Intermediate Risk Localized Prostate Cancer Research Articles

A Japanese multi-institutional phase II study of moderate hypofractionated intensity-modulated radiotherapy with image-guided technique for prostate cancer.

The aim of this multi-institutional phase II study was to confirm the safety and the potential efficacy of moderately hypofractionated intensity-modulated radiotherapy (IMRT) with prostate-based image-guidance for Japanese patients. Patients with low- or intermediate-risk localized prostate cancer were eligible. Patients with a part of high risk (having only one of the following factors, cT3a, 20 < PSA ≤ 30, or GS = 8 or 9) were also included. Hypofractionated IMRT using daily image-guided technique with prostate matching was performed with a total dose of 70Gy in 28 fractions. Neoadjuvant hormonal therapy for 4-8months was mandatory for patients with intermediate or high-risk prostate cancer. From 20 institutions, 134 patients enrolled. The median follow-up was 5.16years (range, 1.43-6.47years). The number of patients with low, intermediate, and high-risk prostate cancer was 20, 80, and 34, respectively. The 5-year overall, biochemical failure-free, and clinical failure-free survival was 94.5%, 96.0%, and 99.2%, respectively. The 5-year biochemical failure-free survival for patients with low-, intermediate-, and high-risk disease was 94.1%, 97.4%, and 93.9%, respectively. The incidences of grade 2 gastrointestinal (GI) and genitourinary (GU) late toxicities at 5years were 5.3% and 5.3%, respectively. There are no acute or late toxicities ≥ grade 3. Of 124 patients who were followed for up to 5years, the grade 2 late GU or GI toxicities were 10.5% (90% confidence intervals, 6.3-16.2%, p = 0.0958). The safety and efficacy of moderately hypofractionated IMRT with prostate-based image-guidance was confirmed among Japanese patients with prostate cancer.

Prostate specific membrane antigen positron emission tomography (PSMA PET) avidity in a granular cell tumour of the left supraspinatus muscle: a case report

Abstract Granular cell tumour is a rare, mostly benign, soft tissue, neuroectodermal tumour, most commonly seen in the skin and peripheral soft tissue. There are no publications to date of PSMA-PET avidity in a granular cell tumour. In this 60 year old male, staging PSMA-PET for a localized intermediate risk prostate cancer incidentally identified a PSMA-avid left supraspinatus lesion, which was subsequently biopsy-proven as a granular cell tumour. We present the first case of PSMA-avid granular cell tumour and add to the growing literature documenting PSMA-PET avidity in benign and malignant lesions apart from prostate cancer.

ONE SHOT - single shot radiotherapy for localized prostate cancer: 18-month results of a single arm, multicenter phase I/II trial

PurposeTo assess in a prospective, multicenter, single-arm phase I/II study the early safety and efficacy profile of single fraction urethra-sparing stereotactic body radiotherapy (SBRT) for men with localized prostate cancer. Material and methodsPatients with low- and intermediate-risk localized prostate cancer without significant tumor in the transitional zone were recruited. A single-fraction of 19 Gy was delivered to the prostate, with 17 Gy dose-reduction to the urethra. Intrafraction motion was monitored using intraprostatic electromagnetic transponders with intra-fraction correction of displacements exceeding 3 mm. Genitourinary (GU), gastrointestinal (GI), and sexual toxicity during the first 18 months were evaluated using the CTCAE v4.0 grading scale. Quality of life was assessed using the International Prostate Symptom Score, the Expanded Prostate Cancer Index composite 26 score, and the International Index of Erectile Function score. ResultsAmong the 45 patients recruited in 5 centers between 2017 and 2022, 43 received the single fraction without protocol deviations, and 34 had a minimal follow-up of 18 months. The worst GU toxicity was observed at day-5 after SBRT (42.5 % and 20 % with grade 1 and 2, respectively), returning to baseline at week-12 and month-6 (<3% with grade 2), with a 12 % grade 2 flare at month 18. Gl toxicity was mild in the acute phase, with no grade ≥ 2 events (12 % grade 1 at month 6). Grade-3 proctitis was observed in one patient at month 12, with < 3 % grade 2 toxicity at month 18. Mean GU and GI bother scores showed a decline at day 5, a complete recovery at month 6, and a flare between month 12 and 18. Mean PSA dropped from 6.2 ng/ml to 1.2 ng/ml at month 18 and 0.7 ng/ml at month 24. After a median follow-up time of 26 months, 3 biochemical failures (7 %) were observed at month 17, 21 and 30. ConclusionsIn this multicenter phase I/II trial, we demonstrated that a 19 Gy single-fraction urethra-sparing SBRT is feasible and associated with an acceptable toxicity rate, mostly returning to the baseline at week-12 and with a symptoms flare between months 12 and 18. Longer follow-up is needed to assess the potential long-term adverse effects and the disease control efficacy.

