Prognostic value of PSMA PET in predicting long-term biochemical control following curative intent treatment for prostate cancer.

INTRODUCTION: The aim of this study is to investigate the prognostic value of 68Ga-labelled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) metrics in predicting long-term biochemical failure-free survival (BFFS) following curative intent treatment for prostate cancer. METHODS: We completed a prospective study that followed men who had PSMA PET for staging of newly diagnosed prostate cancer between 2015 and 2017 who went on to have curative intent treatment with radiotherapy (RT) or radical prostatectomy (RP). PSMA PET CT imaging was reported and the intraprostatic maximum standardised uptake value (SUVmax) was recorded. The primary outcome was BFFS. Statistical analysis included descriptive statistics, Cox proportional hazards (PH) models, Kaplan-Meier survival analysis and a regression tree structured method. RESULTS: A total of 183 men were included in the analysis with a median age of 66 years and the majority of patients (55.2%) had ISUP grade 1-3 disease. All patients had PSMA PET staging prior to curative intent treatment with RP (66.1%) or external beam radiotherapy (33.9%). PSMA-avid pelvic nodes were present in 26 patients but were not associated with worse biochemical control. A PSMA SUVmax of the prostate primary greater than the median (>5.6) was associated with a lower BFFS (HR: 4.4, 95% CI 1.42-3.72, P = 0.01). A multivariate Cox model incorporating initial biopsy grade, age and PSMA SUVmax showed that PSMA SUVmax was an independent predictor of BFFS. The RT-structured method identified an optimal threshold of 6.8 for PSMA SUVmax, above which patients with ISUP 1-3 disease had a significantly worse BFFS. CONCLUSION: PSMA SUVmax is a strong predictor of BFFS in patients with non-metastatic prostate cancer who underwent curative intent treatment. Patients with low-risk disease on biopsy (ISUP 1-3) but high PSMA SUVmax may have biochemical failure risk analogous to higher-risk disease (ISUP 4-5). These findings allow for further risk stratification and prognosis of patients with newly diagnosed prostate cancer planned for definitive treatment.

Computer classification and construction of a novel prognostic signature based on moonlighting genes in prostate cancer.

Advanced prostate cancer (PRAD) patients have poor prognosis and rising morbidity despite the ongoing iteration of molecular therapeutic agents. As newly discovered proteins with several functions, Moonlighting proteins have showed an important role in tumor progression but has not been extensively investigated in PRAD. Our study aimed to identify moonlighting-related prognostic biomarkers and prospective PRAD therapy targets. 103 moonlighting genes were gathered from previous literatures. A PRAD classification and multivariate Cox prognostic signature were constructed using dataset from The Cancer Genome Atlas (TCGA). Subsequently, we tested our signature's potential to predict biochemical failure-free survival (BFFS) using GSE21032, a prostate cancer dataset from Gene Expression Omnibus (GEO). The performance of this signature was demonstrated by Kaplan-Meier (KM), receiver operator characteristic (ROC), areas under ROC curve (AUC), and calibration curves. Additionally, immune infiltration investigation was conducted to determine the impact of these genes on immune system. This signature's influence on drug susceptibility was examined using CellMiner's drug database. Both training and validation cohorts demonstrated well predictive capacity of this 9-gene signature for PRAD. The 3-year AUCs for TCGA-PRAD and GSE21032 were 0.802 and 0.60 respectively. It can effectively classify patients into various biochemical recurrence risk groups. These genes were also assessed to be connected with tumor mutation burden (TMB), immune infiltration and therapy. This work created and validated a moonlighting gene signature, revealing fresh perspectives on moonlighting proteins in predicting prognosis and improving treatment of PRAD.

A comparative analysis between low-dose-rate brachytherapy and external beam radiation therapy for low- and intermediate-risk prostate cancer in Asian men.

OBJECTIVE: To report the long-term clinical outcomes of low-risk (LR) and intermediate-risk (IR) prostate cancer patients treated with low-dose-rate brachytherapy (LDR-BT) and external beam radiation therapy (EBRT). PATIENTS AND METHODS: Men with biopsy-proven low- and intermediate-risk prostate cancer received EBRT and LDR-BT in an Asian academic center from 2000 to 2019 were reviewed. Kaplan-Meier survival analysis was performed to compare biochemical failure-free survival (bFFS) and overall survival (OS) between LDR and EBRT in the low- and intermediate-risk cohorts. RESULTS: 642 patients (521 EBRT and 121 LDR-BT) with low- and intermediate-risk prostate cancer were included for analysis. In the intermediate-risk group, 5- and 10-year bFFS was 96%, 89% and 86%, 61% for LDR-BT and EBRT, respectively. LDR-BT was associated with a statistically significant improvement of bFFS in the intermediate-risk cohort (HR 2.7, p = 0.02). In the low-risk cohort, no difference of bFFS was found between LDR-BT and EBRT (HR 1.9, p = 0.08). Hormone therapy was more common in EBRT than LDR-BT for intermediate-risk group (71% versus 44%, p < 0.05). Prostate cancer-specific mortality was low in both EBRT (1%) and LDR-BT (2%) cohorts. No significant difference in OS was found between LDR-BT and EBRT in low- and intermediate-risk group (HR 2.1, p = 0.2 and HR = 1.7, p = 0.3). CONCLUSION: In our retrospective study, LDR-BT is associated with superior bFFS compared with EBRT in Asian men with intermediate-risk prostate cancer.

