PSA Level Research Articles

(087) Testosterone Replacement Therapy in Men on Active Surveillance for Prostate Cancer: Using a Novel Database to Examine Disease Progression

Abstract Introduction Traditionally, the use of testosterone replacement therapy (TRT) in hypogonadal men on active surveillance (AS) with prostate cancer (PC) has been controversial, and for many providers, contraindicated. However, studies suggesting a need to revisit the association between TRT and prostate cancer progression have contributed to a recent paradigm shift in this approach. More studies are needed to analyze this relationship, especially due to the psychosocial and biological consequences of testosterone deficiency. Objective We aim to examine the effects of TRT on PC progression in hypogonadal men on active surveillance. Methods In this retrospective chart review, data from men diagnosed with hypogonadism and PC at a single hospital system between 2009 to 2022 were compiled into a database. Inclusion criteria for this specific study included men who underwent TRT while being on AS protocol for PC. Men receiving prior treatment for PC such as prostatectomy or radiation therapy were excluded. For each patient, PSA and total testosterone (TT) levels were recorded at 12 and 6 months prior to TRT, at the onset of TRT, and 3, 6, and 12 months following TRT initiation. One-way ANOVA was used to analyze variance in mean PSA and TT. Mean TT levels pre-TRT and post-TRT were calculated and analyzed for a significant difference. Progression to PC treatment was noted for each patient. Results 30 men meet the study criteria. The table below demonstrates the mean PSA and TT levels at each time interval. There was a significant variation in mean TT (P=0.0031) while there was no significant difference in mean PSA levels (P=0.3003) throughout the 2-year study period. Mean TT before initiation of TRT was 297.97 ng/dL, and mean TT after TRT was 716.15 ng/dL. There was an increase in mean TT after starting TRT (P=0.00072). One patient (3.3%) eventually underwent radiation therapy for PC five years after initiating TRT. Conclusions In hypogonadal men on AS for PC, no significant change in PSA level was observed after initiating TRT, despite an increase in testosterone. As we grow the database, we aim to increase the power of this study. Our findings contribute to the mounting evidence demonstrating TRT may be a viable option for hypogonadal men on AS. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Disclosures: Consultant for AbbVie, Marius, Tolmar, Endo, Petros, Boston Scientific, Coloplast Investor: Sprout.

(221) Outcomes of Transurethral Surgery After IPP

Abstract Introduction Inflatable penile prosthesis (IPP) effectively restores erectile function with very high patient satisfaction rates. However, some patients may require subsequent treatments for urethral stricture, enlarged prostate and bladder tumors. These underlying conditions oftentimes coexist with erectile dysfunction (ED). Transurethral surgery (TUS) treatment of coexisting conditions in patients with IPP can be challenging and associated with a theoretical risk of mechanical injury and infection of the implant. There is a lack of literature reporting on IPP issues after TUS. Objective The aim of this study was to evaluate postoperative outcomes in patients who underwent TUS following IPP placement. Methods After IRB approval, we reviewed the medical records of all patients who underwent Greenlight laser enucleation of the prostate (GLEP)(Wolf© 26 Fr cystoscope), Rezum© vaporization ( 21 Fr delivery device), transurethral bladder tumor resection (TURBT)(21 and 22 Fr cystoscopes) and Optilume balloon dilation surgeries (19 Fr cystoscope and 24 Fr balloon) after IPP placement at our institution from 2014 to 2023. We excluded patients who underwent TUS prior to IPP placement and only included patients who had an in situ IPP at the time of the TUS procedure. Parameters such as IPSS score, PSA, postvoid residual volume (PVR) and transrectal ultrasound were used for assessment before and after surgery. All surgeries were performed by a single surgeon. Postoperative progress was assessed at multiple follow-up visits. Results Seven patients with IPP underwent eight TUS. Four patients (71%) received surgical BPH treatment, one patient was treated for bladder tumors and one patient developed a bladder neck contracture (BNC) after GLEP and required a second TUS. One patient developed a pendulous stricture after erosion from an IPP cylinder placed by a different surgeon 23 years prior. The patient underwent IPP removal and replacement at our facility 63 months prior to Optilume® balloon dilation. The mean time between IPP placement and TUS was 34.86 ± 30.96 months. The average prostate volume was 41.3 ± 25.9 mL, and the mean parameters of PVR, Maximum flow rate (Q max), IPSS, and PSA before surgery were 140.6 ± 100.8 mL, 8.4 ± 7.2 ml/s, 16.3 ± 4.3, and 2.7± 2.7 ng/ml, respectively. An average of 31.6 ± 26.7 grams of prostate tissue was resected during GLEP. Postoperative parameters of PVR, Q max and PSA were 35.5 ± 31.3 ml, 17.2 ± 8.8 ml/s and 0.8 ± 0.65 ng/dl, respectively. There were no cases of postoperative infections or IPP malfunctions reported during a mean follow-up of 34.14±36 months. Conclusions Our experience shows that TUS performed after IPP placement is effective and safe in addressing underlying conditions such as BPH, bladder tumors and urethral strictures. Our findings indicate favorable postoperative outcomes in terms of PVR and PSA levels, without any reported infections or malfunctions of the IPP. However, it is important to consider the limitations of this study, including the small sample size. Further research with larger sample sizes would be beneficial to validate these findings and provide more comprehensive insights into the outcomes of TUS following IPP placement. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast, Irrisept.

