Elsevier

Clinical Genitourinary Cancer

Volume 17, Issue 5, October 2019, Pages 332-347.e2
Clinical Genitourinary Cancer

Review
Quality-of-Life Assessment and Reporting in Prostate Cancer: Systematic Review of Phase 3 Trials Testing Anticancer Drugs Published Between 2012 and 2018

Presented in part at the American Society of Clinical Oncology Genitourinary Cancers Symposium, San Francisco, CA, February 14-16, 2019.
https://doi.org/10.1016/j.clgc.2019.07.007Get rights and content

Abstract

Quality of life (QoL) is not included among the end points in many studies, and QoL results are underreported in many phase 3 oncology trials. We performed a systematic review to describe QoL prevalence and heterogeneity in QoL reporting in recently published prostate cancer phase 3 trials. A PubMed search was performed to identify primary publications of randomized phase 3 trials testing anticancer drugs in prostate cancer, issued between 2012 and 2018. We analyzed QoL inclusion among end points, presence of QoL results, and methodology of QoL analysis. Seventy-two publications were identified (15 early-stage, 20 advanced hormone-sensitive, and 37 castration-resistant prostate cancer [CRPC]). QoL was not listed among study end points in 23 studies (31.9%) (40.0% early stage, 40.0% advanced hormone sensitive, and 24.3% CRPC). QoL results were absent in 15 (30.6%) of 49 primary publications of trials that included QoL among end points. Overall, as a result of absent end point or unpublished results, QoL data were lacking in 38 (52.8%) primary publications (53.3% early stage, 55.0% in advanced hormone sensitive, and 51.4% in CRPC). The most commonly used QoL tools were Functional Assessment of Cancer Therapy–Prostate (FACT-P) (21, 53.8%) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (EORTC QLQ-C30) (14, 35.9%); most common methods of analysis were mean changes or mean scores (28, 71.8%), time to deterioration (14, 35.9%), and proportion of patients with response (10, 25.6%). In conclusion, QoL data are lacking in a not negligible proportion of recently published phase 3 trials in prostate cancer, although the presence of QoL results is better in positive trials, especially in CRPC. The methodology of QoL analysis is heterogeneous for type of instruments, analysis, and presentation of results.

Introduction

The treatment landscape of prostate cancer has undergone substantial changes over the past years, with several drugs approved by regulatory agencies in the setting of metastatic castration-resistant prostate cancer (CRPC), metastatic hormone-sensitive prostate cancer, and, most recently, nonmetastatic CRPC. Although these new treatments have produced encouraging results in terms of efficacy, it is critical for new therapies to show an improvement not only in terms of quantity of life but also quality of life (QoL).1

Patient-reported outcomes (PROs), which are outcomes evaluated directly by patients themselves,2 are currently considered to be the reference standard for the assessment of patient experience of the disease and its treatment.3 Health-related QoL is a specific and multidimensional type of PRO, defined as “the patient’s subjective perception of the impact of his disease and its treatment(s) on his daily life, physical, psychological and social functioning and well-being.”2 The evaluation of QoL is of paramount importance for patients with prostate cancer. The balance between disease-related symptoms and treatment-related adverse effects is even more delicate in this population because of advanced age, frequent comorbidities, and risk of frailty. The longer life expectancy of prostate cancer patients and the improved efficacy of new treatments cause prolonged drug assumption and risk of developing treatment-related adverse events,4 and can greatly affect patients’ QoL. This is becoming even more relevant in recent years, with the progressive intensification of treatment by moving to earlier-stage therapies that were initially approved only in the setting of metastatic CRPC. Furthermore, in a context like prostate cancer, where the number of existing options keeps growing, the evaluation of QoL could be the ace in the hole in the process of decision making,5 especially if alternative treatments produce similar efficacy results. Prostate cancer working groups recognize the importance of evaluating PROs in both clinical trials and in routine clinical care.6, 7 Notably, the Prostate Cancer Clinical Trials Working Group 3 recommends the measure of disease-related symptoms, including pain intensity and interference as well as physical functioning, using validated instruments.6 The Advanced Prostate Cancer Working Group of the International Consortium for Health Outcomes Measurement, although recognizing the existence of logistic challenges, suggests that patient-reported health status should be regularly evaluated in clinical practice.7

Even though the entire oncologic community agrees on the relevance of QoL evaluation to better define the value of treatments tested in clinical trials and to optimize patients’ management in clinical practice, the adoption of QoL tools is actually far from optimal. In a previous systematic review of phase 3 randomized controlled trials conducted in all solid tumors published by major journals between 2012 and 2016, QoL was not included among end points in 210 (47%) of 446 of the primary publications analyzed—a not insignificant number.8 Moreover, we found that even when QoL is included as an end point, QoL results are underreported and have a substantial delay in publication compared to primary results.

In this systematic review, we sought to describe QoL prevalence as an end point in randomized phase 3 trials published between 2012 and 2018 that tested anticancer drugs in prostate cancer patients. In addition, we evaluated QoL reporting deficiencies by investigating the underreporting of QoL results and the methodology of QoL assessment.

Section snippets

Methods

A literature search was performed of the PubMed database on March 1, 2019, to identify all primary publications of randomized phase 3 trials testing anticancer drugs in patients with prostate cancer published between 2012 and 2018. The following keywords were used: prostate AND (cancer OR *carcinoma) AND (random* OR “phase 3”) AND (“2012”[Date - Publication]: “2018”[Date - Publication]).

Trials testing supportive-care drugs were excluded from the analysis unless their outcome was anticancer

Study Characteristics

A flowchart of the study selection process is shown in Supplemental Figure 1 in the online version. Overall, 72 eligible publications were included in the analysis including a total number of 60,158 randomized patients.10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79,

Discussion

This systematic review of recently published randomized phase 3 trials evaluating anticancer drugs in prostate cancer patients found that QoL data are absent in a high proportion of publications, although we found that QoL results were more frequently reported in positive trials, especially in the CRPC setting. Furthermore, the methodology of QoL analysis is heterogeneous in terms of type of instruments, methodology of analysis, and presentation of results.

These results demonstrate the need for

Conclusion

Our systematic review, based on prostate cancer trials published during the last few years, shows that the adoption of QoL among end points, as well as attention to timely and exhaustive reporting of QoL results, requires improvement. Indeed, QoL information is lacking in a not negligible proportion of recently published phase 3 trials in prostate cancer, either as a result of the absence of QoL among trial end points or the absence of such results in the publication. Disappointingly, despite a

Disclosure

M.A. has received fees for consulting or advisory board roles from Bristol-Myers Squibb, Merck, and Roche. G.V.S. has received honoraria from Roche, Pfizer, AstraZeneca, Lilly Pharma, and Merck Sharp & Dohme. F.P. has received personal fees from Bayer, Sandoz, Incyte, Celgene, AstraZeneca, Pierre Fabre, and Janssen-Cilag. M.D.M. has received personal fees from Bristol Myers Squibb, Merck Sharp & Dohme, Roche, AstraZeneca, Janssen, and Takeda. The other authors have stated that they have no

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