Treatment Modality For Prostate Cancer Research Articles

A scoping review of the management of prostate cancer in Africa

Prostate cancer is one of the most frequently diagnosed cancers in menand a major cause of cancer-related deaths in men, globally. The managementof prostate cancer in Africa is unique; most patients present withadvanced disease as result of a largely under-developed healthcare delivery.However, due to the underdeveloped healthcare system in Africa,there are unique limitations to delivering these treatments. Thus, the needfor this scoping review on the management of prostate cancer in Africa.Aim: To give an account of the pattern of presentation, histological types,investigative and treatment modalities of prostate cancer in Africa. A literaturesearch through PubMed, Google Scholar, and African Journal Onlineon the management of prostate cancer in Africa was conducted. Results arethen reported according to the Preferred Reporting Items for SystematicReview and Meta-analyses extension for Scoping Review. Forty-three articlesfully satisfied the inclusion criteria and were used for this review.The commonest presentation of prostate cancer was lower urinarytract symptoms, followed by bone pain and urinary retention in that order.Adenocarcinoma was the commonest histological type for 98.5% of thestudy. A total 23.3% of patients had hormonal treatment which was the commonesttreatment option. Chemotherapy and open radical prostatectomywere used in 17.7 and 12.9% cases respectively. The use of robot-assistedradical prostatectomy was not an option of care noted in the review. Thefindings of this study highlight the need for integration of modern investigativemodalities and treatment options for prostate cancer in Africa.

Radiotherapy Related Bowel and Bladder Toxicity after Prostate Cancer Irradiation

Background: Pelvic radiotherapy is a primary treatment modality for organ-confined prostate cancer and early-stage endometrial cancer. While effective in improving survival rates and reducing recurrence, it is associated with a range of side effects that can impact patient quality of life. Objective: The study aimed to assess the incidence, management, and resolution of acute and chronic side effects of pelvic radiotherapy in prostate and endometrial cancer patients, focusing on bowel and bladder functions. Methods: This single-center, observational study included 50 patients diagnosed with prostate or endometrial cancer who underwent pelvic radiotherapy with a dose of 66-70 Gy using a four-field technique on a linear accelerator. Patients were assessed for bladder and bowel dysfunction, with follow-up at 6, 12, and 18 months post-treatment. Statistical analysis involved univariate weighted distribution of response frequencies and paired t-tests for ordinal scale scores, using SPSS version 25 for data analysis. Results: Of the participants, 22% experienced dysuria, 64% reported bladder outlet obstruction, and 20% had constipation. Acute bowel symptoms like diarrhea occurred in 32%, and chronic proctitis developed in 22% of patients. Urinary symptoms appeared by the third week and generally resolved within weeks; however, bowel symptoms persisted longer but returned to baseline by 18 months post-treatment. Approximately 70% of patients reported good tolerance to radiotherapy. Conclusion: Pelvic radiotherapy is effective in treating prostate and endometrial cancers but requires management of transient side effects to improve patient outcomes. Advanced radiotherapy techniques such as IMRT and 3D CRT have shown potential in reducing these side effects, emphasizing the need for continuous technological advancements and patient-centered care in radiotherapy.

Assessing the Efficacy and Long-Term Outcomes of Surgical Intervention Versus Radiotherapy: A Comprehensive Systematic Review and Meta-Analysis of Prostate Cancer Treatment Modalities.

There is controversy regarding the most effective primary treatment of choice for prostate cancer (PCa) in terms of patient outcomes, such as surgery or radiotherapy (RT). This study evaluated the comparative efficacy and long-term outcomes of radical prostatectomy (RP) and RT for PCa treatment. A thorough literature review of relevant databases was conducted, focusing on academic and clinical studies published from 2019 onwards. The inclusion criteria included randomized controlled trials (RCTs) and other observational studies comparing survival outcomes in patients treated with surgery and RT. We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines to provide an overview of the data. We selected 19 studies based on the inclusion criteria. Of the total 19 studies, 12 advocated RP as the preferred treatment to improve survival outcomes in patients with PCa. The results of our synthesis showed that prostate cancer-specific mortality (PCSM) was lower in patients treated with RT. The total effect size for the analysis was calculated as Z=1.19 (p-value=0.23). The heterogeneity in the studies was as follows: Tau2=0.09, Chi2=20.25, df=4, I2=80%. Moreover, overall survival (OS) was shown to be higher in patients who underwent prostatectomy. The combined effect for the analysis was found to be: HR=0.97 (0.93, 1.01). The total effect was calculated as Z=1.33 (p-value= 0.18). The heterogeneity was found to be Tau2=0.00, Chi2=1.33, df=2, and I2=0%. However, overall mortality (OM) was shown to be independent of the treatment modality. RT is the preferred strategy for PCa treatment, as it balances efficacy and long-term outcomes. Clinical decision-making should consider individual patient characteristicsand future research should delve into specific subpopulations and long-term outcomes to further refine the treatment guidelines.

