Development, validation and evaluation of an instrument for active monitoring of men with clinically localised prostate cancer: systematic review, cohort studies and qualitative study

Abstract

BackgroundActive surveillance [(AS), sometimes called active monitoring (AM)],is a National Institute for Health and Care Excellence-recommended management option for men with clinically localised prostate cancer (PCa). It aims to target radical treatment only to those who would benefit most. Little consensus exists nationally or internationally about safe and effective protocols for AM/AS or triggers that indicate if or when men should move to radical treatment.ObjectiveThe aims of this project were to review how prostate-specific antigen (PSA) has been used in AM/AS programmes; to develop and test the validity of a new model for predicting future PSA levels; to develop an instrument, based on PSA, that would be acceptable and effective for men and clinicians to use in clinical practice; and to design a robust study to evaluate the cost-effectiveness of the instrument.MethodsA systematic review was conducted to investigate how PSA is currently used to monitor men in worldwide AM/AS studies. A model for PSA change with age was developed using Prostate testing for cancer and Treatment (ProtecT) data and validated using data from two PSA-era cohorts and two pre-PSA-era cohorts. The model was used to derive 95% PSA reference ranges (PSARRs) across ages. These reference ranges were used to predict the onset of metastases or death from PCa in one of the pre-PSA-era cohorts. PSARRs were incorporated into an active monitoring system (AMS) and demonstrated to 18 clinicians and 20 men with PCa from four NHS trusts. Qualitative interviews investigated patients’ and clinicians’ views about current AM/AS protocols and the acceptability of the AMS within current practice.ResultsThe systematic review found that the most commonly used triggers for clinical review of PCa were PSA doubling time (PSADT) < 3 years or PSA velocity (PSAv) > 1 ng/ml/year. The model for PSA change (developed using ProtecT study data) predicted PSA values in AM/AS cohorts within 2 ng/ml of observed PSA in up to 79% of men. Comparing the three PSA markers, there was no clear optimal approach to alerting men to worsening cancer. The PSARR and PSADT markers improved the modelc-statistic for predicting death from PCa by 0.11 (21%) and 0.13 (25%), respectively, compared with using diagnostic information alone [PSA, age, tumour stage (T-stage)]. Interviews revealed variation in clinical practice regarding eligibility and follow-up protocols. Patients and clinicians perceive current AM/AS practice to be framed by uncertainty, ranging from uncertainty about selection of eligible AM/AS candidates to uncertainty about optimum follow-up protocols and thresholds for clinical review/radical treatment. Patients and clinicians generally responded positively to the AMS. The impact of the AMS on clinicians’ decision-making was limited by a lack of data linking AMS values to long-term outcomes and by current clinical practice, which viewed PSA measures as one of several tools guiding clinical decisions in AM/AS. Patients reported that they would look to clinicians, rather than to a tool, to direct decision-making.LimitationsThe quantitative findings were severely hampered by a lack of clinical outcomes or events (such as metastases). The qualitative findings were limited through reliance on participants’ reports of practices and recollections of events rather than observations of actual interactions.ConclusionsPatients and clinicians found that the instrument provided additional, potentially helpful, information but were uncertain about the current usefulness of the risk model we developed for routine management. Comparison of the model with other monitoring strategies will require clinical outcomes from ongoing AM/AS studies.FundingThe National Institute for Health Research Health Services and Delivery Research programme.

Prostate‐specific antigen patterns in US and European populations: comparison of six diverse cohorts

“… PSA change in the six cohorts: change for a man with an initial PSA at age 50 of 2 ng/mL (left); change using actual estimated PSA at age 50 (right) .…”

“…To use PSA in AS programmes, a model for 'normal' PSA levels is needed as a comparator for observed PSA levels in men on AS. From 1 PSA change in the six cohorts: change for a man with an initial PSA at age 50 of 2 ng/mL (left); change using actual estimated PSA at age 50 (right) [42]. [5,31,32].…”

Establishing nurse-led active surveillance for men with localised prostate cancer: development and formative evaluation of a model of care in the ProtecT trial

“…Interviews were conducted by JW or CES (credentials in online supplementary appendix C), during which views on nurse-led AM were explored. In a related study exploring urologist-led AS practice in three centres not involved in the ProtecT trial, 22 purposive sampling was used to identify men across the age and socioeconomic range with low-risk localised PCa at diagnosis (Gleason score 6 and PSA ≤10 ng/mL) who had undergone AS for at least 12 months and were judged by their clinician to show no evidence of disease progression. Twenty men were given or sent a recruitment information pack which asked them to contact LR if they wished to participate in an interview with LR or JW about their views of AS.…”

“…Health professionals : All 12 urologists and 3 clinical nurse specialists (CNSs) delivering consultant-led AS in three clinics not involved in the ProtecT trial were invited for interview with LR or JW to discuss their views about AS. 22 All 11 urologists and 23 research nurses currently working in the ProtecT trial were invited to complete questionnaires about their experiences of delivering nurse-led AM.…”

Active monitoring, radical prostatectomy and radical radiotherapy in PSA-detected clinically localised prostate cancer: the ProtecT three-arm RCT

“…In a further study to evaluate the management of AM, the views of 22 of the core participants in the qualitative serial interview study were combined with data from 11 urologists and 23 nurses delivering ProtecT trial AM and 20 men, with prostate cancer managed in urology clinics elsewhere in the UK, with in-depth interviews with urologists and three specialist nurses working in these clinics. 199…”