Treatment Of Localized Prostate Cancer Research Articles

Precision low-dose brachytherapy of prostate cancer under PSMA-receptor molecular visualization

Brachytherapy with implantation of micro sources based on isotope 125I is a preferred treatment for localized prostate cancer without signs of germination of the gland capsule and in the absence of signs of metastases (stage cT1-T23aN0M0). Structural imaging methods (ultrasound, computed tomography, and magnetic resonance imaging) do not have high specificity in the differential diagnosis of prostate cancer. Hybrid technologies of radiation imaging (single-photon emission computed tomography/computed tomography, positron emission tomography/computed tomography, and positron emission tomography/magnetic resonance imaging) combine the advantages of high sensitivity of cross-sectional structural imaging methods (computed tomography and magnetic resonance imaging) and high specificity of molecular imaging methods (single-photon emission computed tomography and positron emission tomography) with tumorotropic radiopharmaceuticals. In this original clinical study, based on seven observations of localized prostate cancer (Gleason 67), it was shown that the precision of low-dose brachytherapy using 125I micro sources of localized prostate carcinomas, along with targeted biopsy, can be increased using hybrid methods of PSMA-receptor molecular imaging (single-photon emission computed tomography/ computed tomography, positron emission tomography/ computed tomography). The single-photon emission computed tomography/ computed tomography method is more accessible than positron emission tomography/ computed tomography. Moreover, when coupled with cold kits (HYNIC-PSMA), it allows research within any radioisotope diagnostics laboratory equipped with single-photon emission computed tomography/ computed tomography. The innovative technology of PSMA-navigation biopsy and brachytherapy, under the control of hybrid molecular imaging, can be used in primary and recurrent cases of localized prostate cancer, increases the accuracy and reduces the traumatic nature of procedures, and increases the medical and economic efficiency of low-dose brachytherapy with 125I micro sources. Further research is needed to improve the technology and evaluate its long-term results.

ASO Author Reflections: High-Intensity Focused Ultrasound will Become the Routine Practice for Treatment of Localized Prostate Cancer.

PAST: Most prostate cancers are slow growing and are often diagnosed at an old age, which may result in treatment never being needed. However, definitive treatments such as radical prostatectomy and radiation therapy are often associated with many serious adverse effects, harming the physical and mental health of patients. PRESENT: In recent years, different types of minimally invasive therapy have been developed to achieve cancer control, continence, and even potency preservation, such as high-intensity focused ultrasound (HIFU). HIFU has been proposed for prostate cancer patients to provide an equivalent oncologic result to definitive treatment, with a reduced adverse effect profile, thus increasing the interest in HIFU for the treatment of localized prostate cancer. FUTURE: Sonablate® HIFU performed an outstanding cancer control in treating localized prostate cancer, with low biochemical recurrence and complication rates. As further long-term follow-up data mature, we anticipate the routine application of HIFU for localized prostate cancer within the next few years.

Высокомощностная брахитерапия в монорежиме у пациентов с локализованным раком предстательной железы.

Introduction. Prostate cancer is the second most common cancer among men. In Russia the number of patients with stage I-II prostate cancer increased from 47,7% in 2010 to 60,7% in 2021. One of the main methods of treatment of localized prostate cancer is high-dose-rate brachytherapy, which today provides high accuracy of prostate dose coverage and minimizes the impact on nearby risk organs. Within ever-increasing publications, high-dose-rate brachytherapy is considered as a method of safe and effective radical treatment of prostate cancer. Materials and methods. Relevant publications were searched for in the PubMed and е-Library databases with the use of the keywords «brachytherapy», «highdose-rate brachytherapy», «brachytherapy as monotherapy». As a result of the search, 52 sources were selected and included in the given literature review. Results and discussion. The first report on the use of brachytherapy as monotherapy appeared in 2000 where published the results of treatment and demonstrated the safety and effectiveness of the method. Despite the large number of studies conducted all over the world with various options of dose delivery per fraction, the optimal dose and fractionation mode for high-dose-rate brachytherapy as monotherapy have not been determined yet. Conclusions. Currently high-dose-rate brachytherapy of localized prostate cancer as monotherapy has become widespread. However, the available modern data on fractionation modes require further study and research.

