To evaluate the safety and efficacy of neoadjuvant radiohormonal therapy for oligometastatic prostate cancer (OMPC), we conducted a 3 + 3 dose escalation, prospective, phase I/II, single-arm clinical trial (CHiCTR1900025743), in which long-term neoadjuvant androgen deprivation was adopted 1 month before radiotherapy, comprising intensity modulated radiotherapy to the pelvis, and stereotactic body radiation therapy to all extra-pelvic bone metastases for 4-7 weeks, at 39.6, 45, 50.4, and 54 Gy. Robotic-assisted radical prostatectomy was performed after 5-14 weeks. The primary outcome was treatment-related toxicities and adverse events; secondary outcomes were radiological treatment response, positive surgical margin (pSM), postoperative prostate-specific antigen (PSA), pathological down-grading and tumor regression grade, and survival parameters. Twelve patients were recruited from March 2019 to February 2020, aging 66.2 years in average (range, 52-80). Median baseline PSA was 62.0 ng/mL. All underwent RARP successfully without open conversions. Ten patients recorded pathological tumor down-staging (83.3%), and 5 (41.7%) with cN1 recorded negative regional lymph nodes on final pathology. 66.7% (8/12) recorded tumor regression grading (TRG) -I and 25% (3/12) recorded TRG-II. Median follow-up was 16.5 months. Mean radiological progression-free survival (RPFS) was 21.3 months, with 2-year RPFS of 83.3%. In all, neoadjuvant radiohormonal therapy is well tolerated for oligometastatic prostate cancer.
Male ; Humans ; Prostatic Neoplasms/radiotherapy* ; Prostate-Specific Antigen/therapeutic use* ; Neoadjuvant Therapy ; Androgen Antagonists/therapeutic use* ; Prospective Studies

Predicting treatment responses in advanced prostate cancer (PCa) currently centres on prostate-specific antigen (PSA) kinetics and on being able to visualize measurable changes in imaging modalities. New molecular markers have emerged as potential diagnostic and prognostic indicators; these were summarized in Part I of this review in the Asian Journal of Andrology. A number of molecular markers are now being used to enhance PCa imaging and staging. However, management options for advanced and hormone-resistant PCa (HRPC) are limited and additional therapeutic options are needed. Molecular markers have been proposed as potential therapeutic targets using gene therapy and immunomodulation. Additionally, markers identified in early PCa and precursor lesions may offer novel targets for chemoprevention and vaccine development. This review summarizes the current advances regarding the roles of these markers in the management of PCa.
Antineoplastic Agents ; therapeutic use ; Biomarkers, Tumor ; genetics ; metabolism ; Cancer Vaccines ; therapeutic use ; Genetic Therapy ; Humans ; Immunologic Factors ; therapeutic use ; Male ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; metabolism ; therapy

BACKGROUNDEpidemiological studies have shown that lycopene has anti-prostate cancer effect. In vitro tests also confirmed that it can promote apoptosis of prostate cancer cells. We investigated the effect of whole-tomato supplement lycopene on the prostate-specific antigen velocity in selected prostate cancer patients.

METHODSTwenty selected prostate cancer patients were given whole-tomato supplement lycopene 10 mg per day for about 6 months. Blood samples of patients were collected weekly to measure serum prostate-specific antigen (PSA) values. PSA velocity slope, which reflects the change of PSA, and the degree of change were also calculated. By comparing the values of average PSA velocity slope (rise or fall of PSA) before and after the administration of lycopene, the effect of lycopene can be evaluated. Blood chemistry analysis was regular followed as safety control.

RESULTSThree patients in the research group withdrew within 3 weeks because of inability to conform. The rest 17 patients continued for an average period of 6 months. Two patients withdrew because of cancer progression (PSA rise) who later received active treatment. The average fall in PSA was equivalent to 2.56% over (i.e. an average slope/d of -0.000 28) the first 3 months. In the last 3 months, average fall in PSA was equivalent to 31.58% (i.e. an average slope/d of -0.003 51). The Wilcoxon rank-sum test showed a statistically significant decrease of PSA velocity slope overall (P = 0.000 9). Analysis of the PSA doubling time (pre- vs. post-treatment) showed a median increase over 3 months but this was not statistically significant (P = 0.21). No toxic side effect was observed during the whole process. The results indicate that the average PSA change is "decline" in patients, and the degree of the decline is accelerated.

