Tag: prostate specific antigen

Posts

Editorial: Prostate cancer risk prediction and the persistence of uncertainty

March 2, 2016/by Dara Lundon

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.

Read the full article

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

Article of the Month: The PROMEtheuS Project: Bringing PHI to prostate Cancer

April 1, 2015/1 Comment/by admin Z.9

Every week the Editor-in-Chief selects the Article of the Week 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.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Dr. Alberto Abrate, discussing his paper.

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

Clinical performance of Prostate Health Index (PHI) for prediction of prostate cancer in obese men: data from a multicenter European prospective study, PROMEtheuS project

Alberto Abrate, Massimo Lazzeri, Giovanni Lughezzani, Nicolòmaria Buffi, Vittorio Bini*,Alexander Haese†, Alexandre de la Taille‡, Thomas McNicholas§, Joan Palou Redorta¶,Giulio M. Gadda, Giuliana Lista, Ella Kinzikeeva, Nicola Fossati, Alessandro Larcher,Paolo Dell’Oglio, Francesco Mistretta, Massimo Freschi** and Giorgio Guazzoni

Division of Oncology, Unit of Urology, URI, **Department of Pathology, IRCCS Ospedale San Raffaele, UniversitàVita-Salute San Raffaele, Milan, *Department of Internal Medicine, University of Perugia, Perugia, Italy,†Martini-ClinicProstate Cancer Center, University Clinic Hamburg-Eppendorf, Hamburg, Germany,‡Department of Urology, APHPMondor Hospital, Créteil, France,§South Bedfordshire and Hertfordshire Urological Cancer Centre, Lister Hospital,Stevenage, UK, and¶Urologic Oncology Section of the Department of Urology and Radiology Department, FundaciòPuigvert, Barcelona, Spain

Read the full article

OBJECTIVES

To test serum prostate-specific antigen (PSA) isoform [-2]proPSA (p2PSA), p2PSA/free PSA (%p2PSA) and Prostate Health Index (PHI) accuracy in predicting prostate cancer in obese men and to test whether PHI is more accurate than PSA in predicting prostate cancer in obese patients.

PATIENTS AND METHODS

The analysis consisted of a nested case-control study from the pro-PSA Multicentric European Study (PROMEtheuS) project. The study is registered at https://www.controlled-trials.com/ISRCTN04707454. The primary outcome was to test sensitivity, specificity and accuracy (clinical validity) of serum p2PSA, %p2PSA and PHI, in determining prostate cancer at prostate biopsy in obese men [body mass index (BMI) ≥30 kg/m²], compared with total PSA (tPSA), free PSA (fPSA) and fPSA/tPSA ratio (%fPSA). The number of avoidable prostate biopsies (clinical utility) was also assessed. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis.

RESULTS

Of the 965 patients, 383 (39.7%) were normal weight (BMI <25 kg/m²), 440 (45.6%) were overweight (BMI 25–29.9 kg/m²) and 142 (14.7%) were obese (BMI ≥30 kg/m²). Among obese patients, prostate cancer was found in 65 patients (45.8%), with a higher percentage of Gleason score ≥7 diseases (67.7%). PSA, p2PSA, %p2PSA and PHI were significantly higher, and %fPSA significantly lower in patients with prostate cancer (P < 0.001). In multivariable logistic regression models, PHI significantly increased accuracy of the base multivariable model by 8.8% (P = 0.007). At a PHI threshold of 35.7, 46 (32.4%) biopsies could have been avoided.

CONCLUSION

In obese patients, PHI is significantly more accurate than current tests in predicting prostate cancer.

Editorial: Time to replace PSA with the PHI?

April 1, 2015/by Stacy Loeb

Yet more evidence that the PHI consistently outperforms PSA across diverse populations

The Prostate Health Index (PHI) has regulatory approval in >50 countries worldwide and is now being incorporated into prostate cancer guidelines; for example, the 2014 National Comprehensive Cancer Network Guidelines for early prostate cancer detection discuss the PHI as a means to improve specificity, using a threshold score of 35 [1]. The PHI is also discussed in the Melbourne Consensus Statement [2], and it has been incorporated into the multivariable Rotterdam risk calculator smartphone app for use in point-of-care decisions [3].

As the use of this test continues to expand, more data on its performance in specific at-risk populations are of great interest. The investigators from the PROMEtheus multicentre European trial have previously validated the use of the PHI in men with a positive family history of prostate cancer [4]. The new study by Abrate et al. in this issue of BJUI instead addresses another high-risk population – obese men – who have previously been shown to have a greater risk of aggressive prostate cancer [5].

Among the 965 participants in the PROMEtheus study, 14.7% were considered obese based on a body mass index ≥30 kg/m². In this group, 45.8% were diagnosed with prostate cancer from a ≥12-core biopsy, and 67.7% had a Gleason score ≥7. Overall, the PHI significantly outperformed PSA for prostate cancer detection in men with a body mass index ≥30 kg/m² (area under the curve 0.839 vs 0.694; P < 0.001). At 90% sensitivity, the threshold for PHI in obese men was 35.7, with a specificity of 52.3%. The PHI also had the best performance for the detection of Gleason ≥7 disease, with an area under the curve of 0.89.

These findings add to the highly consistent body of evidence supporting the use of the PHI in early prostate cancer detection and risk stratification. In fact, all published studies to date have shown that the PHI outperforms PSA for detection of overall and high-grade prostate cancer detection on biopsy [6]. Numerous studies have also shown a role for the PHI in patient selection and monitoring during active surveillance [7, 8]. Expanded use of this test is warranted to reduce unnecessary biopsies and better identify cancers with life-threatening potential.

Read the full article

Stacy Loeb

Department of Urology and Population Health, New York University, New York, NY, USA

References

1 National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Prostate Cancer Early Detection Version 2014. https://www.nccn.org/professionals/physician_gls/pdf/prostate_detection.pdf.Accessed May 26, 2014

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 Roobol M, Salman J, Azevedo N. Abstract 857: The Rotterdam Prostate Cancer Risk Calculator: Improved Prediction with More Relevant Pre-Biopsy Information, Now in the Palm of Your Hand. Stockholm: European Association of Urology, 2014

4 Lazzeri M, Haese A, Abrate A et al. Clinical performance of serum prostate-speciﬁc antigen isoform [-2]pr oPSA (p2PS A) and its derivatives, %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer: results from a multicentre European study, the PROMEtheuS project. BJU Int 2013; 112:313–21

5 Freedland SJ, Banez LL, Sun LL, Fitzsimons NJ, Moul JW. Obese men have higher-grade and larger tumors: an analysis of the duke prostate center database. Prostate Cancer Prostatic Dis 2009; 12: 259–63

6 Filella X, Gimenez N. Evaluation of [-2] proPSA and Prostate Health Index (phi) for the detection of prostate cancer: a systematic review and meta-analysis. Clin Chem Lab Med 2013; 51: 729–39

7 Tosoian JJ, Loeb S, Feng Z et al. Association of [-2]proPSA with Biopsy Reclassiﬁcation During Active Surveillance for Prostate Cancer. J Urol2012; 188: 1131–6

8 Hirama H, Sugimoto M, Ito K, Shiraishi T, Kakehi Y. The impact of baseline [-2]proPSA-related indices on the prediction of pathological reclassiﬁcation at 1 year during active surveillance for low-risk prostate cancer: the Japanese multicenter study cohort. J Cancer Res Clin Oncol2014; 140: 257–63

Video: Clinical performance of PHI for prediction of prostate cancer: data from the PROMEtheuS project

April 1, 2015/by admin Z.9