Reply to Nelson Martinez Merizalde Balarezo, Mark Monroe Rivera, and Romina A. Tejada's Letter to the Editor

We would like to thank Dr. Martinez Merizalde Balarezo and colleagues for their interest in our systematic review and their valuable comments. We agree that health-related quality of life (HRQOL) is an important outcome measure for the evaluation of new therapies.
For approval of new drugs, both the US Food and Drug Administration (FDA) and the European Medicine Agency (EMA) are increasingly taking HRQOL measures into account. The FDA has proposed a uniform strategy in which patient-reported outcomes are measured via a separate analysis of symptomatic adverse events, physical function, and disease-related symptoms. In addition, the European Society for Medical Oncology (ESMO) has developed the ESMO Magnitude of Clinical Benefit Scale to compare clinical benefit outcomes among clinical trials, taking into account efficacy, safety, and quality of life.
Assessment of HRQOL has only recently started to be incorporated in clinical trials in urological cancers. HRQOL was assessed in three out of six randomized clinical trials (RCTs) included in our systematic review on immune checkpoint inhibition in urological cancers. HRQOL outcomes were reported in the primary publication for only one of these studies. For the other two studies, HRQOL outcomes were presented more recently or have not been published yet. As inclusion of HRQOL measures was very limited in the selected trials, a detailed analysis of HRQOL results could not be included in our systematic review. To overcome this limitation, we mentioned the HRQOL results from two RCTs in our systematic review. In patients with advanced urothelial cell cancer, the HRQOL score (measured by the European Organization for Research and Treatment of Cancer core 30 quality of life questionnaire) remained stable from baseline to week 15 in the pembrolizumab arm, whereas a decrease was observed in the chemotherapy arm. Patients treated with pembrolizumab also experienced a longer time to deterioration compared to those who received chemotherapy. Finally, HRQOL outcomes improved in patients without disease progression during pembrolizumab treatment, whereas the scores deteriorated in patients who received chemotherapy. In the RCT comparing nivolumab with everolimus in renal cell cancer (RCC) patients, HRQOL was assessed using the Functional Assessment of Cancer Therapy–Kidney Symptom Index–Disease Related Symptoms (FKSI-DRS) and European Quality of Life-5 Dimensions questionnaires. Compared to patients treated with everolimus, patients who received nivolumab experienced a greater improvement in HRQOL outcomes. In another recent trial, HRQOL (determined using the FKSI-19 questionnaire) improved in RCC patients treated with first-line nivolumab plus ipilimumab when compared to first-line sunitinib. In all three RCTs, a thorough analysis of HRQOL was performed, confirming that this outcome measure is gaining importance in current clinical trials in urological cancer. Although a lack of uniformity in the evaluation of HRQOL remains, as also mentioned by Martinez Merizalde Balarezo et al. and illustrated above, the increasing assessment of HRQOL outcomes in urological cancer will allow for detailed review in the future.