DIAGNOSTICS OF PROSTATE CANCER: A 10 YEARS SYSTEMATIC REVIEW

Background: Prostate cancer ranks as the second most common malignancy in men globally, following lung cancer. The present method of diagnosing prostate cancer is marked by a significant level of diagnostic uncertainty. This uncertainty has led to both overtreating and undertreating, leaving the medical community unsure about the most effective approach for prostate cancer diagnosis. This study aims to to provide a 10 year systematic review of prostate cancer diagnosis. Methods: This systematic review adhered to the PRISMA 2020 standards and included full-text English literature published between 2014 and 2024. Exclusion criteria involved editorials, review articles from the same journal, and submissions lacking a DOI. Literature was gathered from online sources such as PubMed and SagePub. Result: Our search in PubMed yielded 24,278 articles, while SagePub produced 5,016 articles. Focusing on the year 2014, PubMed had 270 articles, and SagePub had 502. Ultimately we selected 5 papers that met our criteria, 3 from PubMed and 2 from SagePub. Conclusion: This study concludes that prostate cancer diagnosis can be done with biopsy in combinations to other modalities such as vibrational spectroscopy, PSA level and PSA-density, mpMRI, and biomarkers such as PCA3 and AMACR.

Prospective evaluation of the Kaiser Permanente prostate cancer risk calculator in biopsy-naïve men with mild PSA elevations.

290 Background: To assess the impact on biopsy outcomes in biopsy-naïve men with mild PSA elevations (<10 ng/ml) when provided risk estimates using a novel prostate cancer risk calculator. Methods: This prospective study was conducted in urology departments in Kaiser Permanente Northern California in men with PSA elevations that were <10 ng/ml between March 2021 and March 2023. Patient variables (age, race, family history of prostate cancer, body mass index, and PSA level) were entered into our validated calculator. Risk estimates for high-grade cancer (Gleason score ≥7) and overall cancer were shared with the patient who accepted or declined the biopsy. We compared age, race, family history for prostate cancer, BMI, PSA level, predicted high-grade and overall cancer risks between those that accepted and those that declined biopsy. The outcomes of those who underwent biopsy were compared to historical data of biopsy-naïve men with PSA elevations <10 ng/ml who underwent biopsy in the three years prior to the Covid pandemic between January 2016 and December 2019 (n=5141). Results: After 24 months, the calculator was used to estimate risk for 1962 biopsy-naïve men with mild PSA elevations. 1455 (74%) accepted the biopsy. Those with a family history for prostate cancer were slightly more likely to accept biopsy. Age (continuous and categorical), and BMI (continuous and categorical) were not associated with decision for biopsy. Similarly, race/ethnicity when analyzed as four categories (White, Black, Asian, Hispanic) or as two categories (Black vs. all others) was not associated with decision for biopsy. The men who accepted the biopsy had higher predicted median high-grade cancer risks (24% [IQR 17-31%] vs. 20% [IQR 14-29%]; p<0.0001) and higher predicted median overall cancer risks (48% [IQR 40-56%] vs 45% [IQR 37-53%], respectively; p<0.0001) than those who declined the biopsy. Compared to the historical group, use of the risk calculator resulted in a biopsy population enriched with high-grade cancer: 29% vs 25%; similar rates of low-grade cancer: 24% vs 24%; and fewer negative biopsies: 47% vs. 51%, respectively; overall p=0.013. Conclusions: In biopsy-naïve men with mild PSA elevations, use of our risk calculator resulted in a biopsy population that had more high-grade cancer and fewer negative biopsies compared to a historical group. Only family history and higher predicted cancer risks by the calculator were associated with biopsy acceptance.

Impact of race on outcomes to 177Lu-PSMA-617 (LuPSMA) for metastatic castrate-resistant prostate cancer (mCRPC).

