Midlife baseline prostate-specific antigen, velocity, and doubling time association with lethal prostate cancer and mortality.

BACKGROUND: Midlife baseline prostate-specific antigen (MB PSA), defined as a single PSA value measured between 40-59 years of age, has been proposed as a tool that can limit potential harms of PSA screening. This study aimed to examine the ability of MB PSA versus PSA doubling time (PSADT) and PSA velocity (PSAV) in assessing the likelihood of developing of lethal prostate cancer (PCa) in a diverse and contemporary North American population. METHODS: Men 40-59 years old, who received their first PSA between the years 1995 and 2019, were included. For MB PSA values, the first PSA test result was included. For PSADT, the first two PSA test results were included. For PSAV, the first three PSA test results within 30 months were included. Selection criteria resulted in a total of 77,594 patients with at least two PSA test results and 11,634 patients with at least three PSA test results. Multivariable Fine-Gray regression was used to examine the impact of the value of the PSA testing methods on the development of lethal PCa (defined as death from PCa or development of metastatic disease either at diagnosis or during follow-up). Time-dependent receiver operating characteristic/area under the curve (AUC) at 5, 10, and 15 years were plotted. RESULTS: In the main cohort, patients were most frequently in the 50-54 age category (32.8%), had a Charlson comorbidity index of 0 (70.5%), and were White (63.2%). Of these, 9.3% had the midlife baseline PSA in the top 10th percentile, and 0.4% had a PSADT 0-6 months. Lethal PCa was diagnosed in 593 (0.8%) patients. The median (interquartile range) time to lethal PCa was 8.6 (3.2-14.9) years. In the main cohort, MB PSA and PSADT showed significant associations with the occurrence of lethal PCa, with a hazard ratio (HR) of 6.10 (95% confidence interval [CI], 4.85-7.68) and HR of 2.20 (95% CI, 1.07-4.54) for patients in the top 10th percentile MB PSA group and in the PSADT between 0 to <6 months group, respectively. In patients with three PSA results available, MB PSA and PSAV showed significant associations with the occurrence of lethal PCa, with a HR of 3.95 (95% CI, 2.29-6.79) and 3.57 (95% CI, 2.17-5.86) for patients in the top 10th percentile MB PSA group and in the in the PSAV >0.4 ng/mL/year group, respectively. PSADT and PSAV did not exhibit higher AUCs than MB PSA in assessing the likelihood of lethal PCa. Specifically, they were 0.818 and 0.708 at 10 and 15 years, respectively, for the PSADT; 0.862 and 0.756 at 10 and 15 years, respectively, for the PSAV; and 0.868 and 0.762 at 10 and 15 years, respectively, for the MB PSA (all p > .05). CONCLUSIONS: The study findings are that PSAV or PSADT were not superior to midlife baseline in assessing the likelihood of developing lethal PCa. This suggests that these variables may not have practical use in enhancing PSA screening strategies in a clinical setting.

Size and SUVmax define the contribution of nodal metastases to PSA in oligorecurrent prostate cancer.

BACKGROUND: To evaluate how prostate-specific antigen (PSA) levels decrease after removal of isolated prostate cancer (PCa) nodal metastases in relation to their diameter/volume ("PSA-density of PCa-metastases") and maximum standardized uptake value (SUVmax). METHODS: A total of 83 consecutive patients with solitary nodal recurrence after radical prostatectomy who underwent prostate-specific membrane antigen-radioguided salvage surgery were retrospectively analyzed. Using multivariable linear regression models, the PSA-decrease after removal of each PCa-metastases (=PSA-contribution of each PCa-metastases) was correlated with the long axis diameter/estimated volume and the SUVmax of each removed metastasis. Sizes were measured by imaging and histopathologic examination. RESULTS: A total of 83 patients were included with a median (interquartile range [IQR]) PSA-decrease of 0.56 [0.22, 1.31] ng/mL after salvage surgery. The median [IQR] long axis diameters in imaging and histopathological examination were 8.0 [6.0, 11.0] mm and 8.4 [5.5, 11.1] mm, respectively. The median [IQR] estimated volumes were 0.13 [0.05, 0.32] cc (imaging) and 0.05 [0.02, 0.17] cc (pathology). In multivariable linear regression analyses, the estimated PSA-contribution ([95% confidence interval [CI]) of each millimeter of long axis diameter was 0.09 [0.03, 0.14] ng/mL (imaging) or 0.08 [0.03, 0.12] ng/mL (histology). The minimum diameter for biochemical recurrence (PSA ≥ 0.2 ng/mL) was >2.2 mm (imaging) or >2.5 mm (histology). The estimated PSA-contribution [95% CI] of each cc cancer volume was 1.23 [0.51, 1.94] ng/mL (imaging) or 1.46 [0.40, 2.52] ng/mL (histology). SUVmax as surrogate parameter for tissue composition was associated with increased PSA-contribution of PCa-metastases (+0.03-0.05 ng/mL per unit increase). CONCLUSIONS: The diameter/volume and SUVmax of metastatic tissue correlate with its contribution to PSA levels. Therefore, very small metastases may produce too little PSA for biochemical recurrence.