Increase of prostate-specific antigen doubling time predicts survival in metastatic castration-resistant prostate cancer patients undergoing radium therapy.

Radium-223 (Ra-223) is an important treatment modality for bone-dominant metastatic castration-resistant prostate cancer (mCRPC). However, there is currently a lack of effective markers to monitor treatment response during treatment. We aim to investigate the response in prostate-specific antigen doubling time (PSADT) as a potential marker for assessing Ra-223 treatment in mCRPC patients. We retrospectively collected data from mCRPC patients who underwent radium treatment at our institution between August 2020 and June 2023. Prostate-specific antigen (PSA) measurements prior to treatment and during treatment were collected. Baseline PSADT was calculated from PSA measurements prior to Ra-223 treatment; interim PSADT was calculated from PSA measurements before Ra-223 treatment and prior to the fourth course injection. Overall survival was calculated from the start of treatment to the date of death. Univariable and multivariable analysis using the Cox proportional hazards model were performed to examine the association of factors with overall survival. We included 35 patients from our institution, with a median overall survival of 13.3months. Eighteen (51.4%) completed all six courses of treatment. PSA dynamic response (interim PSADT > baseline PSADT or decreased PSA) was observed in 20 patients. Overall survival was associated with a PSA dynamic response (HR = 0.318, 95% CI 0.133-0.762, p = 0.010) when compared to patients without response. Dynamic changes in PSADT were associated with survival in mCRPC patients receiving radium therapy. Comparing interim and baseline PSADT could serve as a valuable marker for determining treatment benefits.

Clinical Management of Advanced Prostate Cancer: Where Does Radiopharmaceutical Therapy Fit in the Treatment Algorithm?

Most men with newly appreciated metastatic prostate cancer are optimally treated with a backbone consisting of androgen receptor-directed therapy with or without taxane chemotherapy. Despite improvements in disease outcomes, prostate cancer remains an extremely heterogeneous disease with variable mechanisms of therapeutic resistance. As a result, it remains a leading cause of cancer-related death in men. Radiopharmaceutical therapy has emerged as an alternative, non-androgen receptor-directed treatment modality for metastatic castration-resistant prostate cancer that impacts patient survival and represents a potentially more personalized approach. In this review, we aim to outline the current treatment landscape for metastatic prostate cancer with a focus on radiopharmaceutical therapy, specifically 177Lu-PSMA-617. In addition, we illustrate various clinical challenges with 177Lu-PSMA-617 treatment to date and explore investigative efforts to leverage radiopharmaceutical therapies as part of combination regimens or earlier in the treatment algorithm to further improve patient outcomes. Finally, we introduce ongoing studies of alternative radiopharmaceutical therapies in metastatic prostate cancer that may be incorporated into the treatment algorithm pending further study.

Comprehensive 3DCRT Hypofractionated Radiotherapy Schedule for Localized Prostate Adenocarcinoma in the Era of IMRT: Dosimetric and Endoscopic Analysis.

Background: Moderate hypofractionated radiotherapy (MHRT) has emerged as the preferred treatment modality for localized prostate cancer based on randomized controlled studies regarding efficacy and toxicity using contemporary radiotherapy techniques. In the setting of MHRT, available data on dosimetric parameters and late rectal toxicity are limited. Aim: To present the effects of MHRT on late rectal toxicity while conducting an extensive dosimetric analysis in conjunction with rectoscopy results. Methods: This is a prospective study including patients with intermediate-risk prostate adenocarcinoma. All patients were treated with MHRT 44 Gy in 16 fractions to the seminal vesicles and to the prostate, followed by a sequential boost to the prostate alone of 16.5 Gy in 6 fractions delivered with three-dimensional conformal radiation therapy (3DCRT). Acute and late toxicity were assessed. Endoscopy was performed at baseline, every 3 months post-therapy for the first year, and every 6 months for the year after. The Vienna Rectoscopy Score (VRS) was used to assess rectal mucosal injury related to radiotherapy. Dosimetric analysis for the rectum, rectal wall, and its subsegments (upper, mid, and low 1/3) was performed. Results: Between September 2015 and December 2019, 20 patients enrolled. Grade 1 late gastrointestinal toxicity occurred in 10% of the patients, whereas 5% had a grade ≥2. Twelve months post radiotherapy: 4 (20%) patients had VRS 1; 2 (10%) patients had VRS 2; 1(5%) patient had VRS 3. 24 months post radiotherapy, VRS 1 was observed in 4 patients (20%) and VRS 2 in 3 (15%) patients. The dosimetric analysis demonstrated noticeable variations between the rectum, rectal wall, and rectal wall subsegments. The dosimetric analysis of the rectum, rectal wall, and its mid and low segments with respect to rectoscopy findings showed that the higher dose endpoints V52.17Gy and V56.52Gy are associated with rectal mucosal injury. Conclusions: A thorough delineation of the rectal wall and its subsegments, together with the dosimetric analysis of these structures, may reduce late rectal toxicity. Dosimetric parameters such as V52.17Gy and V56.52Gy were identified to have a significant impact on rectal mucosal injury; additional dose endpoint validation and its relation to late GI toxicity is needed.

