Preoperative and Postoperative radiotherapy and survival in colorectal cancer

Sir--The Colorectal Cancer Collaborative Group¹ clearly show that neither preoperative nor postoperative radiation therapy has an appreciable effect on overall survival in patients with this disease.

Patients who received postoperative radiation therapy did have a 9% lower risk of death from rectal cancer than controls. But this survival advantage was all but wiped out by the more frequent deaths from other causes in the radiation therapy group. Overall, the risk of death from causes other than rectal cancer was 15% higher in those who received radiation therapy than in those who did not, a significant difference.

The Collaborative Group state that there was no clear benefit of radiotherapy for overall survival. Yet, B Minsky, in his Oct 20 commentary,² believes that the study results support the use of adjuvant radiation therapy for rectal cancer. That conclusion arises because preoperative radiation therapy did decrease the chance of a recurrence at 5 years by 7%. The Collaborative Group also believe that since uncontrolled local recurrence can have a devastating effect on patients' quality of life, improved local control with radiotherapy might be a sufficient benefit to justify this treatment's use.

Yes, uncontrolled local recurrences are devastating. But so too are excess deaths caused by radiation therapy, such as through cardiovascular disease, infections, and other, unknown, causes. The researchers and Minsky do not mention that the side-effects to the bowel of radiation therapy can devastate patients' quality of life. Patients receiving radiation therapy for rectal cancer have more chronic bowel dysfunction than do those who undergo surgical resection alone.³ Diarrhoea, bleeding, tenesmus, and pain on defecation are frequent during therapy.

These symptoms commonly subside when treatment stops. However, 6 months to 1 year or more later, delayed postradiation symptoms can develop. In one textbook these symptoms are described: "There may be two to four or even eight or more bowel movements a day, and the urgency may be compelling. Blood is also often seen. Tenesmus is frequent, and cramping pain is often associated with defecation. Radiation proctitis frequently is associated with pain and bleeding; the latter may be severe and persistent, occasionally requiring transfusions . . . Severe or complete obstruction may develop."⁴

Any assessment of radiation therapy must take into account not just the statistical effect of treatment on recurrences, but what patients actually experience as a result of the treatment. What patients and their families need is the complete picture, of costs as well as benefits, without which it is impossible for them to make educated treatment decisions. But how many rectal cancer patients, I wonder, are told that adjuvant radiation therapy has not been proven to extend life but may in fact cause serious short-term and long-term adverse effects? How many are told that adjuvant radiation may in fact lead to their untimely deaths?

Ralph W Moss

The Moss Reports, PO Box 8183, State College, PA 16803, USA (e-mail:moss@cancerdecisions.com)

1 Colorectal Cancer Collaborative Group. Adjuvant radiotherapy for rectal cancer: a systematic overview of 8507 patients from 22 randomised trials. Lancet 2001; 358: 1291-304. [Text]

2 Minsky BD. Adjuvant radiation therapy for rectal cancer: is there finally an answer? Lancet 2001; 358: 1285-86. [Text]

3 Kollmorgen CE, Meagher AP, Wolff BG, Pemberton JH, Martenson JA, Illstrup DM. The long-term effect of adjuvant postoperative chemoradiotherapy for rectal carcinoma on bowel function. Ann Surg 1994; 1220: 676-82.

4 Fajardo LF, Berthrong M, Anderson RE. Radiation Pathology. Oxford: Oxford University Press, 2001: 244-45.

Authors' reply

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We agree with Ralph Moss that the benefits of radiotherapy in preventing recurrence and death from rectal cancer need to be balanced against short-term and long-term adverse effects. However, we believe that the available data suggest that the benefits from adding radiotherapy to surgery for rectal cancer probably outweigh the negative consequences for many patients. Radiotherapy, at adequate preoperative doses, significantly improved overall survival, even though some of the included trials used outdated--and hazardous--radiation techniques. Thus, although an extension of life has not been the primary aim of radiotherapy, modern techniques that deliver radiotherapy more accurately will probably produce a net survival benefit. Long-term follow-up of late effects in recent trials is needed to be sure, but adverse effects on quality of life so far seem mild.^1,2

Finally, we believe that most patients offered radiotherapy for rectal cancer are adequately informed about the potential negative consequences as well as the established benefits. It would not be helpful to list the postradiation symptoms cited by Moss, however, since they are hardly ever seen with the doses used to kill microscopic disease that might be left after apparently curative rectal cancer surgery.

*Richard Gray, Bengt Glimelius, Robert Hills, Joanna Marro, Rebecca Stowe, for the Colorectal Cancer Collaborative Group

Birmingham Clinical Trials Unit, Park Grange, Edgbaston, Birmingham B15 2RR, UK (e-mail:R.Gray@bham.ac.uk)

1 Glimelius B, Isacsson U. Preoperative radiotherapy for rectal cancer--is 5x5 Gy good or a bad schedule? Acta Oncol 2001; 40: 958-67. [PubMed]

2 Marijnen CAM, Kapiteijn E, van de Velde CJH, et al. Acute side-effects and complications after short-term preoperative radiotherapy combined with total mesorectal excision in primary rectal cancer: report of a multicenter randomized trial. J Clin Oncol 2002; 20: 817-25. [PubMed]