Three Decades in the Making: Advancing Rectal MRI at MSK

A Q&A with Dr. Marc J. Gollub, MSK’s Director of Gastrointestinal Radiology

Memorial Sloan Kettering Cancer Center (MSK) has one of the busiest rectal cancer practices and likely performs the most rectal magnetic resonance imaging (MRI) exams in the United States.

In this Q&A with Marc J. Gollub, MD, Director of Gastrointestinal Radiology at MSK, we discuss MSK’s pioneering work in rectal MRI, how it differs from endorectal ultrasound (ERUS), its role in groundbreaking clinical trials for patients with rectal cancer, why expertise matters, and new frontiers for future improvements to rectal MRI.

What was MSK’s role in pioneering rectal MRI?

A little over 30 years ago, when I joined MSK as a gastrointestinal imaging specialist right out of fellowship from New York University, my colleague, also an early-career radiologist, Lawrence Schwartz, MD, now our Chair of the Department of Radiology at MSK, was my mentor. He was the Director of MRI then and encouraged me to get involved in rectal MRI as he recognized its potential to make a large contribution to patient care.

Thanks to Dr. Schwartz’s vision and guidance, we wrote an institutional review board protocol for its routine use, which, at the time, met with certain pragmatic obstacles, including insurance coverage and competing institutional priorities. Interestingly, had that succeeded, we may have gotten a jump start on the Europeans, who shortly thereafter pioneered its routine use and showed that rectal MRI was as good as, or better than, endorectal ultrasound (ERUS) for staging rectal cancer.

Dr. Schwartz had been using dynamic contrast-enhanced MR imaging (DCE-MRI) with intravenous (IV) gadolinium contrast in rectal and prostate cancers from the very beginning. A little more than a decade ago, he moved to Columbia Presbyterian to become Chair of Radiology, but we continued working together on several observational studies and investigations using medical physics and pharmacokinetic modeling to see whether IV contrast was useful in rectal cancer. Although we were able to show that rectal DCE-MRI could predict pathologic complete response when used with certain anti-angiogenic drugs, those drugs are no longer used in the non-metastatic setting, so our success with DCE-MRI was not reproduced. However, we, along with our esteemed surgeons, did enhance awareness of the need to predict pathological complete response in rectal cancer since it occurred up to 25% of the time, leading to potentially unnecessary surgery.

How does rectal MRI differ from ERUS?

ERUS had traditionally been considered the optimal technique for staging rectal cancer. However, through extensive original research, MRI was shown to have the ability to provide additional information in staging rectal cancer and held certain advantages over ERUS. MRI is not operator-dependent, resulting in significantly less variability in the results. MRI allows visualization of the entire pelvis, whereas sound waves in ERUS do not penetrate deep enough beyond the rectal wall to evaluate the surrounding fat. MRI can image high rectal cancers or stricturing or stenosing lesions, whereas the ultrasound probe can only reach so far. Finally, MRI can evaluate all pelvic lymph nodes, including those that are high up and in the lateral pelvic side wall, which ERUS cannot do. ERUS has thus been replaced by routine rectal MRI. Some experts feel that ERUS remains superior to MRI for its ability to distinguish between T1 and T2 early disease.

Recently, I conceived and led a small study here at MSK that looked at short-term outcomes of discordant tumor assessments between diffusion-weighted imaging (DWI)-MRI and flexible sigmoidoscopy in patients with rectal cancer who had residual tumor-bed diffusion restriction after treatment. The issue is that while patients who achieve a clinical complete response have excellent outcomes, they require regular surveillance since up to 30% can develop tumor regrowth.

The scenario involved what happens during routine surveillance, which includes MRI, digital rectal exam, and flexible sigmoidoscopy (flexsig) several times per year, when the findings at MRI do not match those at flexsig. We found that MRI detected residual tumor or tumor regrowth in 20% of cases that are invisible to the surgical endoscopist because MRI can detect suspicious areas beneath the mucosal lining. Therefore, when MRI detects a suspicious area not found on simultaneous flexsig, it cannot always be assumed to represent a false positive; In 20% of cases, MRI detects tumor earlier than flexsig. We published this in European Radiology.  ⁽¹⁾

What advance made rectal MRI invaluable for determining treatment response?

DWI marked a substantial advance over T2-weighted imaging (T2WI) in rectal cancer following the development of its use in prostate cancer. To this day, rectal cancer research receives less funding than prostate cancer research, in part because rectal cancer carries a greater stigma, and as such, many advances in rectal cancer mimic those in prostate cancer with a slight lag time.

