PCa is found on autopsy in a similar proportion of Russian and Japanese men. More than 50% of cancers in ASI and nearly 25% of cancers in CAU men have a GS of 7 or greater. Our results suggest that the definition of clinically insignificant PCa might be worth re-examining.
Purpose
Preclinical evaluation of
PCA3
and
AMACR
transcript simultaneous detection in urine to diagnose clinical significant prostate cancer (prostate cancer with Gleason score ≥7) in a Russian cohort.
Patients and Methods
We analyzed urine samples of patients with a total serum PSA ≥2 ng/mL: 31 men with prostate cancer scheduled for radical prostatectomy, 128 men scheduled for first diagnostic biopsy (prebiopsy cohort).
PCA3
,
AMACR
,
PSA
and
GPI
transcripts were detected by multiplex reverse transcription quantitative polymerase chain reaction, and the results were used for scores for calculation and statistical analysis.
Results
There was no significant difference between clinically significant and nonsignificant prostate cancer PCA3 scores. However, there was a significant difference in the AMACR score (patients scheduled for radical prostatectomy
p
=0.0088, prebiopsy cohort
p
=0.029). We estimated AUCs, optimal cutoffs, sensitivities and specificities for PCa and csPCa detection in the prebiopsy cohort by tPSA, PCA3 score, PCPT Risk Calculator and classification models based on tPSA, PCA3 score and AMACR score. In the clinically significant prostate cancer ROC analysis, the PCA3 score AUC was 0.632 (95%CI: 0.511–0.752), the AMACR score AUC was 0.711 (95%CI: 0.617–0.806) and AUC of classification model based on the
PCA3
score, the AMACR score and total PSA was 0.72 (95%CI: 0.58–0.83). In addition, the correlation of the AMACR score with the ratio of total RNA and RNA of prostate cells in urine was shown (tau=0.347,
p
=6.542e–09). Significant amounts of nonprostate RNA in urine may be a limitation for the AMACR score use.
Conclusion
The AMACR score is a good predictor of clinically significant prostate cancer. Significant amounts of nonprostate RNA in urine may be a limitation for the AMACR score use. Evaluation of the AMACR score and classification models based on it for clinically significant prostate cancer detection with larger samples and a follow-up analysis is promising.
IntroductionStrong epidemiologic evidence supports correlation between lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH) and erectile dysfunction (ED). The link has biologic plausibility given phosphodiesterase type 5 (PDE5) expression in pelvic structures. PDE5 inhibitors target pathophysiologic processes implicated in LUTS/BPH.Material and methodsThis review highlights the efficacy and safety of the daily use of a PDE5 inhibitor tadalafil in LUTS/BPH, with a focus on LUTS/BPH medical management in Russia.ResultsAlpha–blockers and phytotherapy are major components of the current LUTS/BPH therapy in Russia. Russian regulatory authorities granted approval for once–daily tadalafil for treatment of LUTS/BPH in January 2012. In a pivotal study, tadalafil 5 mg once–daily significantly improved International Prostate Symptom Score (IPSS) over 12 weeks vs. placebo (P = .004) regardless of baseline ED severity. IPSS improvement was maintained at 12 weeks. Integrated analysis of randomized studies showed that tadalafil 5 mg once–daily resulted in significant symptom improvements across a range of men with LUTS/BPH. Relief of LUTS due to tadalafil was independent of improvement in ED; improvements in IPSS and erectile function were only weakly correlated (r = –0.229). Another pooled analysis found similar improvement in LUTS/BPH between men with or without ED, with non–significant P values for treatment–by–ED–status interactions for total IPSS ( P = .73). Non–registration studies of tadalafil and alpha–blocker co–therapy in LUTS/BPH suggest an additive effect, but co–therapy is not recommended in current tadalafil prescribing instructions.ConclusionsTadalafil results in symptom improvements across a range of men with LUTS/BPH and represents a new treatment option for patients in Russia with LUTS/BPH.
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