Establishment and Validation of Extra-transitional Zone Prostate Specific Antigen Density (ETzD), a Novel Structure-based Parameter for Quantifying the Oncological Hazard of Prostates with Enlarged Stroma

Abstract

Extra-transitional zone density (ETzD), a novel parameter is proposed to stratify the deviation of prostate specific antigen (PSA) due to structural change according to stromal hyperplasia of prostate. ETzD was conducted on a concept to estimate the PSA density (PSAD) after hypothetical enucleation of the transitional zone of an enlarged prostate by a non-linear regression prediction model with intrinsic linearity, from the retrospective analysis of PSA change observed actual enucleation by laser. The performance to predict the presence and severity of malignancy was validated by two cohorts of 3,440 prostate biopsies and 2,783 radical prostatectomy specimens. The performance of ETzD was compared with conventional parameters. The receiver operative curve of area under curve (AUC) of ETzD to predict the presence of malignacy was 0.862 (95% CI; 0.843~0.881), better than PSA, PSAD or transitional zone PSAD (TzPSAD). The AUC of ETzD to predict an unfavorable cancer among prostate cancer patients was 0.736 (95% CI; 0.705~0.768), which performs better than PSA and comparable to PSAD or TzPSAD. In summary, the performance of ETzD as a universal parameter to quantify the oncological hazard of a prostate was validated and the superiority to conventional parameters was verified.

Is PSA density of the peripheral zone as a useful predictor for prostate cancer in patients with gray zone PSA levels?

“…Relative extra-transitional zone PSA (RETzPSA) was calculated by dividing the value of the total prostate volume without transitional zone volume by the total prostate volume measured with TRUS and multiplying this ratio by the total PSA value. Estimated post-holmium laser enucleation of the prostate PSA (EPHPSA) was calculated using the formula (1.068 + 0.016 x PSA + 0.004 x prostate volume -1.02 x transitional volume/prostate volume) according to Kim et al [19]. PSAD was measured by dividing the total serum PSA level by the prostate volume measured with TRUS.…”

“…Peripheral zone PSA density (PZPSAD), according to Koo et al [20], was obtained by dividing the total serum PSA level by the calculated peripheral prostate volume. Extratransitional zone density (ETzD) was calculated by dividing the EPHPSA value, according to Kim et al [19], by the size of the extra-transitional zone, which excluded the transitional zone volume from the total prostate volume.…”

“…However, measuring PSA produced only in the peripheral zone is challenging. Kim et al [19] attempted to estimate the PSA value, excluding those produced in the transitional zones due to prostatic hyperplasia. Changes in serum PSA levels before and 6 months after HoLEP were measured, and this was formulated to calculate EPHPSA.…”

“…HoLEP is a safe and effective treatment, expected to continue to resolve bladder outlet obstruction (BOO) for a long time [17,18]. There is a high interest in the development of prostate cancer in the remaining prostate tissue after adenoma enucleation [19]. It is considered that treatment can be administered by a different method, radical prostatectomy instead of TURP or HoLEP, depending on the presence or absence of prostate cancer when prostate cancer is suspected in the preoperative peripheral zone.…”

Is PSA Density of the Peripheral Zone as a Useful Predictor for Prostate Cancer in Patients With Gray Zone PSA Levels?

“…Peripheral zone PSA density (PZPSAD), according to Koo et al [20], was obtained by dividing the total serum PSA level by the calculated peripheral prostate volume. Extra-transitional zone density (ETzD) was calculated by dividing the EPHPSA value, according to Kim et al [19], by the size of the extra-transitional zone, which excluded the transitional zone volume from the total prostate volume.…”