When DWI arrived on the scene, I joined forces with one of the two renowned radiologists in Europe, Dr. Regina Beets-Tan, who is now Chair of Radiology at the Netherlands Cancer Institute. Following our collaboration while she was at MSK for a year in 2008, extensive research was conducted worldwide on DWI-MRI, which is now considered critical for determining response.

MSK sponsored the groundbreaking multi-institutional OPRA trial that found rectum preservation was achievable in half of patients with stage 2 or 3 rectal cancer treated with total neoadjuvant therapy (TNT) alone, with no negative impact on three-year disease-free survival compared with patients treated with chemoradiotherapy, total mesorectal excision, and postoperative chemotherapy. What was your role in the study?

I served as the radiologic principal investigator (PI) for the OPRA trial (NCT02008656).⁽²⁾  The lead PI Julio Garcia-Aguilar, MD, PhD, Chief of the Colorectal Service and the Benno C. Schmidt Chair in Surgical Oncology at MSK, and I, along with an expert panel convened at MSK prior to OPRA’s inception, devised a three-tier grading schema for stratifying clinical tumor response. Our goals were to maximize patient eligibility for organ preservation after TNT and to establish a consistent decision rule across the 17 collaborating centers that participated in the trial.

The schema differentiated between clinical complete response (cCR), clinical near complete response (nCR), and clinical incomplete response (iCR) according to digital rectal examination, flexsig, T2WI-MRI, and DWI-MRI. ⁽³⁾ As the study began in 2013, the protocol recommended prioritizing endoscopic assessment over MRI due to some indications of its superiority. However, MRI was also mandatory at restaging before or after flexible sigmoidoscopy.

What additional insights have come from the OPRA trial?

There has been good agreement on clinical management for patients with complete response and incomplete response to TNT. However, near-complete response is more subjective and challenging to manage.

To address this issue, I recently participated in an international expert panel. We proposed that the first MRI upon completion of TNT, which represents a clinical decision point, can result in one of the three tiers of response guiding treatment. If a patient has an iCR, they must proceed to surgery, and those with a cCR or nCR can enter a watch-and-wait surveillance program. Those with an nCR on endoscopy or MRI have one more chance to achieve a cCR in a repeat assessment three to four months later. Those that do not achieve a cCR at that time should proceed to surgery.  ⁽⁴⁾

In 2024, we published a secondary analysis of OPRA data that confirmed the safety of the watch-and-wait strategy for stage 2 or 3 rectal cancers that achieve a cCR or nCR after total neoadjuvant therapy (TNT). ⁽⁵⁾ We noted that combining flexsig and MRI, may improve the identification of patients most likely to achieve long-term organ preservation and that new tools, such as artificial intelligence and narrow-band imaging could potentially be combined with endoscopy to improve accuracy.

The OPRA Consortium recently published a pooled analysis of OPRA and the CAO/ARO/AIO-12 trial led by the German Rectal Cancer Study Group. The results further confirmed the safety and benefits of the watch-and-wait strategy for patients with locally advanced rectal cancer and a good response to TNT. ⁽⁶⁾

What sets rectal MRI at MSK apart from other centers?

MSK is a high-volume center for treating patients with rectal cancer, with a dedicated team of multidisciplinary subspecialists. A major benefit for patients treated at MSK is that every patient has a rectal MRI at diagnosis and throughout treatment to assess response. This is not necessarily the standard of care everywhere.

Also, the radiologists reading patients’ rectal MRIs are a small, highly trained subset that sees hundreds of cases per year, typically far more than an average radiologist. Incidentally, I would like to take this opportunity to acknowledge and thank my exceptional team including Drs. Fuqua, Petkovska, Paroder, Golia-Pernicka, Kim, Javed-Tayyab, Fernandes, El Homsi, Rucker, and Argiriadi.

Throughout my career, I have become increasingly involved nationally and internationally with societies working to improve rectal MRI quality, as it is essential to provide surgeons with the best possible information.

