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Prostate-specific antigen (PSA) isoform p2PSA in prostate cancer screening: systematic review of current evidence and further perspectives

L’isoforma p2PSA dell’antigene prostatico specifico (PSA) nello screening del cancro prostatico: review sistematica sui dati attualmente disponibili e sulle nuove prospettive

  • Articolo Originale
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La Rivista Italiana della Medicina di Laboratorio - Italian Journal of Laboratory Medicine

Summary

Background

There is now evidence that the advantages of screening for prostate cancer based only on prostate specific antigen (PSA) are probably offset by the health and economic disadvantages arising from over-diagnosis and over-treatment. Among novel and promising biomarkers, attention has recently been focused on the PSA isoform p2PSA, alone or in combination with free PSA (as %p2PSA), and in combination with total and free PSA as the prostate health index (phi).

Methods

We performed an electronic search for original articles published in English, French, Spanish and Italian reporting studies that assessed the diagnostic performance of %p2PSA for prostate cancer screening in direct comparison with PSA, using the keywords “Prostate Cancer”, and “Measurement” or “Screening”, and “proPSA” or “p2PSA” or “[-2]proPSA”. Titles, abstracts and full texts were carefully read, and articles not matching the inclusion criteria were excluded. Heterogeneity was evaluated by the I-squared test. The pooled estimates of accuracy and the resulting area under the receiver operator characteristic curve (AUC) were calculated using a random effect model.

Results

On the basis of the electronic search, 11 articles and 12 studies, including a total of 5,139 subjects (2,338 with prostate cancer) and with modest heterogeneity (Isquared, 66%) were selected. The %p2PSA pooled estimates were always greater than those of PSA, and so was the cumulative pooled AUC (0.687 versus 0.538; p<0.001). The diagnostic odds ratio was more than double for %p2PSA than for total PSA (4.0 versus 1.7). With a sensitivity of 0.95, routine p2PSA testing may result in up to 10% fewer unnecessary biopsies than the use of PSA for screening. The AUC of phi was slightly but not significantly better than that of %p2PSA (0.736 versus 0.717; p=0.21).

Conclusions

These findings provide a rationale for planning further studies to assess whether %p2PSA testing may generate more favourable outcomes in terms of mortality and quality of life. Direct comparison does not permit the conclusion that the phi is globally superior to %p2PSA for detecting prostate cancer.

Riassunto

Premesse

È stato dimostrato che i benefici dello screening del cancro prostatatico con l’antigene prostatico specifico (PSA) sono probabilmente superati da svantaggi clinici ed economici, soprattutto relativi a un eccesso di diagnosi e interventi terapeutici. Tra i vari biomarcatori, l’isoforma p2PSA del PSA ha focalizzato molta attenzione negli ultimi anni, sia usata da sola, oppure come %p2PSA in combinazione con PSA libero, o come Prostate Health Index (phi), in combinazione con il PSA totale e libero.

Metodi

Abbiamo eseguito una ricerca elettronica per articoli originali pubblicati in inglese, francese, spagnolo e italiano, che hanno studiato le prestazioni diagnostiche di %p2PSA per lo screening del tumore della prostata in confronto diretto con PSA, utilizzando le parole chiave “Prostate Cancer”, e “Measurement” o “Screening”, e “proPSA” o “p2PSA” o “[-2]proPSA”. Titolo, riassunto e testo sono stati attentamente letti e gli articoli non corrispondenti ai criteri d’inclusione sono stati esclusi. L’eterogeneità è stata valutata mediante test di I-quadrato. Le stime cumulative delle performance e l’area sotto la curva (AUC) mediante analisi receiver operator characteristic (ROC) sono state calcolate in base ad un modello ad effetto casuale.

Risultati

Undici articoli e dodici studi, per un totale di 5.139 soggetti (2.338 con cancro prostatico) e con modesta eterogeneità (I-quadrato: 66%) sono stati selezionati. Le performance diagnostiche di %p2PSA sono sempre risultate superiori a quelle del PSA, cosÌ come l’AUC cumulativa (0,687 versus 0,538; p <0,001). La diagnostic odds ratio è doppia per %p2PSA rispetto a PSA totale (4,0 versus 1,7). Alla sensibilità di 0,95, l’esecuzione routinaria del p2PSA può risparmiare fino al 10% di biopsie non necessarie rispetto al PSA. L’AUC del phi non è superiore ma non significativamente migliore di quella del %p2PSA (0,736 versus 0,717; p = 0,21).

Conclusioni

Questi risultati forniscono una base razionale ad ulteriori studi volti a valutare se l’uso del %p2PSA può generare risultati più favorevoli in termini di mortalità e qualità della vita. Il confronto diretto non permette invece di concludere che phi sia globalmente superiore a p2PSA% per lo screening del cancro della prostata.

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Authors and Affiliations

  1. Unità Operativa Diagnostica Ematochimica, Dipartimento di Patologia e Medicina di Laboratorio, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy

    Giuseppe Lippi & Rosalia Aloe

  2. Servizio Governance Clinica, Ospedale di Trento, Trento, Italy

    Camilla Mattiuzzi

  3. Unità Operativa Diagnostica Ematochimica, Dipartimento di Patologia e Medicina di Laboratorio, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci, 14, 43126, Parma, Italy

    Giuseppe Lippi

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  1. Giuseppe Lippi
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Correspondence to Giuseppe Lippi.

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Lippi, G., Aloe, R. & Mattiuzzi, C. Prostate-specific antigen (PSA) isoform p2PSA in prostate cancer screening: systematic review of current evidence and further perspectives. Riv Ital Med Lab 8, 231–238 (2012). https://doi.org/10.1007/s13631-012-0067-7

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  • DOI: https://doi.org/10.1007/s13631-012-0067-7

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