(107) Evaluating the Impact of Prior Prostate Cancer Hormonal Therapy on Satisfaction Rates in Post Implantation of Inflatable Penile Prosthesis

Abstract Introduction Androgen deprivation therapy (ADT), a vital treatment modality for prostate cancer, effectively reduces androgens (testosterone & dihydrotestosterone) through inhibiting its production or blocking its action, thereby impeding the growth and even causing shrinkage of prostate cancer cells. It has been utilized in the treatment of early-stage, recurrent, and metastatic cases of prostate cancer. Common side effects were hot flashes, fatigue, decreased bone density, mood changes, decrease libido and sexual dysfunction. Inflatable penile prosthesis (IPP) implantation has already emerged as a highly successful treatment option, garnering significant satisfaction rates among the general population with erectile dysfunction (ED) and specifically in prostate cancer patients who underwent radical prostatectomy (RP) or radiation therapy (XRT). Nevertheless, there remains a dearth of literature examining satisfaction rates specifically in patients with hormonal therapy history post-IPP implantation Objective Our study aims to comprehensively evaluate patient satisfaction rates post IPP implantation for ED, in relation to their ADT status for prostate cancer. Methods A retrospective chart review from our institutional database was conducted to identify 529 patients who underwent IPP at our institution by a single surgeon from 2017 to 2022. Eligible patients for inclusion included those with histological confirmation of prostate cancer treated by RP or XRT with or without hormonal therapy, followed by IPP implantation for ED, and had completed the 11-item Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) validated questionnaire with data available for review. All EDITS questionnaires were administered at least 6 months from operative date or later. Eligible patients were screened for placement into one of two groups depending on their ADT status. To prevent crossover confounding; patients with history of other types of hormonal therapy for non prostate cancer patients were excluded. Results A total of 96 patients were included and categorized into group 1 (ADT, n=30) and group 2 (No ADT, n=66). All patients' demographics were summarised in Table 1. The study revealed notable results regarding the impact of ADT on post IPP satisfaction rates which exhibited a significantly lower EDITS score compared to group 2 (P= 0.034) (Figure 1). Furthermore, group 1 showed no significant changes in post IPP satisfaction with relation to type of prostate cancer treatment offered. While group 2 demonstrated a significantly higher EDITS score post IPP in RP patients compared to XRT, which aligns with the reported literature. Conclusions Our initial findings suggest that despite IPP implantation for managing erectile dysfunction, which is expected to yield high satisfaction rates compared to other available treatment options, Yet the previous or ongoing history of androgen deprivation therapy continues to influence such patients' satisfaction. These observations provide valuable insights; however, further investigation on a larger scale is essential to validate these trends. Additionally, it is crucial to offer proper counseling to these patients regarding the expected outcomes to assist them in making informed decisions regarding the management of their ED. Lastly, the routine use of validated questionnaires has demonstrated significant value in quantifying device and sexual satisfaction following IPP implantation and should be considered as an integral evaluation tool Disclosure No.

(161) Is there a Difference in Inflatable Penile Prosthesis Mechanical Failure and Infections Rates in Relation to Prostate Cancer Treatment Modality (Radiation Therapy vs Radical Prostatectomy)

Abstract Introduction Inflatable Penile Prosthesis (IPP) implantation as a treatment for ED has high satisfaction rates in the general population; however, there is limited literature on quantification of complication rates as stratified by ED etiology. Objective Our aim was to compare mechanical failure and infection rates in patients undergoing IPP implantation for ED following Radical Prostatectomy (RP) versus radiation therapy (RT) for prostate cancer. Methods A retrospective chart review from our institutional database was conducted to identify 405 patients who underwent IPP placement at our institution from 2015–2019, then selecting for those whose etiology of ED was following RP or RT. To prevent crossover confounding; patients with history of pelvic radiation or salvage radiotherapy were excluded from the RP group and patients with history of RP were excluded from the RT group. Data was obtained from 75 patients who met criteria for inclusion: 44 patients in the RP group and 31 patients in the RT group. Mechanical failure, infection rates, mean EDITS scores and additional survey questions were compared between the radiation and RP groups. Results Patient demographic information and IPP complication and satisfaction rates are listed below in Table 1 and Figure 1. There was a statistically significant difference in number of patients experiencing IPP complications, 19.4% (n=6) of patients in the RT cohort and 4.5% (n=2) in the RP cohort, respectively. There was no statistically significant difference found in stratified complications- infection rates, device erosion rates, mechanical failure rates, or device removal and/or replacement rates between the two groups. The RP cohort had a significantly higher mean Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire score versus the RT cohort, 91.58 to 76.02, respectively. Conclusions These preliminary findings, while requiring large-scale follow up, suggest that there is a higher rate of IPP related complications in patients with device placement following RT for prostate cancer versus RP. Disclosure No.

