Low PSA Research Articles

Clinical Factors Associated With Suspicious 18F-DCFPyL PSMA PET Activity in Patients Initially Managed With Radical Prostatectomy Including Prostate-Specific Antigen < 0.5 ng/mL.

There are limited data on PSMA PET/CT for workup of recurrence after radical prostatectomy (RP) at low PSA values. We evaluated a PSMA PET/CT cohort of patients with post-RP, focusing on patients with PSA < 0.5 ng/mL. We identified a retrospective cohort who underwent piflufolastat F-18 PSMA PET/CT across an 11 hospital system from July 2021 to February 2023. Prostate-specific membrane antigen (PSMA) positivity was determined by radiology reports. Univariable and multivariable logistic regression identified factors associated with suspicious PSMA activity. Median PSA was 0.37 ng/mL (IQR, 0.15-1.29 ng/mL), with 49% of patients overall having at least 1 suspicious PSMA-avid lesion. Rates of scan positivity among patients with PSA < 0.2 and 0.2 to 0.5 ng/mL were 34% and 38%, respectively. Among all patients, 25% (104/415) had pelvic disease (prostate bed or N1) and 24% (100/415) had M1 disease. Among patients with PSA < 0.5 ng/mL, prior postoperative radiation was associated with suspicious PSMA activity. In the overall cohort, age, PSA at PSMA PET/CT, and RP Gleason grade were associated with PSMA positivity. PSADT, EAU risk, and CAPRA-S were all associated with suspicious PSMA activity. Over one-third of patients with PSAs < 0.2 ng/mL had imaging findings concerning for recurrence. Prior postoperative radiation was associated with higher rates of PSMA positivity among patients with PSA < 0.5 ng/mL, and half of patients with evidence of PSMA avid distant metastatic disease underwent metastasis-directed therapy. PET-PSMA imaging at low PSAs can be considered to inform salvage therapies.

Enhancing Prostate Cancer Staging: Association of 68Ga-PSMA PET/CT Imaging with Histopathological Grading in Treatment-Naive Patients.

This study aimed to evaluate the correlation between 68Ga-PSMA uptake in PSMA PET/CT in primary prostate cancer (PC) and its histopathological grading (Gleason score and ISUP grade). Additionally, we compared preoperative biopsy histopathological findings with definitive pathology results in radical prostatectomy (RP) specimens. We retrospectively analyzed 86 patients who underwent 68Ga-PSMA PET/CT for primary PC staging, of which 40 patients later underwent radical prostatectomy. PET/CT results, including SUVmax values, were correlated with GS and PSA concentrations. Histopathology reports were analyzed and compared between biopsy and final pathology results following RP. A significant positive correlation was observed between SUVmax and ISUP grades (Pearson's ρ = 0.34, p < 0.001), with higher SUVmax values associated with more advanced grades. A cut-off SUVmax value of 5.64 was determined to predict upstaging in patients, yielding a sensitivity of 76% and a specificity of 60% (AUC = 0.82, 95% CI: 0.70-0.94). Additionally, 57.5% of patients experienced a grade shift following RP, with a 35% upgrade and 22.5% downgrade in ISUP grades. 68Ga-PSMA PET/CT demonstrated high sensitivity in detecting high-risk prostate cancer, particularly in patients with GS > 7 or PSA levels ≥ 10 ng/mL. The findings suggest that this imaging modality may be less effective for the staging of patients with lower GS or PSA values, that is, low-risk PCa. Further prospective studies are necessary to validate these results.

Clinico-Pathological Factors and AR-LBD Mutations in Early and Late Castration-Resistant Prostate Cancer.