Diagnostic capability of 18F-PSMA PET-MRI and pelvic MRI plus bone scan in treatment-naive prostate cancer: a single-center paired validating confirmatory study.

Radical prostatectomy with pelvic lymph node dissection for the treatment of high-risk localized prostate cancer (PCa) results in long-term benefits in selected patients. But insufficient sensitivity of conventional examinations which are pelvic MRI and bone scan, limits the diagnosis of bone and lymph node metastasis of PCa. This affects the surgical management strategy of a large number of patients. The purpose of this study was to investigate whether 18F-prostate-specific membrane antigen (PSMA) PET-MRI could improve the clinical detection of PCa metastases compared with the conventional pelvic MRI plus bone scan. From April 2020 to April 2023, we prospectively enroled 472 patients with histologically proven PCa in our centre, and 120 patients underwent 18F-PSMA PET-MRI, multiparametric MRI, and bone scan before laparoscopic radical prostatectomy plus lymph node dissection. The accuracy of imaging results in detecting lymph node and bone metastatic lesions was compared between PSMA PET-MRI and MRI plus bone scan. In diagnosing lymph node metastasis, PSMA PET-MRI had an area under the curve (AUC) of 0.844 (95% CI: 0.738-0.949, P < 0.001), sensitivity and specificity of 75% and 96%, which performed apparently better than MRI [AUC=0.615 (95% CI: 0.480-0.750, P =0.073)]. PSMA PET-MRI showed excellent expression in the diagnosis of bone metastases, with an AUC of 0.910 (95% CI: 0.840-0.981, P <0.001) compared to 0.700 (95% CI: 0.577-0.823, P =0.001) in bone scanning. PSMA PET-MRI also had higher sensitivity than bone scanning (90% vs. 43%), while lower specificity (92% vs. 97%). PSMA PET-MRI is superior to conventional imaging at diagnosing metastases in lymph nodes and bones in PCa and can provide a more accurate stagement.

Secondary Bladder Cancer After Prostate Cancer Treatment: An Age-matched Comparison Between Radiation and Surgery

BackgroundSecondary malignancy is a long-term risk of radiation. External beam radiation therapy (EBRT) for prostate cancer treatment has been associated with later development of bladder cancer and worse bladder cancer features. ObjectiveWe sought to provide an updated comparison of the long-term risk of bladder cancer after different localized prostate cancer treatments. Design, setting, and participantsUsing the Surveillance, Epidemiology, and End Results (SEER) cancer registry, we compared an age-matched subset of patients who underwent radical prostatectomy (RP) with those who underwent EBRT, brachytherapy (BT), EBRT + BT, and RP followed by EBRT (RPtoEBRT) between 2000 and 2018. Our final cohort included 261 609 patients with a median follow-up of 11.6 yr. Outcome measurements and statistical analysisOur primary outcomes were time to bladder cancer diagnosis, muscle-invasive bladder cancer diagnosis, and bladder cancer death. We used cause-specific hazard models considering death as a competing event. A similar analysis was performed on lung cancer, as a surrogate marker for smoking. We also compared proportions of variant histology, high-grade, and invasive disease among bladder cancers that occurred after radiation versus RP using chi-square testing. Results and limitationsAll radiation groups were associated with bladder cancer diagnosis; hazard ratios (HRs) were 1.72, 1.85, 1.80, and 1.53 for EBRT, BT, EBRT + BT, and RPtoEBRT, respectively, using RP as a referent (all p < 0.001). HRs for bladder cancer death were even higher: 2.39, 2.57, and 3.02 for EBRT, BT, and EBRT + BT, respectively (all p < 0.001), except for RPtoEBRT (HR 1.43, p = 0.28). Lung cancer diagnosis was also associated with radiation but at lower HRs—1.63, 1.32, 1.42, and 1.30 for EBRT, BT, EBRT + BT, and RPtoEBRT, respectively (all p < 0.001). There were a higher proportion of ≥T2, ≥T3, and sarcomatoid variant bladder cancers after radiation (all p < 0.01) ConclusionsThe risk of developing and dying from bladder cancer is increased in patients treated with radiation compared with those treated with RP. The risk was similar for BT and EBRT. Bladder cancers after radiation are more likely to be sarcomatoid variant and present as muscle invasive. Patient summaryWe observed the rates of bladder cancer after patients had undergone surgery or radiation for prostate cancer, and found higher rates of bladder cancer after radiation. We also observed that bladder cancers that occur after radiation tend to be more aggressive.

