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Background: Prostate cancer patients with pathological prognostic factors have a poor prognosis, but it is unclear whether pathological prognostic factors are associated with prognosis limited to low-risk patients with good prognosis according to NCCN guidelines. The present study examined whether prognosis is influenced by pathological prognostic factors using radical prostatectomy (RP) specimens from low-risk patients., Methods: We evaluated diagnostic accuracy by examining biochemical recurrence (BCR)-free survival with respect to clinical and pathological prognostic factors in 419 all-risk patients who underwent RP. Clinical prognostic factors included age, prostate-specific antigen (PSA) levels, PSA density, and risk stratification, while pathological prognostic factors included grade group, lymphovascular space invasion, extraprostatic extension, surgical margins, seminal vesicle invasion, intraductal carcinoma of the prostate (IDCP), and pT. In a subsequent analysis restricted to 104 low-risk patients, survival curves were estimated for pathological prognostic factors using the Kaplan-Meier method and compared using log-rank and generalized Wilcoxon tests., Results: In the overall risk analysis, the presence of pathological prognostic factors significantly shortened BCR-free survival (p < 0.05). Univariable analysis revealed that PSA density, risk categories, and pathological prognostic factors were significantly associated with BCR-free survival, although age and PSA were not. In multivariable analysis, age, risk categories, grade group, IDCP, and pT significantly predicted BCR-free survival (p < 0.05). Conversely, no statistically significant differences were found for any pathological prognostic factors in low-risk patients., Conclusions: In low-risk patients, pathological prognostic factors did not affect BCR-free survival, which suggests that additional treatment may be unnecessary even if pathological prognostic factors are observed in low-risk patients with RP., (© 2023. The Author(s).)

In patients with prostate cancer (PCa), serum prostate-specific antigen (PSA) is a useful marker for evaluating the effects of androgen deprivation therapy (ADT). Intuitively, most urologists expect that a more rapid PSA decline in response to ADT would be positively associated with extended survival. Recently, we have reported that prolonged gradual serum PSA decline after ADT is strongly associated with favorable prognosis in PCa patients, however, the mechanism remains unknown. We investigated the role of fibroblasts in serum PSA decline after ADT. We performed in vitro experiments using androgen-sensitive, androgen receptor (AR)-positive prostate epithelial cell lines (LNCaP, 22Rv1, and RWPE-1 cells), commercially available prostate stromal cells (PrSC), and primary cultures of prostate fibroblasts (pcPrFs). In LNCaP and 22Rv1 cells, PSA production was increased by co-culture with fibroblasts under androgen-deprived conditions. In an in vivo model using LNCaP cells, serum PSA declined rapidly after ADT becoming undetectable within 14 days in mice inoculated with LNCaP cells alone. In contrast, when LNCaP cells were co-inoculated with fibroblasts, serum PSA levels were still high on 14 days post ADT and did not drop to undetectable levels until 21 days post ADT. Tumor volumes and Ki67 labeling indices were not altered between days 14 and 21 post ADT in mice inoculated with LNCaP cells; however, those in mice inoculated with LNCaP cells plus fibroblasts decreased gradually. PSA protein was detected in all tumors on 21 days post ADT by immunohistochemical staining. Microvessel densities were higher on 14 days post ADT for tumors from mice inoculated with LNCaP cells plus fibroblasts as compared with LNCaP cells alone. In summary, co-inoculation of fibroblasts with LNCaP cells prolonged serum PSA decline after ADT and enhanced the efficacy of ADT. Prolonged serum PSA decline may indicate the presence of protective fibroblasts that preserve the AR dependence of PCa cells, improving treatment efficacy.