CONCLUSIONAdministration of lycopene was able to reduce PSA velocity in this study group.

Aged ; Carotenoids ; therapeutic use ; Dietary Supplements ; Female ; Humans ; Male ; Prostate-Specific Antigen ; metabolism ; Prostatic Neoplasms ; blood ; drug therapy

The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial showed improvement in overall survival (OS) and other efficacy endpoints with apalutamide plus androgen deprivation therapy (ADT) versus ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC). As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer, a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation. Event-driven endpoints were OS, and time from randomization to initiation of castration resistance, prostate-specific antigen (PSA) progression, and second progression-free survival (PFS2) on first subsequent therapy or death. Efficacy endpoints were assessed using the Kaplan-Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity. Participating Asian patients received once-daily apalutamide 240 mg ( n = 111) or placebo ( n = 110) plus ADT. After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide, apalutamide reduced the risk of death by 32% (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.42-1.13), risk of castration resistance by 69% (HR: 0.31; 95% CI: 0.21-0.46), PSA progression by 79% (HR: 0.21; 95% CI: 0.13-0.35) and PFS2 by 24% (HR: 0.76; 95% CI: 0.44-1.29) relative to placebo. The outcomes were comparable between subgroups with low- and high-volume disease at baseline. No new safety issues were identified. Apalutamide provides valuable clinical benefits to Asian patients with mCSPC, with an efficacy and safety profile consistent with that in the overall patient population.
Male ; Humans ; Prostatic Neoplasms/pathology* ; Androgen Antagonists/therapeutic use* ; Prostate-Specific Antigen ; Castration ; Prostatic Neoplasms, Castration-Resistant/drug therapy*

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Male ; Humans ; Prostate-Specific Antigen ; Treatment Outcome ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies

OBJECTIVETo investigate the effect of antibiotics and a nonsteroidal anti-inflammatory agent on the level of total prostate specific antigen (PSA) and free PSA ratio (F-PSAR) in patients with chronic prostatitis IIIA.

METHODSA total of 228 outpatients diagnosed as with chronic prostatitis III A received 4-week antibiotic and anti-inflammatory treatment. The PSA level and F-PSAR were determined before and after the treatment, and the changes analyzed.

RESULTSSignificant variations were observed in the median PSA concentrations (3.51 microg/L and 2.75 microg/L) and F-PSAR (0.25% and 0.27%) 4 weeks after the treatment. Sixty-five of the patients (28.5%) presented with serum PSA greater than 4 ng/ml, the mean PSA decreased by 32.9%, from 6.24 microg/L before the treatment to 4.58 microg/L 4 weeks after the treatment (P < 0.05), and the serum PSA was normalized in 18 of the 65 patients (27.7%). The median variation of F-PSAR (0.16% and 0.22%) was greater than that of PSA. The variation indexes obtained 4 weeks after the treatment showed no statistical difference from those observed 8 weeks after the treatment.

CONCLUSIONChronic prostatitis IIIA appears to contribute to increased serum PSA levels in some men. Antibiotic and anti-inflammatory treatment could significantly reduce the PSA level and increase F-PSAR.

Adult ; Aged ; Anti-Bacterial Agents ; therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal ; therapeutic use ; Chronic Disease ; Humans ; Male ; Middle Aged ; Prostate-Specific Antigen ; blood ; Prostatitis ; blood ; drug therapy

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

OBJECTIVETo evaluate the efficacy of periprostatic nerve block anesthesia (PPNB) for pain relief in transrectal ultrasound-guided systematic prostate biopsy (PBx).

METHODSWe reviewed the data of patients undergoing initial PBx at our center from November, 2013 to January, 2015. Only the patients with 12-core systemic PBx were included and 111 patients were eligible for this study, among whom 52 patients received PPNB and 59 did not. PPNB was achieved by an injection of 5 mL of 1% lidocaine at the angle between the seminal vesicle and base of the prostate on each side before biopsy. The DRE pain score, probe insert pain score, and biopsy pain score were assessed by visual analogue scale (VAS) immediately after the biopsy. The complications were recorded and evaluated immediately after and at 7 days after the biopsy.