Gold nanoshells for prostate cancer treatment: evidence for deposition in abdominal organs.

Gold-silica nanoshell therapy [AuroShells with subsequent focal laser therapy (AuroLase)] is an emerging targeted treatment modality for prostate cancer. We reviewed pre- and post-treatment unenhanced CT imaging to assess for retained gold-silica nanoshells in the abdomen and pelvis. This single-institution retrospective study identified patients in the AuroLase pilot who underwent pre- and post-treatment unenhanced abdominopelvic CT. The attenuation, before and after gold-silica nanoshell administration, of the liver, spleen, pancreas, kidneys, prostate, blood pool, paraspinal musculature, and abnormal lymph nodes were manually measured by two readers. After inter-reader agreement was calculated using intraclass correlation (ICC), a permutation test was used to assess pre- and post-therapy attenuation differences. Four patients met the inclusion criteria. Mean age was 72.3 ± 5.9years. Median time interval between pre-treatment CT and treatment, and between treatment and post-treatment CT, was 232days and 236.5days, respectively. The two readers' attenuation measurements had very high agreement (ICC = 0.99, p < 0.001). The highest differences in organ attenuation between pre- and post-therapy scans were seen in all four patients in the liver and spleen (liver increased by an average of 28.9 HU, p = 0.010; spleen increased by an average of 63.7 HU, p = 0.012). A single measured lymph node increased by an average of 58.9 HU. In the remainder of the measured sites, the change in attenuation from pre- to post-therapy scans ranged from -0.1 to 3.8 HU (p > 0.05). Increased attenuation of liver and spleen at CT can be an expected finding in patients who have received gold-silica nanoshell therapy.

(283) Evaluating The Impact of Prior Prostate Cancer Hormonal Therapy on Satisfaction Rates in Post Implantation of Inflatable Penile Prosthesis

Abstract Introduction Androgen deprivation therapy (ADT), a vital treatment modality for prostate cancer, effectively reduces androgens (testosterone &amp; dihydrotestosterone) through inhibiting its production or blocking its action, thereby impeding the growth and even causing shrinkage of prostate cancer cells. It has been utilized in the treatment of early-stage, recurrent, and metastatic cases of prostate cancer. Common side effects were hot flashes, fatigue, decreased bone density, mood changes, decrease libido and sexual dysfunction. Inflatable penile prosthesis (IPP) implantation has already emerged as a highly successful treatment option, garnering significant satisfaction rates among the general population with erectile dysfunction (ED) and specifically in prostate cancer patients who underwent radical prostatectomy (RP) or radiation therapy (XRT). Nevertheless, there remains a dearth of literature examining satisfaction rates specifically in patients with hormonal therapy history post-IPP implantation Objective Our study aims to comprehensively evaluate patient satisfaction rates post IPP implantation for ED, in relation to their ADT status for prostate cancer. Methods A retrospective chart review from our institutional database was conducted to identify 529 patients who underwent IPP at our institution by a single surgeon from 2017 to 2022. Eligible patients for inclusion included those with histological confirmation of prostate cancer treated by RP or XRT with or without hormonal therapy, followed by IPP implantation for ED, and had completed the 11-item Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) validated questionnaire with data available for review. All EDITS questionnaires were administered at least 6 months from operative date or later. Eligible patients were screened for placement into one of two groups depending on their ADT status. To prevent crossover confounding; patients with history of other types of hormonal therapy for non prostate cancer patients were excluded. Results A total of 96 patients were included and categorized into group 1 (ADT, n=30) and group 2 (No ADT, n=66). All patients' demographics were summarised in Table 1. The study revealed notable results regarding the impact of ADT on post IPP satisfaction rates which exhibited a significantly lower EDITS score compared to group 2 (P= 0.034) (Figure 1). Furthermore, group 1 showed no significant changes in post IPP satisfaction with relation to type of prostate cancer treatment offered. While group 2 demonstrated a significantly higher EDITS score post IPP in RP patients compared to XRT, which aligns with the reported literature. Conclusions Our initial findings suggest that despite IPP implantation for managing erectile dysfunction, which is expected to yield high satisfaction rates compared to other available treatment options, Yet the previous or ongoing history of androgen deprivation therapy continues to influence such patients' satisfaction. These observations provide valuable insights; however, further investigation on a larger scale is essential to validate these trends. Additionally, it is crucial to offer proper counseling to these patients regarding the expected outcomes to assist them in making informed decisions regarding the management of their ED. Lastly, the routine use of validated questionnaires has demonstrated significant value in quantifying device and sexual satisfaction following IPP implantation and should be considered as an integral evaluation tool. Disclosure No.

