Volume 134, Issue 1 p. 1-2
Editorial
Free Access

Screening and active surveillance in prostate cancer: the dilemma continues

Freddie C. Hamdy

Corresponding Author

Freddie C. Hamdy

University of Oxford, Oxford, UK

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Peter C. Albertsen

Peter C. Albertsen

UConn Health, Farmington, Connecticut, USA

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Jenny L. Donovan

Jenny L. Donovan

University of Bristol, Bristol, UK

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First published: 21 March 2024

In this month's issue of the Journal, Takahashi questions the value of PSA screening because studies have failed to show a decline in overall mortality [1]. This is a very high public health standard as lethal prostate cancer is a relatively rare disease. Only 3% of men die from this disease annually in most Western countries, and demonstrating a meaningful decline in overall mortality requires studies with enormous sample sizes. Large population-based tumour registries and PSA screening trials have shown significant relative declines in prostate cancer mortality since the advent of PSA testing [2]. But as Takahashi points out, these gains have come at the significant cost of overdiagnosis and overtreatment with its associated side-effect profiles [3, 4]. The United States Preventive Service Task Force (USPSTF) raised these concerns in both their 2012 and 2018 reports.

Recent advances in imaging modalities, particularly the introduction of multiparametric MRI in the pre-diagnostic space to target Prostate Imaging-Reporting and Data System (PI-RADS) lesions for biopsy have reduced the overdetection of low-risk prostate cancer, and biomarkers such as four-kallikrein panel (4K) testing have helped clinicians identify patients who can safely be managed with active surveillance rather than radical treatments. Based upon the 15-year outcomes of the Prostate Testing for Cancer and Treatment (ProtecT) trial, Takahashi suggests that all men diagnosed with screen-detected prostate cancer should be placed under active surveillance, as the trial demonstrated no survival benefit associated with surgery or radiation.

We challenge his arguments as follows. First, the ProtecT trial cohort consisted primarily of patients with low- and intermediate-risk prostate cancer, and therefore we cannot make conclusions on the impact of radical treatments vs active monitoring in high-risk disease [3]. As we know that high-grade prostate cancer is frequently a lethal disease, most treatment guidelines support early radical treatments, with multimodality approaches as required [5]. Second, although disease-specific and overall mortality were unaffected by radical treatments in the ProtecT trial, radical prostatectomy or external beam radiotherapy with neoadjuvant androgen suppression did reduce the incidence of metastases at the 10- and 15-year median follow-ups. It is unclear whether this will translate into survival benefits in the long-term. Third, it is incorrect that no studies demonstrate that low-risk disease has a benign course [3, 6].

Finally, the definition of ‘clinically significant disease’ is being used differently across studies and in practice, with some including any disease above Grade Group 1, some Grade Group 2 and above, and others Grade Group 3 and higher. ProtecT found no evidence of differences in treatment efficacy according to the PSA level, clinical stage, Gleason Grade Group, tumour length, or risk stratification according to the Cancer of the Prostate Risk Assessment (CAPRA), D'Amico, or Cambridge Prognostic group [3, 7]. We need new, more reliable criteria to categorise the lethal potential of disease. We agree that the way forward is to improve the screening pathway using better risk stratification to minimise the unnecessary diagnosis of low-risk cancers and their overtreatment. While active surveillance helps to reduce overtreatment of clinically insignificant disease, it does not resolve the issue of overdetection, where the problem lies. Even with recent advances, it is unlikely that any screening programme will eliminate the problem. Clinicians often underestimate the impact of an unnecessary cancer diagnosis on quality-of-life in healthy and asymptomatic men, giving them an unwanted ‘prostate cancer passport’ for the rest of their lives. Efforts must be made in the post-diagnostic space to stratify patients reliably and to offer necessary treatments to those men likely to succumb to prostate cancer and prevent both treatment and disease complications for those men who will live with the disease for many years.

Disclosure of Interests

FCH is Chief Investigator of the ProtecT HTA NIHR trial, co-PI of the Cancer Research UK CAP screening trial, and Editor-in-Chief of the BJU International; PCA is former chair of the ProtecT Trial Steering Committee, member of the Cause of Death Evaluation Committee for the ProtecT and CAP trials, and Associate Editor of the BJU International; JLD is co-PI of the ProtecT and CAP Trials and Associate Editor of the BJU International.