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Article of the Month: ERSPC and PCPT risk calculators in prostate cancer risk prediction

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Every Month the Editor-in-Chief selects an Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Prostate cancer risk prediction using the novel versions of the European Randomised Study for Screening of Prostate Cancer (ERSPC) and Prostate Cancer Prevention Trial (PCPT) risk calculators: independent validation and comparison in a contemporary European cohort

Cedric Poyet, Daan Nieboer*, Bimal Bhindi†, Girish S. Kulkarni†, Caroline Wiederkehr, Marian S. Wettstein, Remo Largo, Peter Wild‡, Tullio Sulser and Thomas Hermanns 

 

Department of Urology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, *Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands, †Division of Urology, Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada, and ‡Institute of Surgical Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland

 

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Objectives

To externally validate and compare the two novel versions of the European Randomised Study for Screening of Prostate Cancer (ERSPC)-prostate cancer risk calculator (RC) and Prostate Cancer Prevention Trial (PCPT)-RC.

Patients and Methods

All men who underwent a transrectal prostate biopsy in a European tertiary care centre between 2004 and 2012 were retrospectively identified. The probability of detecting prostate cancer and significant cancer (Gleason score ≥7) was calculated for each man using the novel versions of the ERSPC-RC (DRE-based version 3/4) and the PCPT-RC (version 2.0) and compared with biopsy results. Calibration and discrimination were assessed using the calibration slope method and the area under the receiver operating characteristic curve (AUC), respectively. Additionally, decision curve analyses were performed.

MarchATOM1

Results

Of 1 996 men, 483 (24%) were diagnosed with prostate cancer and 226 (11%) with significant prostate cancer. Calibration of the two RCs was comparable, although the PCPT-RC was slightly superior in the higher risk prediction range for any and significant prostate cancer. Discrimination of the ERSPC- and PCPT-RC was comparable for any prostate cancer (AUCs 0.65 vs 0.66), while the ERSPC-RC was somewhat better for significant prostate cancer (AUCs 0.73 vs 0.70). Decision curve analyses revealed a comparable net benefit for any prostate cancer and a slightly greater net benefit for significant prostate cancer using the ERSPC-RC.

Conclusions

In our independent external validation, both updated RCs showed less optimistic performance compared with their original reports, particularly for the prediction of any prostate cancer. Risk prediction of significant prostate cancer, which is important to avoid unnecessary biopsies and reduce over-diagnosis and overtreatment, was better for both RCs and slightly superior using the ERSPC-RC.

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Editorial: Prostate cancer risk prediction and the persistence of uncertainty

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Poyet et al. [1] have performed the largest external validation of the European Randomised Study for Screening of Prostate Cancer (ERSPC) and Prostate Cancer Prevention Trial (PCPT) v2.0 risk calculators (RCs) to date, having retrospectively identified 1996 men undergoing prostate biopsy in a Swiss tertiary care facility.

Asides from the validatory nature of this paper [1], there are several other findings though less novel, which are further important additions to the urological literature.

This study confirms the superior discriminative performance of multi-factorial RCs over PSA alone in the assessment of prostate cancer: where the area under the receiver operating characteristic curve (AUC) for the prediction of significant prostate cancer for PSA alone was 0.65, comparing less favourably than 0.73 and 0.70 for the ERSPC and PCPT v2.0 RCs, respectively.

The authors performed sensitivity analysis showing higher detection rates for prostate cancer (29.4% vs 18.1%) and significant prostate cancer (15.9% vs 5.9%) in patients receiving a 12-core biopsy than in those receiving a 6–8 core biopsy.

Supplementary analysis by the authors evaluated the performance of previous versions of the PCPT-RC, specifically v1.0 and PCPT-RC v1.0 with prostate volume. The inclusion of prostate volume demonstrated an improved predictive ability of this RC. The AUC for the prediction of significant prostate cancer using the PCPT-RC v1.0 with prostate volume was 0.74. This contrasts with the ERSPC risk tool: AUC of 0.73 (which includes a trichotomised estimation of prostate volume), and the novel PCPT-RC v2.0; AUC of 0.70 (which does not include prostate volume as a factor).

The authors conclude that the prediction of significant prostate cancer was superior using the ERSPC-RC compared with the PCPT-RC v2.0, in risk thresholds of 8–35%. Their data also shows that the PCPT-RC v2.0 offers a superior net benefit to the ERPSC-RC to a large number of men outside of this range of threshold probabilities. Their findings suggest that the older PCPT-RC v1.0 with prostate volume may offer benefits superior to both the ERSPC and PCPT v2.0 RCs.

The authors assessment of novel risk tools confirms the rationale for guidelines and consensus statements that PSA testing should not be considered on its own, but rather as part of a multivariate approach [2, 3]. This current work suggests that although calibration of risk tools is still not optimal, they offer superior discriminative ability and superior net benefit in identifying patients with significant prostate cancer. This work affirms the role for variables such as DRE, and the importance of prostate volume in addition to PSA in prostate cancer assessment.

Although further refinement of risk tools is necessary, this work encourages confidence in and should garner further traction for the routine use of such tools in the assessment and counselling of patients before prostate biopsy.

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Dara J. Lundon*†
*Conway Institute of Biomedical and Biomolecular Science, University College Dublin School of Medicine and Medical Sciences, University College Dublin, Belfield, and †Department of Urology, Mater Misericordiae University Hospital, Dublin, Ireland

 

References

 

1 Poyet C, Nieboer D, Bhindi B et al. Prostate cancer risk prediction using the novel versions of the European Randomised Study for Screening of Prostate Cancer (ERSPC) and Prostate Cancer Prevention Trial (PCPT) risk calculators: independent validation and comparison in a contemporary Europe. BJU Int 2016; 117: 401–8

 

2 Murphy DG, Ahlering T, Catalona WJ et al. The Melbourne Consensus Statement on the early detection of prostate cancer. BJU Int 2014; 113: 186–8

 

3 Heidenreich A, Abrahamsson PA, Artibani W et al. Early detection of prostate cancer: European Association of Urology recommendation. Eur Urol 2013; 64: 347–54

 

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