First experiences using transurethral ultrasound ablation (TULSA) as a promising focal approach to treat localized prostate cancer: a monocentric study

PurposeTo share our experience using transurethral ultrasound ablation (TULSA) treatment for focal therapy of localized prostate cancer (PCa).Materials and methodsBetween 10/2019 and 06/2021 TULSA treatment for localized PCa was performed in 22 men (mean age: 67 ± 7 years, mean initial PSA: 6.8 ± 2.1 ng/ml, ISUP 1 in n = 6, ISUP 2 in n = 14 and 2 patients with recurrence after previous radiotherapy). Patients were selected by an interdisciplinary team, taking clinical parameters, histopathology from targeted or systematic biopsies, mpMRI and patients preferences into consideration. Patients were thoroughly informed about alternative treatment options and that TULSA is an individual treatment approach. High-intensity ultrasound was applied using an ablation device placed in the prostatic urethra. Heat-development within the prostatic tissue was monitored using MR-thermometry. Challenges during the ablation procedure and follow-up of oncologic and functional outcome of at least 12 months after TULSA treatment were documented.ResultsNo major adverse events were documented. In the 12 month follow-up period, no significant changes of urinary continence, irritative/obstructive voiding symptoms, bowel irritation or hormonal symptoms were reported according to the Expanded Prostate Cancer Index Composite (EPIC) score. Erectile function was significantly impaired 3–6 months (p < 0.01) and 9–12 months (p < 0.05) after TULSA. PSA values significantly decreased after therapy (2.1 ± 1.8 vs. 6.8 ± 2.1 ng/ml, p < 0.001). PCa recurrence rate was 23% (5/22 patients).ConclusionEstablishment of TULSA in clinical routine was unproblematic, short-term outcome seems to be encouraging. The risk of erectile function impairment requires elaborate information of the patient.

Randomized phase II trial of MRI-guided salvage radiotherapy for prostate cancer in 4 weeks versus 2 weeks (SHORTER)

BackgroundUltra-hypofractionated image-guided stereotactic body radiotherapy (SBRT) is increasingly used for definitive treatment of localized prostate cancer. Magnetic resonance imaging-guided radiotherapy (MRgRT) facilitates improved visualization, real-time tracking of targets and/or organs-at-risk (OAR), and capacity for adaptive planning which may translate to improved targeting and reduced toxicity to surrounding tissues. Given promising results from NRG-GU003 comparing conventional and moderate hypofractionation in the post-operative setting, there is growing interest in exploring ultra-hypofractionated post-operative regimens. It remains unclear whether this can be done safely and whether MRgRT may help mitigate potential toxicity. SHORTER (NCT04422132) is a phase II randomized trial prospectively evaluating whether salvage MRgRT delivered in 5 fractions versus 20 fractions is non-inferior with respect to gastrointestinal (GI) and genitourinary (GU) toxicities at 2-years post-treatment.MethodsA total of 136 patients will be randomized in a 1:1 ratio to salvage MRgRT in 5 fractions or 20 fractions using permuted block randomization. Patients will be stratified according to baseline Expanded Prostate Cancer Index Composite (EPIC) bowel and urinary domain scores as well as nodal treatment and androgen deprivation therapy (ADT). Patients undergoing 5 fractions will receive a total of 32.5 Gy over 2 weeks and patients undergoing 20 fractions will receive a total of 55 Gy over 4 weeks, with or without nodal coverage (25.5 Gy over 2 weeks and 42 Gy over 4 weeks) and ADT as per the investigator’s discretion. The co-primary endpoints are change scores in the bowel and the urinary domains of the EPIC. The change scores will reflect the 2-year score minus the pre-treatment (baseline) score. The secondary endpoints include safety endpoints, including change in GI and GU symptoms at 3, 6, 12 and 60 months from completion of treatment, and efficacy endpoints, including time to progression, prostate cancer specific survival and overall survival.DiscussionThe SHORTER trial is the first randomized phase II trial comparing toxicity of ultra-hypofractionated and hypofractionated MRgRT in the salvage setting. The primary hypothesis is that salvage MRgRT delivered in 5 fractions will not significantly increase GI and GU toxicities when compared to salvage MRgRT delivered in 20 fractions.Trial registrationClinicalTrials.gov Identifier: NCT04422132. Date of registration: June 9, 2020.

