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Surgery Still Preferred Over Non-Operative Management of Rectal Cancer

Fuerst, Mark L.

doi: 10.1097/01.COT.0000533701.45184.ce
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NEW YORK—Surgery remains the standard of care for rectal cancer patients who achieve clinical complete response (cCR) with initial treatment, although non-operative management (NOM) shows encouraging promise, according to two experts who participated in a debate at the Great Debates & Updates in Gastrointestinal Malignancies, held March 23-24.

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Non-Operative Management

NOM is ready for prime time and should be the standard of care for complete responders, said Christopher Crane, MD, Radiation Oncologist at Memorial Sloan Kettering Cancer Center, New York City. “There has been interest in this strategy for decades. It can be done successfully with good quality assurance,” noted Crane. “There are no pitfalls with NOM. And it's ready to do in the community.”

In contrast to NOM, the complications of total mesorectal excision (TME) are many, he said. These include permanently altered bowel function and often colostomy, urinary dysfunction in up to two-thirds of patients, impotence in 15-100 percent of patients; and retrograde ejaculation in up to one-third of patients.

For complete responders, NOM yields similar local control, disease-free survival (DFS), and overall survival to TME. “With close follow-up, salvage is effective. Proctoscopy is most important and should be done every 3-4 months,” he said, adding that MRI is also important.

Yet unpublished data examined 1,070 rectal cancer patients treated at Memorial Sloan Kettering from 2006 to 2015 with chemo-radiation 45-54 Gy plus 5-fluorouracil or capecitabine and FOLFOX before or afterward. From 2013 to the present, 113 patients with NOM achieved cCR and 136 patients with TME achieved pathologic complete response (pCR).

In the NOM group, 5-year DFS was 90 percent and 5-year distant-free metastases was 8 percent; in the surgical group, 98 percent achieved 5-year DFS and 4 percent had distant-free metastases.

Crane noted the biologic difference between the two groups—“the TME group was all pCR. In the NOM group, 20 percent were pathologic incomplete responders who had slightly worse biology.” He noted that tumor regrowth usually means distant spread. Some 22 patients had tumor regrowth, and eight of these 22 patients showed regrowth of distant metastatic disease. “It's important to pick up regrowth early to give tumors less opportunity to spread,” noted Crane.

The quality of NOM is more consistent than TME. “NOM is a more straightforward approach and is less quality-dependent. The quality of TME is quite variable,” he said. “NOM should be the standard after cCR with or without local excision. Close follow-up and timely salvage is critical. NOM may be more scalable than TME and is less quality-dependent.”

Future research needs to expand the pool of responders to NOM and examine radiation sensitization, he noted.

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Surgical Management

Surgery remains the standard of care for rectal cancer with cCR, said Jose Guillem, MD, colorectal surgeon at Memorial Sloan Kettering.

“It is one thing to say you have spared someone an operation. It is another thing to say you have spared an operation indefinitely, without affecting quality of life or survival,” he noted. “Since patients with a cCR have a favorable outcome following resection, can these patients be managed successfully without surgery to spare them the perioperative and long-term morbidity of rectal resection?”

NOM has its challenges, including the diagnosis of cCR. “A clinical exam underestimates response. Digital rectal exam (DRE) and endoscopy are subjective. We can't rely on PET or CT scans that the tumor is gone,” said Guillem. “Also, the durability of NOM based on follow-up ranges from a high of 18 percent to a low of 0 percent.”

Memorial Sloan Kettering data demonstrate a problem with long-term follow-up of NOM. “Clinical examination following perioperative chemo-radiation for rectal cancer is not a reliable surrogate endpoint,” he said, adding that DRE underestimates response in three-quarters of patients. “PET and CT cannot distinguish between a complete and an incomplete pathologic response. No MRI, PET, or CT parameters utilizing different techniques or tracers reliably predict a pCR.”

The durability of cCR with NOM also is uncertain. In distant failures, tumors tend to be aggressive, he stated.

Guillem expressed other concerns about NOM. “Is NOM going to flip the frequency of failures from distant to local or local to distant? Does it decrease the rate of sphincter preservation in patients requiring salvage surgery? Have we selected out a clone of radio-resistant cells too small to visualize in the mesorectum yet highly virulent and capable of distant metastases and death?” he asked.

Quality of life also weighs heavily with rectal cancer patients. “NOM requires painstaking 3- to 6-month follow-up, not to mention the looming anxiety associated with the uncertainty of when and how you will recur,” explained Guillem.

In addition, NOM studies have limitations, including non-randomized designs based on small sample sizes that include about one-quarter of patients with early-stage disease. “Follow-up has been short-term; local salvage may require abdominoperineal resection or a flap, and there is a question of increased distant failure rates,” he said.

In conclusion, “Surgery remains a standard component of the treatment of rectal cancer,” Guillem noted. “The NOM approach is encouraging, but remains investigational. More consistent strategies are needed for recognition of cCR, along with reliable methods to confirm the tumor has been eradicated, that are more accurate surrogates for pCR. A rational, systematic, meticulous clinical, pathologic, and imaging follow-up program is needed for a safe NOM approach.”

The ideal candidate for NOM may be a patient with challenging anatomy and/or comorbidities with a very distal rectal cancer requiring an abdominoperineal resection with good but limited likelihood of lymph node metastases that has demonstrated a cCR to neoadjuvant therapy, he noted.

Mark L. Fuerst is a contributing writer.

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