NATIONAL HARBOR, MD. – It may sound like heresy, but select patients with locally advanced rectal cancer may be spared surgery and its associated complications, a cancer surgeon suggested at the annual Society of Surgical Oncology Cancer Symposium.
Approximately 10%-25% of patients with locally advanced rectal cancer will have clinical complete responses (cCR) to neoadjuvant chemotherapy and radiation, said Dr. Philip B. Paty, an attending surgeon in the colorectal surgery service at Memorial Sloan-Kettering Cancer Center in New York City.
Dr. Philip Paty
"The vast majority of these patients will avoid rectal resection, at least within the first 5 years," Dr. Paty added.
Although local failure occurs in 10%-25% of patients, most of the failures occur within the first 18 months, and most of these cases can be salvaged with R0 resections. Patients treated with nonoperative management appear to have rates of distant recurrence and survival similar to those of patients with pathologic complete responses (pCR) treated with total mesorectal resection, he said.
If surgery is required, local excision may be sufficient for some patients with stage T1 lesions and a select few with T2 lesions, said Dr. Heidi Nelson, professor of surgery in the department of colon and rectal surgery at the Mayo Clinic in Rochester, Minn.
If a patient has a favorable T1 lesion and would otherwise face a life-altering procedure such as abdominal perineal resection (APR) and colostomy, the surgeon should at least show the patient the data and discuss local excision as a safe and effective alternative with results comparable to more extensive resections, she said.
T2 lesions are more problematic, but a select few patients with this tumor type might be spared the morbidity of standard rectal resection, she added.
Hold the surgery?
Dr. Paty noted that, with standard management of stage T3 or T4 rectal cancers, the combination of neoadjuvant chemoradiotherapy, surgery, and adjuvant chemotherapy resulted in a 76% overall survival rate with less than 0.3% local recurrence after 5 years (Ann. Surg. 2005;241:829-36).
"What we have not dwelt on much is the morbidity of surgery, which is very significant. Having a rectal resection is a life-changing event for every patient that has one. Surgeons know that, and patients know that even better than surgeons," he said.
Rectal resections are associated with significant perioperative morbidity, colostomy, altered bowel function, sexual dysfunction, and infertility, he noted.
Pathologic complete responses to neoadjuvant therapy occur in 10%-44% of patients, and patients who have a pCR have markedly better oncologic outcomes than patients with less robust responses.
Of course, pCR can only be determined after surgery, raising the question of whether a clinical CR is sufficient for determining whether a patient might be spared rectal resection.
There are currently more data on pCR in rectal cancer than cCR, "probably because clinical CR criteria right now are quite stringent; we don’t want to not operate on patients who have disease," Dr. Paty said.
His criteria for clinical complete response include a flat mucosa with no nodularity or mass on digital rectal examination. Smooth induration or minor scarring without nodularity is acceptable, "but it has to have a benign feel to it," he said.
In addition, on proctoscopy the mucosa must appear normal and flat, and if a scar is present it should be pale or white in appearance. Alternatively, there can be telangiectasias, he said.
"What’s not clear is whether ulceration is an exclusion criterion [for nonoperative management]. For me it is. Any time I see ulceration I feel there is something ongoing in that tumor that is not resolved and I don’t feel comfortable calling it a complete response," Dr. Paty commented.
Take local route
Dr. Heidi Nelson
When surgery is required, local excision rather than total mesorectal resection may suffice, Dr. Nelson said. Suitable patients may be those who are frail or elderly or have limited life expectancy or serious medical conditions that might preclude more extensive surgery.
Tumors that may be good candidates for local excision include smaller lesions (less than 2-3 cm) below the peritoneal reflection that are not amenable to lower anterior resection. The tumors should be subject to full thickness excision, and the team should be able to confirm negative margins, she noted.
Favorable pathologic findings include well-differentiated tumors with the absence of lymphovascular invasion, mucinous features, or signet ring features, she said.
"Local excision really just takes care of the primary, of course. It doesn’t deal with the lymphatics, which is always the hidden game," Dr. Nelson said.
She noted that a 1989 study showed that the likelihood of untreated lymph node disease in patients who had undergone local excision was 0% for patients with T1 tumors, 28% for those with T2 tumors, 36% for T3, and 53% for T4 lesions, showing a significant increase in risk associated with tumor depth (Cancer 1989;63:1421-9).