QoL is a cool tool
Authors: L. Procaccio, S. Lonardi, F. Loupakis, M. Di Maio
Journal: Annals of Oncology (2017)

We read the manuscript by Dr Schuurhuizen et al., questioning the validity of the global quality of life (QoL) measurements in metastatic colorectal cancer (mCRC) [1.Schuurhuizen C.S.E.W. Braamse A.M.J. Konings I.R.H.M. et al.Does severe toxicity affect global quality of life in patients with metastatic colorectal cancer during palliative systemic treatment? A systematic review.Ann Oncol. 2017; 28: 478-486Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar]. Over the last decade, an increasing number of published studies reported QoL outcomes, and regulatory agencies have emphasized the relevance of patient-reported outcomes in the balanced evaluation of benefits and risks associated with new treatments. Nevertheless, measuring QoL poses more challenges than traditional endpoints. The need for improving QoL analyses is crucial and several efforts are underway, such as the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) initiative [2.Bottomley A. Pe M. Sloan J. et al.Analysing data from patient-reported outcome and quality of life endpoints for cancer clinical trials: a start in setting international standards.Lancet Oncol. 2016; 17: e510-e514Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar]. Schuurhuizen et al. lay the basis of their work on the question ‘does severe toxicity affect global QoL?’ Here arises the confusion: description of side-effects and QoL measurement give complementary, but very different information. QoL is a complex and multi-dimensional concept that refers to patients’ subjective perception of the effect of their disease and treatment on physical, psychological and social aspects of daily life [2.Bottomley A. Pe M. Sloan J. et al.Analysing data from patient-reported outcome and quality of life endpoints for cancer clinical trials: a start in setting international standards.Lancet Oncol. 2016; 17: e510-e514Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar]. The need for exploring the correlation between toxicity, survival and QoL in mCRC is not new. Back in 2006, de Kort et al. [3.de Kort S.J. Willemse P.H. Habraken J.M. et al.Quality of life versus prolongation of life in patients treated with chemotherapy in advanced colorectal cancer: a review of randomized controlled clinical trials.Eur J Cancer. 2006; 42: 835-845Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar] already reported that out of 17 trials where toxicity was significantly higher in the experimental arm, QoL was negatively affected in only two. The authors judiciously concluded that toxicity and QoL are two different, independent variables that cannot be exchanged with or that neutralize each other. In the context of palliative treatments, the goal is defined as prolonging life with preservation of QoL. Indeed, we doubt that the metastatic setting, where treatment may cause both side-effects and control of tumour-related symptoms, is a good setting for exploring the correlation between toxicity and QoL. Even in other solid tumours, there are many examples of trials that compared treatments associated with definitely different toxicity, without demonstrating a significant difference in global QoL. For instance, in patients with advanced non-small cell lung cancer, a platinum-based combination was associated with a relevant increase in toxicity compared with a platinum-free doublet, but without difference in global QoL, suggesting that the magnitude of symptom control can be at least as important as treatment toxicity in modifying global QoL [4.Gridelli C. Gallo C. Shepherd F.A. et al.Gemcitabine plus vinorelbine compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer: a phase III trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada Clinical Trials Group.J Clin Oncol. 2003; 21: 3025-3034Crossref PubMed Scopus (237) Google Scholar]. On the contrary, when a treatment is clearly better in terms of disease control, the difference in global QoL can be quite clear [5.Di Maio M. Leighl N.B. Gallo C. et al.Quality of life analysis of TORCH, a randomized trial testing first-line erlotinib followed by second-line cisplatin/gemcitabine chemotherapy in advanced non-small-cell lung cancer.J Thorac Oncol. 2012; 7: 1830-1844Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar]. Two additional points weaken the analysis presented by Schuurhuizen. Results are presented without distinguishing specific side-effects. How would the authors argument towards the potential biases of trials with anti-EGFRs (whose dermatological toxicity is correlated to treatment efficacy) or with oxaliplatin (causing cumulative neuropathy, which increases with duration of treatment, potentially implying higher toxicity in responding patients)? Schuurhuizen et al. concluded that ‘the use of global QoL for comparing treatment arms in RCTs for patients with mCRC does not provide information of clinical relevance’. Based on the above reported observations, we found this statement to be rather hasty and disputable. It poses the risk of throwing the baby out with the bathwater. None declared.