Detection of Germline Variants in Patients with Localized and Metastatic Prostate Cancer through Guideline-Based Testing.

PURPOSE: There is increasing awareness that patients with prostate cancer frequently harbor germline variants that may carry important implications for them and their family members. Given variable clinical guidelines, there remains a need to better understand which patients with prostate cancer are likely to harbor pathogenic or likely pathogenic (P/LP) germline variants. We sought to understand factors associated with P/LP germline variants in patients with metastatic or localized prostate cancer qualifying for NCCN genetic testing criteria. MATERIALS AND METHODS: Patients diagnosed with prostate cancer were offered genetic testing in accordance with National Comprehensive Cancer Network (NCCN) guidelines. Patient-level factors, including demographic, clinical, and pathologic data, were tracked in a prospectively collected registry. The association of the presence of a P/LP variant in germline testing results with patient-level factors was assessed using univariate and multivariate logistic regression. Variables were tested for overall significance with chi-squared tests. RESULTS: 505 patients underwent germline testing and had clinical data available. Rates of P/LP germline variants were 7.6% (20/264) in patients with metastatic disease, and 11.2% (27/241) in patients with localized disease. The most prevalent P/LP variants were CHEK2 (34%), BRCA2 (22%), ATM (10%), and HOXB13 (10%). CONCLUSIONS: In this cohort of patients undergoing guideline-informed germline testing, P/LP germline variants were found in similar proportions across all age ranges and clinical characteristics. Only age at genetic testing for patients with metastatic disease was demonstrated to be predictive of the presence of a P/LP germline variant, highlighting the challenges associated with refining current clinical testing guidelines.

Transperineal biopsy devices in people with suspected prostate cancer - a systematic review and economic evaluation.

Background: People with suspected prostate cancer are usually offered either a local anaesthetic transrectal ultrasound-guided prostate biopsy or a general anaesthetic transperineal prostate biopsy. Transperineal prostate biopsy is often carried out under general anaesthetic due to pain caused by the procedure. However, recent studies suggest that performing local anaesthetic transperineal prostate biopsy may better identify cancer in particular regions of the prostate and reduce infection rates, while being carried out in an outpatient setting. Devices to assist with freehand methods of local anaesthetic transperineal prostate may also help practitioners performing prostate biopsies. Objectives: To evaluate the clinical effectiveness and cost-effectiveness of local anaesthetic transperineal prostate compared to local anaesthetic transrectal ultrasound-guided prostate and general anaesthetic transperineal prostate biopsy for people with suspected prostate cancer, and local anaesthetic transperineal prostate with specific freehand devices in comparison with local anaesthetic transrectal ultrasound-guided prostate and transperineal prostate biopsy conducted with a grid and stepping device conducted under local or general anaesthetic. Data sources and methods: We conducted a systematic review of studies comparing the diagnostic yield and clinical effectiveness of different methods for performing prostate biopsies. We used pairwise and network meta-analyses to pool evidence on cancer detection rates and structured narrative synthesis for other outcomes. For the economic evaluation, we reviewed published and submitted evidence and developed a model to assess the cost-effectiveness of the different biopsy methods. Results: We included 19 comparative studies (6 randomised controlled trials and 13 observational comparative studies) and 4 single-arm studies of freehand devices. There were no statistically significant differences in cancer detection rates for local anaesthetic transperineal prostate (any method) compared to local anaesthetic transrectal ultrasound-guided prostate (relative risk 1.00, 95% confidence interval 0.85 to 1.18) (n = 5 randomised controlled trials), as was the case for local anaesthetic transperineal prostate with a freehand device compared to local anaesthetic transrectal ultrasound-guided prostate (relative risk 1.40, 95% confidence interval 0.96 to 2.04) (n = 1 randomised controlled trial). Results of meta-analyses of observational studies were similar. The economic analysis indicated that local anaesthetic transperineal prostate is likely to be cost-effective compared with local anaesthetic transrectal ultrasound-guided prostate (incremental cost below £20,000 per quality-adjusted life-year gained) and less costly and no less effective than general anaesthetic transperineal prostate. local anaesthetic transperineal prostate with a freehand device is likely to be the most cost-effective strategy: incremental cost versus local anaesthetic transrectal ultrasound-guided prostate of £743 per quality-adjusted life-year for people with magnetic resonance imaging Likert score of 3 or more at first biopsy. Limitations: There is limited evidence for efficacy in detecting clinically significant prostate cancer. There is comparative evidence for the PrecisionPoint™ Transperineal Access System (BXTAccelyon Ltd, Burnham, UK) but limited or no evidence for the other freehand devices. Evidence for other outcomes is sparse. The cost-effectiveness results are sensitive to uncertainty over cancer detection rates, complication rates and the numbers of core samples taken with the different biopsy methods and the costs of processing them. Conclusions: Transperineal prostate biopsy under local anaesthetic is equally efficient at detecting prostate cancer as transrectal ultrasound-guided prostate biopsy under local anaesthetic but it may be better with a freehand device. local anaesthetic transperineal prostate is associated with urinary retention type complications, whereas local anaesthetic transrectal ultrasound-guided prostate has a higher infection rate. local anaesthetic transperineal prostate biopsy with a freehand device appears to meet conventional levels of costeffectiveness compared with local anaesthetic transrectal ultrasound-guided prostate. Study registration: This study is registered as PROSPERO CRD42021266443. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR134220) and is published in full in Health Technology Assessment Vol. 28, No. 60. See the NIHR Funding and Awards website for further award information.