Treatment prediction with machine learning in prostate cancer patients

There are various treatment modalities for prostate cancer, which has a high incidence. In this study, it is aimed to make predictions with machine learning in order to determine the optimal treatment option for prostate cancer patients. The study included 88 male patients diagnosed with prostate cancer. Independent variables were determined as Gleason scores, biopsy, PSA, SUVmax, and age. Prostate cancer treatments, which are dependent variables, were determined as hormone therapy(n = 30), radiotherapy(n = 28) and radiotherapy + hormone therapy(n = 30). Machine learning was carried out in the Python with SVM, RF, DT, ETC and XGBoost. Metrics such as accuracy, ROC curve, and AUC were used to evaluate the performance of multi-class predictions. The model with the highest number of successful predictions was the XGBoost. False negative rates for hormone therapy, radiotherapy, and radiotherapy + hormone therapy treatments were, respectively, 12.5, 33.3, and 0%. The accuracy values were computed as 0.61, 0.83, 0.83, 0.72 and 0.89 for SVM, RF, DT, ETC and XGBoost, respectively. The three features that had the greatest influence on the treatment model prediction for prostate cancer with XGBoost were biopsy, Gleason score (3 + 3), and PSA level, respectively. According to the AUC, ROC and accuracy, it was determined that the XGBoost was the model that made the best estimation of prostate cancer treatment. Among the variables biopsy, Gleason score, and PSA level are identified as key variables in prediction of treatment.

Comparative effectiveness of new treatment modalities for localized prostate cancer through patient-reported outcome measures

PurposeThere is scarce comparative effectiveness research on the new treatment modalities for localized prostate cancer. We aim to compare through Patient-Reported Outcome Measures (PROMs) the impact of active surveillance, robot-assisted radical prostatectomy (RARP), intensity-modulated radiotherapy (IMRT), and real-time brachytherapy, considering side effects (incontinence, irritative/obstructive urinary symptoms, sexual dysfunction and bowel symptoms) and physical and mental health. Materials and MethodsProspective cohort of men diagnosed with clinically localized prostate cancer (age 50-75y, T1-T2, and low risk including Gleason 3 + 4 in T1c) from 18 Spanish hospitals, followed up to 24 months. Treatment decisions were jointly made by patients and physicians (n = 572). The Expanded Prostate cancer Index Composite (EPIC-26) and Short-Form 36 (SF-36v2) were administered through telephone interviews before and three, six, 12, and 24 months after treatment. To account for correlation among repeated measures, generalized estimating equation models were constructed. All analyses were performed with propensity score weights to solve treatment selection bias. ResultsThe PROMs completion rate at 24 months was 95.0 %. Active surveillance entails the fewest side effects, but with significant sexual (0.4 standard deviations [SD], p < 0.001) and physical health deterioration (0.5 SD, p < 0.001); and moderate mental health improvement (0.4 SD, p = 0.001) at 24 months. Compared with active surveillance, RARP presented greater urinary incontinence (p = 0.030), and IMRT and real-time brachytherapy worse bowel symptoms (p = 0.027 and p = 0.007) at 24 months. ConclusionsMost side effects of the new treatment modalities seem to be limited to short-term deteriorations, except for moderate-large urinary incontinence in patients who had undergone RARP and moderate bowel deterioration in patients treated with IMRT or with real-time brachytherapy. Furthermore, patients under active surveillance, IMRT, and real-time brachytherapy showed a moderate improvement in mental health.