27 Background: Prior work suggests that African American (AA) and other minority patients (pts) derive equal benefit from taxane chemotherapy and androgen receptor pathway inhibitors (ARPIs) for mCRPC as white pts. LuPSMA showed an overall survival (OS) benefit in mCRPC pts after prior taxane and ARPI. However, there are no data on racial differences in outcomes to LuPSMA. Methods: We queried an IRB-approved registry of all pts treated with at least 2 cycles of LuPSMA between June 2022 and August 2023 at two academic medical centers in Boston, MA. Clinical data, including self-reported race, was abstracted from the electronic medical record. Pts of AA, Hispanic/Latino and Asian race were categorized as minorities. Outcomes of interest were the proportion of patients with ≥50% decrease in PSA levels during LuPSMA therapy (PSA50) and OS, defined from the date of the first cycle of LuPSMA. PSA50 and OS between races were compared with the Chi-Square and log-rank tests, respectively. Results: A total of 156 pts were included. Median age at LuPSMA initiation was 73 years (range 53-92) and the median number of prior lines of therapy was 5 (range 2-12); all pts had received ≥1 taxane and ≥1 ARPI. 136 (87%), 10 (6%), 6 (4%) and 4 (3%) pts were White, AA, Hispanic/Latino and Asian, respectively. The median number of LuPSMA cycles received in the entire cohort was 4 (range 2-7), and median follow-up was 7.1 months. A numerically higher proportion of minority pts had visceral disease at baseline compared to White pts (50% vs. 31%, (X2 = 2.87, p=0.090). Overall, 86 pts (55%) had a PSA50, with PSA50 of 55% (n=75), 60% (n=6), 67% (n=4) and 25% (n=1) amongst White, AA, Hispanic/Latino and Asian pts, respectively. There was no significant difference in PSA50 between White and minority pts (X2 = 0.00, p=0.990). Median OS in the entire cohort was 12.9 months and was not significantly different between White and minority pts (12.9 months vs. 8.5 months, p=0.533). The Table summarizes outcomes by race. Conclusions: PSA50 and OS were comparable between minority and White pts receiving LuPSMA for mCRPC, despite minority pts tending to present with more visceral disease, a known adverse prognostic factor. Validation of these findings and efforts to widen access to LuPSMA amongst minorities are required, given that pts of all racial backgrounds appear to benefit equally from LuPSMA. [Table: see text]

Clinical outcomes with systemic therapy given after progression on prostate specific membrane antigen radioligand therapy (PSMA-RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC).

78 Background: PSMA-RLT is a novel therapeutic modality that improves overall survival in mCRPC. However, outcomes for systemic therapy given after progression on PSMA-RLT are not well described. We investigated treatment choices and outcomes in patients (pts) with mCRPC who experienced disease progression after PSMA-RLT. Methods: We performed a single center retrospective cohort study of pts with mCRPC, who received PSMA-RLT at the Jewish General Hospital between 2020 and 2023. Clinical characteristics, PSA50, further lines of therapy post PSMA-RLT and survival were abstracted from chart review. A log-rank test was used to assess overall survival (OS). Post-PSMA-RLT specific OS (Post-RLT-OS) was defined from the date of first systemic treatment after PSMA-RLT failure to death or last follow up. Results: We identified 42 pts who received PSMA-RLT for mCRPC. The median age was 63 years (47-89) and the majority (56.1%) of pts received PSMA-RLT as a 3rd or later line of therapy in mCRPC setting. Amongst these pts, 15/42 (35.7%) achieved a PSA50 response to PSMA-RLT; 36 pts experienced disease progression, and 25/36 with disease progression (69.4%) received subsequent active systemic therapy. Post-PSMA-RLT systemic therapy included chemotherapy (n=17), PARP inhibitors (PARPi) (n=3), bipolar androgen therapy (BAT) followed by androgen receptor-axis targeted agent (ARAT) (BAT+ARAT) (n=2), Radium (n=2), BAT (n=1), and different PSMA-RLT agent (n=1). Amongst the pts who received post-PSMA-RLT therapy, 5/25 (20%) achieved a PSA50 response. PSA50 responses were observed in pts who received chemotherapy (n=2), BAT+ARAT (n=2) and PARPi (n=1). After a median follow-up of 10 months, the median Post-RLT-OS in the entire cohort was 11.7 months. Post-RLT-OS was significantly associated with PSA levels at the time of post-PSMA-RLT systemic therapy. The median Post-RLT-OS for pts with PSA < 100 (n=11), 100 ≤ PSA < 1000 (n=5) PSA ≥ 1000 (n=5) was 15, 15.7, and 8.6 months respectively (P = 0.014). Conclusions: Some pts derive benefit from post-PSMA-RLT systemic therapy; however, the overall response rate is low and therapeutic options are limited. More research is needed to define mechanisms of resistance to PSMA-RLT, and to identify novel therapeutic opportunities in this patient population.

Prostate-specific membrane antigen SPECT-CT in patients with intermediate and high-risk prostate cancer in primary diagnosis: A comparative analysis with 18F-PSMA PET/CT.