A prostate biopsy can help determine if a person has prostate cancer. The main ways of performing a prostate biopsy involve taking small samples of the prostate out through the rectum (back passage) or through the perineum ­ the skin area between the anus and the scrotum (testicles). Both methods use ultrasound images from a probe inserted into the rectum to help the clinician see what they are doing. Taking samples through the rectum is usually carried out under local anaesthetic, whereas taking samples through the perineum is usually carried out under general anaesthetic. We wanted to find out if taking samples through the perineum under local anaesthetic (instead of general anaesthetic) would be equally effective at detecting prostate cancer as the other biopsy methods and whether there was any improvement or change in the sorts of side effects people may have. We also wanted to know if people found the biopsy painful or not. We carried out searches of computer research databases to find relevant clinical and cost-effectiveness studies and compared the effectiveness of the different biopsy methods they used. We read and summarised the results of the studies we found in our search. Our findings showed that taking biopsy samples through the perineum under local anaesthetic had rates of detecting prostate cancer similar to those of the other biopsy methods. But if the clinician also used a freehand device that helps guide the biopsy needle as part of the procedure, then this may be a better method for detecting cancer. The studies we found agreed that performing this prostate biopsy under local anaesthetic was not too painful for most people. Our economic estimates suggest that using a freehand device for local anaesthetic perineal (through the skin of the perineum) biopsy may be a cost-effective use of National Health Service resources.

[Risk factors analysis and nomogram model construction of postoperative pathological upgrade of prostate cancer patients with single core positive biopsy].

OBJECTIVE: To analyze the risk factors for postoperative pathological upgrade of prostate cancer patients with single core positive biopsy, and to attempt to build a mathematical model for predicting postoperative pathological upgrade in these cancer patients with single core positive biopsy. METHODS: A retrospective analysis was conducted on 1 349 patients diagnosed with prostate cancer and undergoing radical prostatectomy at Peking University First Hospital from January 2015 to August 2020. The patients' age, body mass index, clinical stage, prostate imaging reporting and data system (PI-RADS) scores, prostate volume in magnetic resonance imaging (MRI), Gleason score of biopsy, serum prostate specific antigen (PSA) before biopsy and operation, surgical method and pathological stage were inclu-ded in the analysis. The variables with P < 0.1 in univariate analysis were included to construct multi-variate Logistic regression and the nomogram was drawn. The model was evaluated using the receiver operating curve. RESULTS: A total of 71 patients were included in this research, with 34 patients in the upgraded group and 37 patients in the non-upgraded group. There were no significant differences in the patients' age (P=0.585), body mass index (P=0.165), operation method (P=0.08), prostate volume in MRI (P=0.067), clinical stage (P=0.678), PI-RADS score (P=0.203), difference of PSA density (P=0.063), Gleason score in biopsy (P=0.068), PSA before puncture (P=0.359) and operation (P= 0.739) between the two groups. However, there were significant differences in the proportion of tumor tissue (P=0.007), postoperative pathological stage (P < 0.001) and postoperative Gleason score (P < 0.001) between the two groups. The preoperative variables with a P value of less than 0.1 (prostate volume in MRI, difference of PSA density, proportion of tumor tissue and Gleason score in biopsy) in univariate analysis were included in the Logistic regression, and the nomogram was drawn. Only the prostate volume in MRI had a P value of less than 0.05. The area under the curve of the model was 0.773. CONCLUSION: In patients with single core positive biopsy, if the prostate volume is small or the proportion of tumor in positive core is small, clinicians should be alert to the possibility of postoperative pathology upgrading, preoperative risk stratification should be carefully considered for patients with possible pathological upgrading. This model can be used to predict the pathological upgrade of patients with single core positive biopsy.