Exploring the anticancer potential of sulfate-hydroxy-butanone derivatives: insights from experimental and quantum chemical investigations

Abstract Urinary incontinence and erectile dysfunction represent enduring adverse outcomes resulting from prostate cancer, a leading cause of global mortality. Given this critical context, there exists an imperative to explore efficacious therapeutic interventions. In this context, a comprehensive investigation of the potential roles of 4-(3ʹ-O-sulfate-4ʹ-hydroxyphenyl)-2-butanone (CDR1), 4-(3ʹ-O-sulfate-4ʹ-hydroxyphenyl)-2(R)-butanol (CDR2), and dihydrodehydrodiconiferyl alcohol 9-O-sulfate (CDR3) as agents for prostate cancer is of paramount importance. These compounds, extracted from the mangrove plant Acrostichum aureum, have been meticulously characterized through GC-MS, FT-IR, and NMR analyses. Detailed insights into the molecular structures, reactivity, bonding nature, and vibrational behaviors of these studied compounds were gleaned via rigorous examination at the DFT/B3LYP-GD3BJ/6-311+G (d,p) level of theory. Moreover, in-depth in-silico molecular docking investigations were conducted, delineating their potential as agents against castration-resistant prostate cancer. Electronic assessments underscored the reactivity of the studied compounds, while analysis of natural bond orbitals affirmed their stability, thus signifying their prospective utility as potent anticancer agents. The bioactivity and compatibility profiles of the investigated compounds in relation to cancer proteins were meticulously evaluated through molecular docking analyses, and the results were meticulously benchmarked against recommended drugs. Among the discernible outcomes, compound CDR3 emerged as a standout candidate, boasting binding affinities of −6.7, −8.6, and −6.4 kcal/mol, predicated on pivotal hydrogen bonding interactions, which inherently dictate the potency of a potential therapeutic agent. Importantly, CDR3 exhibits promising characteristics as an anticancer agent, surpassing its counterparts, and even the recommended drug dorlutamide, thus positioning it favorably for further consideration in prostate cancer treatment modalities.

IU1 and enzalutamide combination yields synergistic effects on castration-resistant prostate cancer.

Androgen deprivation therapy (ADT) is one of the main treatment modalities for prostate cancer (PCa); however, almost all patients treated with ADT eventually progress into castration-resistant PCa (CRPC). Although second-generation androgen receptor (AR) antagonists, such as enzalutamide, have been approved for CRPC treatment, AR signaling in CRPC cells is reactivated through multiple mechanisms, resulting in resistance to treatment and tumor progression with a very poor prognosis. The present study aimed to explore the anticancer effect of a treatment combining AR antagonist enzalutamide with AR degrader IU1 on PCa cells. The joint effects of enzalutamide and IU1 on PCa cell proliferation and apoptosis and associated cell signaling were evaluated in vitro. Mechanistically, the ubiquitination level and half-life of AR were examined under the combination treatment. The binding of IU1 and enzalutamide to AR was further verified using cellular thermal shift analysis and isothermal dose-response curve fingerprinting. The combination of IU1 and three AR antagonists showed synergistic effects in different prostate cell lines. IU1 and enzalutamide synergistically promoted the degradation of AR and AR-V7 proteins, as well as suppressed the expression levels of AR and AR-V7 downstream target genes at the transcriptional and protein levels. The combination also synergistically blocked the PCa cell cycle and promoted apoptosis in PCa cell lines. Mechanistically, the combination promoted increased levels of AR ubiquitination. In CRPC cell lines and in the presence of increased androgen concentrations, enzalutamide was still able to bind AR competitively with androgens, reducing the stability of AR and thus promoting the degradation effect of IU1 on AR, synergistically producing an inhibitory effect on PCa cells. Taken together, our findings suggest that the combination of AR degrader and enzalutamide potentially represents a new therapeutic strategy for CRPC.

Factors affecting the selection of eligible candidates for focal therapy for prostate cancer.

Focal therapy (FT) is a treatment modality for prostate cancer that aims to reduce side effects. However, it remains difficult to select eligible candidates. We herein examined eligibility factors for hemi-ablative FT for prostate cancer. We identified 412 patients who were diagnosed with unilateral prostate cancer by biopsy and had undergone radical prostatectomy between 2009 and 2018. Among these patients, 111 underwent MRI before biopsy, had 10-20 core biopsies performed, and did not receive other treatments before surgery. Fifty-seven patients with prostate-specific antigen ≥ 15ng/mL and biopsy Gleason score (GS) ≥ 4 + 3 were excluded. The remaining 54 patients were evaluated. Both lobes of the prostate were scored using Prostate Imaging Reporting and Data System version 2 on MRI. Ineligible patients for FT were defined as those with ≥ 0.5mL GS6 or GS ≥ 3 + 4 in the biopsy-negative lobe, ≥ pT3, or lymph node involvement. Selected predictors of eligibility for hemi-ablative FT were analyzed. Among our cohort of 54 patients, 29 (53.7%) were eligible for hemi-ablative FT. A multivariate analysis identified a PI-RADS score < 3 in the biopsy-negative lobe (p = 0.016) as an independent predictor of eligibility for FT. Thirteen out of 25 ineligible patients had GS ≥ 3 + 4 tumors in the biopsy-negative lobe, half of whom (6/13) also had a PI-RADS score < 3 in the biopsy-negative lobe. The PI-RADS score in the biopsy-negative lobe may be important in the selection of eligible candidates for FT. The findings of this study will help reduce missed significant prostate cancers and improve FT outcomes.