43 Background: Prostate cancer (PC) is a leading cause of cancer death in men worldwide. Imaging plays a key role in disease detection and initial staging. Emerging data has shown the superiority of 68Gallium and 18Fluorine labeled-PSMA imaging with PET/CT over conventional imaging for primary diagnosis. Despite the success, there are challenges in meeting the high demand and expensive costs especially in low-income countries. These challenges stimulated interest in 99mTechnetium-labeled-PSMA agents. Single photon emission computer tomography (SPECT/CT) is more worldwide available, and the imaging agent is low cost, which is more promising. The aim of this study is to compare the diagnostic accuracy of 99mTc‐PSMA-SPECT/CT to 18F-PSMA-PET/CT in the primary diagnosis of PC and impact on clinical staging. Methods: Prospective controlled study, total of 16 patients with histologically confirmed PC (intermediate unfavorable and high risk) were recruited to undergo 18F-PSMA-PET/CT and 99mTc-HYNIC-PSMA-SPECT/CT. Mean age of patients was 71 (54-75) years and the median PSA level was 31.5 (4.3-920) ng/ml. Lesions were divided into prostate, seminal vesicles, lymph nodes (LN) (locoregional [LR] and non-locoregional [NLR]), bone, and visceral metastases. The size of LN with PSMA avidity on 99mTc‐PSMA-SPECT/CT were determined. Lesions detected were read independently of PET/CT findings with two experienced nuclear medicine physicians. Volumetric analysis was also performed between the two imaging modalities (Tumoral Total Volume [TTV]) and correlated with PSA levels. Results: A total of 233 lesions were detected on 18F-PSMA-PET/CT; prostate (n=16), seminal vesicles (n=11), LN LR (n=54), NLR (n=66), bone (n=82) and visceral (n=4); of these 99mTc‐PSMA-SPECT/CT both reviewers detected 100% of the lesions in prostate (16/16), seminal vesicles (11/11) and visceral (4/4); LN LR (51/54; 94%), NLR (51/66; 77%) and bone (70/82; 85%). Between reviewers there was discordance in just 3 LN (<4 mm) and 1 bone metastases. The lowest diameter of positive LN detected by SPECT/CT was 4 mm (range 4-18). Pearson-correlation coefficient between PSA and TTV SPECT was r=0.68 (p=0.003) and for TTV PET r=0.71 (p=0.002). There were not statistically significant differences between TTV SPECT and TTV PET (T-student p=0.48). Five cases with high volume disease were detected by both methods. All patients were classified according to miTNM showing no difference. Conclusions: 99mTc‐PSMA-SPECT/CT may be a useful in primary diagnosis of PC. Despite it showed a slightly lower lesion detection rate compared to 18F-PSMA-PET/CT, it exhibited no impact on clinical staging and consequently the initial treatment intension. Our results show that 99mTc‐PSMA-SPECT/CT could be used as a cost-efficient alternative with wider availability and no significant difference.

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, >20-25, >25-30 or >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>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>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>20-25. In adjusted analyses, veterans with BMI>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>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]

Testosterone suppression and recovery in patients with advanced prostate cancer treated with intermittent androgen deprivation therapy (iADT) with relugolix.

70 Background: Many patients with advanced prostate cancer do not want to pursue continuous androgen deprivation therapy (cADT) because of concerns about side effects, and pursue iADT. However, even intermittent treatment with GNRH agonist therapy may not lead to rapid recovery of testosterone during the off-treatment period. In the pivotal HERO trial of relugolix (GNRH antagonist) the testosterone recovery time was in weeks [PMID 32469183]. The objective of the study was to measure the time to testosterone suppression to castrate level and time to recovery of serum testosterone to non-castrate level in real-world patients with advanced prostate cancer undergoing intermittent relugolix therapy. Methods: In this IRB-approved retrospective study, the eligibility was: patients with advanced prostate cancer undergoing iADT with relugolix. iADT with relugolix was defined as initiating relugolix at PSA ≥ 10 ng/ml and holding relugolix when PSA ≤ 4 ng/ml. The primary endpoints were: 1) time to serum castrate level of testosterone after relugolix initiation and 2) time to recovery to non-castrate level after discontinuation of relugolix. Castrate level of serum testosterone was defined as serum testosterone level ≤ 50 ng/dL. Results: Overall 25 consecutive patients with advanced prostate cancer treated with iADT with relugolix were eligible and included. The median age was 75 [range 68-88]. Patients with a Gleason score of ≥ 8 comprised 44% of the cohort. The median PSA at the start of therapy was 18.2 ng/ml [5.1 – 99.1 ng/ml]. Median time to testosterone ≤ 50 ng/dl after relugolix initiation was 1.13 months [0.67 – 2.5 months], and median time to testosterone recovery after relugolix discontinuation was 1.4 months [0.83 – 6.57 months]. The median PSA nadir achieved with relugolix was 2.02 ng/ml [0.1 – 4.8], and median time to PSA nadir was 1.35 months from initiation of therapy (0.67 – 4.8 months). Median time to PSA relapse ≥ 10 ng/dl after holding relugolix was 3.4 months (0.9 – 8.23 months). Conclusions: This is the first real-world study to show that iADT with relugolix is associated with a rapid time to testosterone suppression and recovery. These results may guide patients’ counseling, monitoring of serum testosterone and PSA levels in patients wishing to pursue iADT for advanced prostate cancer. These hypothesis-generating data need external validation.

A Comprehensive Review of the Current State of Robot-assisted Laparoscopic Salvage Prostatectomy.