Economic evaluations of robot-assisted radical prostatectomy and the factors affecting its cost-effectiveness: a systematic review.

This systematic review aims to summarize the progress made in the study of the cost-effectiveness of robot-assisted radical prostatectomy (RARP) worldwide and to analyze the economic factors influencing this, in an attempt to provide methodological guidance for conducting economic evaluation studies in a domestic context, and to put forward suggestions for improving the cost-effectiveness of RARP in emerging markets. We conducted a systematic literature review and analysis of studies published worldwide from January 2000 to July 2024 concerning the economic evaluation of RARP compared with laparoscopic radical prostatectomy (LRP) or open radical prostatectomy (ORP). A total of 16 papers were included. The literature was generally of good quality. Methodological approaches. varied among studies, leading to inconsistent economic findings. The choice of research settings, including the perspective of the study and time horizon, as well as differences in parameters such as surgical volumes and cost of equipment purchases, were the main factors that affected the cost-effectiveness of RARP. Based on the methodology used in the included studies, we suggest that short-term, localized economic evaluations should be carried out first, based on follow-up studies in emerging markets, whereas long-term economic evaluations can be performed when sufficient data are available. Referring to the analysis of the economic factors influencing cost-effectiveness in the included studies, we suggest that different research settings should be chosen according to the purpose for which policymakers allocate public funds, and that the cost-effectiveness of RARP can be enhanced through technical improvements and resource optimization.

Connecting Gene Variation to Treatment Outcomes in Metastatic Castration-Resistant Prostate Adenocarcinoma: Insights into Second-Generation Androgen Receptor Axis-Targeted Therapies.

Prostate cancer (PC) is one of the most commonly diagnosed tumours among men. Second-generation androgen receptor axis-targeted (ARAT) agents, namely abiraterone acetate (AbA) and enzalutamide (ENZ), are currently used in the management of metastatic castration-resistant PC (mCRPC). However, the treatment is challenging due to the lack of prognostic biomarkers. Meanwhile, single-nucleotide polymorphisms (SNPs) have emerged as potential prognostic indicators of mCRPC. Thus, this study evaluated the impact of relevant SNPs on the treatment outcomes of 123 mCRPC patients enrolled in a hospital-based cohort study. The CYP17A1 rs2486758 C allele was associated with a 50% reduction in the risk of developing castration resistance (hazard ratio (HR) = 0.55; p = 0.003). Among patients without metastasis at tumour diagnosis and under AbA, a marginal association between YBX1 rs10493112 and progression-free survival was detected (log-rank test, p = 0.056). In the same subgroup, significant associations of HSD3B1 rs1047303 (CC/CA vs. AA; HR = 3.41; p = 0.025), YBX1 rs12030724 (AT vs. AA; HR = 3.54; p = 0.039) and YBX1 rs10493112 (log-rank test, p = 0.041; CC vs. AA/AC; HR = 3.22; p = 0.053) with overall survival were also observed, which were confirmed by multivariate Cox analyses. Although validation with larger cohorts is required, these findings suggest that SNPs could enhance the prognosis assessment of mCRPC patients, leading to a more personalised treatment.

Androgen Deprivation Benefits in Low-Dose-Rate Brachytherapy With Hydrogel Spacer.

INTRODUCTION: We aim to investigate the impact of rectal dose reduction of both androgen deprivation therapy (ADT) and concurrent hydrogel spacer placement (HSP) in patients treated with low-dose-rate (LDR) brachytherapy for prostate cancer and to determine whether there are variations in the degree of efficacy of dose reduction across different segments of the rectum. METHODS: This study involved 130 consecutive patients treated with I-125 LDR brachytherapy, with (ADT: n = 66) or without (nADT: n = 64) prior ADT, from June 2017 to April 2021. Among these, 13 ADT and 17 nADT patients underwent HSP following induction in May 2020, whereas the remaining patients (nHSP) included 53 ADT and 47 nADT individuals. In the post plan, a rectal dose assessment was made using the rectal volume (RV), divided by horizontal sections into three equal-length subparts (sRVs), such as high-, mid-, and low-RV. The mean sRV100 values were compared between the nADT and ADT patient groups, both with and without HSP. Similarly, mean sRV100 was compared between the nHSP and HSP patient groups, both with and without ADT. RESULTS: In nADT patients, HSP significantly reduced the mean RV100 of the high-RV (0.002 cc versus 0.086 cc, p < 0.05) and mid-RV (0.127 cc versus 0.377 cc, p < 0.05), but not of the low-RV (0.060 cc versus 0.150 cc, p = 0.06). In contrast, in ADT patients, HSP significantly reduced the RV100 at all three sites (0.002 cc versus 0.031 cc, p < 0.05; 0.034 cc versus 0.269 cc, p < 0.05; and 0.015 cc versus 0.151 cc, p < 0.05, respectively). No significant difference was observed when comparing mean sRV100 with or without ADT in both HSP and nHSP patients. CONCLUSION: The combination of ADT and HSP for LDR prostate brachytherapy showed the potential to significantly reduce RV100, especially in the lower rectum.