Tissue expression of LC3B autophagy marker as a potential biomarker of prostate cancer recurrence after treatment with high-intensity focused ultrasound (pilot study)

Background. The role of autophagy markers in prostate tumor recurrence has not been sufficiently investigated. We hypothesized that autophagy activation may be one mechanism by which prostate cancer cells survive exposure to high-intensity focused ultrasound (HIFU).Aim. To compare tissue expression of autophagic LC3B marker in prostate biopsies before and after treatment of localized prostate cancer by HIFU ablation.Materials and methods. 45 patients with localized morphologically confirmed prostate cancer were examined: group 1 – 25 patients of 65.6 ± 8.4 years without signs of recurrence or progression of the disease; group 2 – 20 patients of 67.5 ± 7.9 years with tumor recurrence proven during morphological examination. Immunohistochemical examination was performed by streptavidin-biotin method. In all cases, Anti-LC3B antibody ab48394 was used. The reaction results were quantified using the Histochemical score (Hs) system.Results. Prior to treatment, all patients of group 1 showed moderate cytoplasmic expression (Hs = 111 [111; 115]) of antibodies against LC3B in prostate adenocarcinoma cells, 5 % of patients – weak cytoplasmic expression in muscle connective stromal cells (Hs = 47 [43; 50]), 10 % of patients – weak positive LC3B reaction in the vessel wall (Hs = 28 [20; 35]). After treatment, the expression of LC3B in adenocarcinoma cells became negative, in the cytoplasm of muscle connective stromal cells weak (Hs = 75 [67.5; 80.0]), in the endothelium of the vascular wall even weaker (Hs = 55 [45.5; 60.0]) (p &lt;0.001). Prior to treatment in group 2, LC3B expression in tumor tissue was moderate in 89 % of patients (Hs = 151.5 [137.5; 160.0]), weak in muscle connective stromal cells in 12 % of patients (Hs = 44 [35; 51.5]), and weak in the vascular wall in 5 % of patients (Hs = 30 [25; 35]). After treatment, LC3B expression in adenocarcinoma cells became pronounced (Hs = 260 [250; 285]), in muscle connective stromal cells – moderate (Hs = 118 [100; 130]), in the vascular wall – weak (Hs = 45 [30; 55]) (p &lt;0.001). There was a significant correlation between tumor recurrence and LC3B overexpression (r = 0.51; p &lt;0.001).Conclusion. The development of prostate cancer recurrence is associated with increased expression of autophagic LC3B protein. Increased LC3B expression, which is interpreted as evidence of autophagy activation and correlates with the risk of disease progression, is used by the tumor as an oncogenic advantage.

Comparative analysis of 10-year functional outcomes of robot-assisted radical prostatectomy and radical retropubic prostatectomy. Experience of the Urology Clinic of the A.I. Evdokimov Moscow State University of Medicine and Dentistry