Prostate cancer (PCa) is not well understood because of its enormous biological heterogeneity and unreliable progression. We conducted this retrospective analysis to examine the variables predicting early and late progression to castration-resistant PCa (CRPC) for better management of this disease. This single institutional retrospective study was conducted from January 2018 to January 2022. A total of 98 consecutive men meeting with the diagnosis of CRPC as per the inclusion criteria were included in the study and were stratified in four quartiles on the basis of time to CRPC (time to castration resistance [TTCR]) development. Early CRPC (1st quartile, TTCR = 6-12 months) and late CRPC (4th quartile, TTCR = 38-120 months) were then compared on the basis of different clinical, pathological and AR-LBD sequence to find the correlation with response duration. Median time to develop castration resistance was 25 ± 26.44 months. The mean age of the patients was 66.8 ± 9.20 years and median baseline PSA was calculated 100±685.06 ng/mL respectively. Higher Gleason score (≥7-10) was found to be significantly associated with early development of CRPC (p<0.001) and lower nadir PSA was significantly indicating late CRPC progression (p<0.005). No mutations were found in androgen receptor exon-5, 6, 7 except a homozygous mutation in the 7th intronic region, which is involved in splice variants formation playing noteworthy role in CRPC development. Time for metastatic PCa to CRPC ranges from 6-120 months revealing its heterogeneous nature. Early age presentation in the clinic and high initial PSA and high grade (GS>7) at diagnosis were positively associated with early CRPC while lower nadir PSA was correlated with late CRPC progression. No remarkable genomic mutations were discovered. Therefore, more data are needed and further research is required with large no. of patients to discover the predictive prognostic biomarkers for better patients' management.

520: Low PSA nadir is a powerful predictor of tumour control and survival after HDR-brachytherapy boost

520: Low PSA nadir is a powerful predictor of tumour control and survival after HDR-brachytherapy boost

Isolated spermatic cord metastasis of prostate cancer after radiotherapy detected with 18F-PSMA PET/CT: a case report and literature review.

We report the case of a 65year-old male with prostate cancer previously treated with external beam radiotherapy and 2years of androgen deprivation therapy. His nadir PSA reached undetectable level but gradually increased to 0.89ng/dL. 18F-PSMA PET/CT demonstrated a PSMA-avid lesion at left spermatic cord. Left groin exploration revealed an 8mm left vas deferens mass. Mass excision was performed and pathology result showed prostatic adenocarcinoma. The metastatic route is unknown but the possible routes are intraluminal route via ejaculatory duct, hematogenous route and lymphatic route. This case also highlights the role of 18F-PSMA PET/CT to detect a recurrent lesion at an atypical site in biochemical failure patients even at the low PSA level.

Evaluation of perioperative risk factors for bladder neck contracture after bipolar transurethral resection of the prostate.

Bladder neck contracture after transurethral resection of the prostate is a common complication but without clear predisposing factors. In this prospective study, we evaluated the perioperative risk factors associated with bladder neck contracture after bipolar transurethral resection of the prostate. The study included 391 patients who were admitted for bipolar transurethral resection of the prostate between October 2020 to October 2023 by three experienced surgeons. Forty three patients had bladder neck contracture and their perioperative parameters were compared with randomly chosen 172 patients without bladder neck contracture. There were no significant differences between the studied groups regarding the general and present history characteristics. Re-catheterization after transurethral resection of the prostate, post-operative recurrent urinary tract infection, resection speed, and associated urethral stricture were significantly higher among the bladder neck-contraction group (P < 0.05), while total PSA, total prostate weight, post void residual urine volume, resected gland weight, resection time and catheter duration were significantly lower among the bladder neck-contraction group (P < 0.05). Bladder neck contracture after bipolar transurethral resection of the prostate is more common among patients with small fibrotic prostate, low total PSA, small post- void residual urine volume, those with a higher incidence of post-operative recurrent urinary-tract infection and patients with a higher incidence of re-catheterization after transurethral resection of the prostate.

Estimating the Effect of Radical Prostatectomy: Combining Data From the SPCG4 and PIVOT Randomized Trials With Contemporary Cohorts.

Two randomized trials (SPCG4 and PIVOT) have compared surgery to conservative management for localized prostate cancer. The applicability of these trials to contemporary practice remains uncertain. We aimed to develop an individualized prediction model for prostate cancer mortality comparing immediate surgery at a high-volume center to active surveillance. We determined whether the relative risk of prostate cancer mortality with surgery vs observation varied by baseline risk. We then used various estimates of relative risk to estimate 15-year mortality with and without surgery using, as a predictor, risk of biochemical recurrence calculated from a model. We saw no evidence that relative risk varied by baseline risk, supporting the use of a constant relative risk. Compared with observation, surgery was associated with negligible benefit for patients with Grade Group (GG) 1 disease (0.2% mortality reduction at 15 years) and small benefit for patients with GG2 with lower PSA and stage (≤5% mortality reduction). Benefit was greater (6%-9%) for patients with GG3 or GG4 though still modest, but effect estimates varied widely depending on choice of hazard ratio for surgery (6%-36% absolute risk reduction). Surgery should be avoided for men with low-risk (GG1) prostate cancer and for many men with GG2 disease. Surgical benefits are greater in men with higher-risk disease. Integration of findings with a life expectancy model will allow patients to make informed treatment decisions given their oncologic risk, risk of death from other causes, and estimated effects of surgery.

