assumptions and giving some patients the opportunity to preserve both life and quality of life.
About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. He brings a wealth of expertise to the complex and challenging world of oncology.
Disclosures:
Dr. Thomas serves as a speaker and/or advisory board for Bristol Myers Squibb (BMS), Merck, Ipsen, Natera, Immunocore, Pfizer, Amgen, Novartis, and SpringWorks. He also receives industry grants in support of numerous clinical trials.