Background. Prostate cancer is the 3rd most common diagnosis among malignant tumors. The first robot-assisted radical prostatectomy (RARP) was performed in 2001. Studies comparing RARP and radical retropubic prostatectomy (RRP) are limited. In Russia, the Da Vinci robot was first installed in 2007. At the Urology Clinic of the A.I. Evdokimov Moscow State University of Medicine and Dentistry the program of robot-assisted surgery started in November of 2008.Aim. To perform first in Russia evaluation of 10-year functional treatment outcomes for patients with localized prostate cancer after RARP. To perform comparative analysis with RRP outcomes.Materials and methods. Medical histories of 211 patients from the Urology Clinic of the A.I. Evdokimov Moscow State University of Medicine and Dentistry were analyzed. Among them, 62 patients did not satisfy the inclusion criteria. Therefore, the study included 149 patients who underwent surgical treatment for localized prostate cancer between January of 2009 and December of 2011. Depending on the technique of surgical intervention, patients were divided into 2 groups: 1st – RARP (n = 82), 2nd – RRP (n = 67). All RARP were performed by a single surgeon, RRP by 2 experienced surgeons (experience &gt;1000 RRP).Results. Median follow-up was 120 months in both groups. Overall survival in the 1st and 2nd groups was 85.4 and 86.6 %, respectively (p &gt;0.05). For accuracy of functional outcomes analysis, patients who died during follow-up were excluded from the study. Frequency of neurovascular bundle preservation in the 1st and 2nd groups was 60.9 % (50/82) and 40.2 % (27/67), respectively (p = 0.01). Erectile function was preserved in 60.0 and 44.4 % males of the 1st and 2nd groups, respectively (p = 0.01). Age below 60 years (р = 0.009) and disease stage рТ2 (p = 0.026) were predictors of erectile function preservation after RARP. Continence frequency was 92.7 and 82.1 % in the 1st and 2nd groups, respectively (p = 0.048).Conclusion. Ten-year comparative analysis shows that RARP allows to achieve significantly better parameters of urinary continence and erectile function preservation in men with localized prostate cancer than RRP.

The role of localised prostate cancer treatment in renal transplant patients: A systematic review.

To systematically review and critically appraise all treatment options for localised prostate cancer in renal transplant candidates and recipients. A systematic review was conducted adhering to PRISMA guidelines. Searches were performed in the Cochrane Library, Embase, Medline, the Transplant Library and Trip database for studies published up to September 2022. Risk of bias was assessed with the Cochrane Risk of Bias in Non-Randomised Studies of Interventions for non-randomised studies tool. A total of 60 studies were identified describing 525 patients. The majority of studies were either retrospective non-randomised comparative or case series/reports of poor quality. The vast majority of studies were focussed on prostate cancer after renal transplantation. Overall, 410 (78%) patients underwent surgery, 93 (18%) patients underwent radiation therapy or brachytherapy, one patient underwent focal therapy (high-intensity frequency ultrasound) and 21 patients were placed on active surveillance. The mean age was 61 years old, the mean PSA level at diagnosis was 9.6ng/mL and the mean follow-up time was 31 months. The majority of patients had low-risk disease with 261 patients having Gleason 6 prostate cancer (50%), followed by 220 Gleason 7 patients (42%). All prostate cancer mortality cases were in high-risk prostate cancer (≥Gleason 8). The cancer-specific survival results were similar between surgery and radiotherapy at 1 and 3years. Localised prostate cancer treatment in renal transplant patients should be risk stratified. Surgery and radiation treatment for localised prostate cancer in renal transplant patients appear equally efficacious. Given the limitations of this study, future research should concentrate on developing a multicentre RCT with long-term registry follow-up.

Evaluation of sexual function after robot-assisted radical prostatectomy: A farewell to IIEF questionnaire.

Longevity with localized prostate cancer (PCa) has been achieved, and the contribution of robot-assisted radical prostatectomy (RARP) to cancer control is evident. The next step to investigate in the treatment of localized PCa is improvement of the quality of life (QOL) after RARP. Erectile dysfunction has been considered a major surgical complication, and patient satisfaction after RARP has not improved despite the development of nerve preservation and penile rehabilitation. To comprehensively understand sexual dysfunction after RARP, we must investigate other complications with regard to sexual health, including low sexual desire, disturbed orgasmic function (i.e., anejaculation, orgasm intensity, painful orgasm, and climacturia), shortening of penile length, penile curvature (Peyronie's disease) and unique psychological alterations after the diagnosis of PCa, which are neglected side effects after prostatectomy. In this context, routine evaluation of erectile function by the International Index of Erectile Function only is not sufficient to understand patients' difficulties. A questionnaire is just one way of enabling patients to evaluate their pre- and postoperative concerns; listening to patients face-to-face is warranted to detect symptoms. Understanding the relationship between symptoms and preserved nerve localization can ultimately provide an individualized nerve-sparing procedure and improve patient satisfaction after RARP. In combination with psychological counseling, including the partner and medical treatment, such as testosterone replacement, it is time to reconsider ways to improve sexual dysfunction after RARP.