Recovery of Social Continence and Sexual Function in Men With High-risk Prostate Cancer After Radical Prostatectomy: Results From a Statewide Collaborative

OBJECTIVESTo examine post-operative urinary and sexual functional outcomes for men with high-risk prostate cancer (HRPCa) who underwent radical prostatectomy (RP) within the Michigan Urological Surgery Improvement Collaborative (MUSIC). METHODSWe identified patients who underwent RP for HRPCa in MUSIC between 2014-2023. HRPCa was defined according to American Urological Association criteria. Patients completed Expanded Prostate Cancer Index Composite (EPIC-26) pre-RP and 3-, 6-, 12-, and 24-months postoperatively. Primary outcomes included social continence, defined as 0-1 pads used daily; and recovery of sexual function, defined as the ability to achieve erections firm enough for intercourse. Multivariable and bivariate analyses were performed to identify factors associated with recovery of social continence and sexual function. RESULTS1323 patients were included in the post-RP urinary continence analysis and 422 men in the sexual function analysis. 58% and 86% of patients achieved social continence at 3- and 12-months post-RP, respectively. Continence recovery was associated with higher baseline EPIC-26 urinary continence scores (OR 1.10, per 5 points, 95% CI 1.06-1.15, p<0.001), and negatively associated with increasing age (OR 0.78 per 5-year increase, 95% CI 0.71-0.85 p<0.001). 15% of patients had recovery of sexual function at 12-months post-RP. On bivariate analysis, recovery of sexual function was associated with nerve-sparing at time of RP, lower pre-operative PSA, and not receiving post-RP ADT/RT. CONCLUSIONSRP for HRPCa has acceptable rates of postoperative social continence. However, post-RP recovery of sexual function remains a challenge. This information has important implications for pre-operative counseling and post-operative follow-up for patients with HRPCa.

Real world data of 177 Lutetium-PSMA-617 for metastatic castration resistant prostate cancer (mCRPC): Analysis of patients treated from 2 large reference centers.

e17050 Background: 177Lu-PSMA-617 was recently approved for the treatment of patients with mCRPC in the USA. While treatment is associated with improved survival, responses to therapy are lower in patients with visceral metastasis and with FDG avid disease. In this study, we aim to characterize response to the therapy trying to optimize patient selection for 177Lu-PSMA-617. Methods: Patients treated from 2020 to 2023 in 2 large oncology centers in Brazil were analyzed. Our primary endpoint was to investigate the PSA response rate. Secondary endpoints included overall survival (OS), time to next sequential therapies (TNST) and PSA response in patients with visceral disease. Patients were treated after being submitted to a double image consisting of PET-CT PSMA and a PET-CT FDG (as indicated by the TheraP trial, Hoffman et al.) confirming disease uptake without divergent disease. Results: A total of 32 patients with mCRPC were included in this analysis. The median age was 73 years. Median number of prior lines of therapy for mCRPC was 3 with 20 receiving more than one androgen receptor signaling inhibitor (ARSI) and 5 receiving more than one taxane. The percentage with a PSA response was 48,5% and visceral disease was present in 56,3% of patients. Response rate for pts with visceral disease versus non-visceral was 21,9% vs 43,8%. The Medians of TNST and OS were respectively 7 and 9,6 months. The characteristics of patients with and without a PSA response are detailed in the table. Conclusions: Our cohort, characterized by advanced age, extensive prior treatments, and elevated PSA values, exhibited a PSA response that aligns with patients treated in randomized trials. Notably, our patients with visceral disease demonstrated a lower PSA response. [Table: see text]

Salvage Radiotherapy PSMA PET/CT-guided in Men With PSA Recurrence.

