The role of the PCA3 assay in predicting prostate biopsy outcome in a South African setting

Abstract

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? The PCA3 assay has shown significant potential amongst the initial studies carried out in Western countries. This assay performed in line with previous studies. We have shown this marker to perform independent of prostatic volume and have identified potential indications for its use in our setting. However, we have not observed the PCA3 assay to outperform the PSA level across the risk spectrum. OBJECTIVES To evaluate the investigational role, ideal threshold and indications of the Prostate CAncer gene 3 (PCA3) assay in a South African context. To better define the universality of the above marker since this is the pioneer study on the continent of Africa. PATIENTS AND METHODS We prospectively evaluated 105 consecutive South African men referred for a prostate biopsy at two tertiary centres in the capital city, Pretoria. Sequentially, PSA levels and post DRE urine samples were taken within 24 h before prostate biopsy. The urine specimen was tested using the PROGENSATM PCA3 assay and a score was generated as (PCA3 mRNA/PSA mRNA) × 1000. The performance of this assay in predicting biopsy outcome was assessed, and compared with that of serum PSA. RESULTS Median patient age was 67 years with a positive biopsy incidence of 42.9%. The higher the PCA3 score the greater the probability of a positive biopsy (P = 0.003). This score performed independently of prostatic volume (P = 0.3889) or the presence of a concurrent primary malignancy (P = 0.804). A threshold of 60 revealed a positive predictive value of 60% with an odds ratio of 4, whereas setting a limit of 35 revealed a positive predictive value of 54% and odds ratio of 3.5. Using receiver operating characteristics for overall performance comparison, the PSA level (area under the curve 0.844) performed better than the PCA3 score (area under the curve 0.705). CONCLUSION PCA3 assay has shown consistency and performed in line with previous studies but it did not surpass serum PSA in this population. A PCA3 assay threshold of 60 performed better than the conventional limit of 35. This assay may have a potential niche in a certain subset of South African men that includes patients with larger glands, previous negative biopsies and altered baseline PSA levels.

Recommendations from the EGAPP Working Group: does PCA3 testing for the diagnosis and management of prostate cancer improve patient health outcomes?

“…However, 12 additional studies included matched results of PCA3 and the comparators but enrolled men with both initial and repeat biopsies or they did not report biopsy history. 10,11,[35][36][37][38][39][40][41][42][43][44] Most often, the results from these studies were not stratified by biopsy history.…”

“…Fifteen studies [9][10][11]30,32,[34][35][36][37][38][39][40][41][42][43]46 reported AUC estimates for tPSA and PCA3 in the same population. Overall, 13 [9][10][11]30,32,34,35,37,38,[40][41][42]46 of the15 studies found that the AUC of PCA3 was higher than that of tPSA.…”

“…Seven studies 9,33,36,37,39,40,43 reported the sensitivity and specificity of PCA3 at a cutoff of 35. Six 9,33,36,37,40,43 of the seven studies reported a higher sensitivity in PCA3.…”

Test urinaire PCA3, cancer de la prostate et autres pathologies prostatiques

“…Une explication réside d'ailleurs dans le fait que l'affirmation d'une HBP reste toujours difficile sur le seul examen histologique de biopsies prostatiques. Certains auteurs ont parfois précisé que des patients avec HBP avaient été inclus [8,10,48] et ont considéré d'emblée que le score PCA3 dans cette population ne devait pas être différent de celui du groupe de patients avec prostate normale [31]. Ainsi, dans cette étude à gros effectif (étude nord-américaine portant sur 570 patients), 96 des 364 patients avec biopsies négatives (26 %) avaient soit une prostate histologiquement normale soit une HBP et ont été regroupés sous la rubrique no pathology.…”

“…Finalement, la meilleure explication d'un score PCA3 aussi bas dans l'HBP est que la prostate reste parfaitement saine. Cela est conforté par la démonstration, par plusieurs équipes, de l'absence de corrélation entre le score PCA3 et le volume prostatique [27,28,31,48].…”