Purpose: Active surveillance (AS) is one potential solution to avoiding the overtreatment of favorable prostate cancer. By handling the AS strategy more safely, tumor aggressiveness may be evaluated more accurately. The aim of the present study was to evaluate the predictive impact of baseline prostate-specific antigen (PSA) isoform [-2]proPSA (p2PSA)-related indices on the pathological reclassification at 1 year during an AS program., Methods: Between 2002 and 2003, 134 males diagnosed with low-risk prostate cancer were registered in the Japanese multicenter study cohort as candidates for AS, and 118 (88 %) males actually proceeded to AS. Of the 118 patients, the 67 that underwent protocol biopsy at 1 year after beginning AS were enrolled in the present study. The predictive significance of various baseline clinicopathological features and p2PSA-related indices on pathological reclassification at 1 year after beginning AS were investigated., Results: The pathological reclassification rate was 37.3 %. According to the univariate analysis, prostate volume (p = 0.049), number of biopsy cores (p = 0.047), percentage of positive biopsy cores (p = 0.023), p2PSA to free PSA ratio (%p2PSA) (p = 0.003) and prostate health index (phi) (p = 0.010) at baseline were significantly different between the reclassification and non-reclassification groups. By multivariate logistic regression analysis, baseline %p2PSA (p = 0.008) and phi (p = 0.008) were the only independent predictive factors for pathological upgrade at 1 year after AS commencement., Conclusions: Baseline %p2PSA and phi may predict the pathological reclassification at 1 year after starting AS, which could be due to the under detection of clinically significant prostate cancer at AS enrollment.

Prostate-specific antigen (PSA) gene expression is regulated by androgen receptor (AR) through androgen response elements (AREs) in the promoter region of the PSA gene. A single nucleotide polymorphism with guanine (G) to adenine (A) substitution is identified at position -158 in the ARE of the PSA gene. The purpose of this study was to investigate the allelic differences in the PSA promoter activity in vitro and the relation to several clinical factors of prostate cancer patients in the Japanese population. No significant differences of promoter activity in luciferase assay and binding activity of androgen receptor were noted between the two alleles in vitro. The PSA -158 G/A polymorphism was determined by PCR amplification and restriction digestion assays in 101 organ-confined prostate cancer (PC) patients who underwent radical prostatectomy and 52 controls with benign prostatic hyperplasia. The results revealed that homozygosity for the A allele in Japanese is less common (only 8.5%) than in ethnic populations. There were no significant differences in serum PSA value at the time of diagnosis, differentiation of cancer, pathological stage, cancer volume or ratio of serum PSA/ cancer volume. However, cancer volume after neoadjuvant endocrine therapy was significantly smaller in GG genotype than in AA + AG genotypes. Our data indicate that the PSA -158 G/A polymorphism has no effect on the PSA promoter activity in vitro and no association with the serum PSA level in Japanese men, however suggest that the patients with GG genotype of ARE1 may be more sensitive to androgen ablation therapy. Taken together, the ARE1 polymorphism in the PSA gene promoter may be one of the biomarkers for response to androgen deprivation therapy.

Objective: To distinguish good candidates for watchful waiting from those who need immediate treatment in localized prostate cancer., Methods: Prostate specific antigen (PSA)-doubling time (DT) was calculated by a log-linear regression model for 78 patients with clinically localized prostate cancer (T1c: 47, T2a: 6, T2b: 21, and T3: 4) under surveillance. Median observation period was 37.5 months. The first 1-year PSA-DT was compared with the overall PSA-DT in 41 patients who had been under surveillance for more than 3 years., Results: There was significant difference in the PSA-DT distribution between a pooled group of T1c and T2a and a group of T2b and T3 patients (median 58.8 versus 33.3 months, P = 0.0052). A combination of three parameters consisting of initial PSA level less than 10 ng/ml, WHO grade 1, one or two positive core per six to eight systematic biopsy cores with 50% or less cancer involvement significantly correlated with PSA-DT distribution in the T1c plus T2a group (P = 0.0034). The first year assessment of PSA-DT was identical to the overall assessment in 48.8%, 2 years or more in 36.6%, while it was 2 years or less (possibly over-estimated) in 14.6%., Conclusion: PSA-DT can be predictable to some extent with the initial PSA level and biopsy features in early stage prostate cancers. Prospective study is needed to clarify whether temporary observation together with PSA-DT estimation is a safe strategy and is complementary to clinico-pathological parameters at diagnosis.