Pathological Assessment of Men with Grade Group 2 Prostate Cancer.

PURPOSE: A variety of treatment options are now available for men with localized prostate cancer (PC); however, there is still debate in determining how and when to intervene for Grade Group (GG) 2 disease. Our study aims to formulate strategies to identify men at risk of upgrading and having adverse pathological outcomes. MATERIALS AND METHODS: This retrospective study includes 243 patients with GG2 PC that were treated with radical prostatectomy between 2015 and 2021. Patients on active surveillance, previous history of prostate biopsy, hormonal and/or radiation therapy prior to surgery were excluded from this study. A retrospective analysis was conducted using clinicopathological data obtained from medical records. RESULTS: Prostate-specific antigen (PSA) and Prostate Imaging Reporting and Data System (PI-RADS) score were statistically significant variables for risk of upgrading. In men who had presence of composite poor outcomes, PSA, PI-RADS score, presence of extraprostatic extension and seminal vesical invasion on MRI, number of positive cores, percentage of high grade (pattern 4/5) on prostate biopsy and Gleason pattern 4 volume on biopsy were all statistically significant variables. Strategy 8 (PI-RADS 5 lesion or percentage high grade [Gleason pattern 4] on prostate biopsy grade >10% or >3 cores positive on prostate biopsy) had significant association to identifying the highest number of men with upgrading and composite poor outcomes. CONCLUSIONS: Our study supports the use of strategy 8 in treatment decision making of men with GG2 PC. Further validation of the use of this strategy is warranted.

Predicting Survival in Patients with Neuroendocrine Prostate Cancer: A SEER-Based Comprehensive Study.

PURPOSE: Neuroendocrine prostate cancer (NEPC) represents a particularly aggressive subtype of prostate cancer with a challenging prognosis. The purpose of this investigation is to craft and confirm the reliability of nomograms that can accurately forecast the 1-, 3-, and 5-year overall survival (OS) and cancer-specific survival (CSS) rates for individuals afflicted with NEPC. MATERIALS AND METHODS: Data pertaining to patients diagnosed with NEPC within the timeframe of 2010 to 2020 was meticulously gathered and examined from the Surveillance, Epidemiology, and End Results Program (SEER). To predict OS and CSS, we devised and authenticated two distinct nomograms, utilizing predictive variables pinpointed through both univariate and multivariate Cox regression analyses. RESULTS: The study encompassed 393 of NEPC patients, who were systematically divided into training and validation cohorts at a 2:1 ratio. Key prognostic factors were isolated, verified, and integrated into the respective nomograms for OS and CSS. The performance metrics, denoted by C-indices, stood at 0.730, 0.735 for the training set, and 0.784, 0.756 for the validation set. The precision and clinical relevance of the nomograms were further corroborated by the analysis of receiver operating characteristic curves, calibration plots, and decision curve analyses. CONCLUSIONS: The constructed nomograms have demonstrated impressive efficacy in forecasting the 1-, 3-, and 5-year OS and rates for patients with NEPC. Implementing these predictive tools in clinical settings is anticipated to considerably enhance the care and treatment planning for individuals diagnosed with this aggressive form of prostate cancer, thus providing tailored and more precise prognostic assessments.

Long Term Cardiovascular Safety of Testosterone Therapy: A Review of the TRAVERSE Study.

TRAVERSE (TheRapy for Assessment of long-term Vascular events and Efficacy ResponSE in hypogonadal men) is multicentre randomized, double-blind, placebo-controlled, noninferiority trial of testosterone therapy, enrolling 5,246 men 45 to 80 years of age who had pre-existing or a high risk of cardiovascular disease and who reported symptoms of hypogonadism. Subjects required two fasting testosterone levels of less than 10.4 nmol/L. Patients were randomly assigned to receive daily transdermal 1.62% testosterone gel (dose adjusted to maintain testosterone levels between 12 nmol/L and 26 nmol/L) or placebo gel for a mean 27.1 months. The primary cardiovascular safety end point was the first occurrence of any component of a composite of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke, assessed in a time-to-event analysis. TRAVERSE found no increase in major adverse cardiac events or prostate related events, including prostate cancer, effectively addressing the concerns raised by the United States Food and Drug Administration.

Molecular Hallmarks of Prostate-specific Membrane Antigen in Treatment-naïve Prostate Cancer.