To evaluate the clinical outcome in men with recurrent prostate cancer (PCa) treated by salvage radiotherapy (sRT) prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT)-guided. From January 2021 to January 2023, 33 patients who previously underwent definitive/systemic therapy were submitted to sRT PSMA PET/CT-guided for PCa recurrence: 16 (48.5%) on the prostate bed (PB), 12 (36.4%) on the lymph node (LN) and five (15.1%) on the bone. The median PSA value was 3.3 ng/ml (range=0.3-15.5 ng/ml): 0.2-0.5 ng/ml (18.2% cases), 0.51-1 ng/ml (39.4% cases) and >1 ng/ml (42.4% cases). Median 18F PSMA PET/CT standardized uptake value (SUVmax) was evaluated on PB, vs. LN vs. bones PCa recurrences and was equal to 12.5 vs. 19.0 vs. 30.1, respectively. Overall, at a median follow up of 12 months, 23/33 patients (69.7%) had local control without distant progression (PSA and SUVmax evaluation): 14/16 (87.5%) vs. 7/12 (58.3%) vs. 2/5 (40%) underwent sRT on the PB vs. LN vs. bone metastases, respectively. PSMA PET/CT allows to perform sRT early in men with PCa recurrence and low PSA values obtaining a complete clinical response in approximately 70% of the cases one year from treatment.

Nutritional Supplement With Fermented Soy in Men With an Elevated Risk of Prostate Cancer and Negative Prostate Biopsies: General and Oncological Results From the Prospective PRAECAP Trial

Introduction & ObjectivesTo investigate the effect of a dietary supplement containing fermented soy on PSA, IPSS, changes in prostate volume and prostate cancer development after a 6-month challenge in men at increased risk of prostate cancer and negative previous biopsies. Materials & MethodsPatients with an elevated risk of PCa, defined by either 1 of the following criteria: PSA > 3 ng/ml, suspect lesion at digital rectal examination (DRE), suspect lesion at transrectal ultrasound (TRUS) / magnetic resonance imaging (MRI) and previous negative prostate biopsies (at least 8 cores) within 12 months before inclusion. Statistical analysis was carried out using a non-parametric one-sided paired Wilcoxon rank sum test, chi-square test and Fisher's exact test. ResultsIn this trial, 94 patients where eligible for analysis. A PSA response was detected in 81% of the cases. In 25.8% (24/93) of patients, a decrease of at least 3 points on the IPSS was observed. The median prostate volume did not statistically change after 6 months (p=0.908). Patients with PSA modulation required fewer investigations and had fewer positive biopsies (p<0.001) and significantly fewer ISUP≥3 lesions (p=0.02). ConclusionsWe observed a significantly lower PSA level after a 6-month challenge with a fermented soy-containing supplement, and an effect on IPSS in a subset of patients. Prescribing a fermented soy supplement in patients with an increased PCa risk could lead to a better selection of patients at real increased risk of having occult PCa.

Clinicopathologic characteristics and outcomes of prostate cancer incidentally discovered at the time of radical cystoprostatectomy: a population-based cohort study.

This study aimed to comprehensively analyze the clinical characteristics and prognosis of patients with concomitant bladder cancer (BCa) and prostate cancer (PCa) using a large population-based database. Within the Surveillance, Epidemiology, and End Results (SEER) database (2000-2019), we identified patient with concomitant PCa at the time of radical cystoprostatectomy (RCP). Logistic regression and propensity score matching (PSM) analyses were employed to identify risk factors and mitigate confounders, respectively. Kaplan-Meier survival curves were used to estimate cancer-specific survival (CSS). A total of 14,199 BCa patients undergoing RCP were identified, with 28.8% incidentally discovered to have concurrent PCa. Among them, 89.9% exhibited organ-confined (T1-2) PCa. An increased risk of concomitant tumors was observed among older age, white race, and high tumor grade of BCa. Survival analysis revealed no significant difference in CSS between patients with BCa alone and those with concurrent PCa (5-year CSS rate: 71.3% vs. 67.2%, P =0.076). Subgroup analysis and multivariable analysis, however, indicated that concurrent high-risk PCa adversely impacted survival (5-year CSS rate: 71.3% vs. 63.4%, HR 1.27, 95% CI 1.01-1.58, P =0.038) compared to solitary BCa. Notably, the presence of low/intermediate-risk PCa did not affect survival outcomes ( P =0.584). In conclusion, incidentally discovered PCa in RCP specimens is frequent and characterized by organ-confined presentation, lower PSA levels, and Gleason scores. Patients with concurrent high-risk PCa have a worse prognosis compared to those with solitary BCa, while the presence of low/intermediate-risk PCa does not influence oncological prognosis.