Salvage robot assisted radical prostatectomy (sRARP) is performed for patients with biochemical or biopsy proven, localized prostate cancer recurrences after radiation or ablative therapies. Traditionally, sRARP has been avoided by lower volume surgeons due to technical demand and high complication rates. Post-radiation sRARP outcomes studies exist but remain few in number. With increasing use of whole gland and focal ablative therapies, updates on sRARP in this setting are needed. The aim of this narrative review is to provide an overview of recently reviewed studies on the oncologic outcomes, functional outcomes, and complications after post-radiation and post-ablative sRARP. Tips and tricks are provided to guide surgeons who may perform sRARP. We performed a non-systematic literature search of PubMed and MEDLINE for the most relevant articles pertaining to the outlined topics from 2010-2022 without limitation on study design. Only case reports, editorial comments, letters, and manuscripts in non-English languages were excluded. Key Content and Findings: Salvage robotic radical prostatectomy is performed in cases of biochemical recurrence after radiation or ablative therapies. Oncologic outcomes after sRARP are worse compared to primary surgery (pRARP) though improvements have been made with the robotic approach when compared to open salvage prostatectomy. Higher pre-sRARP PSA levels and more advanced pathologic stage portend worse oncologic outcomes. Patients meeting low-risk, EAU-biochemical recurrence criteria have improved oncologic outcomes compared to those with high-risk BCR. While complication rates in sRARP are higher compared to pRARP, Retzius sparing approaches may reduce complication rates, particularly rectal injuries. In comparison to the traditional open approach, sRARP is associated with a lower rate of bladder neck contracture. In terms of functional outcomes, potency rates after sRARP are poor and continence rates are low, though Retzius sparing approaches demonstrate acceptable recovery of urinary continence by 1 year, post-operatively. Advances in the robotic platform and improvement in robotic experience have resulted in acceptable complication rates after sRARP. However, oncologic and functional outcomes after sRARP in both the post-radiation and post-ablation settings are worse compared to pRARP. Thus, when engaging in shared decision making with patients regarding the initial management of localized prostate cancer, patients should be educated regarding oncologic and functional outcomes and complications in the case of biochemically recurrent prostate cancer that may require sRARP.

The Impact of Physical Activity on the Outcomes of Active Surveillance in Prostate Cancer Patients: A Scoping Review

Introduction: Active surveillance has emerged as a valid therapeutic option in patients with low-risk prostate cancer, allowing for the deferral of definitive treatment until the time of possible disease progression. Although it is known that physical activity plays a protective role in the onset and progression of this tumor, its impact on patients with low-risk disease who are managed with active surveillance remains unclear. Our scoping review aims to summarize the existing evidence on this subject. Evidence Acquisition: On 9 April 2023, a systematic search was conducted using the PubMed and Scopus databases. The search employed the combination of the following terms: (“prostate cancer” OR “prostate tumor”) AND (“active surveillance”) AND (“physical activity” OR “physical exercise” OR “physical intensive activity” OR “intensive exercise”) AND (“lifestyle”). Out of the 506 identified articles, 9 were used for the present scoping review, and their results were reported according to the PRISMA-ScR statement. Evidence Synthesis: We discovered a lack of uniformity in the assessment of PA and its stratification by intensity. There was no consensus regarding what constitutes cancer progression in patients choosing expectant management. In terms of the impact of PA on AS outcomes, conflicting results were reported: some authors found no correlation, while others (six of total studies included) revealed that active men experience smaller increases in PSA levels compared to their sedentary counterparts. Additionally, higher levels of exercise were associated with a significantly reduced risk of PCa reclassification. Conclusion: Due to the heterogeneity of the methodologies used in the available studies and the conflicting results reported, it is not possible to draw definitive conclusions concerning the role physical activity may play in the risk of prostate cancer progression in men managed with active surveillance.

Performance of the F-PSMA 1007 PET/CT for high-risk prostate cancer staging: Experience from a Latin American reference center.

286 Background: Diagnostic staging in high-risk prostate cancer patients seeks to define the local extent of the disease as well as determine the presence of lymph nodes and distant metastases. Molecular imaging, such as PET PSMA, provides higher sensitivity and specificity for the detection of nodal and distant metastases compared to conventional imaging. 18F-PSMA-1007 is radiotracer that represents a cost-effective alternative to 68Ga-PSMA-11, although evidence is limited. We aim to describe the performance of PSMA-1007 in the staging of patients with high risk for prostate cancer in a Latin America reference center. Methods: We performed a cross-sectional study that included prostate cancer patients who underwent 18F-PSMA1007 PET/CT for initial staging in our center of reference between 2020-2023. Descriptive analysis was performed with frequencies for discrete variables, and central tendency and dispersion measures for continuous variables. High risk was defined using the NCCN prostate cancer guidelines. Contingency tables were designed to evaluate associations between groups. To compare categorical variables, we use Chi-square and ANOVA for continuous variables. This analysis was performed using Jamovi 2.3.21 statistical software. Results: Two hundred and seventeen patients were included. The median age was 67 years. The median PSA distribution was 12 ng/ml. The most frequent Gleason group was group 4 (42,7%), followed by group 3 (25,5%). The most prevalent results on the PET pattern are presented in Table. 32% of the patients presented positive lymph node findings. Before the F-PSMA 1007 PET/CT, 24% of the patients had lymph node involvement identified and 33.2% had negative lymph nodes with conventional imaging. These values changed to 39% and 56% respectively, with the F-PSMA 1007 PET/CT. Bone was the most frequent metastasis site (14,3%), followed by extrapelvic lymph node metastasis (12%). A favorable correlation between higher PSA levels and stratified risk assessment by PSMA pattern was evident (p< 0.001). Conclusions: 18F-PSMA-1007 is an innovative radiotracer that can be used to evaluate the extension of prostate cancer involvement. Future studies with prospective cohorts should be carried out to establish analyses between 18F-PSMA-1007 use and its influence on the oncological management of these patients.[Table: see text]

