ECC 2013 Report: Gastrointestinal malignancies – colorectal cancer

LM Wiltink, Leiden University Medical Center, the Netherlands; Hans-Joachim Schmoll, Martin Luther University Halle – Wittenberg, Germany.  A unique 14-year follow-up study from the universities of Leiden in the Netherlands and Aarhus in Denmark shows that although radiation therapy prior to excision of CRC reduces the risk of local recurrence, patients pay a considerable price in terms of long-term quality of life. Dr LM Wiltink presented results from a health-related quality of life (HRQL) analysis in patients included in the Dutch Total Mesorectal Excision (TME) trial in the late 1990s.

The TME trial investigated the benefit of adding a short course of radiotherapy prior to TME in 1,530 patients diagnosed with CRC between 1996 and 1999. Although the primary analysis failed to show a significant benefit in terms of overall survival, the adjuvant radiation significantly reduced the risk of local tumour recurrence compared with TME alone  [1]. In 2012, a total of 583 patients were still alive and could be located. These patients were sent a comprehensive package of HRQL questionnaires, including the cancer-specific EORTC QLQ-C30 tool, the EORTC QLQ-C29 for specific colorectal symptoms, the 2003 HRQL questionnaire adapted for binary yes/no responses, the low anterior resection syndrome (LARS) score, and several scales for assessing sexual function.

A total of 478 patients responded, equivalent to a response rate of 82%, with a median follow up of 14.6 years. Although overall HRQL and functioning was similar in the two original treatment groups, significantly more patients in the radiation group reported bowel dysfunction and use of incontinence pads. Male patients also reported more erectile dysfunction (Table 1). The team also compared the 14-year HRQL findings with data reported for the Dutch population in general and found that the TME patients had lower functioning scores and reduced sexual quality of life.

Table 1. Overview of key results, 14-year HRQL follow-up

	Mean score		P
	PRT (N=241)	TME (N=237)
Physical functioning	77.4	80.9	0.08
Role functioning	79.4	81.4	0.30
Emotional functioning	86.1	85.8	0.35
Cognitive functioning	83.3	84.0	0.33
Social functioning	86.8	87.7	0.59
Global health status	77.2	78.5	0.16
Stool frequency	26.3	19.4	<0.01
Faecal leakage	22.5	10.1	<0.001
Frequency of use of pads for faecal leakage	56.4	38.4	<0.001
Involuntary urine loss	41.8	41.3	0.88
Frequency of use of pads for urine loss	46.5	44.1	0.73
Sexually active	38.0	41.3	0.08
Difficulty getting or maintaining an erection	79.3	66.8	<0.01

PRT, preoperative short-term radiotherapy; TME, total mesorectal excision.

In his discussion of the study, Dr Robert Glynne-Jones from London pointed out that very few randomised clinical trials in this setting have captured HRQL data, especially beyond the first few years after surgery, which makes this dataset very important for understanding the balance between ongoing quality of life and risk in patients undergoing radical surgery. Dr Glynne-Jones was particularly impressed with the 82% response rate which he described as ‘amazing’.

Another study to provide important secondary endpoints for discussion in this session was the PETACC-6 trial, which aimed to investigate whether the addition of oxaliplatin to preoperative oral fluoropyrimidine-based chemoradiation (CRT) followed by postoperative adjuvant fluoropyrimidine-based chemotherapy (CT) improves disease-free survival (DFS) in locally advanced rectal cancer. Professor Hans-Joachim Schmoll from Halle in Germany reported on an analysis of data from 1,094 patients with rectal cancer within 12 cm from the anal verge who received preoperative CRT with capecitabine followed by CT with capecitabine with or without the addition of oxaliplatin before and after surgery. The results showed that adjuvant oxaliplatin caused higher toxicity levels and reduced treatment compliance, with no clinically relevant improvement in R0 resection rate (87.2% vs 92.3% with no oxaliplatin; p<0.01), ypT0N0 rate (13.0% vs 11.5%; p=ns) or sphincter preservation (65.4% vs. 69.3%; p=ns). The final primary analysis of DFS in the two treatment arms will be presented next year. In the discussion of the results, Dr Glynne-Jones predicted that the argument whether the clinical benefit of adjuvant oxaliplatin after 5-fluorouracil-based chemoradiation will continue for some time yet; however, in his view PETACC-6 is an innovative study which will add important knowledge on how to best integrate chemotherapy into radiotherapy schedules.

Reference

1.   Kapiteijn, E., et al., Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med, 2001. 345(9): p. 638-46.