Standard treatment for locally advanced rectal cancer: some concerns remain

This review highlights the existing concerns facing treatment of locally advanced rectal cancer patients with preoperative chemotherapy.

Locally advanced rectal cancer indicates that the cancer has spread beyond the lining of the rectum or has spread to the nearby lymph nodes. Preoperative chemoradiotherapy (PCRT; chemotherapy and radiation administered before surgery) is used to treat locally advanced rectal cancer. It was shown to decrease the rate of local recurrence (return of the cancer close to the place of the initial cancer) and cause lower treatment-related toxicity compared with chemoradiotherapy administered after surgery.

These findings led to a change from chemoradiotherapy after to before surgery, and PCRT is now the standard treatment for locally advanced rectal cancer.

This shift in the timing of chemoradiotherapy has improved patient outcome but a series of concerns remain. This study highlights four of these concerns.

Concern 1: Will the patient respond to treatment?

One major concern is that not all tumors respond to chemoradiotherapy. For non-responders, undergoing PCRT delays surgery and exposes the patient to unnecessary levels of drugs, which can have side effects. Currently there is no way of predicting which patients will or will not respond to treatment; further research is required, as this would greatly benefit patient care.

Concern 2: Is too much bowel being removed?

After PCRT, total mesorectal excision (TME) is the standard surgery for patients with locally advanced rectal cancer, which involves removing the tumor and a large portion of bowel surrounding it. However, for patients who have complete regression (disappearance) of the tumor this may be an unnecessary risk.

It may be possible to treat these patients with local excision (minimal amounts of intestine are removed), while other patients may benefit form a “wait and watch” treatment approach. “Wait and watch” avoids surgery, and patients are instead monitored for any signs of the cancer returning. Initial studies found that 5-year rates of survival were similar for patients with a complete response in the “wait and watch” group (100%) compared to the surgery group (88%). However, newer studies have not been able to recreate these early results and concern surrounding the safety of "wait and watch" exists, especially for patients with cancer that has spread to the outer layers of the rectum. The “wait and watch” approach may still be useful for older or more vulnerable patients who may not by fit for standard surgery.

Concern 3: Is there really less risk of sphincter injury?

Early studies found that PCRT improved the chance of sphincter preservation (the ring of muscle surrounding the anal canal remains unaffected by surgery; patients with sphincter injury may need to wear a pouch to collect the waste produced by the bowel). However, no trial since 1980 have been able to repeat this finding. When the results of all recent trials were pooled together there was a small trend towards improved sphincter preservation in patients who received PCRT (6% lower risk). Again further research is required.

Concern 4: Do all patients need chemotherapy after surgery?

The current guidelines include administering chemotherapy to patients after their surgery. However, some doctors are concerned that this exposes some patients to unnecessary levels of drugs. Again, being able to predict which patients will benefit from treatment would greatly benefit patient care. However, it is certain that if patients have not responded to PCRT they should receive a different chemotherapy drug after surgery.

The authors concluded that some concerns regarding the treatment for locally advanced rectal cancer still need to be addressed. They suggest that improvements in predicting patients’ responses to PCRT would be beneficial.