Can immunotherapy for some solid tumors replace surgery?

Neoadjuvant treatment with programmed cell death 1 (PD-1) inhibitors induces a complete clinical response, leading to organ preservation in the majority of patients with early stage mismatch repair (MMRD) solid tumors – new data from phase 2 studies were presented regardless of tumor type.

Six months of treatment supply I-III MMRD rectal tumor and non-rectal tumor stage patients led to non-surgical management. And, in all patients with a complete clinical response, organs were preserved without additional treatment.

Early stage solid tumors are treated in a therapeutic setting with a combination of chemotherapy, radiation therapy and surgery. These can have a negative “life-changing” effect on the quality of life of these patients during their survival.

“These findings are very important for patients with early stage MMRD tumors because if they are treated with sufficient timely immunotherapy, they are likely to not require surgery or radiation,” Cercek added.

Cercek presented the data at a press conference on April 27th. American Cancer Research Association (AACR) Annual Meeting 2025. The survey results were It's also published in New England Journal of Medicine.

“Exciting” early data confirmed

Overall, around 2% to 3% of all solid tumors are MMRD, but more common in certain tumors. Rectal cancer (10%-15%), Cercek explained.

Metastatic MMRD tumors are sensitive to immune checkpoint blockade using single agent anti-PD-1 therapy and PD-1/cytotoxic T-lymphocyte-associated protein 4 therapy.

Previous data Current studies show that PD-1 blockade using Dostarlimab led to a complete clinical response in 100% of early-stage MMRD rectal cancer.

“Given that exciting data and the durability of these responses in the rectal group, we really wanted to ask the question: Can non-surgical management of MMRD tumors extend beyond rectal cancer?” Celsek said.

The researchers expanded the trial to include 117 patients with locally advanced solid tumors of MMRD. At the data cutoff, 14 people were treated with dostallimab and 103 completed the treatment. This included 49 people with rectal cancer and 54 people with solid non-rectal tumors including esophagus, stomach, hepatotoxicity, reproductive organs, urine, colon, and gynecological endometrial cancer.

Patients who had a complete response to 6 months of neoadjuvant dostallimab were able to choose to proceed with surgical management, while patients with residual disease proceed with surgery.

Of all 103 patients who completed treatment, 84 showed a complete clinical response, and 82 did not undergo surgery.

All 49 patients with rectal cancer showed complete clinical response and chose non-surgical management. Thirty-seven of these patients showed persistent clinical complete responses at 12 months, which met criteria for efficacy studies.

Of the 54 patients with MMRD non-rectal solid tumors who completed dostallimab treatment, 35 (65%) showed complete clinical response, and 33 chose to skip the surgery.

Complete response rates were seen in 100% of urothelial tumors and 82% of colon cancer. The most common tumor types without a complete clinical response were prostate and gastroesophageal tumors.

Cercek noted that the complete clinical response is durable. Recurrence was rare (<5%) and subsequently responded to recharge with PD-1 blockage. Circulating tumor DNA was a "reliable liquid biopsy and markers of reaction and recurrence," Cercek said.

For the rectal cohort, the median follow-up was 30.2 months, with a 2-year, non-recurrence survival rate of 96%. In the non-rectal solid tumor cohort, the median follow-up period was short (14.9 months) and the 2-year, non-recurrence-free survival rate was 85%.

A patient-centered approach

Cercek noted that the effectiveness of immune checkpoint blockade appears to be a relatively tumor disorder driven primarily by the MMRD phenotype rather than the tumor site of the tumor.

She also said that the effects seen are likely not inherent to dostallimab. “We don't think it's drug-specific, but rather it's merely inherent in immune checkpoint blockade.”

“The opportunity for patients to receive potentially curative immunotherapy without the need for surgery or other pathological treatment is truly amazing,” said Dr. Ryan B. Colcoran, PhD, of the Mass General Research Institute in Boston.

Invited debate Michael J. Overman, along with the University of Texas MD Anderson Cancer Center in Houston, said that both surgical and non-surgical approaches for early stage MMRD solid tumors can “coexist.”

He said, “After six months of PD-1 therapy, salvage surgery for incomplete responders appears to be a successful approach. This is truly an important takeaway from this presentation.”

Oberman also emphasized the need for a patient-centered discussion of which approach is best. “This really reaches the goals of the patient and is based on the risk-benefit argument,” he said.

This study revealed the relationship between Swim Avers America, GSK, Standing Up Up Up To -HayStack Oncology, Simon and Eve Colin Foundation, Dalton Foundation and National Institutes of Health and National Cancer Institute grant Cercek revealed the relationship between Abbvie, Amgen, Agenus, Daiichi Sankyo, GSK, Merck, Regeneron, Roche, and Pfizer. Oberman revealed his relationship with Roche, BMS, Medimune, Merck, Amgen, Takeda, Janssen, Pfizer, Array, Gritstone Bio, 3DMed, Nouscom, Atreca, Bayer, Lilly, and Phanes Therapeutics.