Quantified treatment effect at the individual level is more indicative for personalized radical prostatectomy recommendation: implications for prostate cancer treatment using deep learning

BackgroundThere are potential uncertainties and overtreatment existing in radical prostatectomy (RP) for prostate cancer (PCa) patients, thus identifying optimal candidates is quite important.PurposeThis study aims to establish a novel causal inference deep learning (DL) model to discern whether a patient can benefit more from RP and to identify heterogeneity in treatment responses among PCa patients.MethodsWe introduce the Self-Normalizing Balanced individual treatment effect for survival data (SNB). Six models were trained to make individualized treatment recommendations for PCa patients. Inverse probability treatment weighting (IPTW) was used to avoid treatment selection bias.Results35,236 patients were included. Patients whose actual treatment was consistent with SNB recommendations had better survival outcomes than those who were inconsistent (multivariate hazard ratio (HR): 0.76, 95% confidence interval (CI), 0.64–0.92; IPTW-adjusted HR: 0.77, 95% CI, 0.61–0.95; risk difference (RD): 3.80, 95% CI, 2.48–5.11; IPTW-adjusted RD: 2.17, 95% CI, 0.92–3.35; the difference in restricted mean survival time (dRMST): 3.81, 95% CI, 2.66–4.85; IPTW-adjusted dRMST: 3.23, 95% CI, 2.06–4.45). Keeping other covariates unchanged, patients with 1 ng/mL increase in PSA levels received RP caused 1.77 months increase in the time to 90% mortality, and the similar results could be found in age, Gleason score, tumor size, TNM stages, and metastasis status.ConclusionsOur highly interpretable and reliable DL model (SNB) may identify patients with PCa who could benefit from RP, outperforming other models and clinical guidelines. Additionally, the DL-based treatment guidelines obtained can provide priori evidence for subsequent studies.

Clinical assessment of TGFB1 and HP Relative Gene Expression in the Peripheral Blood of Prostate Cancer Patients.

This study aimed to assess the relative gene expression level of transforming growth factor-β1 (TGFB1) and haptoglobin (HP) in the peripheral blood of prostate cancer (PCa) patients and evaluate their diagnostic ability. A total of 125 participants were enrolled in the present study. Among them, 75 PCa patients, 25 benign prostatic hyperplasia (BPH) patients, and 25 healthy volunteers served as the control group. The relative TGFB1 and HP gene expression level was quantified using real-time polymerase chain reaction. Further, free and total PSA levels were determined using electrochemiluminescence assays. TGFB1 was significantly over-expressed, whereas HP was significantly downregulated in the peripheral blood of PCa patients compared to BPH and control groups (p-value ranges from 0.034 to <0.001). Moreover, the high expression level of TGFB1 was associated with an increased risk of PCa development with OR=1.412 (95%CI: 1.081-1.869, p= 0.012). TGFB1 and HP relative expression levels had lower diagnostic performance to differentiate PCa from normal and BPH individuals compared to PSA, however, the combination of the tested parameters improved the diagnostic efficacy. TGFB1 and HP relative expression have moderate diagnostic efficacy in discriminating patients with PCa from BPH and healthy subjects. Furthermore, over-expression of TGFB1 may contribute to the pathogenesis of PCa.

Interim analyses from the PROSPET-BX trial: [G8Ga]PSMA PET/CT vs. mpMRI in patients with suspicion of prostate cancer and previous negative biopsy.

282 Background: Herein we present the results of the interim analyses of our prospective trial (Identifier: NCT05297162), designed to compare [68Ga]PSMA PET/CT with mpMRI in men with a high suspicion of prostate cancer (PCa) after at least one previous negative biopsy. Methods: From April 2022 until September 2023, overall, 94 patients were screened, 78 were enrolled and 64 completed all study investigations. Inclusion criteria: PSA&gt;4.0ng/ml; free-to-total PSA ratio &lt;20%; progressive rise of PSA levels in two consecutive samples; at least one previous negative biopsy; negative digital rectal examination. [68Ga]PSMA PET/CT and 3T mpMRI were performed within one month, followed by TRUS-fusion prostate biopsy. Target lesions were defined based on PI-RADS v2.1 for mpMRI and Primary Score, SUVmax and SUVratio for [68Ga]PSMA PET/CT, then correlated to pathology findings. Results: Median age was 64 years (range 51-83) and median PSA 10.4 ng/ml (range 4.3-25,9). Most patients (76.6%) had one previous negative biopsy. According to re-biopsy results, 10 patients presented with clinically significant PCa (csPCa), 4 with GS 6, while the majority had a negative biopsy (78%). mpMRI results were: 40 patients with PI-RADS 2 (62.5%), 3 with PI-RADS 3 (4.7%), 15 with PI-RADS 4 (23.4%), and 6 with PI-RADS 5 (9.4%). Primary scores were: 45 score 1-2 (70%), and 19 score 3-5. PI-RADS and Primary scores were significantly correlated (P=0.0006). Median SUVmax and SUVratio were 3.7 and 1.35 for benign versus 8.9 and 3 for malignancy, respectively (P&lt;0.001). ROC analyses identified optimal cut-off points for csPCA, with SUVmax&gt;7.48 (AUC 0.756; 95%CI 0.633-0.855) and SUVratio&gt;2.79 (AUC 0.748; 95%CI 0.624-0.848). PI-RADS, Primary score, SUVmax and SUVratio proved significantly associated to biopsy results. When combining [68Ga]PSMA PET/CT with mpMRI data, the detection rate was 90% for csPCa, and the combination of both modalities could spare 87.5% of unnecessary re-biopsies. Conclusions: In these interim results, [68Ga]PSMA PET/CT parameters predict biopsy results as mpMRI in patients who are candidates to re-biopsy; the combination of both modalities can spare most unnecessary re-biopsies, by granting a 90% detection rate for csPCa. Clinical trial information: NCT05297162 .