BACKGROUND AND OBJECTIVE: We characterized tumor prostate-specific membrane antigen (PSMA) levels as a reflection of cancer biology and treatment sensitivities for treatment-naïve prostate cancer. METHODS: We first correlated PSMA positron emission tomography (PET) maximum standardized uptake values (SUVmax) in primary prostate cancer with tumor FOLH1 (PSMA RNA abundance) to establish RNA as a proxy (n = 55). We then discovered and validated molecular pathways associated with PSMA RNA levels in two large primary tumor cohorts. We validated those associations in independent cohorts (18 total; 5684 tumor samples) to characterize the pathways and treatment responses associated with PSMA. KEY FINDINGS AND LIMITATIONS: PSMA RNA abundance correlates moderately with SUVmax (ρ = 0.41). In independent cohorts, androgen receptor signaling is more active in tumors with high PSMA. Accordingly, patients with high PSMA tumors experienced longer cancer-specific survival when managed with androgen deprivation therapy for biochemical recurrence (adjusted hazard ratio [AHR] 0.54 [0.34-0.87]; n = 174). PSMA low tumors possess molecular markers of resistance to radiotherapy. Consistent with this, patients with high PSMA tumors experience longer time to recurrence following primary radiotherapy (AHR 0.50 [0.28-0.90]; n = 248). In the SAKK09/10 trial (n = 224), patients with high PSMA tumors who were managed with salvage radiotherapy experienced longer time to progression in the 64-Gy arm (restricted mean survival time [RMST] +7.60 [0.05-15.16]), but this effect was mitigated in the 70-Gy arm (RMST 3.52 [-3.30 to 10.33]). Limitations include using PSMA RNA as a surrogate for PET SUVmax. CONCLUSIONS AND CLINICAL IMPLICATIONS: PSMA levels in treatment-naïve prostate cancer differentiate tumor biology and treatment susceptibilities. These results warrant validation using PET metrics to substantiate management decisions based on imaging.

Feasibility and Outcomes of Same-Day Discharge after Multiport Robot-Assisted Radical Prostatectomy.

Introduction: Robot-assisted radical prostatectomy (RARP) provides much quicker recovery for men than open prostatectomy. In most centers, discharge is planned the morning after operation. However, after several years, we observed that no routine intervention was required for a majority of men over the first evening. Here, we detail our institution's outcomes for multiport RARP (MP-RARP) with same-day discharge (SDD). Methods: After excluding patients with single-port RARP (n = 25) and overnight stays (n = 30), data from 224 patients (n = 224/279, 88.2%) who underwent MP-RARP from May 2021 to September 2023 were collected. All patients were placed on an Enhanced Recovery After Surgery protocol and were given instructions regarding SDD. Patients were considered as SDD if they were discharged on the day of operation. Data regarding messages and phone calls to health care providers, urology clinic, and emergency department visits were recorded for analysis in the week postoperation. Results: The mean (±standard deviation [SD]) operative time was 142.5 ± 25.2 minutes, with a mean (±SD) console time of 95.1 ± 25.6 minutes. The median (interquartile range [IQR]) estimated blood loss was 50 (50-100) mL, and the mean (±SD) length of hospitalization was 163.2 ± 64.6 minutes. No intraoperative complications occurred in this cohort. The median (IQR) patient-reported pain score at 1 hour after operation was 3.5 (0-7), compared with 2 (0-4) at discharge. Of the 145 (64.7%) patients who reported their postoperative pain management, only 50 (34.4%) endorsed using opioids, and of those, 8 (16%) were known chronic opioid users. In the week after operation, 14 (6.3%) patients had unplanned visits to the health care facility. Additionally, 56 (25%) of patients contacted the clinic regarding the postoperative course during the same time frame. Conclusions: SDD after RARP is predictable and safe. SDD helps reduce the costs associated with inpatient stays without compromising surgical outcomes for patients.

Association of Free-to-Total PSA Ratio and 18F-DCFPyL Prostate-Specific Membrane Antigen PET/CT Findings in Patients with Biochemical Recurrence After Radical Prostatectomy: A Prospective Single-Center Study.