Hypofractionated versus conventional fractionation external beam radiotherapy in intermediate and high risk localized prostate cancer

BackgroundProstate cancer is the second most common malignancy in men, and its incidence is increasing which is attributed to increased screening programs. The treatment options of intermediate and high risk prostate cancer include radical prostatectomy, radiotherapy and androgen deprivation therapy. Hypofractionated radiotherapy is becoming more popular lately due to better understanding of the radiobiology of prostate cancer and favorable logistics.ObjectiveTo compare the toxicity and efficacy of hypofractionated versus conventional fractionation external beam radiotherapy in patients with intermediate and high risk localized prostate cancer treated in Shaukat Khanum Memorial Hospital and Research Center, Lahore (SKMCH & RC).MethodologyWe retrospectively conducted this study on histopathologically confirmed 114 patients with prostate adenocarcinoma who underwent treatment from January 2013 till December 2018. These patients were treated with radical radiotherapy along with hormonal therapy as per indication. Data was collected from electronic hospital system and analyzed by SPSS version 23.Results114 patients were selected according to the inclusion criteria. Mean age was 68 years (61–75). 88% of patients had stage III-IVA disease at the time of diagnosis. Mean PSA and GS was 33 ± 39 SD and 7 ± 0.9 SD respectively. 89% (n = 102) received radiotherapy with 69% of patients receiving dose of 60 Gy in 20 fractions. Among patients who received hypofractionated dose, 86% (n = 61) of them were categorized as high risk and 14% (n = 10) were intermediate risk, whereas among conventional group 90% (n = 28) were high risk patients and 10% (n = 3) were of intermediate risk. In hypofractionated dose group, 14% (n = 10) developed grade 2 proctitis and 8% (n = 6) developed grade 2 cystitis, in contrast to conventional dose group in which only 3 patients (5%) developed grade 2 GI toxicity and 2 patients (2.9%) had grade 2 GU toxicity. However, these toxicities and their grade were clinically insignificant when compared with the dose groups (p = 0.11). 5 year overall survival for hypofractionated radiotherapy versus conventional dose was 100% and 90% respectively with 95% Cl and p value of 0.3 (clinically insignificant), whereas 5 year disease free survival was 100% and 75% for hypofractionation versus conventional EBRT respectively with 95% CI and p value of 0.04 (clinically significant).ConclusionHypofractionated radiotherapy in patients with intermediate and high risk localized prostate cancer has better disease free survival at the expense of higher risk for proctitis and cystitis but no difference in overall survival as compared to conventional dose of radiation.

Longitudinal analysis of T2 relaxation time variations following radiotherapy for prostate cancer

Aim of this paper is to evaluate short and long-term changes in T2 relaxation times after radiotherapy in patients with low and intermediate risk localized prostate cancer. A total of 24 patients were selected for this retrospective study. Each participant underwent 1.5T magnetic resonance imaging on seven separate occasions: initially after the implantation of gold fiducials, the required step for Cyberknife therapy guidance, followed by MRI scans two weeks post-therapy and monthly thereafter. As part of each MRI scan, the prostate region was manually delineated, and the T2 relaxation times were calculated for quantitative analysis. The T2 relaxation times between individual follow-ups were analyzed using Repeated Measures Analysis of Variance that revealed a significant difference across all measurements (F (6, 120) = 0.611, p << 0.001). A Bonferroni post hoc test revealed significant differences in median T2 values between the baseline and subsequent measurements, particularly between pre-therapy (M0) and two weeks post-therapy (M1), as well as during the monthly interval checks (M2 - M6). Some cases showed a delayed decrease in relaxation times, indicating the prolonged effects of therapy. The changes in T2 values during the course of radiotherapy can help in monitoring radiotherapy response in unconfirmed patients, quantifying the scarring process, and recognizing the therapy failure.

MRI-guided Minimally Invasive Focal Therapies for Prostate Cancer.

Two cases involving patients diagnosed with localized prostate cancer and treated with MRI-guided focal therapies are presented. Patient selection procedures, techniques, outcomes, challenges, and future directions of MRI-guided focal therapies, as well as their role in the treatment of low- to intermediate-risk localized prostate cancer, are summarized.

Transperineal focal diode laser ablation for low and intermediate risk localized prostate cancer. A five years pilot prospective study

Transperineal focal diode laser ablation for low and intermediate risk localized prostate cancer. A five years pilot prospective study

Comparison of the Efficacy of Low Dose Tadalafil with Tamsulosin against Lower Urinary Tract Symptoms and Sexual Dysfunction after Low Dose Rate Prostate Brachytherapy.