Contribution of 68 Ga-DOTA-FAPI-04 PET/CT to Prostate Cancer Imaging : Complementary Role in PSMA-Negative Cases.

Prostate-specific membrane antigen (PSMA)-targeted PET/CT is a well-established imaging method in prostate cancer (PC) for both staging and restaging, and also for theranostic applications. An alternative imaging method is crucial for 15% PSMA-negative cases. We aimed to investigate the contribution of 68 Ga-DOTA-FAPI-04 PET/CT to PC imaging. Thirty-six patients diagnosed with PC were included. Patients underwent both 68 Ga-PSMA PET/CT and 68 Ga-DOTA-FAPI-04 PET/CT imaging within 1 week. In staging group, primary tumor uptake values were compared, and also correlations were done with histopathological findings, MRI findings, and total PSA levels. In biochemical recurrence group, the uptake values in prostatic region and metastases were evaluated to define the local recurrence or metastatic disease. In staging group, PSMA PET showed increased uptake in the primary lesion area in 14/27 (52%) patients, whereas 20/27 (74%) patients were positive in FAPI-04 PET. FAPI-04 positivity was found to be quite high, such as 54%, in PSMA-negative patients. A significant difference was observed between ISUP grade 1-3 patients and ISUP grade 4-5 patients in FAPI-04 PET ( P = 0.03). Local recurrence was detected in 3 patients, pelvic lymph node metastasis in 1 patient, and sacrum metastasis in 1 patient in biochemical recurrence group, and all of the lesions had more intense uptake in PSMA PET than FAPI-04 PET. FAPI PET imaging seems to have a potential to contribute PSMA PET imaging with FAPI positivity in more than half of PSMA-negative cases. Also, FAPI-targeted radionuclide therapy may be a promising method in patients resistant to PSMA-targeted therapy.

Prognostic Value of Prostata Specific Antigen and Digital Rectal Examination at Prostate Biopsy

Abstract Prostate cancer is a worldwide health concern with an increasing global incidence. In the Republic of Serbia, it is the third most commonly diagnosed cancer in men. The research aims to determine the influence of PSA value and digital rectal examination on the pathohistological findings of prostate biopsy in men in Central Serbia. The study was designed as a retrospective, cross-sectional analytical study conducted in the period from December 2021 to December 2022 after receiving the confirmation of the Ethics Committee of the University of Applied Sciences Kragujevac. Among 151 respondents aged 49 to 88 who underwent consecutive biopsies during the study period, prostate cancer was detected in 65 (42%). Out of 65 positive biopsies, 33 subjects had a Gleason score of up to 7, while 32 subjects had a Gleason score over 7. Prostate biopsies significantly correlated with PSA levels (p=0.02), while DRE and prostate volume did not show statistical significance on the prostate biopsy result. PSA level testing leads to early detection of prostate disease in the elderly. PSA value was the only clinical variable associated with an increased rate of prostate cancer in men ≥ 70 and older (p=0.02). DRE, PSA, and prostate volume are important parameters associated with an increase in prostate cancer detection rate in men over 70 years of age.

Bilateral Subcapsular Orchidectomy as Surgical Castration: A Reasonable Aesthetic Alternative to Bilateral Total Orchidectomy in Patients with Metastatic Hormone-sensitive Prostate Cancer