In Canada and across the globe, access to PSMA PET/CT is limited and expensive. For patients with biochemical recurrence (BCR) after treatment for prostate cancer, novel strategies are needed to better stratify patients who may or may not benefit from a PSMA PET scan. The role of the free-to-total prostate-specific antigen (PSA) ratio (FPSAR) in posttreatment prostate cancer, specifically in the PSMA PET/CT era, remains unknown. Our aim in this study was to determine the association of FPSAR in patients referred for 18F-DCFPyL PSMA PET/CT in the BCR setting and assess the correlation between FPSAR and 18F-DCFPyL PSMA PET/CT positivity (local recurrence or distant metastases). Methods: This prospective study included 137 patients who were referred for 18F-DCFPyL PSMA PET/CT and had BCR with a total PSA of less than 1 ng/mL after radical prostatectomy (RP) (including adjuvant or salvage radiotherapy). Blood samples were collected on the day of 18F-DCFPyL PSMA PET/CT. FPSAR was categorized as less than 0.10 or as 0.10 or more. A positive 18F-DCFPyL PSMA PET/CT scan was defined by a PROMISE classification lesion score of 2 or 3, irrespective of the site of increased tracer uptake (e.g., prostate, pelvic nodes, bone, or viscera). Results: Overall, 137 blood samples of patients with BCR after RP were analyzed to calculate FPSAR. The median age at 18F-DCFPyL PSMA PET/CT was 68.6 y (interquartile range, 63.0-72.4 y), and the median PSA at 18F-DCFPyL PSMA PET/CT was 0.3 ng/mL (interquartile range, 0.3-0.6 ng/mL). Eighty-six patients (62.8%) had an FPSAR of less than 0.10, whereas 51 patients (37.2%) had an FPSAR of 0.10 or more. An FPSAR of 0.10 or more was identified as an independent predictor of a positive 18F-DCFPyL PSMA PET/CT scan, with an odds ratio of 6.99 (95% CI, 2.96-16.51; P < 0.001). Conclusion: An FPSAR of 0.10 or more after RP independently correlated with increased odds of a positive 18F-DCFPyL PSMA PET/CT scan among BCR post-RP patients. These findings may offer an inexpensive method by which to triage access to 18F-DCFPyL PSMA PET/CT in jurisdictions where availability is not replete.

Changing times: trends in risk classification, tumor upstaging, and positive surgical margins after radical prostatectomy - results from a contemporary National Cancer Database study.

PURPOSE: Recent advancements in screening, prostate MRI, robotic surgery, and active surveillance have influenced the profile of patients undergoing radical prostatectomy (RP). We sought to examine their impact on trends in clinicodemographic, risk classification, and adverse pathology in men undergoing surgery. METHODS: We queried the National Cancer Database for clinicodemographic, risk group, and pathology data in men undergoing upfront RP between 2006 and 2020. Patients were categorized by NCCN risk groups, and trends were assessed among 2006-2010, 2011-2015, and 2016-2020 periods. Endpoints included rates of pT3, positive surgical margins (PSM), pathologic upstaging, and Gleason grade group (GG) upgrading. RESULTS: 610,762 patients were included. There were significant increases in African Americans (9.8-14.1%), comorbidities (2.1-5.2% with Charlson scores > 1), and robot-assisted RP (78-84%). Over the three time periods, high-risk cases increased from 15 to 20 to 27%, and intermediate-risk from 54 to 51 to 60%. Overall rates of pT3 rose from 20 to 38%, and PSM from 20 to 27% (p < 0.001). Pathologic upstaging increased in low (6-15%), intermediate (20-33%), and high-risk groups (42-58%) -p < 0.001. Gleason upgrading rose in low-risk (45-59%, p < 0.001), with slight reductions in the intermediate and high-risk groups. CONCLUSIONS: Recent trends in RP indicate a shift towards more advanced disease, evidenced by increasing rates of pT3, PSM, and pathologic upstaging across all NCCN risk groups. These findings emphasize the need for a careful balance in applying fascia and nerve-sparing techniques to avoid compromising oncological safety.

Impact of the COVID-19 pandemic on cancer mortality in Brazil.

BACKGROUND: In the first year of the COVID-19 pandemic, data projections indicated an increase in cancer mortality for the following years due to the overload of health services and the replacement of health priorities. The first studies published with data from mortality records have not confirmed these projections. However, cancer mortality is not an outcome that occurs immediately, and analyses with more extended follow-up periods are necessary. This study aims to analyze the impact of the COVID-19 pandemic on the mortality from all types and the five most common types of cancer in Brazil and investigate the relationship between the density of hospital beds and mortality from COVID-19 in cancer patients in Brazil's Intermediate Geographic Regions (RGIs). METHODS: The Brazilian Mortality Information System provided data on the deaths from trachea, bronchus, and lung, colorectal, stomach, female breast, and prostate cancer and all types of cancer, and from COVID-19 in individuals who had cancer as a contributing cause of death. Predicted rates for 2020-2022 were compared with the observed ones, through a rate ratio (RR). An association analysis, through multivariate linear regression, was carried out between mortality from COVID-19 in cancer patients, the rate of hospital beds per 100,000 inhabitants, and the Human Development Index of the 133 RGIs of Brazil. RESULTS: In 2020, 2021, and 2022, mortality from all cancers in Brazil was lower than expected, with an RR of 0.95, 0.94, and 0.95, respectively, between the observed and predicted rates. Stomach cancer showed the largest difference between observed and expected rates: RR = 0.89 in 2020 and 2021; RR = 0.88 in 2022. Mortality from COVID-19 in cancer patients, which reached its peak in 2021 (6.0/100,000), was negatively associated with the density of hospital beds in the public health system. CONCLUSIONS: The lower-than-expected cancer mortality during 2020-2022 seems to be partly explained by mortality from COVID-19 in cancer patients, which was probably underestimated in Brazil. The findings suggested a protective role of the availability of hospital care concerning deaths due to COVID-19 in this population. More extensive follow-up is needed to understand the impact of the COVID-19 pandemic on cancer mortality.