Patients with clinically localized prostate cancer (PCa) can be curatively treated with different modalities, including low dose rate (LDR) prostate brachytherapy (PB). LDR-PB allows the patient a relatively short recovery time compared with other treatment modalities such as prostatectomy. However, PB might exert distinct impact on quality of life, lower urinary tract symptoms (LUTS) and sexual dysfunction (SD) are two major concerns. The aim of present study was to assess prospectively the efficacy of low dose tadalafil treatment on both SD and LUTS compared with tamsulosin treatment in patients treated PB for localized PCa. Patients scheduled for PB with I-125 seeds for low or intermediate-risk localized PCa at our institution were eligible for this study. The prescribed dose was set at 160 gray. Participants were randomized into two groups; those started treating with a daily use of 0.2 mg of tamsulosin hydrochloride or 5 mg of tadalafil just after PB. The duration of the study was 12 months and the patients were assessed for urinary and sexual function status at baseline, and 1, 3, 6, and 12 months after PB. The primary study endpoints were both changes from baseline in urinary and sexual function status. Between July 2015 and August 2020, 120 participants were enrolled in this study. The median age was 68 years with the median PSA of 6.5 ng/ml. A total 15 patients were excluded within 6 months after randomization. All subjective LUTS findings, including International Prostate Symptom Score (IPSS), and Over Active Bladder Symptom Score (OABSS), were significantly deteriorated at 1, 3, and 6 months after PB compared with baseline in both groups, respectively (p<0.05). Among objective LUTS findings, a significant decrease in maximum urinary flow rate (Qmax) was found at 1, 3, 6, and 12 months after PB compared with baseline in both groups, respectively (p<0.05). A significant increase in post void residual urine (PVR) was found at 1, 3, and 6 months after PB compared to baseline in tadalafil group, whereas no significant increase was seen in tamsulosin group. There were no statistically significant differences between the 2 groups in scores of the total International Index of Erectile Function (IIEF)-15 and Erection Hardness Score (EHS) before and at 1 month post PB. The EHS was significantly higher in tadalafil group compared with tamsulosin group at 3, 6 and 12 months (p = 0.001, p = 0.004, and p = 0.019, respectively). The EHS after PB in tadalafil group was not significantly decreased from baseline. After LDR-PB, tamsulosin treatment significantly decreased PVR compared with tadalafil. On the other hand, tadalafil contributed to maintain erection hardness compared with tamsulosin.

Radiation Therapy and Irreversible Electroporation for Intermediate Risk Prostate Cancer (RTIRE)

The objective of the RTIRE clinical trial (NCT05345444) is to demonstrate the feasibility, safety, and early oncologic efficacy of combining MRI-guided stereotactic body radiation therapy (MRgSBRT) with irreversible electroporation (IRE) for men with intermediate-risk localized prostate cancer. Inclusion criteria: 1) Men aged ≥18, 2) ECOG 0 -1, 3) Histologically confirmed intermediate risk prostate cancer per NCCN guidelines, 4) Focal grade group 2 (GG2) or 3 (GG3) cancer in multi-parametric magnetic resonance imaging (mpMRI) target, 5) Gland size < 80cc, 6) Ability to undergo IRE, 7) Ability to receive MRI-guided SBRT, 8) Ability to complete the HRQOL assessment surveys, 9) Willingness to undergo 12 month follow up biopsy. 1) Prior TURP, 2) Prior history of focal therapy, 3) Prior history of receiving pelvic radiotherapy, 4) Patient with history of inflammatory bowel disease, 5) History of bladder neck or urethral stricture. Study Design/Endpoints: This is a feasibility and safety study assessing the ability to perform IRE followed by real-time MRgSBRT. Subjects will undergo focal IRE followed by MRgSBRT (≥6 weeks after IRE) to the prostate +/- seminal vesicles prescribed to 32.5 Gy in 5 fractions. The primary endpoint of the first portion of the trial is feasibility, defined as at least 80% of subjects (8 of 10 subjects) undergoing assessment at 12-weeks post-IRE and at 6-weeks post-MRgSBRT within 1 year from enrollment of the first subject. The expansion phase will include an additional 40 subjects to assess side effect profile and early oncologic efficacy (n = 50) at 12 months post RTIRE. RTIRE has enrolled 8 subjects in 3 months and will proceed to the expansion phase. Secondary endpoints include: 1) short-term safety as measured by treatment-related adverse events, 2) oncologic efficacy as measured by number of subjects with presence of ≥GG2 cancer at 12 months post-RTIRE therapy, 3) health-related quality of life (HRQOL) as measured by Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP), International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF-5) 4) post-RTIRE prostate-specific antigen (PSA) kinetics including time to PSA nadir and post-nadir PSA stability, 5) assessment of pre and post-RTIRE mpMRI changes to evaluate the area of necrosis and presence of residual tissue, 6) rates of biochemical and clinical progression and the need for secondary or adjuvant treatment following RTIRE. Enrollment: 11 Subjects RESULTS: To be determined. To be determined.

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.