MFAST-SeqS based aneuploidy score in circulating cell-free DNA and role as early response marker in patients with metastatic prostate cancer treated with androgen receptor signaling inhibitor.

5058 Background: Several treatment modalities in metastatic castration resistant prostate cancer (mCRPC) are available to prolong progression-free and overall survival. With the arrival of additional treatment modalities, the need for accurate monitoring of treatment response is becoming more eminent and research for biomarkers pivotal. Cell-free circulating tumor DNA (ctDNA) has emerged as a promising prognostic and predictive biomarker. Several techniques have been employed for the detection and characterization of ctDNA within the total pool of cell-free DNA (cfDNA), one of which is the modified Fast Aneuploidy Screening Test-Sequencing System (mFAST-SeqS). This affordable and robust assay enables the quantitation of a sample’s ctDNA using a genome-wide aneuploidy score (GWA). Our aim was to investigate whether estimation of the GWA by mFAST-SeqS can be used to evaluate early response to treatment and predict response to treatment at baseline in patients with mCRPC. Methods: We prospectively enrolled mCRPC patients before start of treatment with androgen receptor signaling inhibitor (ARSI) abiraterone or enzalutamide. Blood samples were collected at baseline before start of treatment (BL, n= 134) and at an early treatment time point during treatment (ET, n= 20). We isolated cfDNA from plasma collected at both time points using the QiaSymphony or Maxwell system, and performed mFAST-SeqS on 1 ng cfDNA by amplifying and sequencing long interspaced nuclear elements (LINE-1) throughout the genome. The GWA-scores were calculated by taking the summed square of individual Z scores per chromosome arm relative to healthy controls. GWA-score was dichotomized in high (GWAhigh) and low (GWAlow), based on the previously described cut-off of 5. Clinical outcome, defined as treatment duration with ARSI, was compared for patients with a GWAhigh and GWAlow score at baseline and at an early time point. In addition, conversion of GWA score from baseline to early time point was explored. Results: Median age at start of treatment was 68.5 years (inter-quartile range (IQR): 63-73). Median time between start treatment and blood draw at BL and ET was 3 (IQR: 0-10 days before treatment) and 28 (IQR: 18-62 days during treatment) days, respectively. Median number of prior therapy lines was 1 (IQR: 0-10). Treatment duration was significantly shorter in the GWAhigh group versus the GWAlow group both at BL and at ET in patients treated with ARSI (BL: p&lt;0.001, log-rank test, median 221 and 82 days; ET: p&lt;0.01, log-rank test, median 123 and 42 days). Conclusions: The genome-wide aneuploidy score, based on mFAST-SeqS of cfDNA, is a useful tool to predict response to ARSI in patients with mCRPC. The current dataset will be extended to 199 samples at baseline and 78 samples at early time point, and also include mCRPC patients treated with taxanes. Clinical trial information: NCT01855477 , NTR732 .

Comparison of treatment costs for primary localized prostate cancer in Austria and Vienna: an economic analysis.

Prostate cancer is the most common cancer in men. Several efficient treatments are available for primary prostate cancer, but an economic comparison of these modalities has not been done in Austria. The current study provides an economic comparison of radiotherapy and surgery for prostate cancer in Vienna and Austria. We analyzed the catalog of medical services of the Austrian Federal Ministry of Social Affairs, Health, Care and Consumer Protection and present the treatment costs for the public health sector with an LKF-point value and monetary value in 2022. External beam radiotherapy, especially ultrahypofractionated, is the least costly treatment modality for low-risk prostate cancer, with costs of 2,492 € per treatment. For intermediate-risk prostate cancer, differences between moderate hypofractionation and brachytherapy are small, with costs of 4,638-5,140 €. In a high-risk setting, differences between radical prostatectomy and radiotherapy with androgen deprivation therapy are small (7,087 € vs. 7474.06 €). From a purely financial point of view, treatment of low- and intermediate-risk prostate cancer in Vienna and Austria should consist of radiotherapy as long as the current catalog of services is up to date. For high-risk prostate cancer, no major difference was found.

Impact of newly diagnosed prostate cancer at time of evaluation for renal transplantation.

