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Article of the Week: Prostate Health Index density improves detection of clinically significant prostate cancer

Every Week the Editor-in-Chief selects an 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 discussing the paper.

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

Prostate Health Index density improves detection of clinically significant prostate cancer

Jeffrey J. Tosoian*, Sasha C. Druskin*, Darian Andreas*, Patrick Mullane*, Meera Chappidi*, Sarah Joo*, Kamyar Ghabili*, Mufaddal Mamawala*, Joseph Agostino*, Herbert B. Carter*, Alan W. Partin*, Lori J. Sokoll*§ and Ashley E. Ross*§

 

*Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, Virginia Commonwealth University School of Medicine, Richmond, VA, Department of Pathology, and §Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Abstract

Objectives

To explore the utility of Prostate Health Index (PHI) density for the detection of clinically significant prostate cancer (PCa) in a contemporary cohort of men presenting for diagnostic evaluation of PCa.

Patients and Methods

The study cohort included patients with elevated prostate-specific antigen (PSA; >2 ng/mL) and negative digital rectal examination who underwent PHI testing and prostate biopsy at our institution in 2015. Serum markers were prospectively measured per standard clinical pathway. PHI was calculated as ([{−2}proPSA/free PSA] × [PSA]½), and density calculations were performed using prostate volume as determined by transrectal ultrasonography. Logistic regression was used to assess the ability of serum markers to predict clinically significant PCa, defined as any Gleason score ≥7 cancer or Gleason score 6 cancer in >2 cores or >50% of any positive core.

Results

Of 118 men with PHI testing who underwent biopsy, 47 (39.8%) were found to have clinically significant PCa on biopsy. The median (interquartile range [IQR]) PHI density was 0.70 (0.43–1.21), and was 0.53 (0.36–0.75) in men with negative biopsy or clinically insignificant PCa and 1.21 (0.74–1.88) in men with clinically significant PCa (P < 0.001). Clinically significant PCa was detected in 3.6% of men in the first quartile of PHI density (<0.43), 36.7% of men in the IQR of PHI density (0.43–1.21), and 80.0% of men with PHI density >1.21 (P < 0.001). Using a threshold of 0.43, PHI density was 97.9% sensitive and 38.0% specific for clinically significant PCa, and 100% sensitive for Gleason score ≥7 disease. Compared with PSA (area under the curve [AUC] 0.52), PSA density (AUC 0.70), %free PSA (AUC 0.75), the product of %free PSA and prostate volume (AUC 0.79), and PHI (AUC 0.76), PHI density had the highest discriminative ability for clinically significant PCa (AUC 0.84).

Conclusions

Based on the present prospective single-centre experience, PHI density could be used to avoid 38% of unnecessary biopsies, while failing to detect only 2% of clinically significant cancers.

Editorial: Prostate cancer biomarkers: new scenarios in the multi-parametric magnetic resonance imaging era

The management of prostate cancer poses difficult challenges, which is largely because we lack the necessary tools to predict its presence, and discern between indolent disease with a small chance of clinical manifestation and aggressive tumours that are more likely to be lethal.

Despite the fact that novel blood and urine tests are available, which may predict aggressive disease better than PSA; they are not routinely used due to a lack of clinical validity studies.

Tosoian et al. [1] in the present study explored the utility of prostate health index (PHI) density for detection of clinically significant prostate cancer in a contemporary cohort of men presenting for diagnostic evaluation of prostate cancer. Very interestingly the authors hypothesised that, similar to PSA density, PHI density could further improve upon the discriminative ability of PHI to detect prostate cancer. The PHI density calculation was performed using prostate volume, as determined by TRUS. Logistic regression was used to assess the ability of serum markers to predict clinically significant prostate cancer, defined as any Gleason score ≥7 cancer or Gleason score 6 cancer in >2 cores or >50% of any positive core.

They showed, albeit in a small sample size, that PHI density could further improve upon the discriminative ability of PHI and appears to be superior to PSA and other PSA derivatives for the identification of clinically significant disease [1].

However, it is noteworthy that in all studies on urine or serum biomarkers such as this, the ‘gold standard’ for cancer detection is pathological examination of multiple non-targeted systematic TRUS-guided prostate biopsies, not radical prostatectomy specimens. Intrinsically, this approach implies that no cancer predicted by the biomarker may still mean cancer missed by the biopsy.