Survival After Cryotherapy Versus Radiotherapy in Low and Intermediate Risk Localized Prostate Cancer

BackgroundFocal therapy, including cryotherapy, reduces overtreatment in low- and intermediate-risk prostate cancer (PCa) patients with multiple comorbidities, which seems to increase in popularity compared with whole gland treatment. However, there is currently no consensus regarding the medium-term outcomes of cryosurgery as a prospective alternative to radiotherapy (RT) for such patients. Our study aims to find the available evidence that directly compares the medium-term overall survival (OS) and cancer-specific mortality (CSM) outcomes between cryotherapy and RT in patients with low- and intermediated-risk PCa. Materials and MethodUsing the Surveillance, Epidemiology, and End Results (SEER) database, we identified 47,787 patients with low- and intermediate-risk PCa diagnosed between 2004 and 2015, of which 46,853 (98%) received treatment with RT, while only 934 (2.0%) received treatment with cryotherapy. Kaplan–Meier methods were used to estimateOS and cancer-specific survival (CSS) between the 2 groups. We performed multivariable Cox regression analysis to assess overall mortality (OM), while the cumulative incidence function (CIF) was used to illustrate cancer-specific mortality (CSM) and noncancer-specific mortality (non-CSM) for all patients. Additionally, competing risks regression (Fine-Gray) was implemented to evaluate any differences. After propensity score matching (PSM), all the aforementioned analyses were repeated. After the inverse probability of treatment weighting (IPTW), we repeated Kaplan–Meier methods on OS and CSS, and performed multivariable Cox regression analysis to assess OM in cryotherapy versus RT. Sensitivity analyses were conducted by excluding patients who died of cardiovascular disease. ResultsAfter applying 1:4 PSM to the cryotherapy group with the RT group, the resulting RT cohort consisted of 3,736 patients who were matched with 934 patients in the cryotherapy cohort. The 5‐year OS and cumulative CSM rates for PS-matched groups (N = 4670) receiving cryotherapy (N = 934) or RT (N = 3736) were 89% versus 91.8%, 0.65% versus 0.57, respectively. Multivariable Cox regression analysis demonstrated that cryotherapy was associated with a poorer OS outcome compared to RT (hazard ratio [HR] 1.29, 95% confidence interval [CI]: 1.07-1.55, p < .01). Multivariate competing risk regression analysis revealed that both treatments were not associated with CSS, with HR = 1.07 (95% CI: 0.55-2.08, p = .85). IPTW-adjusted analyses showed that the 5-years OS rates were 89.6% versus 91.8% for cryotherapy versus RT, respectively. Multivariate regression analysis for OS demonstrated that cryotherapy was more likely to have inferior OS in comparison to RT (HR = 1.30; 95%CI: 1.09-1.54; p < .01). The outcome of sensitivity analyses indicates that there was no significant difference in OS and CSS between the 2 groups. ConclusionFor low- and intermediate-risk PCa patients treated by cryotherapy or RT, we could not demonstrate a survival difference. Cryotherapy may be a feasible option as a viable alternative to traditional radiation therapy.

High-dose-rate brachytherapy as monotherapy versus as boost in unfavorable intermediate-risk localized prostate cancer: A matched-pair analysis

PURPOSEHigh-dose-rate brachytherapy as monotherapy (HDR-M), or as a boost combined with external beam radiotherapy (HDR-B), are both suitable treatments for intermediate-risk prostate cancer. However, data directly comparing these two approaches for men with unfavorable intermediate-risk (UIR) patients are lacking. METHODS AND MATERIALSPatients with NCCN-defined UIR prostate cancer treated from 1997 to 2020 were identified in a prospectively maintained, single institution database. HDR-M and HDR-B patients were matched using three factors: age ±3 years; Gleason score (major and minor); and clinical T stage. Biochemical failure was defined as PSA nadir (nPSA) + 2. Available acute and chronic toxicities are additionally reported. RESULTSA total of 247 patients were identified (170 receiving HDR-B, 77 receiving HDR-M), ultimately yielding 70 matched pairs (140 patients) for inclusion. The median followup time was 5.2 years for HDR-M compared with 9.3 years for HDR-B (p < 0.001). The two cohorts had similar calculated prostate EQD2 (HDR-B 118 Gy vs. HDR-M 115 Gy, p = 0.977). No significant differences in OS, CSS, DM, LRR, or FFBF were identified. HDR-B had an increased rate of any acute grade 2+ gastrointestinal toxicity and worse acute dysuria and diarrhea. Chronic gastrointestinal and genitourinary toxicity was similar. CONCLUSIONSThese data suggest that HDR brachytherapy as monotherapy is an effective treatment option for selected patients with unfavorable intermediate-risk prostate cancer and provides a more favorable gastrointestinal toxicity profile than HDR-B. Prospective trials should be conducted to refine the selection process for this heterogeneous cohort of patients.

