Multidisciplinary approach improves rectal cancer outcomes

February 25, 2009

STOCKHOLM-For rectal cancer patients, a multidisciplinary team is critical to success because it increases the possibility of a curative resection, Andres Cervantes, MD, associate professor of medicine at University Hospital, Valencia, Spain, said at ESMO 2008. “Every patient should be treated within an expert multidisciplinary team,” he emphasized.

ABSTRACT: A team of specialists addressing the perioperative management of rectal cancer ensures optimal selection of patients for pre- and postoperative therapy.

STOCKHOLM-For rectal cancer patients, a multidisciplinary team is critical to success because it increases the possibility of a curative resection, Andres Cervantes, MD, associate professor of medicine at University Hospital, Valencia, Spain, said at ESMO 2008. “Every patient should be treated within an expert multidisciplinary team,” he emphasized.

Core team members include an imaging specialist with experience in MRI, at least two surgeons well trained in total mesorectal excision (TME), a pathologist familiar with the particulars of rectal tumors, a radiation oncologist with a focus on rectal cancer, a medical oncologist, and clinical nurse specialists.

“The anticipated benefits of such a group include improved coordination of care, ability to consider each case from different perspectives and offer a range of treatments, an environment that supports the sharing of professional concerns, feedback from pathologists to other team members, and an optimal setting for clinical research,” Dr. Cervantes said.

The convergence of these various perspectives has led to a new approach to treating rectal cancer that involves MRI staging, multidisciplinary team discussion, TME resection, pathology assessment and risk estimation, and optimal selection of patients for preoperative treatment and postoperative chemotherapy if indicated.

Discussions among a multidisciplinary team have been shown to change care in a large percentage of cases. Gina Brown, MD, and colleagues showed that when potentially curative cases were not discussed by a team, 100% of patients were treated with surgery alone. When multidisciplinary discussions were held, 59% had surgery alone while 41% also underwent preoperative chemoradiotherapy on the basis of tumor size, nodal involvement, or predicted circumferential resection margin (CRM) positivity. Without team discussion, more patients also had histologically positive CRMs, 26% vs 1% when cases were discussed (Br J Cancer 94:391-397, 2006).

Make MRI mandatory
For staging, the use of high-resolution MRI, which consistently shows the mesorectal fascia, optimizes the selection of patients at risk of a positive CRM, and identifies other prognostic factors, such as venous invasion, distance to the mesorectal fascia, and sphincter involvement. This approach, therefore, can prevent incomplete surgical resection and can identify patients who need preoperative chemoradiotherapy.

“CRM involvement is the crucial prognostic factor after multimodality treatment in patients with locally advanced rectal cancer,” Dr. Cervantes noted. Th e importance of the CRM in predicting outcomes was shown in a 2008 review of more than 17,500 patients. CRM was found to be a valid shortterm outcome parameter of local relapse, distant metastases, and poor survival (J ClinOncol 26:303-312, 2008).

Preoperative staging by MRI is now advocated in guidelines and is in use by many centers. At the World Congress on Gastrointestinal Cancer 2007 in Barcelona, an expert panel devised recommendations for the diagnosis and management of rectal cancer (Ann Oncol 19[suppl 6]:vi1-vi8, 2008.)

“The task ahead is to make MRI mandatory for all patients with rectal cancer before treatment decisions are made at multidisciplinary meetings,” Dr. Cervantes said.

Preoperative strategies
The multidisciplinary treatment of rectal cancer offers the potential for a curative surgical resection with microscopic-free margins. “Treatments designed to improve the rate of radical resectability are of great importance,” Dr. Cervantes said.

Radiotherapy improves local control. In general, preoperative treatment is preferred to postoperative treatment. Recently, several randomized trials have confirmed the value of short-course preoperative radiotherapy and long-term fractionated preoperative radiotherapy with concurrent chemotherapy for local disease (see Table on page 25). In all the studies, short-course preoperative radiotherapy increased local control over surgery alone.

The concurrent administration of chemotherapy with preoperative long-term fractionated radiotherapy is now considered by many a standard of care for localized disease, Dr. Cervantes said.

Chemoradiotherapy induces higher curative resection and pathologic complete response rates than radiation alone, with significant prolongation of time to treatment failure and improvement in cancer specific survival. Trials have not, however, shown improvements in overall survival.

The preoperative use of chemoradiotherapy offers better local control with less acute or long-term toxicity than adjuvant chemoradiotherapy. In a randomized phase III trial, Rolf Sauer, MD, and co-investigators found that grade 3-4 toxicities, both acute and chronic, were almost half as likely with preoperative treatment (N Engl J Med 351:1731-1740, 2004).

Dr. Cervantes noted that recent trials, showing no definitive effect of preoperative chemoradiotherapy on survival, enrolled patients based on clinical rather than MR staging. Also, TME was not progressively established during the trial period, and the involvement of the CRM was not always described in these studies.

“In future trials, the standardization of surgery and pathology reports should make the sample more homogeneous and allow for more appropriate interpretation of results,” he said.

Dr. Cervantes called the recent achievements in local control “amazing,” with local relapse rates of 6% to 9% in recent trials, vs more than 25% in trials from the 1980s. “Unfortunately, the rate of distant metastases remains similar for the two time periods, which makes the development of effective adjuvant chemotherapy a priority,” Dr. Cervantes said.

While level one evidence for adjuvant chemotherapy is lacking, a pooled analysis of group trial data on nearly 4,000 patients showed a survival benefit for adding chemotherapy to surgery or surgery plus radiation. And the recent QUASAR trial, which evaluated 5-FU-based adjuvant chemotherapy vs observation in colorectal cancer patients (30% rectal) at low risk for recurrence, documented a 3% absolute survival benefit for adjuvant chemotherapy. This benefit was maintained in the rectal cancer subgroup (Lancet 370:2020-2029, 2007).

The benefi t of chemoradiotherapy in unresectable tumors was shown in a Scandinavian trial of 207 patients with T4 tumors. Patients were randomized to receive chemotherapy concurrently with radiotherapy plus adjuvant chemotherapy for 16 weeks after surgery or radiotherapy alone. At five years, chemoradiotherapy signifi cantly improved local control (82% vs 67%), time to treatment failure (63% vs 44%), and cancer-specific survival (72% vs 55%). Overall survival was improved numerically but not statistically (66% vs 53%). Grade 3-4 toxicity occurred in 29% and 6%, of patients respectively (J Clin Oncol 26:3687-3694, 2008).

“There is no consensus on the use of adjuvant chemotherapy in patients with resected rectal cancer, but its use is widespread,” Dr. Cervantes added. “Benefits may also be extrapolated from colon cancer trials.”

In the future, survival may be further increased with chemotherapy to control micrometastases and with the use of newer agents such as oxaliplatin (Eloxatin), bevacizumab (Avastin), and cetuximab (Erbitux), which have become established in colon cancer.