Introducing mpMRI before prostate biopsy has the potential to improve prostate cancer sampling ink that is the most practical way to make mpMRI before biopsy economically viable for universal NHS adoption.

The aim should be the development of a clinical decision support system based on mpMRI and circulating biomarkers, as in this case PHI density evaluation, to stratify patients according to their risk of prostate cancer progression, using pathological assessment after prostatectomy as the reference standard.

Francesco Porpiglia and Stefano De Luca
Division of Urology, San Luigi Gonzaga Hospital and University of Torino, Orbassano, Italy

 

 

References

 

1 Tosoian JJDruskin SCAndreas D et al. Prostate health index density improves detection of clinically significant prostate cancer. BJU Int2017; 120: 7938.

 

2 Mottet NBellmunt JBolla M et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: Screening, diagnosis, and local treatment with curative intent.  Eur Urol 2016; pii: S0302-2838(16)30470-5. [Epub ahead of print]. doi: 10.1016/j.eururo.2016.08.003.

 

3 Russo FRegge DArmando E et al. Detection of prostate cancer index lesions with multiparametric magnetic resonance imaging (mp-MRI) using whole-mount histological sections as the reference standard. BJU Int 2016; 118: 8494.

 

 

5 Porpiglia FManfredi MMele F et al. Diagnostic pathway with multiparametric magnetic resonance imaging versus standard pathway: results from a randomized prospective study in biopsy-naıve patients with suspected prostate cancer. Eur Urol 2016; pii: S0302-2838(16)30509-7. [Epub ahead of print]. doi: 10.1016/j.eururo.2016.08.041

 

6 Wegelin Ovan Melick HHHooft L et al. Comparing three different techniques for magnetic resonance imaging-targeted prostate biopsies: a systematic review of in-bore versus magnetic resonance imaging- transrectal ultrasound fusion versus cognitive registration. Is there a preferred technique?. Eur Urol 2016; pii: S0302-2838(16)30446-8. [Epub ahead of print]. doi: 10.1016/j.eururo.2016.07.04

 

Video: Prostate Health Index density improves detection of clinically significant prostate cancer

Prostate Health Index density improves detection of clinically significant prostate cancer

Abstract

Objectives

To explore the utility of Prostate Health Index (PHI) density for the detection of clinically significant prostate cancer (PCa) in a contemporary cohort of men presenting for diagnostic evaluation of PCa.

Patients and Methods

The study cohort included patients with elevated prostate-specific antigen (PSA; >2 ng/mL) and negative digital rectal examination who underwent PHI testing and prostate biopsy at our institution in 2015. Serum markers were prospectively measured per standard clinical pathway. PHI was calculated as ([{−2}proPSA/free PSA] × [PSA]½), and density calculations were performed using prostate volume as determined by transrectal ultrasonography. Logistic regression was used to assess the ability of serum markers to predict clinically significant PCa, defined as any Gleason score ≥7 cancer or Gleason score 6 cancer in >2 cores or >50% of any positive core.

Results

Of 118 men with PHI testing who underwent biopsy, 47 (39.8%) were found to have clinically significant PCa on biopsy. The median (interquartile range [IQR]) PHI density was 0.70 (0.43–1.21), and was 0.53 (0.36–0.75) in men with negative biopsy or clinically insignificant PCa and 1.21 (0.74–1.88) in men with clinically significant PCa (P < 0.001). Clinically significant PCa was detected in 3.6% of men in the first quartile of PHI density (<0.43), 36.7% of men in the IQR of PHI density (0.43–1.21), and 80.0% of men with PHI density >1.21 (P < 0.001). Using a threshold of 0.43, PHI density was 97.9% sensitive and 38.0% specific for clinically significant PCa, and 100% sensitive for Gleason score ≥7 disease. Compared with PSA (area under the curve [AUC] 0.52), PSA density (AUC 0.70), %free PSA (AUC 0.75), the product of %free PSA and prostate volume (AUC 0.79), and PHI (AUC 0.76), PHI density had the highest discriminative ability for clinically significant PCa (AUC 0.84).

Conclusions

Based on the present prospective single-centre experience, PHI density could be used to avoid 38% of unnecessary biopsies, while failing to detect only 2% of clinically significant cancers.

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