Abstract B049: Radiogenomic profiling of prostate tumors prior to external beam radiotherapy (EBRT) converges on a transcriptomic signature of TGF-beta activity driving tumor recurrence

Abstract Background: In patients who receive definitive therapy for locally advanced prostate cancer, biochemical recurrence is due to local recurrence and/or the presence of undetected metastatic disease at the time of initial diagnosis and treatment. Approximately 25-40% of patients who receive radiotherapy plus androgen deprivation therapy (ADT) with curative intent are expected to recur within 5-10 years. We hypothesized that applying multiparametric (mp) MRI, gene expression, and genomic analyses to prostate tumors prior to EBRT+ADT would identify biomarkers predictive of recurrence (NCT01834001). Methods: At baseline and 6 months after completion of radiotherapy, mpMRI was performed and lesions were manually contoured. MR/ultrasound-fusion biopsies acquired at baseline targeted to up to three distinct MR lesions per patient. 29 patients with intermediate and high risk localized prostate cancer treated with EBRT+ADT with sufficient baseline biopsy tissue were selected for this analysis (median follow-up: 91 months). Tumor tissues were macrodissected to obtain DNA and RNA from 60 distinct biopsy regions (1-4 per patient). DNA was used for generating whole-exome sequencing libraries (92.5 × median coverage); RNA was converted into cDNA and hybridized to Affymetrix Human Exon 1.0 microarrays. Secondary gene expression cohorts with clinical annotation were obtained from the University of Miami and Queen’s University Belfast. Gene expression signatures were processed using Ingenuity Pathway Analysis (IPA) and the Decipher GRID. Results: Five of the 29 patients experienced biochemical failure by the time of data analysis; four of these patients were identified to have distant metastases with no evidence of local recurrence at the time of biochemical failure. Baseline and posttreatment lesion volumes by MRI and posttreatment ADCmax (apparent diffusion coefficient) were positively associated with recurrence (p&amp;lt;0.05). The Decipher signature positively correlated with these three MR features. Comparison of gene expression using a linear mixed-effect model identified 1,120 differentially expressed transcripts. IPA nominated TGF-beta signaling as the topmost enriched upstream regulator (z=3.32). This result was validated in the Miami (z=2.54) and Belfast (z=3.67) cohorts. By network analysis, genes that independently tracked with the baseline and posttreatment volumes and posttreatment ADCmax MR features similarly converged to the TGF-beta pathway. Co-occurrence of biallelic TP53 alterations with 1- or 2-copy PTEN losses was observed exclusively in patients who recurred. Conclusions: Genomic, transcriptomic and radiomic analyses have nominated predictive biomarkers that identify the subset of patients with locally advanced prostate cancer destined to recur after definitive EBRT+ADT. Identification of molecular features predictive of failure suggests that aggressive pre-existing subclones harboring these alterations have metastatic potential. Emerging systemic therapies including TGF-beta ligand traps targeted to these tumors may improve overall outcomes. Citation Format: Adam G. Sowalsky, Anson T. Ku, Uma Shankavaram, Shana Y. Trostel, Houssein A. Sater, Stephanie A. Harmon, Nicole V. Carrabba, Yang Liu, Radka Stoyanova, Elai Davicioni, Alan Pollack, Baris Turkbey, Deborah E. Citrin. Radiogenomic profiling of prostate tumors prior to external beam radiotherapy (EBRT) converges on a transcriptomic signature of TGF-beta activity driving tumor recurrence [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B049.

Eliciting men's preferences for decision-making relative to treatments of localized prostate cancer with a good or moderate prognosis.

In diseases where there is no real consensus regarding treatment modalities, promoting shared decision-making can contribute to improving safety and quality of care. This is the case in low- or intermediate-risk localized prostate cancer (PC) treatment. The aim of this study was to investigate the preferences guiding men's decisions regarding the characteristics of the treatment strategies for PC to help physicians adopt a more patient-centered approach. This prospective multicenter study used a discrete choice experiment (DCE). The attributes and the modalities were identified from a qualitative study and a literature review. Relative preferences were estimated using a logistic regression model. Interaction terms (demographic, clinical and socio-economic characteristics) were added to the model to assess heterogeneity in preferences. 652 men were enrolled in the study and completed a questionnaire with 12 pairs of hypothetical therapeutic alternatives between which they had to choose. Men's choices were significantly negatively influenced by the risk of impotence and urinary incontinence, death, and the length and frequency of care. They preferred treatments with a rescue possibility in case of deterioration or recurrence and the use of innovative technology. Surprisingly, the possibility of undergoing prostate ablation negatively influenced their choice. The results also highlighted differences in trade-offs according to socio-economic level. This study confirmed the importance of considering patients' preferences in the decision-making process. It appears essential to better understand these preferences to allow physicians to improve communication and promote case-by-case decision-making.

Salvage Radical Prostatectomy after Primary Focal Ablative Therapy: A Systematic Review and Meta-Analysis.