Transperineal laser ablation (TPLA) with ultrasound/MRI fusion guidance in the treatment of localized radiotherapy-resistant prostate cancer

Objective The objective of this study was to assess the technical feasibility, safety, and efficacy of transperineal laser ablation (TPLA) guided by ultrasound/magnetic resonance (MR) fusion as a salvage treatment for refractory focal prostate cancer. Methods A total of five patients who had undergone radiation therapy (RT) for prostate carcinoma and biochemical recurrence, confirmed by both prostate-specific antigen (PSA) levels and MRI (3T mpMRI), were enrolled in this study. Focal ablation was performed using a 1064 nm diode laser. Post-ablation follow-up was conducted for a duration of 18 months, which included regular PSA sampling, 3T mpMRI, and ultrasound/MR fusion-guided biopsies systematic and targeted at the site of the focal treatment. Results The focal ablation procedure was carried out in an outpatient setting regimen with optimal clinical and biochemical outcomes. No recurrence was detected throughout the follow-up period. Conclusion TPLA focal treatment effectively manages local recurrences of RT refractory prostate cancer without side-effects or complications. Preservation of quality of life and functional outcomes, along with a &gt;70% reduction in PSA, were achieved. Advances in knowledge Our study investigated TPLA as a salvage treatment for low-risk recurrent prostate cancer after RT, demonstrating its tolerability, feasibility, and effectiveness.

Functional outcomes and safety of focal therapy for prostate cancer: a systematic review on results and patient-reported outcome measures (PROMs).

Focal therapy (FT) is a promising alternative with curative intent for Low- to Intermediate-risk localized Prostate Cancer (PCa), claiming better functional outcomes and safety profile than standard whole-gland treatments. Ten different FT modalities have been described in the literature. The objective of our narrative review is to evaluate the safety profile and functional outcomes of these different modalities and the currentmost used tools of assessment for those outcomes. Literature search was performed on 21stFebruary 2023 using PubMed, EMBASE, and Scopus, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA). Articles reporting whole-gland treatments were excluded. All articles reporting functional outcomes were included. One-hundred-seven studies, reporting data on 6933 patients, were included (26 on High Intensity Focal Ultrasound, 22 on Focal Cryotherapy, 14 on Irreversible Electroporation, 11 on Focal brachytherapy, 10 on Focal Laser Ablation, 8 on Photodynamic Therapy, 3 on Microwave ablation, 3 on Robotic Partial Prostatectomy, 2 on bipolar Radio Frequency Ablation, 1 on Prostatic Artery Embolization, and 7 studies comparing different FTs). Post-operative pad-free rate ranged between 92.3-100%. Greater heterogeneity exists considering the Change in Erectile Function, with Changing in Erectile function- rates ranging between 0-94.4% (Cryotherapy). The most used Patient-Reported Outcome Measures (PROMs) were the International Prostate Symptom Score and the International Index of Erectile Function for incontinence/urinary function and potency, respectively. The most common reportedcomplications were hematuria, infections, and urethral strictures, with rates widely ranging among different treatments. The Clavien-Dindo Classification was the most used (40/88 papers) to describe adverse events. FT is a promising treatment for localized PCa, achieving excellent results in terms of safety and functional outcomes. There is a wide heterogeneity in the definition of PROMS and time of collection between studies. High quality comparative studies with standard treatments are needed to reinforce these findings.

