Quality of life deficits offset benefits of preoperative rectal radiation therapy

ABSTRACT: The quality-of-life outcomes offer a sobering corollary to the previously reported findings of the Medical Research Council CR07 trial.

Although preoperative radiotherapy has been shown to improve recurrence and mortality rates in patients with rectal cancer, a quality-of-life analysis by the same researchers suggests that male sexual dysfunction and fecal incontinence may be the trade-offs for those improved outcomes.

Patients randomized to be treated preoperatively with a short course of radiotherapy were more likely to report impaired male sexual function and unintentional release of stools at two and three years than those who did not receive the preoperative therapy, according to research from St. James’ University Hospital in Leeds, UK. Other quality-of-life measures did not differ significantly between the two groups.

According to the results, preoperative radiotherapy did not appear to impact sexual interest or enjoyment. Male Sexual Functioning (MSF) was negatively affected by surgery at three months (P = .001), but with no difference between treatment arms. Preop radiotherapy did negatively affect MSF mean scores at six months (P = .030) and this difference continued out to three years (P = .078).

The quality-of-life outcomes of the 1,350-patient multinational study offered a somewhat sobering corollary to CR07’s previously reported clinical findings. Based on earlier research, the group reported that three-year local recurrence rates were significantly lower in those who underwent preoperative radiotherapy than in those who did not (4% vs 11%). Disease-free survival and overall survival rates were also higher in the preoperative radiation group (ASCO 2006 abstract 3511).

“This illustrates modern oncology, where we know a treatment may offer a particular benefit but also potential long-term side effects,” said David Sebag-Montefiore, MBBS. “We wanted to evaluate the cost of that treatment. Having done so, that allows us to talk to patients about both risk and benefit, and allows them to make an informed decision.”

All study subjects had potentially operable, nonmetastatic adenocarcinoma of the rectum; 73% were male. Patients in the preop group received five daily fractions of 5 Gy each prior to surgery. Of patients randomized to the other treatment arm, those with confirmed pathology in the resection margins received 45 Gy of postoperative radiotherapy (delivered in 25 fractions over five weeks) plus chemotherapy (ASTRO 2008 abstract 61).

Three months following surgery, male sexual function did not differ significantly between the two groups, suggesting that much of the adverse effect is attributable to the surgery. However, the longer-term findings indicate that the preoperative radiotherapy may have an additional detrimental effect.

“We know the surgical procedure can have an effect on the nerves that interfere with bowel and sexual function,” Dr. Sebag-Montefiore commented. “The radiation damage is probably to the microvasculature of the same structures, but the details are still being worked out.”

The findings are consistent with those of a Dutch study reporting that preoperative radiotherapy was associated with impaired sexual function (in both sexes) and slower recovery of bowel function at two-year follow up (J Clin Oncol 23:6199-6206, 2005).

Nevertheless, Dr. Sebag-Montefiore pointed out that not all patients who received preoperative radiation experienced the same adverse effects, and that researchers are working to identify variables that could predict how a given patient will respond.

“We have to be careful, because we’re talking about mean scores,” he said. “This is preliminary. This is the start. There will be more data to come in the future” (see Sidebar).