Prostate Health Index and its Possible Use in Clinical Practice
With the increasing incidence of prostate cancer, the effort to improve its diagnostics is also growing. The exclusively used and practice-proven prostate-specific antigen (PSA) continues to play an indispensable role in identifying at-risk patients, but some of its isoforms can also provide important information for deciding the patient's further fate. Based on their combination, a so-called prostate health index (PHI) can be determined. A recently published work by Czech authors assessed the usability of PHI as a parameter suitable for evaluating the aggressiveness of prostate cancer (PC) within the PHIMOPLUKTHOM study.
Introduction
Prostate cancer is among the most frequently diagnosed malignant diseases in the male population. In Europe alone, the annual number of newly detected cases is estimated at 2.6 million, with a year-on-year increase of 2–3%. This occurs thanks to improving diagnostic methods, foremost among them being PSA combined with its free fraction (fPSA). The widespread clinical implementation of PSA leads on one hand to the improvement of early PC detection, but on the other hand, its routine collection increases the redundant detection of low-risk so-called clinically insignificant cancer, which would likely not endanger the patient's health in the long run. Therefore, the need for new biomarkers, which would help correctly classify patients with clinically significant PC, is continually discussed.
PHI and its Potential
To increase the sensitivity and specificity of PSA, efforts are being made to introduce other suitable parameters into practice. These include fPSA isoforms, primarily [−2]proPSA (p2PSA), which is predominantly expressed in the peripheral zone of the prostate. By combining the results of total PSA, fPSA, and p2PSA, it is possible to determine the so-called prostate health index (PHI – prostate health index). PHI has shown great potential in many studies for improving PC detection. Its contribution to predicting cancer aggressiveness and in deciding on the optimal procedure for a given patient is also promising. Moreover, in some studies, it appears to be a suitable marker that helps decide whether a biopsy is necessary for a patient with elevated PSA.
Methodology and Study Progress
A recent study from the Czech Republic, involving 4 healthcare facilities, aimed to determine the accuracy of p2PSA and derived parameters in predicting pathological findings in patients who underwent radical prostatectomy for clinically localized PC. The study included 472 patients operated on between 2014 and 2018.
Clinical data included the patient's age at the time of surgery, PSA, fPSA, p2PSA, %p2PSA (p2PSA/fPSA), PHI, the result of per rectum examination (DRE), Gleason score (GS), the total number of samples taken, and the number of positive samples. The evaluated pathological finding (based on postoperative histology after radical prostatectomy) indicated the disease staging, GS, GS upgrading (i.e., a change compared to biopsy-established GS), and the positivity of resection margins.
Findings
In patients with significant PC according to postoperative histology, higher preoperative PHI (p < 0.001), higher preoperative PSA levels (p = 0.002), and a higher frequency of positive DRE (p < 0.05) were found compared to other patients.
The proportion of patients with GS ≥ 7 during biopsy was 37.3%, while according to postoperative histology, it increased to 71.8%. Of the 296 patients with bioptically established GS 6, 60% had GS ≥ 7 according to the postoperative finding. These patients had significantly higher preoperative PHI values than patients with GS 6 according to both biopsy and pathological findings (p < 0.001). PHI was a significantly stronger predictor of pathological GS ≥ 7 than conventional PSA even in multivariable analysis.
A significantly higher PHI value was also found in patients with pT3 findings and positive resection margins.
Discussion and Conclusion
It is known that many already diagnosed prostate cancers behave indolently and thus do not threaten the patient's life; on the contrary, their treatment may cause unnecessary complications that worsen the quality of life. Conversely, up to 30% of patients with bioptically verified low-risk PC have aggressive cancer in subsequent histological examination of the resection after radical prostatectomy.
The study by Czech authors suggests that PHI could be a beneficial predictor of tumor aggressiveness and spread after radical prostatectomy.
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Sources:
1. Novák V., Veselý S., Lukšanová H. et al. Preoperative prostate health index predicts adverse pathology and Gleason score upgrading after radical prostatectomy for prostate cancer. BMC Urol 2020; 20 (1): 144, doi: 10.1186/s12894-020-00711-5.
2. Novák V., Veselý Š. PSA a jeho izoformy jako moderní markery karcinomu prostaty. Česká urologie 2019; 23 (3): 194−202.
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