Effects of 1-Year Hospital Volume on Surgical Margin and Biochemical-Failure-Free Survival in Patients Undergoing Robotic versus Nonrobotic Radical Prostatectomy: A Nationwide Cohort Study from the National Taiwan Cancer Database.

PURPOSE: To examine the effect of hospital volume on positive surgical margin (PSM) and biochemical-failure-free survival (BFS) rates in patients with prostate cancer (PC) undergoing robotic-assisted or nonrobotic-assisted radical prostatectomy (RP). PATIENTS AND METHODS: The patients were men collected in the National Taiwan Cancer Registry diagnosed as having PC without distant metastasis who received RP from 44 multi-institutes in Taiwan. The logistic regression method was used to analyze the risk from RP to PSM in included patients with hospital volume (i.e., number of patients with PC receiving robotic RP per year), and the Cox proportional hazards method was used to analyze the time from the index date to biochemical recurrence. RESULTS: After propensity score adjustment, compared with hospitals with >100 patients/year, the adjusted odds ratios (aORs; 95% confidence intervals) of PSM in the robotic RP group in hospitals with 1-25, 26-50, and 51-100 patients/year were 2.25 (2.10-3.11), 1.42 (1.25-2.23), and 1.33 (1.13-2.04), respectively (type III p < 0.0001). Sensitivity analysis indicated that the aORs of PSM were 1.29 (1.07-1.81), 1.07 (0.70-1.19), and 0.61 (0.56-0.83), respectively, for patients receiving robotic RP compared with nonrobotic RP within hospitals with 1-25, 26-50, and 51-100 patients/year, respectively. Compared with hospitals with >100 patients/year, the adjusted hazard ratios (aHRs) of biochemical failure in the robotic RP group were 1.40 (1.04-1.67), 1.34 (1.06-1.96), and 1.31 (1.05-2.15) in hospitals with 1-25, 26-50, and 51-100 patients/year, respectively. CONCLUSIONS: Hospital volume significantly affected PSM and BFS in robotic RP, but not in nonrobotic RP. When patients with PC want to receive robotic RP, it should be performed in a relatively high-volume hospital (>100 patients/year).

There Are No Differences in Positive Surgical Margin Rates or Biochemical Failure-Free Survival among Patients Receiving Open, Laparoscopic, or Robotic Radical Prostatectomy: A Nationwide Cohort Study from the National Cancer Database.

Purpose: To estimate the rates of positive surgical margin (PSM) and biochemical failure-free survival (BFS) among patients with prostate cancer (PC) receiving open, laparoscopic, or robotic radical prostatectomy (RP). Patients and Methods: The patients were men enrolled in the Taiwan Cancer Registry diagnosed as having PC without distant metastasis who received RP. After adjustment for confounders, logistic regression was used to model the risk of PSM following RP. After adjustment for confounders, Cox proportional regression was used to model the time from the index (i.e., surgical) date to biochemical recurrence. Results: The adjusted odds ratios (95% CIs) of PSM risk after propensity score adjustment for laparoscopic versus open, robotic versus open, and robotic versus laparoscopic RP 95% CIs were 1.25 (0.88 to 1.77; p = 0.2064), 1.16 (0.88 to 1.53; p = 0.2847), and 0.93 (0.70 to 1.24; p = 0.6185), respectively. The corresponding adjusted hazard ratios (95% CIs) of risk of biochemical failure after propensity score adjustment were 1.16 (0.93 to 1.47; p = 0.1940), 1.10 (0.83 to 1.47; p = 0.5085), and 0.95 (0.74 to 1.21; p = 0.6582). Conclusions: No significant differences in PSM or BFS were observed among patients receiving open, laparoscopic, or robotic RP.

Low-dose-rate prostate brachytherapy: 4-8 week postimplant prostate-specific antigen a novel predictor of biochemical failure-free survival.

PURPOSE: The purpose of this study was to determine the relationship between patient, disease, and treatment variables and biochemical failure-free survival (bFFS) following low-dose-rate prostate brachytherapy (LDR-BT). METHODS AND MATERIALS: Data from 624 consecutive patients who received LDR-BT for localized prostate cancer between 2002 and 2012 at a single institution were collected for various patient, disease, and treatment characteristics including a 4-8 week postimplant PSA (4-8wkPSA). Subgroup analysis was stratified by risk category and treatment regimen. Analysis was performed using Kaplan-Meier survival curves, Cox proportional hazard ratios (HRs), and receiver-operator characteristic curves. RESULTS: A total of 624 consecutive patients were included with followup time of 4.0 ± 3.1 years. Predictors of bFFS included PSA nadir and 4-8wkPSA (HR = 2.48, p = 0.000 and HR = 1.24, p = 0.000, respectively) for total population. Diabetes mellitus (p = 0.026), chronic obstructive pulmonary disease (p = 0.000), alcohol use (p = 0.024), and age (p = 0.002) were predictors for specific subgroups. Receiver-operator characteristic curves 4-8wkPSA were found to be significant (p = 0.036). CONCLUSION: 4-8wkPSA is a novel predictor of bFFS for patients receiving LDR-BT across several risk categories and treatment regimens with potential clinical utility as a prognostic indicator. Certain comorbidities and exposure histories also demonstrated significant relationships with bFFS including chronic obstructive pulmonary disease, diabetes mellitus, age, alcohol history, proton pump inhibitor use, PSA nadir, and PSA density.