Preoperative radiotherapy for rectal cancer

Abstract

In their prospective audit of waiting times for the treatment of rectal cancer (March 2004 JRSM1) Sarah Duff and her colleagues state that pre-operative short-course radiotherapy (SRT, 4 days×5 Gy) for rectal cancer reduces the risk of local recurrence and may translate into improved patient survival. However, much of the evidence for this benefit comes from the Swedish Rectal Cancer Trial which showed a relative survival benefit of 21% and an increase in the 5-year survival from 48% to 58% with a reduction of local recurrence from 27% to 11%.2 This would suggest that the benefits of adjuvant radiotherapy are dependent on a high local recurrence rate for surgery alone. With local recurrence rates of less than 10% there are no data demonstrating a beneficial effect with the addition of radiotherapy.3 Whilst local recurrence decreased from 8.2% to 2.4% after a median follow up of 2 years, the surgery-alone arm in the recent Dutch TME and SRT Trial had an unacceptably high local recurrence rate, especially as only mobile tumours were recruited. These data imply a background of oncologically inadequate surgery in a substantial proportion of patients.4 Despite attempts to ‘standardize’ surgery, by workshops and live demonstrations, 24% of specimens did not reach the required TME grade (Quirke grade 1 or 2), on account of violation of the fascial envelope, incision or tearing into the mesorectum and irregularities of the surface. Thus any SRT effect becomes inconclusive because of poor quality TME specimens. Furthermore, only curative resections were considered and no universal pretreatment staging system was used. Finally, though benefit from SRT was demonstrated in some patients for local recurrence, no effect was seen on survival out to 5 years (van de Velde C, personal communication). Predicted local recurrence in the Dutch TME Trial at 5 years would be 16-23% for surgery alone on high-risk rectal carcinoma if 55-80% of all local recurrences were observed during the first 2 years.5 Total mesorectal excision has been demonstrated to achieve a local recurrence rate of 6% at 5 years and 8% at 10 years, for rectal cancers of all stages, and 3% at 5 years and 4% at 10 years for curative resections, in a personal series—which is unique since the percentage of patients receiving preoperative radiotherapy was only 9%.6 Thus a local recurrence rate of 3% can lead to a cure rate of 80% at 5 years and 78% at 10 years. Preoperative radiotherapy is associated with toxicity, early complications and long-term side-effects, and should be used only when it is of benefit. Radiotherapy may be indicated in rectal carcinomas invading near to, or involving, the mesorectal fascia since radiotherapy produces maximal effect on the periphery of the tumour. MRI is the most promising modality to select out cases where the surgical resection margin is threatened. The balance of evidence suggests that the survival from rectal cancer does not change with SRT, which, as currently administered, does not downstage the tumour and does not compensate for surgical positive margins.7