(292) Relationship Between Race, Gleason Score, and Testosterone Levels in Men with Prostate Cancer

Abstract Introduction It has been known in the literature that Black men are disproportionately affected by prostate cancer in the United States. Various mechanistic pathways have been evaluated including PSA and/or testosterone levels (T) in this at-risk population. Based on prior studies, low PSA is suggested to be predictive of low testosterone independent of prostate cancer pathology. In this study, we aim to evaluate the correlation between race and PSA/T levels in men diagnosed with prostate cancer. Objective To further study the relationship between testosterone, PSA, and race in men with prostate cancer. Methods An IRB approved database was utilized to obtain values for prostate cancer patients. Prostate cancer patients who had testosterone, PSA, and Gleason scores (GS) were included in our cohort with demographic information. Patients were stratified by PSA category. Low testosterone was defined as T&amp;lt;300 ng/dL, and very low T as 0–200 ng/dL. Results In our cohort of 653 prostate cancer patients, the mean age was 66 years. The cohort included 34% African American (AA), 62% White, and 4% other. AA men had a median PSA of 8.0 ng/mL, compared to 0.8 ng/mL in white men (p&amp;lt;0.001). For AA men with GS (8–10) and PSA&amp;gt;4, proportions were: very low T (27%), low T (24%) and normal T (49%). For GS (8–10) and PSA&amp;lt;2, very low T (35%), low T (22%) and normal T (43 %) (p&amp;lt;0.05). For White men with GS (8–10) and PSA&amp;gt;4, very low T (33%), low T (17%) and normal T (50%). For GS (8–10) and PSA&amp;lt;2, very low T (37%), low T (20%) and normal (43%) (p&amp;lt;0.05). In GS (8–10), logistic regression demonstrated neither race nor PSA category were statistically significant predictors of low T. Conclusions Our results show that despite significantly higher PSA among AA men with prostate cancer, there was no statistically significant difference in T and GS 8–10 prostate cancer. This finding highlights that racial variation may influence PSA but not GS prostate cancer or T level. Further studies are warranted to elucidate the correlation between PSA and T in higher-risk populations. Disclosure No.

Impact of PSMA PET/CT on the therapeutic decision of Prostate Carcinoma Biochemical Recurrence

Background: Prostate Cancer (PCa) is the most common malignant tumor in males and Biochemical Relapse (BCR) consists of a challenging scenario compared to primary staging due to small volume of disease and low PSA levels. Prostate-Specific Membrane Antigen (PSMA), Positron Emission Tomography (PET) presents superior performance and strongly affects therapeutic choice.

Utility of PSMA PET/CT for imaging ductal carcinoma of the prostate.

49 Background: Ductal carcinoma (DC) is the second most commonly encountered histologic variant of prostate cancer. Previous studies have described its molecular features and aggressive behavior, but few have explored the performance of PSMA PET/CT in the initial staging and follow-up of DC. Methods: To address this gap, we performed a single-institution retrospective analysis using the Mayo Clinic PSMA PET database. All patients receiving a PSMA PET/CT scan in the interval of January 1, 2021, to December 31, 2022, were eligible for inclusion. Cases were filtered and categorized by histology at the time of diagnosis to select for pure DAC and mixed ductal variants. Trained research personnel annotated disease- and treatment-related variables. A board-certified radiologist performed tumor burden segmentation with calculations of SUV max, total lesion SUV mean and volume, and total lesion uptake, and ascribed a miPSMA expression score. Results: We queried 1792 patients from our PSMA PET/CT registry and identified 32 (1.8%) patients with a pathologically confirmed DC, including 8 (25%) patients with pure ductal and 25 (75%) patients with mixed histology. The indication for PSMA PET/CT was biochemical progression or restaging for 29 (91%) patients and initial staging for 3 (9%) patients. The median (IQR) time from prostate cancer diagnosis to PSMA PET scan was 41.6 (11.5-64.7) months, during this time 50% (n= 16) of patients developed CRPC. At the time of the PSMA PET/CT scan, the median age was 70 years, the median (IQR) PSA was 0.5 ng/mL (0.2-2.6). The distribution of metastatic spread and quantitative imaging parameters from PSMA PET are shown in the Table. Conclusions: Despite low PSA at the time of imaging, PSMA PET/CT frequently detected high volume osseous and/or visceral metastases in patients with DC. However, it is noteworthy that more than 50% of patients with DC had a low miPSMA score (0-1). Additional studies are needed to better understand the performance of novel imaging modalities when evaluating variant prostate cancers. [Table: see text]

Association of body-mass index (BMI) with age, PSA, and survival in metastatic prostate cancer.