RESULTSThe mean age, prostate volume, total prostate specific antigen (tPSA), free PSA (fPSA), and abnormal DRE were comparable between the 2 groups (P>0.05). Immediately after the biopsy, no difference was found between the 2 groups in DRE pain score (1.40±0.98 vs 1.39±0.91, P=0.102) or probe insert pain score (2.07±0.96 vs 2.03±0.90, P=0.960), but the biopsy pain score was significantly lower in PPNB group than in no PPNB group (2.54±1.42 vs 3.07±1.43, P=0.033). The incidence of the procedure-related complications was similar between the 2 groups (P>0.05).

CONCLUSIONPPNB can significantly lower the biopsy pain score in PBx without increasing the incidence of complications.

Biopsy ; Humans ; Lidocaine ; therapeutic use ; Male ; Nerve Block ; Pain ; prevention & control ; Pain Management ; methods ; Pain Measurement ; Prostate ; diagnostic imaging ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; diagnosis ; Ultrasonography

Considering that antibiotic treatment may elevated the level of prostate-specific antigen (PSA) and hence limit the specificity of PSA test for prostate cancer, urologists use empiric antibiotic treatment for men with increased PSA levels. But it is controversial whether antibiotic treatment can exclude inflammation in the differential diagnosis of PSA elevation. Some researchers have found that antibiotic treatment can decrease inflammation-induced PSA elevation and help to reduce unnecessary biopsies, while others have reported that antibiotic treatment has no significant effect on the PSA level, and the lowered level of PSA following antibiotic treatment does not mean the decreased risk of prostate cancer. Further researches are needed to confirm the value of antibiotic treatment before biopsy.
Anti-Bacterial Agents ; therapeutic use ; Biomarkers, Tumor ; blood ; Biopsy ; Diagnosis, Differential ; Humans ; Inflammation ; metabolism ; pathology ; Male ; Prostate ; pathology ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; diagnosis ; pathology ; Prostatitis ; pathology

Corticosteroid switching can reverse abiraterone resistance in some patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we investigated the potential biomarkers for predicting the efficacy of corticosteroid switching during treatment with abiraterone acetate (AA). We retrospectively analyzed 101 mCRPC patients receiving corticosteroid switching from West China Hospital and Sun Yat-Sen University Cancer Center between January 2016 and December 2018. All cases received AA plus prednisone as first-line therapy during mCRPC. Primary end points were biochemical progression-free survival (bPFS) and overall survival (OS). The risk groups were defined based on multivariate analysis. A total of 42 (41.6%) and 25 (24.8%) patients achieved 30% and 50% decline in prostate-specific antigen (PSA), respectively, after corticosteroid switching. The median bPFS and median OS on AA plus dexamethasone were 4.9 (95% confidence interval [CI]: 3.7-6.0) months and 18.8 (95% CI: 16.2-30.2) months, respectively. Aldo-keto reductase family 1 member C3 (AKR1C3) expression (hazard ratio [HR]: 2.15, 95% Cl: 1.22-3.80, P = 0.008) and baseline serum alkaline phosphatase (ALP; HR: 4.95, 95% Cl: 2.40-10.19, P < 0.001) were independent predictors of efficacy before corticosteroid switching in the multivariate analysis of bPFS. Only baseline serum ALP >160 IU l^-1 (HR: 3.41, 95% Cl: 1.57-7.38, P = 0.002) together with PSA level at switch ≥50 ng ml^-1 (HR: 2.59, 95% Cl: 1.22-5.47, P = 0.013) independently predicted poorer OS. Based on the predictive factors in multivariate analysis, we developed two risk stratification tools to select candidates for corticosteroid switching. Detection of serum ALP level, PSA level, and tissue AKR1C3 expression in mCRPC patients could help make clinical decisions for corticosteroid switching.
Abiraterone Acetate/therapeutic use* ; Adrenal Cortex Hormones/therapeutic use* ; Androstenes ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Dexamethasone/therapeutic use* ; Disease-Free Survival ; Humans ; Male ; Prednisone/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms, Castration-Resistant/pathology* ; Retrospective Studies ; Treatment Outcome