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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.

Background: Bladder pain syndrome/interstitial cystitis (BPS/IC) is a persistent pain perceived in the urinary bladder region, accompanied by at least one symptom, such as pain worsening with bladder filling and daytime or nighttime urinary frequency without any proven infection or obvious pathology. The aim of this study is to evaluate the efficacy and safety of pentosan polysulfate (PPS) in patients with BPS/IC. Methods: Systematic search was performed by PRISMA checklist. Electronic databases, including PubMed and Cochrane library, were checked until 2021 using keywords: ‘pentosan polysulfate’, ‘pain syndrome’, ‘interstitial cystitis’, and bibliography of relevant papers was checked. Inclusion criteria: Patients with confirmed diagnosis of BPS/IC and cystoscopy criteria – Hunner’s lesions. Exclusion criteria included hypersensitivity, pregnancy, lactation, and oral therapy for BPS/IC in the period of 1 month before the study and abstracts or unpublished papers. Results: In total, 13 clinical trials were included in systematic review and 7 were included in meta-analysis. Studies evaluated the effectiveness and safety of oral PPS versus placebo or other treatment options. In the first meta-analysis, three studies compared oral PPS with placebo: [relative risk (RR) = 2.07, 95% confidence interval (CI): 1.37–3.13, p = 0.0006]. The second meta-analysis of two studies compared oral PPS with another treatment options (intravesical liposome and CyA): (RR = 0.44, 95% CI: 0.10–1.93, p = 0.28). The third meta-analysis of two studies included intravesical regimen of PPS compared with intravesical placebo: (RR = 1.09, 95% CI: 0.54–2.22, p = 0.80). The majority of studies do not report any particular serious side effects. Conclusion: PPS treatment has a statistically significant effect over placebo on the subjective improvement of patients with BPS/IC. There was no difference between PPS and other treatment options. Intravesical regimen of PPS had no significant impact on response rates. None of included studies reported severe side effects after intervention.

Toll-like receptor 5 (TLR5) controls endogenous immune responses to pathogens and is a promising target for pharmacological stimulation of anti-tumor immunity. Mobilan is an innovative gene therapy agent consisting of a non-replicating bicistronic adenovirus directing constitutive expression of human Toll-like receptor 5 (TLR5) and the secreted flagellin-based TLR5 agonist, 502s. In mice, Mobilan injection into prostate tumors resulted in autocrine TLR5 signaling, immune system activation, and suppression of tumor growth and metastasis. Here we report a first-inhuman placebo-controlled clinical study of Mobilan aimed at evaluating safety, tolerability, pharmacokinetics and pharmacodynamics of a single intra-prostate injection of Mobilan in early stage prostate cancer patients. Mobilan was safe and well-tolerated at all tested doses; thus, the maximum tolerated dose was not identified. Injection of Mobilan induced signs of self-resolving inflammation not present in placebo-injected patients, including transient elevation of PSA and cytokine (G-CSF, IL-6) levels, and increased lymphoid infiltration in prostate tissue. The highest dose of Mobilan (10 11 viral particles) produced the best combination of safety and pharmacodynamic effects. Therefore, Mobilan is well-tolerated and induces the expected pharmacodynamic response in humans. These results support further clinical development of Mobilan as a novel immunotherapy for prostate cancer.

Objective Coronavirus disease‐19 (COVID‐19) pandemic caused delays in definitive treatment of patients with prostate cancer. Beyond the immediate delay a backlog for future patients is expected. The objective of this work is to develop guidance on criteria for prioritisation of surgery and reconfiguring management pathways for patients with non‐metastatic prostate cancer who opt for surgical treatment. A second aim was to identify the infection prevention and control (IPC) measures to achieve a low likelihood of coronavirus disease 2019 (COVID‐19) hazard if radical prostatectomy (RP) was to be carried out during the outbreak and whilst the disease is endemic. Methods We conducted an accelerated consensus process and systematic review of the evidence on COVID‐19 and reviewed international guidance on prostate cancer. These were presented to an international prostate cancer expert panel (n = 34) through an online meeting. The consensus process underwent three rounds of survey in total. Additions to the second‐ and third‐round surveys were formulated based on the answers and comments from the previous rounds. The Consensus opinion was defined as ≥80% agreement and this was used to reconfigure the prostate cancer pathways. Results Evidence on the delayed management of patients with prostate cancer is scarce. There was 100% agreement that prostate cancer pathways should be reconfigured and measures developed to prevent nosocomial COVID‐19 for patients treated surgically. Consensus was reached on prioritisation criteria of patients for surgery and management pathways for those who have delayed treatment. IPC measures to achieve a low likelihood of nosocomial COVID‐19 were coined as ‘COVID‐19 cold’ sites. Conclusion Reconfiguring management pathways for patients with prostate cancer is recommended if significant delay (>3–6 months) in surgical management is unavoidable. The mapped pathways provide guidance for such patients. The IPC processes proposed provide a framework for providing RP within an environment with low COVID‐19 risk during the outbreak or when the disease remains endemic. The broader concepts could be adapted to other indications beyond prostate cancer surgery.

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