Patient-reported outcomes (PROs) are being increasingly incorporated into oncology research. Both the American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) have recently supported the routine incorporation of quality of life (QOL) measures in clinical trials.1,2 Patient-reported outcome measures (PROMs) frequently used in oncology research include the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and the National Institute of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS).3
The measurement, validation, and reporting of PROMs can be challenging in clinical trials. However, if it is successfully accomplished, there has been evidence to support that validated PROMs can assist in providing high-quality care and improve a patient’s overall experience.3 Ideally, PROMs can help to improve communication between patients and their healthcare providers, improve symptomatic management, and assist researchers in collecting data that may not have been previously available.3 Consequently, the US Food and Drug Administration has made formal recommendations that PROMs used in clinical trials should include physical functioning, disease-related symptoms, and adverse events.4
Even once a PROM has been validated though clinical trials, it can be challenging to incorporate it into routine care for patients outside of the research setting. Recently, a review article authored by Bergerot and colleagues summarized the key findings from metastatic urinary cancer studies that published PROM-related data in the last 2 years.3
In looking at PROMs for prostate cancer specifically, it is known that many established therapies for metastatic prostate cancer (mPrCa) have known side effects that can affect a patient’s QOL. These include bone pain, erectile dysfunction, bowel and bladder incontinence, and fatigue.3 Six mPrCa studies were included in the review and the most frequently utilized PROMs included Functional Assessment of Cancer Therapy (FACT)-Prostate, EuroQoL (EQ-5D-3L), and Brief Pain Inventory Short Form (BPI-SF). Four of the trials with actual PROM data showed that by using their respective PROMs, there was at least maintenance of or improvement in QOL outcomes. These trials included TERRAIN (ClinicalTrials.gov Identifier: NCT01288911), LATITUDE (ClinicalTrials.gov Identifier: NCT01715285), SPARTAN (ClinicalTrials.gov Identifier: NCT01946204), and PROSPER (ClinicalTrials.gov Identifier: NCT02003924). Two of the 6 studies mentioned do not currently have complete PROM data available and will be interesting to follow-up on in the future.5,6
To further highlight the importance of incorporating PROMs in PrCa studies, Hoffman and colleagues recently published their findings at 5 years comparing multiple treatment modalities for localized PrCa such as active surveillance, surgery, brachytherapy, or external beam radiation (EBRT) with or without androgen deprivation therapy (ADT).7 This study evaluated 1386 men with favorable-risk prostate cancer compared to 619 men with unfavorable-risk prostate cancer in the United States. The PROMs utilized by the authors included the 26-item Expanded Prostate Index Composite (EPIC-26) and Medical Outcomes Study 36-Item Short Form Survey (SF-36) completed by patients 5 years after treatment. EPIC scores ranged from 0 to 100 with higher scores indicating better function. This score has been previously studied and validated, with the minimum clinically important differences (MCIDs) for each domain including 10 to 12 for sexual dysfunction, 6 to 9 for urinary incontinence, 5 to 7 for urinary irritation, 4 to 6 for bowel function, and 4 to 6 for hormonal function. SF-36 evaluated several QOL domains including energy, fatigue, physical functioning, and emotional well-being.
In the favorable-risk prostate cancer group, nerve-sparing prostatectomy was associated with worse urinary incontinence at 5 years (adjusted mean difference [AMD] -10.9; 95% CI, -14.2 to -7.6) and sexual function at 3 years (AMD -15.2; 95% CI, -18.8 to -11.5) when compared with active surveillance. At 1 year, low dose brachytherapy was associated with worse urinary irritation (AMD -7.0; 95% CI, -10.1 to -3.9), sexual function (AMD -10.1; 95% CI, -14.6 to -5.7), and bowel function (AMD -5.1; 95% CI -7.6 to -2.4) compared to active surveillance.
In men with unfavorable prostate cancer, EBRT with ADT had lower bowel function at 1 year (AMD -4.1; 95% CI, -6.3 to -1.9) but better sexual function (AMD 12.5; 95% CI, 6.2 to 18.7) and incontinence at 5 years (AMD 23.2; 95% CI, 17.7 to 28.7) when compared to prostatectomy. In general the researchers found that more invasive treatments, such as surgery, were more likely to negatively affect PROMs, most notably urinary incontinence and sexual dysfunction. In addition to urinary incontinence and sexual dysfunction, radiation therapy can also negatively impact bowel function but not as much as surgery. Combining ADT with EBRT can affect bowel function but still results in better sexual and bladder function compared with surgery.
Continuing to include PROMs in PrCa studies will help further elucidate the effect of treatments on patient outcomes and QOL. Further studies are needed in order to determine which PROMs may provide the most useful data and are the easiest to incorporate into real-life practice. PROMs can also potentially help patients to make more informed decisions about their treatment plan. It is crucial to weigh the results from PROM-dominant studies with the actual clinical outcome data with a healthcare provider in order to make the best informed decision.
- Schnipper LE, Davidson NE, Wollins DS, et al. American Society of Clinical Oncology statement: a conceptual framework to assess the value of cancer treatment options. J Clin Oncol. 2015;33:2563-2577.
- Cherny NI, Sullivan R, Dafni U, et al. Corrections to “A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMOMCBS)”. Ann Oncol. 2015;26:1547-1573.
- Bergerot CD et al. Patient-reported outcome measures in metastatic urinary cancers. Eur Urol Focus. 2020;6(1):26-30.
- Kluetz PG et al. Focusing on core patient-reported outcomes in cancer clinical trials: symptomatic adverse events, physical function, and disease-related symptoms. Clin Cancer Res. 2016;22:1553-1558.
- James ND, de Bono JS, Spears MR, et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017;377:338-351.
- EuroQol Group. EuroQol—a new facility for the measurement of health-related quality of life. Health Policy. 1990;16:199-208.
- Hoffman KE et al. Patient-reported outcomes through 5 years for active surveillance, surgery, brachytherapy or external beam radiation with or without androgen deprivation therapy for localized prostate cancer. JAMA. 2020;323(2):149-163.