I recently oversaw one of my mid-career academic colleagues, Dr. Jen Golia-Pernicka, in running a retrospective study of 461 rectal MRIs performed outside our institution, which were subsequently read by eight subspecialist gastrointestinal radiologists at MSK. We found that second-opinion rectal MRI reviews by our subspecialists would have changed the surgeon’s management plan in about 30% of cases. The results were presented at the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) 2025 Annual Meeting in Amsterdam in May.  ⁽⁷⁾

At MSK, we have also been interested in tackling the imaging challenges associated with mucinous tumors, which occur in 10% to 15% of patients and in a higher proportion of those with mismatch repair-deficient (dMMR) tumors. Historically, patients with mucinous tumors have had worse outcomes. Mucin poses a significant imaging challenge because it appears very bright on DWI-MRI and incurs artifacts. We were able to use artificial intelligence (AI) to improve the prediction of residual tumor in these challenging cases, thanks to our collaboration with Drs. Ibrahim Abdallah, Bisheng Zhao and the AI team of Dr. Schwartz. ⁽⁸⁾However, research by our surgeons and us has shown that the modern treatment using total neoadjuvant therapy (TNT)  has leveled the field, such that mucinous tumors do not need to be treated differently than non-mucinous tumors: It appears safe to let these patients undergo watch-and-wait surveillance as we do for other patients who achieve a good response at endoscopy.  ⁽⁹⁾ Patients with a finding of mucin at less experienced centers may undergo unnecessary surgeries.

What research projects are you working on currently?

I was the radiologic PI for the international PROSPECT study (NCT0151587), the largest U.S. rectal clinical trial ever conducted, involving nearly 1,200 patients. The lead PI, medical oncologist Deb Schrag, MD, FASCO, MPH, the George J. Bosl Chair of the Department of Medicine, myself, surgical oncologist Martin Weiser, MD, the Stuart H.Q. Quan Chair in Colorectal Surgery, and other MSK colleagues had conducted the single institution pilot study, ⁽¹⁰⁾ which led to the phase 3 trial conducted by the Alliance for Clinical Trials in Oncology, a cooperative research network sponsored by the National Cancer Institute . 

PROSPECT demonstrated that five-year disease-free survival and overall survival were the same for patients who received only neoadjuvant chemotherapy with 5-fluorouracil and oxaliplatin (FOLFOX) compared with those treated with standard-of-care pelvic chemoradiation with 5-fluorouracil sensitization (5FUCRT). The results indicated that select patients wishing to avoid radiation prior to surgery can opt to receive chemotherapy only, followed by surgery and still have comparable survival rates. We published the results in The New England Journal of Medicine.  ⁽¹¹⁾

Right now, a colleague and I are retrospectively reanalyzing the 1,400 MRIs from PROSPECT to answer several outstanding questions, such as whether patients who showed a fantastic response to neoadjuvant chemotherapy on rectal MRI might also be candidates to avoid surgery and undergo watch-and-wait. That’s an outstanding question, given that 21.9% of patients receiving the experimental chemotherapy-only approach achieved a pathologic complete response in that trial.

The other project we are working on right now is analyzing rectal MRI data from the groundbreaking immunotherapy trial led by Andrea Cercek, MD, Section Head of Colorectal Cancer and Co-Director of MSK’s Center for Young Onset Colorectal and Gastrointestinal Cancer, and Luis Alberto Diaz Jr, MD, the Grayer Family Chair and Head of the Division of Solid Tumor Oncology at MSK. I was also the radiologic PI for that trial (NCT04165772), and we published the results in The New England Journal of Medicine.  ⁽¹²⁾

The anti-PD-1 agent dostarlimab achieved a 100% cure rate among patients with deficient mismatch repair enzyme (dMMR) rectal tumors, such that no patients needed to proceed to standard chemotherapy and surgery. The trial has now been expanded nationally and to other dMMR malignancies, including colon cancers. ⁽¹¹⁾

The most recent trial, the JANUS trial (NCT05610163), a nationwide phase 2 study led by MSK colorectal surgeon J. Joshua Smith, MD, PhD, FACS, is nearing completion, so we will be digging into that data soon. JANUS evaluated triplet chemotherapy versus doublet chemotherapy along with chemoradiotherapy (TNT) for more than 310 patients with locally advanced rectal cancer using MRI for assessing treatment responses.

What new advances are on your radar for improving rectal MRI?

Next up is investigating the combination of positron emission tomography (PET) and MRI for rectal and anal cancer and looking at lymph nodes. We also need to determine our ability to predict complete response with the use of chemotherapy only. Also, further refinement of the near CR category by MRI, if possible, is a challenge on our radar.

At MSK, the Colorectal Cancer Research Center has several research programs, including precision pathology, biobanking, radiology, precision modeling, computational biology, young-onset, and patient-reported outcomes, all of which are funded by MSK.

In the meantime, we are dedicated to improving patient outcomes and will continue to pursue new clinical trials in collaboration with our rectal cancer subspecialist colleagues.

Learn more about MSK clinical trials for patients with rectal cancer. Access disclosures for Dr. Gollub.