Explainable ML models for a deeper insight on treatment decision for localized prostate cancer

Although there are several decision aids for the treatment of localized prostate cancer (PCa), there are limitations in the consistency and certainty of the information provided. We aimed to better understand the treatment decision process and develop a decision-predicting model considering oncologic, demographic, socioeconomic, and geographic factors. Men newly diagnosed with localized PCa between 2010 and 2015 from the Surveillance, Epidemiology, and End Results Prostate with Watchful Waiting database were included (n = 255,837). We designed two prediction models: (1) Active surveillance/watchful waiting (AS/WW), radical prostatectomy (RP), and radiation therapy (RT) decision prediction in the entire cohort. (2) Prediction of AS/WW decisions in the low-risk cohort. The discrimination of the model was evaluated using the multiclass area under the curve (AUC). A plausible Shapley additive explanations value was used to explain the model’s prediction results. Oncological variables affected the RP decisions most, whereas RT was highly affected by geographic factors. The dependence plot depicted the feature interactions in reaching a treatment decision. The decision predicting model achieved an overall multiclass AUC of 0.77, whereas 0.74 was confirmed for the low-risk model. Using a large population-based real-world database, we unraveled the complex decision-making process and visualized nonlinear feature interactions in localized PCa.

Radiation Safety Considerations of Household Waste Disposal After Release of Patients Who Have Received [177Lu]Lu-PSMA-617.

Patients with metastatic prostate cancer are more likely than other groups to present for radiopharmaceutical therapy with urinary incontinence due to complications from prior local prostate cancer treatment. A consequence of urinary incontinence in patients receiving radiopharmaceutical therapy is the potential production of contaminated solid waste, which must be managed by the licensee and, at home, managed by and disposed of by the patient. Prolonging the patient stay in the treating facility after radiopharmaceutical therapy administration, until the first urinary void or potentially overnight, may moderately reduce the quantity of contaminated waste being managed by the patient at home. However, this approach does not fully mitigate the need for a patient waste-management strategy. In this brief communication, the relative radiation safety merits of contaminated waste disposal in the normal household waste stream in comparison to other waste management strategies are evaluated.

Transperineal laser ablation of the prostate as a treatment for benign prostatic hyperplasia and prostate cancer: The results of a Delphi consensus project

ObjectiveTo evaluate transperineal laser ablation (TPLA) with Echolaser® (Echolaser® TPLA, Elesta S. p.a, Calenzano, Italy) as a treatment for benign prostatic hyperplasia (BPH) and prostate cancer (PCa) using the Delphi consensus method. MethodsItalian and international experts on BPH and PCa participated in a collaborative consensus project. During two rounds, they expressed their opinions on Echolaser® TPLA for the treatment of BPH and PCa answering online questionnaires on indications, methodology, and potential complications of this technology. Level of agreement or disagreement to reach consensus was set at 75%. If the consensus was not achieved, questions were modified after each round. A final round was performed during an online meeting, in which results were discussed and finalized. ResultsThirty-two out of forty invited experts participated and consensus was reached on all topics. Agreement was achieved on recommending Echolaser® TPLA as a treatment of BPH in patients with ample range of prostate volume, from <40 mL (80%) to >80 mL (80%), comorbidities (100%), antiplatelet or anticoagulant treatment (96%), indwelling catheter (77%), and strong will of preserving ejaculatory function (100%). Majority of respondents agreed that Echolaser® TPLA is a potential option for the treatment of localized PCa (78%) and recommended it for low-risk PCa (90%). During the final round, experts concluded that it can be used for intermediate-risk PCa and it should be proposed as an effective alternative to radical prostatectomy for patients with strong will of avoiding urinary incontinence and sexual dysfunction. Almost all participants agreed that the transperineal approach of this organ-sparing technique is safer than transrectal and transurethral approaches typical of other techniques (97% of agreement among experts). Pre-procedural assessment, technical aspects, post-procedural catheterization, pharmacological therapy, and expected outcomes were discussed, leading to statements and recommendations. ConclusionEcholaser® TPLA is a safe and effective procedure that treats BPH and localized PCa with satisfactory functional and sexual outcomes.

Financial burden of men with localized prostate cancer: a process paper.

