Watchful waiting after high-dose chemoradiotherapy safe for some with distal rectal cancer

Last Updated: 2015-07-22

By Will Boggs MD

NEW YORK (Reuters Health) - Watchful waiting after high-dose chemoradiotherapy appears to be a safe strategy for avoiding surgery in many patients with distal rectal cancer, researchers from Denmark report.

"In the end, over half of the treated patients appeared to have tumor control at two years after the end of treatment," Dr. Ane L. Appelt from Vejle Hospital's Colorectal Cancer Center South in Vejle told Reuters Health by email. "These were patients who were originally planned for an abdominoperineal resection, who have so far avoided a permanent stoma."

Previous studies have shown that many patients with distal rectal cancer will have complete responses to neoadjuvant therapy, thus generating interest in the possibility of achieving tumor control with chemoradiotherapy alone.

Dr. Appelt's team investigated whether patients with distal rectal cancer could be managed with high-dose radiotherapy and concomitant chemotherapy alone in a prospective observational trial of 51 patients.

The study was closed prematurely as a result of slower than expected patient accrual, the researchers report in the Lancet Oncology, online July 6.

Forty patients classified as clinical complete responders were allocated to the watchful waiting group, and 11 patients with incomplete responses were referred for resection; only seven underwent surgery as recommended.

Nine patients in the watchful waiting group had local tumor recurrence after a median 10.4 months and were referred for salvage surgery. At the time of data cutoff for the analysis, no patients had local tumor recurrence after the two-year follow-up point.

Salvage surgery was curative for all nine patients with local tumor recurrence, and none of these patients has presented with local recurrence after surgery.

All of the seven incomplete responders who went to surgery had clear resection margins, and two patients had no remaining tumor cells in the pathological specimen. There were no local recurrences over a median 19.3 months of follow-up after surgery.

Five of the 51 patients (three in the observation group and two in the surgery group) developed metastatic disease after a median 26.7 months. Two patients died from new primary cancers (one in each group), but none from rectal cancer.

An estimated 58% of patients treated on trial had local tumor control at two years with chemoradiotherapy alone.

"The main message should, first and foremost, be that watchful waiting appears feasible and safe, provided careful patient selection and close follow-up are used," Dr. Appelt said. "Secondly, this requires a dedicated multidisciplinary team, with close collaboration between radiation oncologists and surgeons in particular. This team should employ well-defined and agreed-on criteria for response assessment and recurrence surveillance."

"We are still examining our data with regards to predictors for clinical complete response and local control after chemoradiotherapy," she added. "Hopefully, we will be able to provide a more information shortly; we are planning several follow-up publications."

"I do think, though, that one should take notice of the way that patients in our study differed quite a bit from patients included in many other reports of 'watch-and-wait' strategies for rectal cancer," Dr. Appelt explained. "They were not 'classic' candidates for preoperative chemoradiotherapy, but rather small T2 and T3 tumors with limited lymph node involvement, and these characteristics may very likely have contributed to the high rate of local control. I believe that this indicates that the ideal candidates for definitive chemoradiotherapy are patients with early disease, with tumors not suitable for local excision, and who have sufficiently low tumors that surgery is likely to provide bad functional results."

In a linked editorial, Dr. Anne J. Breugom and Dr. Cornelis J. H. van de Velde from Leiden University Medical Center in the Netherlands caution that long-term toxicity might still occur in the future.

"The question remains of whether the benefits of intensive chemoradiotherapy followed by observation outweigh the possible long-term adverse effects - especially for patients with clinical T2 rectal cancer, who are not normally given neoadjuvant chemoradiotherapy," they write.

"Although the study of Appelt and colleagues is a valuable contribution to the evidence base of watchful waiting for patients with low rectal cancer, no consensus has been made on policies for optimum selection of patients, method of imaging, assessment of clinical complete response, follow-up, and chemoradiotherapy regimen," the editorial concludes. "More data and long-term outcomes are needed before this strategy could be safely incorporated into medical practice for suitable patients."

SOURCE: http://bit.ly/1JxxN7m and http://bit.ly/1IkwY7a

Lancet Oncol 2015.