96 Background: Increased body-mass index (BMI) is associated with increased prostate cancer incidence and death. However, an ‘obesity paradox’ exists where patients with BMI have longer survival once diagnosed with cancer. We investigated the influence of BMI on overall survival of veterans with metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC). Methods: Two cohorts were identified in the US Veterans Health Affairs. The mHSPC cohort included patients diagnosed with de-novo mHSPC from 2011-2021. The mCRPC cohort was treated with abiraterone or enzalutamide from May 2011 to June 2017. We determined BMI at time of treatment and weight loss during the one year prior. BMI was categorized as ≤20, &gt;20-25, &gt;25-30 or &gt;30 kg/m2. We used Kruskal-Wallis testing for ordinal variables and Cox hazard models to assess the association between BMI, age, Charlson comorbidity index, PSA level at diagnosis, Black race, weight loss, and survival. Results: We identified 5019 veterans with mHSPC and 8159 with mCRPC. Mean BMI was 27.2 (SD 5.9) in mHSPC and 28.2 (SD 5.8) in mCRPC. Mean age was 75.7 years (SD 9.8) in mHSPC and mean age of 74.6 (SD 9.3) in mCRPC. Median overall survival was 25.6 months (95% CI 24.6-26.6) in mHSPC and 20.5 months (95% CI 19.9-21.1) in mCRPC. There were significant differences in age, Black race, and PSA at diagnosis across BMI strata with BMI&gt;30 having the youngest age, lowest percentage of Black race, lowest PSA, and longest survival in mHSPC and mCRPC (see Table). In unadjusted analyses, veterans with BMI&gt;30 had lowest risk of death with Hazard Ratio (HR) 0.66 (95% CI 0.60-0.71) in mHSPC and 0.60 (95% CI 0.56-0.64) in mCRPC compared to BMI&gt;20-25. In adjusted analyses, veterans with BMI&gt;30 had lowest risk of death with adjusted hazard ratio (HR) 0.89 (95% CI 0.81-0.97) in mHSPC and HR 0.77 (95% CI 0.72-0.83) in mCRPC compared to BMI&gt;20-25. Conclusions: Increased BMI is associated with younger age at diagnosis, lower PSA, and longer survival in both mHSPC and mCRPC. Further studies between BMI and prostate cancer are warranted to understand these complex interactions. [Table: see text]

Nucleosome profiling at AR binding sites (ARBS) to provide a prognostic tool for metastatic castration-resistant prostate cancer (mCRPC).

42 Background: Prostate cancer is the second leading cause of cancer death for men in the U.S., and metastatic castration-resistant prostate cancer (mCRPC) is the most advanced form. In previous work, we have reported prognostic significance of PTEN-PI3K-AKT pathway and DNA damage response aberrations detected in cell-free DNA (cfDNA) of mCRPC. Here we utilized nucleosome profiling pattern at androgen receptor (AR) binding sites to further investigate AR signaling pathway dysregulation of mCRPC. Methods: Using the next-generation sequencing PredicineScore liquid biopsy assay (low-pass whole genome sequencing, LP-WGS), we profiled cfDNA fragment coverage centered around AR binding sites (ARBS). For 118 mCRPC patient samples, we quantified sample-level ARBS nucleosome profiling abnormality score (ARBS score) by comparing its centric fragment coverage with normal plasma background using standard Z-score. ARBS score was correlated with clinical outcomes including PSA response rate (PSA RR), progression-free survival and overall survival (OS). Results: By comparing ARBS nucleosome profiling and normal plasma background, we found that mCRPC plasma samples had significant ARBS nucleosome depletion, reflective of transcription factor binding and persistent AR signaling. Notably, ARBS nucleosome depletion was prostate cancer specific, and did not occur in other examined cancer types. ARBS score was highly correlated with tumor fraction (R=0.82), indicating that high tumor fraction mCRPC sample had higher AR binding. Importantly, we found that high ARBS score (&gt;2) in pre-treatment samples (n=86) was associated with significantly shorter OS and lower PSA RR compared with low ARBS (≤2) group for patients receiving AR pathway inhibitor (ARPI) or taxane chemotherapy (13.4 vs. 19.4 months, p=7.3×10-3, 45.7% vs. 77.5%, p=5.2×10-3). By integrating genome-wide DNA methylation profiling, we further found that ARBS was hypo-methylated in mCRPC patients, and identified a strong negative correlation between DNA methylation beta value and ARBS score (R=-0.83). Conclusions: ARBS nucleosome profiling abnormality inferred from LP-WGS can serve as a key prognostic tool for mCRPC patients. Patients with high ARBS score had worse clinical outcomes, highlighting the potential clinical utility of cfDNA fragmentomics analysis for mCRPC patient stratification. Integration of mutation, copy number variation and fragmentomics profiling of ARBS may further enhance our understanding of molecular aberrations and treatment outcomes in mCRPC.