Focal therapy (FT) has been gaining popularity as a treatment option for localized intermediate-risk prostate cancer (PCa) due to the associated lower morbidity compared to whole-gland treatment. However, there is an increased risk of local cancer recurrence requiring subsequent treatment in a small proportion of patients. To conduct a systematic review and meta-analysis to better describe and analyze patient postoperative, oncologic, and functional outcomes for those who underwent salvage radical prostatectomy (sRP) to manage their primary FT failure. A systematic review was completed using three databases (PubMed, Embase, and CINAHL) from October to December 2021 to identify data on outcomes in patients who received sRP for cancer recurrence after prior focal treatment. 12 articles (482 patients) were included. Median time to sRP was 24 months. Median follow-up time was 27 months. A meta-analysis revealed a postoperative complication rate of 15% (95% CI: 0.09, 0.24), with 4.6% meeting criteria for a major complication Clavien (CG) grade ≥3. Severe GU toxicity was seen in 3.6% of the patients, and no patients had severe GI toxicity. Positive surgical margins (PSM) were found in 27% (95% CI: 0.19, 0.37). Biochemical recurrence (BCR) after sRP occurred in 23% (95% CI: 0.17, 0.30), indicating a BCR-free probability of 77% at 2 years. Continence (pad-free) and potency (ability to have penetrative sex) were maintained in 67% (95% CI: 0.53, 0.78) and 37% (95% CI: 0.18, 0.62) at 12 months, respectively. Our evidence shows acceptable complication rates and oncologic outcomes; however, with suboptimal functional outcomes for patients undergoing sRP for recurrent PCa after prior FT. Inferior outcomes were observed for salvage treatment compared to primary radical prostatectomy (pRP). More high-quality studies are needed to better characterize outcomes after this sequence of PCa treatments. We looked at treatment outcomes and toxicity for men treated with sRP for prior FT failure. We conclude that these patients will have significant detriment to genitourinary function, with outcomes being worse than those for pRP patients.

V10-02 SINGLE-PORT TRANSVESICAL PARTIAL PROSTATECTOMY: PREOPERATIVE SURGICAL PLANNING USING A 3D PRINTED MODEL

You have accessJournal of UrologyCME1 Apr 2023V10-02 SINGLE-PORT TRANSVESICAL PARTIAL PROSTATECTOMY: PREOPERATIVE SURGICAL PLANNING USING A 3D PRINTED MODEL Ethan Ferguson, Jason Scovell, Roxana Ramos, Albert Geskin, Jay Chavali, Andres Purysko, and Jihad Kaouk Ethan FergusonEthan Ferguson More articles by this author , Jason ScovellJason Scovell More articles by this author , Roxana RamosRoxana Ramos More articles by this author , Albert GeskinAlbert Geskin More articles by this author , Jay ChavaliJay Chavali More articles by this author , Andres PuryskoAndres Purysko More articles by this author , and Jihad KaoukJihad Kaouk More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003328.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Surgical simulation using 3D printed prostate and kidney models has been developed with proposed benefits in pre-operative planning, training, and patient education. Single-port (SP) transvesical partial prostatectomy has been performed in highly selected patients with localized intermediate risk prostate cancer as an alternative to focal therapy. We sought to record our experience and outcomes of SP transvesical partial prostatectomy using a 3D printed model of the bladder and prostate. METHODS: An otherwise healthy and potent 59 year-old patient was selected with localized Gleason 3+4=7 prostate cancer, arising from a MRI-visible lesion in the left anterior prostate gland and no other positive biopsies. Segmentation of the preoperative prostate MRI was done to isolate the bladder, prostate, prostatic urethra, and DVC. Using this information, a 1:1 scale 3D printed model was created. A rehearsal procedure was performed on the model using the DaVinci SP surgical system prior to the patient’s operation. RESULTS: Transvesical access, docking, catheter insertion, partial prostate excision, and vesico-urethral reconstruction were able to be simulated using the 3D model. On the day of surgery, lesion excision was carried out with assistance of fused MRI and ultrasound images for intraoperative guidance. Pathology showed Gleason 3+4 disease. The patient achieved negative margins despite incidental focal extraprostatic extension and was discharged on the same day of the procedure. The foley catheter was removed on postoperative day 3. He was fully continent immediately following foley catheter removal and regained full potency within one week of surgery. CONCLUSIONS: A 3D printed model of the bladder and prostate can be used to simulate partial prostatectomy prior to the in-vivo operation. This has potential benefits in surgical planning and education, though challenges include simulation of patient physiology such as bleeding and the cost of materials. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e926 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ethan Ferguson More articles by this author Jason Scovell More articles by this author Roxana Ramos More articles by this author Albert Geskin More articles by this author Jay Chavali More articles by this author Andres Purysko More articles by this author Jihad Kaouk More articles by this author Expand All Advertisement PDF downloadLoading ...

PD22-05 IS PRE OPERATIVE PSMA (PROSTATE SPECIFIC MEMBRANE ANTIGEN) PET/CT A RELIABLE PREDICTOR OF PELVIC LYMPH NODE METASTASIS IN INTERMEDIATE AND HIGH RISK LOCALISED PROSTATE CANCER:A MULTI CENTRE RETROSPECTIVE ANALYSIS