Many individuals undergoing cancer treatment experience substantial financial hardship, often referred to as financial toxicity (FT). Those undergoing prostate cancer treatment may experience FT and its impact can exacerbate disparate health outcomes. Localized prostate cancer treatment options include: radiation, surgery, and/or active surveillance. Quality of life tradeoffs and costs differ between treatment options. In this project, our aim was to quantify direct healthcare costs to support patients and clinicians as they discuss prostate cancer treatment options. We provide the transparent steps to estimate healthcare costs associated with treatment for localized prostate cancer among the privately insured population using a large claims dataset. To quantify the costs associated with their prostate cancer treatment, we used data from the Truven Health Analytics MarketScan Commercial Claims and Encounters, including MarketScan Medicaid, and peer reviewed literature. Strategies to estimate costs included: (1) identifying the problem, (2) engaging a multidisciplinary team, (3) reviewing the literature and identifying the database, (4) identifying outcomes, (5) defining the cohort, and (6) designing the analytic plan. The costs consist of patient, clinician, and system/facility costs, at 1-year, 3-years, and 5-years following diagnosis. We outline our specific strategies to estimate costs, including: defining complex research questions, defining the study population, defining initial prostate cancer treatment, linking facility and provider level related costs, and developing a shared understanding of definitions on our research team. Analyses are underway. We plan to include these costs in a prostate cancer patient decision aid alongside other clinical tradeoffs.

Low-dose-rate brachytherapy in low-risk prostate cancer- treatment results, radiation toxicity and quality of life-dissertation project with literature review

Low-dose-rate brachytherapy (LDR-BT) is a an internal radiation therapy method for the treatment of localized prostate cancer The treatment modality has been known for several decades. The choice of the treatment modality for prostate cancer patients depends mainly on the stage of the disease and the prognostic factors. Brachytherapy monotherapy is a well-tolerated procedure compared to alternative treatments. Based on a literature review, we have considered a prospective study on the treatment efficiency after LDR-BT with a permanent iodine-125 (I-125) implant, compared to that of hypo-fractionated external beam radiotherapy (EBRT) alone. The working thesis is to present the advantages and disadvantages of LDR-BT for low-risk prostate carcinoma, compared to a similar group of patients treated with definitive intensity-modulated hypo-fractionated radiotherapy (IMHRT)

A Qualitative Study of Men's Experiences Using Navigate: A Localized Prostate Cancer Treatment Decision Aid.

The Navigate decision aid Web site was created to help Australian men diagnosed with localized prostate cancer (LPC) make an informed decision about their treatment.Navigate was helpful in supporting men's ongoing treatment decision making for LPC.Men's treatment decision making for LPC was greatly influenced by perceived authority and trust in their clinician.Trustworthiness, timing of access, and the clinician's role in empowering men to use available decision aids are crucial.

Saracatinib synergizes with enzalutamide to downregulate AR activity in CRPC.

Prostate cancer (PCa) remains the most diagnosed non-skin cancer amongst the American male population. Treatment for localized prostate cancer consists of androgen deprivation therapies (ADTs), which typically inhibit androgen production and the androgen receptor (AR). Though initially effective, a subset of patients will develop resistance to ADTs and the tumors will transition to castration-resistant prostate cancer (CRPC). Second generation hormonal therapies such as abiraterone acetate and enzalutamide are typically given to men with CRPC. However, these treatments are not curative and typically prolong survival only by a few months. Several resistance mechanisms contribute to this lack of efficacy such as the emergence of AR mutations, AR amplification, lineage plasticity, AR splice variants (AR-Vs) and increased kinase signaling. Having identified SRC kinase as a key tyrosine kinase enriched in CRPC patient tumors from our previous work, we evaluated whether inhibition of SRC kinase synergizes with enzalutamide or chemotherapy in several prostate cancer cell lines expressing variable AR isoforms. We observed robust synergy between the SRC kinase inhibitor, saracatinib, and enzalutamide, in the AR-FL+/AR-V+ CRPC cell lines, LNCaP95 and 22Rv1. We also observed that saracatinib significantly decreases AR Y534 phosphorylation, a key SRC kinase substrate residue, on AR-FL and AR-Vs, along with the AR regulome, supporting key mechanisms of synergy with enzalutamide. Lastly, we also found that the saracatinib-enzalutamide combination reduced DNA replication compared to the saracatinib-docetaxel combination, resulting in marked increased apoptosis. By elucidating this combination strategy, we provide pre-clinical data that suggests combining SRC kinase inhibitors with enzalutamide in select patients that express both AR-FL and AR-Vs.