Systematic screening for prostate cancer is widely recommended in candidates for renal transplant at the time of listing. There are concerns that overdiagnosis of low-risk prostate cancer may result in reducing access to transplant without demonstrated oncological benefits. The objective of the study was to assess the outcome of newly diagnosed prostate cancer in candidates for transplant at the time of listing, and its impact on transplant access and transplant outcomes according to treatment options. This retrospective study was conducted over 10 years in 12 French transplant centers. Patients included were candidates for renal transplant at the time of prostate cancer diagnosis. Demographical and clinical data regarding renal disease, prostate cancer, and transplant surgery were collected. The primary outcome of the study was the interval between prostate cancer diagnosis and active listing according to treatment options. Overall median time from prostate cancer diagnosis to active listing was 25.0 months [16.4-40.2], with statistically significant differences in median time between the radiotherapy and the active surveillance groups (p=.03). Prostate cancer treatment modalities had limited impact on access and outcome of renal transplantation. Active surveillance in low-risk patients does not seem to compromise access to renal transplantation, nor does it impact oncological outcomes.

Disparities in prostate cancer

Despite substantial advances in early detection/prevention and treatments, and improved outcomes in recent decades, prostate cancer continues to disproportionately affect Black men and is the secondleading cause of cancer death in this subgroup. Black men are substantially more likely to develop prostate cancer and are twice as likely to die from the disease compared with White men. In addition, Black men are younger at diagnosis and face a higher risk of aggressive disease relative to White men. Striking racial disparities endure along the continuum of prostate cancer care, including screening, genomic testing, diagnostic procedures, and treatment modalities. The underlying causes of these inequalities are complex and multifactorial and involve biological factors, structural determinants of equity (i.e., public policy, structural and systemic racism, economic policy), social determinants of health (including income, education, and insurance status, neighborhood/physical environment, community/social context, and geography), and health care factors. The objective of this article is to review the sources of racial disparities in prostate cancer and to propose actionable recommendations to help address these inequities and narrow the racial gap.

V10-10 NOVEL TECHNIQUE: PERIVESICAL FAT ROTATIONAL FLAP FOR RECTAL INTERPOSITION COVERAGE IN SALVAGE ROBOTIC RADICAL PROSTATECTOMY

You have accessJournal of UrologyCME1 Apr 2023V10-10 NOVEL TECHNIQUE: PERIVESICAL FAT ROTATIONAL FLAP FOR RECTAL INTERPOSITION COVERAGE IN SALVAGE ROBOTIC RADICAL PROSTATECTOMY Alexander Hwang, Matthew Watson, Michael Tonzi, and Amar Singh Alexander HwangAlexander Hwang More articles by this author , Matthew WatsonMatthew Watson More articles by this author , Michael TonziMichael Tonzi More articles by this author , and Amar SinghAmar Singh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003328.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The 21st-century urologic oncologist has a spectrum of treatment modalities for localized prostate cancer that can be tailored to patients. For patients with low-risk prostate adenocarcinoma, multiple non-prostatectomy treatment options include whole-gland radiotherapy, brachytherapy, proton therapy, cryotherapy, and high-intensity focused ultrasound (HIFU) therapy. Salvage therapies for recurrent localized prostate cancer include surgical (e.g. radical prostatectomy and cystoprostatectomy) and non-surgical (e.g. whole-gland brachytherapy, whole-gland cryotherapy, and whole-gland HIFU). Surgical salvage therapies are plagued with significant morbidity carrying the increased risk for urinary incontinence (>50% requiring use of pads) rectal injuries (3.3-50% requiring diversion in setting of radiation), and anastomotic stricture (17-32%) (1). METHODS: We describe a 67-year-old male who initially presented to our practice after undergoing whole-gland HIFU due to biopsy proven grade group 1 prostate cancer. Unfortunately, he developed biochemical recurrence with a PSA of 2.0 and biopsy discovered grade group 3 localized prostate cancer. After discussing the associated risks, the patient elected to undergo a salvage robotic radical prostatectomy (sRRP). We modified our sPPP approach by performing a posterior dissection to free the seminal vesicles prior to dropping the bladder which allowed us to mobilize our flap through the posterior defect and interpose the flap over the anterior rectal wall and tether it to periurethral tissue with absorbable suture. Please see accompanying video for procedural details. RESULTS: The patient had a negative cystogram and denied bowel or urinary symptoms. He presented to the emergency department 3 months post-operatively complaining of nonspecific abdominal pain and computed tomography demonstrated the perivesical flap appropriately interposed in its new heterotopic location. CONCLUSIONS: The perivesical tissue flap is an anatomically accessible and vascularized tissue that can be mobilized to interpose between a radiated, tenuous anterior rectal wall and vesicourethral anastomosis to reinforce perfusion and prevent fistulas. This technique allows expansion to the armamentarium of reconstructive urology. Source of Funding: No sources of funding to disclose. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e929 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alexander Hwang More articles by this author Matthew Watson More articles by this author Michael Tonzi More articles by this author Amar Singh More articles by this author Expand All Advertisement PDF downloadLoading ...