Purpose: Active surveillance (AS) is one potential solution to avoiding the overtreatment of favorable prostate cancer. By handling the AS strategy more safely, tumor aggressiveness may be evaluated more accurately. The aim of the present study was to evaluate the predictive impact of baseline prostate-specific antigen (PSA) isoform [−2]proPSA (p2PSA)-related indices on the pathological reclassification at 1 year during an AS program. Methods: Between 2002 and 2003, 134 males diagnosed with low-risk prostate cancer were registered in the Japanese multicenter study cohort as candidates for AS, and 118 (88 %) males actually proceeded to AS. Of the 118 patients, the 67 that underwent protocol biopsy at 1 year after beginning AS were enrolled in the present study. The predictive significance of various baseline clinicopathological features and p2PSA-related indices on pathological reclassification at 1 year after beginning AS were investigated. Results: The pathological reclassification rate was 37.3 %. According to the univariate analysis, prostate volume ( p = 0.049), number of biopsy cores ( p = 0.047), percentage of positive biopsy cores ( p = 0.023), p2PSA to free PSA ratio (%p2PSA) ( p = 0.003) and prostate health index (phi) ( p = 0.010) at baseline were significantly different between the reclassification and non-reclassification groups. By multivariate logistic regression analysis, baseline %p2PSA ( p = 0.008) and phi ( p = 0.008) were the only independent predictive factors for pathological upgrade at 1 year after AS commencement. Conclusions: Baseline %p2PSA and phi may predict the pathological reclassification at 1 year after starting AS, which could be due to the under detection of clinically significant prostate cancer at AS enrollment. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the significance of dedicated central pathologic review for Gleason score (GS) correlation between the biopsy and radical prostatectomy (RP) specimens and the prediction of high-grade Gleason patterns. A discrepancy in the GS between the biopsy and RP specimens has been reported. Methods: The Clinicopathological Research Group for Localized Prostate Cancer disease registry collated the data from 1629 patients who had undergone RP from 1997 to 2005. All biopsy and RP specimens were retrospectively re-evaluated by 2 central uropathologists according to the International Society of Urological Pathology consensus. The GS correlation between the biopsy and RP specimens and the presence of high-grade Gleason patterns (4 or 5) were recorded. The GS was categorized into 5 groups (2-4, 5-6, 3 + 4, 4 + 3, and 8-10). Results: Central review significantly increased the exact concordance rate and decreased the undergrading and overgrading rates between the biopsy and RP specimens compared with local review (P < .05 for all). In each GS or prostate-specific antigen group, the central review biopsy GS had a significantly greater exact concordance rate with the RP specimen GS compared with the local review biopsy GS (P < .05 for all). Regarding high-grade Gleason patterns in the RP specimens, central review showed significantly greater sensitivity, positive predictive value, and negative predictive value than local review (P < .05 for all). Conclusions: We have demonstrated that central review using the International Society of Urological Pathology consensus improves the GS correlation and better predicts high-grade Gleason patterns compared with local review. We recommend central pathologic review by dedicated uropathologists for multi-institutional studies using data from prostate biopsy and RP specimens. [ABSTRACT FROM AUTHOR]

Purpose: Pathological assessment of radical prostatectomy specimens has not been uniform among pathologists. We investigated interobserver variability of radical prostatectomy specimen reviews between local and central pathologists. Materials and Methods: We collated data from 50 institutions on 2,015 patients with cT1c-3 prostate cancer who underwent radical prostatectomy between 1997 and 2005. All radical prostatectomy specimens were retrospectively reevaluated by a central uropathologist. Gleason score, extracapsular extension, seminal vesicle invasion, lymph node involvement, positive surgical margin, year of diagnosis and pathology volume were recorded. Results: The exact concordance rate of Gleason score between local and central review was 54.8%, and under grading and over grading rates at local review were 25.9% and 19.2%, respectively. Spearman''s rank correlation coefficient was 0.61 for local and central radical prostatectomy Gleason score. The exact concordance rate of Gleason score 8–10 at local review was significantly lower than that of Gleason score 5–6, 3 + 4 and 4 + 3 at local review (p = 0.011, <0.001 and 0.006). Exact concordance rates between local and central review for extracapsular extension, seminal vesicle invasion, lymph node involvement and positive surgical margin were 82.5%, 97.6%, 99.6% and 87.5%, respectively. High volume institutions and recently diagnosed cohorts showed significantly higher exact concordance rates between local and central review for radical prostatectomy Gleason score and other pathological features (all p <0.001). Conclusions: High volume institutions and recent series show higher concordance between local and central review of radical prostatectomy pathology. However, concordance for high grade Gleason score, extracapsular extension and surgical margin status remains poor. Radical prostatectomy specimens should be reevaluated in a multi-institutional study for more accurate pathological data. [Copyright &y& Elsevier]