You have accessJournal of UrologyCME1 Apr 2023PD22-05 IS PRE OPERATIVE PSMA (PROSTATE SPECIFIC MEMBRANE ANTIGEN) PET/CT A RELIABLE PREDICTOR OF PELVIC LYMPH NODE METASTASIS IN INTERMEDIATE AND HIGH RISK LOCALISED PROSTATE CANCER:A MULTI CENTRE RETROSPECTIVE ANALYSIS Kishore Ta, Dinesh Cherian, Deepak Kaddu, Bikramjit Sodhi, Ravi Chandran, and Ginil Kumar Pooleri Kishore TaKishore Ta More articles by this author , Dinesh CherianDinesh Cherian More articles by this author , Deepak KadduDeepak Kaddu More articles by this author , Bikramjit SodhiBikramjit Sodhi More articles by this author , Ravi ChandranRavi Chandran More articles by this author , and Ginil Kumar PooleriGinil Kumar Pooleri More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003295.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Functional imaging techniques have been incorporated into conventional anatomical imaging to help improve identification of metastasis in normal sized nodes The primary objective of this study was to retrospectively analyse the percentage of patients “negative for metastasis” on 68Ga PSMA PETCT that translated to absent pelvic node metastasis on histopathology (Negative predictive value-NPV). The secondary objective was to analyse if pathological T stage and biopsy ISUP grades influenced the NPV of the PSMA PET CT. METHODS: A total of 217 biopsy-proven, treatment-naive, intermediate and high-risk (D’Amico classification) localised prostate cancer patients from two institutions were included in the study. All the patients had undergone a pre operative PSMA PET/ CT assessment of their pelvic lymph nodes and the patients “negative for metastasis” underwent Robotic assisted radical prostatectomy with extended pelvic lymph node dissection-ePLND. RESULTS: 49/217 patients had positive nodes despite PSMA PET/CT showing no evidence of lymph node metastasis,of which 27(55.10%) of them were obese. Thus the negative predictive value(NPV) was 77.42%. The NPV of PSMA PET CT in patients with intermediate risk prostate cancer was 86.9% compared to 71.43% in patients with high risk prostate cancer. As the ISUP biopsy grade increased the NPV decreased from 94.12% in ISUP 1 to 44.83%(p<0.0001) in ISUP 5.On retrospective analysis, all intermediate risk patients with a <pT3 stage had a 100% NPV on the PSMA PET/CT while high risk patients with a <pT3 had a NPV of 91.6%.The secondary objective was to analyse if T stage influenced the NPV .In comparison to organ confined disease(pT2) the NPV of those with disease extending beyond the prostate(pT3) was significantly lower, (80.36% vs100%) in intermediate risk and (66.97% vs 91.6%)in high risk patients. CONCLUSIONS: PSMA PET CT cannot replace e PLND with respect to accurate preoperative lymph nodal staging in intermediate and high risk prostate cancer since the NPV is below 95% (86.9%,71.43% respectively. PSMA PET CT is also not accurate with the T staging because pre operative T2 was upstaged to pT3 in 66.6 % of intermediate risk and 81.9% of high risk patients.Thus preoperative PSMA PET CT is not reliable for accurate T and N staging and e PLND should be the standard of care for precise staging in intermediate and high risk localized prostate cancer. Source of Funding: Self funded study © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e666 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kishore Ta More articles by this author Dinesh Cherian More articles by this author Deepak Kaddu More articles by this author Bikramjit Sodhi More articles by this author Ravi Chandran More articles by this author Ginil Kumar Pooleri More articles by this author Expand All Advertisement PDF downloadLoading ...

Radiation therapy and irreversible electroporation for intermediate risk prostate cancer (RTIRE).

TPS403 Background: The objective of the RTIRE clinical trial (NCT05345444) is to demonstrate the feasibility, safety, and early oncologic efficacy of combining MRI-guided stereotactic body radiation therapy (MRgSBRT) with irreversible electroporation (IRE) for men with intermediate-risk localized prostate cancer. Methods: Inclusion criteria: 1) Men aged ≥18, 2) ECOG 0 –1, 3) Histologically confirmed intermediate risk prostate cancer per NCCN guidelines, 4) Focal grade group 2 (GG2) or 3 (GG3) cancer in multi-parametric magnetic resonance imaging (mpMRI) target, 5) Gland size &lt; 80cc, 6) Ability to undergo IRE, 7) Ability to receive MRI-guided SBRT, 8) Ability to complete the HRQOL assessment surveys, 9) Willingness to undergo 12 month follow up biopsy. Exclusion criteria: 1) Prior TURP, 2) Prior history of focal therapy, 3) Prior history of receiving pelvic radiotherapy, 4) Patient with history of inflammatory bowel disease, 5) History of bladder neck or urethral stricture. Study Design/Endpoints: This is a feasibility and safety study assessing the ability to perform IRE followed by real-time MRgSBRT. Subjects will undergo focal IRE followed by MRgSBRT (&gt;6 weeks after IRE) to the prostate +/- seminal vesicles prescribed to 32.5 Gy in 5 fractions. The primary endpoint of the first portion of the trial is feasibility, defined as at least 80% of subjects (8 of 10 subjects) undergoing assessment at 12-weeks post-IRE and at 6-weeks post-MRgSBRT within 1 year from enrollment of the first subject. The expansion phase will include an additional 40 subjects to assess side effect profile and early oncologic efficacy (n=50) at 12 months post RTIRE. RTIRE has enrolled 8 subjects in 3 months and will proceed to the expansion phase. Secondary endpoints include: 1) short-term safety as measured by treatment-related adverse events, 2) oncologic efficacy as measured by number of subjects with presence of ≥GG2 cancer at 12 months post-RTIRE therapy, 3) health-related quality of life (HRQOL) as measured by Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP), International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF-5) 4) post-RTIRE prostate-specific antigen (PSA) kinetics including time to PSA nadir and post-nadir PSA stability, 5) assessment of pre and post-RTIRE mpMRI changes to evaluate the area of necrosis and presence of residual tissue, 6) rates of biochemical and clinical progression and the need for secondary or adjuvant treatment following RTIRE. Clinical trial information: NCT05345444 .