Background: The study highlights the historical significance of bilateral orchidectomy as the traditional 'gold standard' for surgical androgen deprivation in treating advanced prostate cancer. The study presented aims to compare total orchidectomy and subcapsular orchidectomy, considering factors such as androgen ablation, disease progression control, and patient satisfaction. Objective: This study aims to compare the effectiveness and patient satisfaction of bilateral subcapsular orchidectomy and bilateral total orchidectomy treatment in managing hormone-sensitive metastatic prostate cancer. Methods and materials: In this prospective study of 18 months at North East Medical College Hospital, 40 participants with Metastatic Carcinoma of Prostate underwent bilateral orchidectomy, among them 20 subcapsular and 20 total orchidectomy. The research focused on evaluating the impact of these treatments on serum testosterone levels, serum PSA levels, employing as outpatient procedures and a 3-month follow-up, utilizing a satisfaction scoring scale. Data, including age, Gleason Grade Group, PSA, and testosterone levels at diagnosis &amp; at 3-month follow-up were recorded and analyzed using IBM SPSS-21 software. Result: The study compared Bilateral Subcapsular Orchidectomy and Bilateral Simple Orchidectomy for Hormone-Sensitive Metastatic Carcinoma of Prostate in 40 patients. The highest frequency was in the 71-75 age group (30%), with a mean age of 66.67 ± 2.21 years. Gleason grade group 3 dominated (40%), followed by 2 (25%). Pre-operative PSA levels were 31.14±1.27 ng/ml for Subcapsular and 35.21±1.70 ng/ml for Total Orchidectomy, decreasing post-operatively to 8.25±0.41 ng/ml and 7.32±0.80 ng/ml, respectively. Pre-operative testosterone levels were 513.21±3.01 ng/dl for Subcapsular and 498.40±2.10 ng/dl for Total Orchidectomy, decreasing post-operatively to 21.14±2.84 ng/dl and 16.90±1.08 ng/dl, respectively, with non-significant p-values. Surgery related Satisfaction scores in the Follow-Up phase were significantly higher for Subcapsular Orchidectomy, 2.91±0.31 comparing with Total Orchidectomy, 2.05±0.45. The results emphasize better patient satisfaction after subcapsular orchidectomy, while maintaining similar cancer control in the form of PSA and testosterone level changes. Conclusion: In conclusion, our study advocates for the reconsideration of bilateral subcapsular orchidectomy as a preferred method for surgical androgen ablation in metastatic prostatic carcinoma, offering comparable efficacy to traditional total orchidectomy approach while prioritizing patient satisfaction and psychological well-being. This suggests a potential paradigm shift in the landscape of cost-effective androgen deprivation therapy within the urological field.

Investigating Efficient Risk-Stratified Pathways for the Early Detection of Clinically Significant Prostate Cancer.

Risk-stratified pathways (RSPs) are recommended by the European Association of Uro-logy (EAU) to improve the early detection of clinically significant prostate cancer (csPCa). RSPs can reduce magnetic resonance imaging (MRI) demand, prostate biopsies, and the over-detection of insignificant PCa (iPCa). Our goal is to analyze the efficacy and cost-effectiveness of several RSPs by using sequential stratifications from the serum prostate-specific antigen level and digital rectal examination, the Barcelona risk calculators (BCN-RCs), MRI, and Proclarix™. In a cohort of 567 men with a serum PSA level above 3.0 ng/mL who underwent multiparametric MRI (mpMRI) and targeted and/or systematic biopsies, the risk of csPCa was retrospectively assessed using Proclarix™ and BCN-RCs 1 and 2. Six RSPs were compared with those recommended by the EAU that, stratifying men from MRI, avoided 16.7% of prostate biopsies with a prostate imaging-reporting and data system score of <3, with 2.6% of csPCa cases remaining undetected. The most effective RSP avoided mpMRI exams in men with a serum PSA level of >10 ng/mL and suspicious DRE, following stratifications from BCN-RC 1, mpMRI, and Proclarix™. The demand for mpMRI decreased by 19.9%, prostate biopsies by 19.8%, and over-detection of iPCa by 22.7%, while 2.6% of csPCa remained undetected as in the recommended RSP. Cost-effectiveness remained when the Proclarix™ price was assumed to be below EUR 200.

Added value of randomised biopsy to multiparametric magnetic resonance imaging-targeted biopsy of the prostate in a contemporary cohort.

To assess the added value of concurrent systematic randomised ultrasonography-guided biopsy (SBx) to multiparametric magnetic resonance imaging (mpMRI)-targeted biopsy and the additional rate of overdiagnosis of clinically insignificant prostate cancer (ciPCa) by SBx in a large contemporary, real-world cohort. A total of 1552 patients with positive mpMRI and consecutive mpMRI-targeted biopsy and SBx were enrolled. Added value and the rate of overdiagnosis by SBx was evaluated. added value of SBx, defined as detection rate of clinically significant PCa (csPCa; International Society of Urological Pathology [ISUP] Grade ≥2) by SBx, while mpMRI-targeted biopsy was negative or showed ciPCa (ISUP Grade 1). rate of overdiagnosis by SBx, defined as detection of ciPCa in patients with negative mpMRI-targeted biopsy and PSA level of <10 ng/mL. Detection rate of csPCa by mpMRI-targeted biopsy and/or SBx was 753/1552 (49%). Added value of SBx was 145/944 (15%). Rate of overdiagnosis by SBx was 146/656 (22%). Added value of SBx did not change when comparing patients with previous prostate biopsy and biopsy naïve patients. In multivariable analysis, a Prostate Imaging-Reporting and Data System (PI-RADS) 4 index lesion (odds ratio [OR] 3.19, 95% confidence interval [CI] 1.66-6.78; P = 0.001), a PI-RADS 5 index lesion (OR 2.89, 95% CI 1.39-6.46; P = 0.006) and age (OR 1.05, 95% CI 1.03-1.08; P < 0.001) were independently associated with added value of SBx. In our real-world analysis, we saw a significant impact on added value and added rate of overdiagnosis by SBx. Subgroup analysis showed no significant decrease of added value in any evaluated risk group. Therefore, we do not endorse omitting concurrent SBx to mpMRI-guided biopsy of the prostate.