Clinical Outcomes in a Locally Advanced Non-metastatic Prostate Cancer Presenting with Low PSA at Diagnosis

Clinical Outcomes in a Locally Advanced Non-metastatic Prostate Cancer Presenting with Low PSA at Diagnosis

Predictors of Early Continence After Single-port Transvesical Robot-assisted Radical Prostatectomy

BackgroundSingle-port (SP) transvesical (TV) robot-assisted radical prostatectomy (RARP) is a feasible approach for patients with clinically localized prostate cancer. Our aim is to identify the factors associated with a short time of return to continence. MethodsWe analyzed the first 110 SP TV RARP consecutive cases performed by one surgeon from 2020 to 2022. Continence was defined as zero to one safety pad. Two statistical analyses were done. First, patients were divided: Group A (n=62) included individuals who achieved continence within the initial week post-catheter removal; Group B (n=48) rest of the patients. Descriptive statistics were compared, followed by logistic regression for independent variables. Second, time to continence was analyzed as a continuous variable employing linear regression. The primary outcomes were the independent variables significantly associated with a short time to continence. ResultsAll cases were completed successfully, without additional ports or conversions. Median urinary catheter duration and time to continence were three and 3.5 days, respectively. Patients achieving continence within one week significantly presented with fewer preoperative urinary tract symptoms, lower PSA levels, and had smaller specimen weights postoperatively. Multivariable logistic regression established low specimen weight as the sole significant factor (p=0.04). Furthermore, linear regression demonstrated that alterations in independent variables accounted for 12.7% of the variance in time to continence (p=0.62). ConclusionsThe regionalization of surgery to the bladder employing a retropubic space-sparing extraperitoneal approach during SP TV RARP contributes to a fast return to continence. According to our model, the factors that significantly predict a shorter time to continence include lower preoperative IPSS, PSA, and postoperative specimen weight.

Metabolomic profiles of intact tissues reflect clinically relevant prostate cancer subtypes

BackgroundProstate cancer (PC) is a heterogenous multifocal disease ranging from indolent to lethal states. For improved treatment-stratification, reliable approaches are needed to faithfully differentiate between high- and low-risk tumors and to predict therapy response at diagnosis.MethodsA metabolomic approach based on high resolution magic angle spinning nuclear magnetic resonance (HR MAS NMR) analysis was applied on intact biopsies samples (n = 111) obtained from patients (n = 31) treated by prostatectomy, and combined with advanced multi- and univariate statistical analysis methods to identify metabolomic profiles reflecting tumor differentiation (Gleason scores and the International Society of Urological Pathology (ISUP) grade) and subtypes based on tumor immunoreactivity for Ki67 (cell proliferation) and prostate specific antigen (PSA, marker for androgen receptor activity).ResultsValidated metabolic profiles were obtained that clearly distinguished cancer tissues from benign prostate tissues. Subsequently, metabolic signatures were identified that further divided cancer tissues into two clinically relevant groups, namely ISUP Grade 2 (n = 29) and ISUP Grade 3 (n = 17) tumors. Furthermore, metabolic profiles associated with different tumor subtypes were identified. Tumors with low Ki67 and high PSA (subtype A, n = 21) displayed metabolite patterns significantly different from tumors with high Ki67 and low PSA (subtype B, n = 28). In total, seven metabolites; choline, peak for combined phosphocholine/glycerophosphocholine metabolites (PC + GPC), glycine, creatine, combined signal of glutamate/glutamine (Glx), taurine and lactate, showed significant alterations between PC subtypes A and B.ConclusionsThe metabolic profiles of intact biopsies obtained by our non-invasive HR MAS NMR approach together with advanced chemometric tools reliably identified PC and specifically differentiated highly aggressive tumors from less aggressive ones. Thus, this approach has proven the potential of exploiting cancer-specific metabolites in clinical settings for obtaining personalized treatment strategies in PC.