Urinary proteome as a prognostic factor in the deterioration of the quality of life of patients with localized prostate cancer during radiotherapy: Radiotoxicity Bladder Biomarkers (RABBIO) prospective trial.

344 Background: Despite improvements in radiation techniques, pelvic radiotherapy is responsible for acute and delayed bladder adverse events, defined as radiation cystitis (CysR). About 50% of irradiated patients present acute symptoms and experience a significant decrease in their quality of life (QOL). The pathophysiology of CysR is not well understood, which limits our ability to study this process and develop treatments. The RABBIO study evaluates the correlation of urinary biomarkers with the intensity of acute CysR and the QOL of patients, assessed with the digital telemonitoring platform Cureety. Methods: Patients with intermediate-risk localized prostate cancer eligible for localized radiotherapy were included. Urinary biomarkers were analyzed before the start of radiotherapy, and at weeks (W) 4, 12 and 48 of irradiation. Between sample collection visits, patients completed various questionnaires related to radiation cystitis symptoms and QOL using a digital remote monitoring platform. Upon receipt of the questionnaires, an algorithm processed the information and classify patients according to the severity of symptoms and adverse events reported according to CTCAE. We also collected FACT-P questionnaires at baseline, W4 and W12. We correlated the levels of urinary biomarkers with the severity of acute CysR symptoms and patient-reported QOL. Results: The study started in March 2022, with 15 patients included to date. The median age was 76 (range 65-99). 80% (15/17) presented a localized prostate cancer de novo and 20% presented a biochemical recurrence. The compliance was 100% at baseline, 93% at W4 and 100% at W12. We collected a total of 172 AE questionnaires over the duration of the study so far, of which 61.0% (105/172) indicated a correct health status and 31.4% (54/172) a compromised status. The mean (range) FACT-P score at baseline for all patients was 33.9 (24 – 40), which changed to 29.8 (20 – 35) at W4, and 38.7 (37 – 42) at W12. Elevated SHBG (p=0.019, r=-0.93) and decreased IL8 (p=0.034, r=0.91) at baseline correlated with worse FACT-P score at W4. Conclusions: This prospective study is the first to explore the overexpression of inflammatory proteins in fluid biopsies from patients with symptoms of acute CysR. Our first results revealed that an elevated SHBG and a decreased IL8 in urine at baseline were a prognostic factor in the deterioration of QOL for localized prostate cancer patients during radiotherapy. The results of this study will allow us to develop strategies to limit radiation damage to the bladder and improve the QOL of patients. Clinical trial information: NCT05246774 .

Large Prostate Volume Does Not Negatively Impact Health-Related Quality of Life in Patients with Prostate Cancer Treated with Ultrahypofractionated Stereotactic Body Radiotherapy

Survival outcomes after primary radiotherapy for localized prostate cancer (PCa) are excellent, regardless of the specific treatment modality. For this reason, health-related quality of life (HRQOL) has come to play an ever more important role in treatment selection. Stereotactic body radiation therapy (SBRT) is increasingly used to treat patients with PCa. However, the impact of prostate volume on HRQOL is not clear. In this study, we aimed to determine whether a large prostate volume negatively influences HRQOL outcomes in patients undergoing ultrahypofractionated SBRT. We conducted a prospective study of 530 men with low- and intermediate-risk localized PCa. All patients were treated from 2013 to 2017 with SBRT (Cyberknife system). HRQOL data were collected at baseline (pre-treatment), immediately after treatment, and at 12 and 24 months. QOL variables were assessed with the European Organization for Research and Treatment of Cancer QLQ-C30 and PR-25 module. Differences in the QLQ-C30 scales were considered clinically relevant when the change was >10 points. For the analysis, patients were classified into two groups according to prostate volume (≤60 vs. >60 cm3). The prostate volume was ≤60 cm3 in 415 patients (78.3%) and >60 cm3 in 115 (21.7%). No between-group differences were observed at baseline for any of the following variables: clinical stage; hormonal therapy; marital status; educational level; or employment status. No clinically-significant deterioration (functional and symptom scales) was observed in either group between the baseline and 24-month assessment. There were no clinically-relevant differences between the groups on any of the HRQOL variables, regardless of the prostate volume. This study shows that a large prostate volume (>60 cm3) does not appear to negatively impact HRQOL outcomes at two years in patients with localized prostate cancer treated with ultrahypofractionated SBRT administered with the CyberKnife system.