Salvage lymphadenectomy or radiation therapy in prostate cancer patients with biochemical recurrence and PET positive lymph nodes after radical prostatectomy: A systematic review and pooled analysis.

OBJECTIVE: To analyze the oncologic outcomes of biochemical recurrence (BCR) patients who received salvage treatment of lymph node dissection (LND) or radiation therapy (RT) for positron emission tomography (PET)-positive lymph node recurrences following radical prostatectomy (RP). METHODS: Research using the MEDLINE, Cochrane, and Web of Science databases was conducted until June 2023. Inclusion criteria were BCR patients that received salvage LND or RT for PET-positive lymph node recurrence following primary RP for prostate cancer. Studies with a follow-up period of less than 12 months were excluded. RESULTS: This study included 2476 patients (995 LND, 1481 RT) from 19 publications. The pooled incidences were 51.1 % and 74.3 % in PSA response, 69.8 % and 26.9 % in PSA progression, 41.5 % and 26.9 % in image progression, 41.5 % and 32.0 % in systemic progression, 0.9 % and 0.5 % in overall mortality, and 6.5 % and 1.3 % in cancer-specific mortality in LND and RT, respectively. Limitations include high heterogeneity. CONCLUSION: Although heterogeneity is high across all studies, the pooled rates of PSA, image, and systemic progressions are higher in LND than in RT concerning BCR patients with PET-positive lymph nodes. For future trial designs in BCR, assessing the optimal timing of PSMA PET scans, concurrent systemic therapy, and salvage therapy type is imperative.

A case of double-negative prostate cancer with BRCA2 mutation and high tumor mutation burden treated sequentially with olaparib and pembrolizumab.

Introduction: Double-negative prostate cancer, an androgen receptor-independent prostate cancer without features of neuroendocrine tumors, is refractory to treatment but could be an ideal candidate for individualized treatment. Case presentation: An 85-year-old patient with metastatic castration-resistant prostate cancer without prostate-specific antigen progression presented with local recurrence and liver and lung metastases 6 months after orchiectomy and apalutamide. A liver tumor biopsy led to a diagnosis of double-negative prostate cancer. FoundationOne® CDx showed BRCA2 mutation and high tumor mutation burden. Olaparib and pembrolizumab were administered sequentially, and the patient responded to each treatment for 5 months until radiographic progression. Conclusion: Sequential use of olaparib and pembrolizumab may be effective for double-negative prostate cancer with BRCA2 mutations and high tumor mutation burden.

Serum Androgens as Predictive Biomarkers: Results From a Randomized Clinical Trial Comparing Enzalutamide and Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer.

INTRODUCTION: The purpose of this study was to investigate the association between baseline androgen concentrations and outcomes in men with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line enzalutamide or abiraterone acetate plus prednisone (AAP). MATERIALS AND METHODS: We previously randomized men with mCRPC to enzalutamide or AAP to compare side-effects and measured androgen concentrations. In this post-hoc analysis, patients were grouped in quartiles (Q) based on their serum androgen values. Kaplan-Meier and Cox regression were used to analyze progression-free and overall survival for baseline androgen groups, treatment subgroups and their interaction. The trial was registered at clinicaltrialsregister.eu (2017-000099-27). RESULTS: Eighty-four patients received enzalutamide and 85 AAP. Overall, higher (Q4) compared with lower (Q1) baseline serum testosterone was associated with longer progression-free survival (24.8 vs. 10.7 months, hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.33; 0.84) and overall survival (52.8 vs. 31.5 months, HR 0.49, 95% CI 0.28; 0.85). The risk reduction in death seemed to be treatment dependent (treatment subgroup interaction P = .04). For men in the AAP subgroup, the Q4 compared with Q1 group had a significant lower risk of death (HR 0.30, 95% CI 0.13; 0.73), while no difference was found for enzalutamide (HR 0.77, 95% CI 0.35; 1.69). Similar results were found for the other androgens. CONCLUSION: Pre-treatment serum testosterone levels may be a clinically useful biomarker for predicting mCRPC treatment responses and guiding treatment selection.