BUFFALO, NY—Over the past several years, the focus of breast cancer treatment has shifted from late detection and radical surgery to early detection, breast-conserving surgery, and multimodality treatment. This “paradigm shift” may also be applicable to colorectal cancer, Glenn D. Steele, Jr., MD, PhD, dean of the Biological Sciences Division, Pritzker School of Medicine, University of Chicago, said at a surgical oncology symposium hosted by Roswell Park Cancer Institute. Dr. Steele was the recipient of the Roswell Park Centennial Award.
For patients with distal rectal adenocarcinoma, there is now a focus on sphincter-preserving surgery and postoperative adjuvant treatment rather than radical abdominoperineal resection, he said. This is similar to the shift from radical mastectomy to lumpectomy and radiation in breast cancer.
“The issues between colorectal cancer and breast cancer are remarkably similar. Early detection and multimodality treatment ‘work’ for both, but the data have some surprises,” Dr. Steele said, referring to an unexpected number of local recurrences seen in a nonrandomized CALGB trial exploring sphincter-sparing surgery in early stage rectal cancer patients.
Randomized trials are needed to confirm that this shift to less radical surgeries that improve quality of life will not compromise survival or local recurrence, Dr. Steele emphasized. For sphincter preservation to be analogous to breast-conserving treatment, he said, “salvage abdominoperineal resection must produce outcomes as good as if such resection was used at the time of the initial therapy.”
Dr. Steele described the results of a CALGB Coordinated Intergroup Trial, which he also presented at the 35th annual meeting of the American Society of Clinical Oncology (Atlanta).
The study looked at 177 patients with distal rectal adenocarcinoma. Patients with T1 lesions (tumor in the submucosa) underwent local excision only, and those with T2 lesions (tumor in the muscularis propria) received local excision plus chemotherapy and radiotherapy.
Of the original 177 patients, 161 underwent a full thickness excision, and 110 were eligible to remain on the study (51 patients did not make the second cut, mostly due to inadequately defined free margins on pathology or free margins that were very difficult to document as being free pathologically). Of the 110 eligible patients, 59 patients were originally classified as T1, and 51 were classified as T2. These patients have currently been followed for 52 months.
Overall, 13 of the 110 patients (12%) had tumor recurrence. In the T1 group, there were four failures. Salvage therapy was used for local recurrence in two patients. One remains disease free and the other died of liver metastases, although a retrospective review of the liver scan suggested that the liver disease may have been present at the time of presentation. The other two patients died of distant metastases.
In the T2 group, there were nine failures. Three had distant disease only and did not receive salvage resection. Salvage therapy was used to treat local recurrence in six patients. Of these six patients, two had local and distant disease and died of their distant disease, and four had local recurrence only at the original site. Of these four patients, three remain disease-free, and one patient died of distant metastases, although this patient was free from local recurrence at the time of death.
Prognostic factors for increased risk of disease recurrence included the presence of perineural invasion, poor differentiation, and lymphatic invasion.
There has been no plateauing of local recurrences in this study. “We expected a moderate number of recurrences, but actually have seen continuing and rather significant recurrences,” he said. Since there are no prospective studies of years to recurrence for T1 and T2 patients, this expectation was based on mostly anecdotal reports in the literature. However, an analysis of a national cancer database indicates that recurrences in these patients may be more frequent and may continue for longer periods than the anecdotal reports suggest, he said.
So far, salvage after local recurrence seems to be quite effective, he said. “If we could salvage almost all of our failures, we would have a situation quite analogous to the biology in breast cancer and the rationale for using a conservative approach first for these early distal rectal carcinomas.”
The caveat about salvage in this study, he said, is the length of follow-up. The median time of follow-up after salvage is still less than 3 years, so we have more time to go before we’re comfortable with the duration of the salvage.”
He added that more research is needed to confirm these early successes.
“Additionally, we will also evaluate preoperative therapy and other surgical techniques, to learn what effect they have on overall survival. We must also continue to focus on quality of life issues for our patients,” Dr. Steele said.
