Urethral Sparing Research Articles

38 - Urethral Sparing versus Trans-vesical Robot-Assisted Simple Prostatectomy: A Comparative Analysis of Perioperative, Postoperative Outcomes, and Ejaculation Preservation

38 - Urethral Sparing versus Trans-vesical Robot-Assisted Simple Prostatectomy: A Comparative Analysis of Perioperative, Postoperative Outcomes, and Ejaculation Preservation

Functional imaging guided stereotactic ablative body radiotherapy (SABR) with focal dose escalation and bladder trigone sparing for intermediate and high-risk prostate cancer: study protocol for phase II safo trial

BackgroundStereotactic ablative body radiotherapy (SABR) is an emerging treatment alternative for patients with localized low and intermediate risk prostate cancer patients. As already explored by some authors in the context of conventional moderate hypofractionated radiotherapy, focal boost of the index lesion defined by magnetic resonance imaging (MRI) is associated with an improved biochemical outcome. The objective of this phase II trial is to determine the effectiveness (in terms of biochemical, morphological and functional control), the safety and impact on quality of life, of prostate SABR with MRI guided focal dose intensification in males with intermediate and high-risk localized prostate cancer.MethodsPatients with intermediate and high-risk prostate cancer according to NCCN definition will be treated with SABR 36.25 Gy in 5 fractions to the whole prostate gland with MRI guided simultaneous integrated focal boost (SIB) to the index lesion (IL) up to 50 Gy in 5 fractions, using a protocol of bladder trigone and urethra sparing. Intra-fractional motion will be monitored with daily cone beam computed tomography (CBCT) and intra-fractional tracking with intraprostatic gold fiducials. Androgen deprivation therapy (ADT) will be allowed. The primary endpoint will be efficacy in terms of biochemical and local control assessed by Phoenix criteria and post-treatment MRI respectively. The secondary endpoints will encompass acute and late toxicity, quality of life (QoL) and progression-free survival. Finally, the subgroup of high-risk patients will be involved in a prospective study focused on immuno-phenotyping.DiscussionTo the best of our knowledge, this is the first trial to evaluate the impact of post-treatment MRI on local control among patients with intermediate and high-risk prostate cancer undergoing SABR and MRI guided focal intensification. The results of this trial will enhance our understanding of treatment focal intensification through the employment of the SABR technique within this specific patient subgroup, particularly among those with high-risk disease, and will help to clarify the significance of MRI in monitoring local responses. Hopefully will also help to design more personalized biomarker-based phase III trials in this specific context. Additionally, this trial is expected to be incorporated into a prospective radiomics study focused on localized prostate cancer treated with radiotherapy.Trial registrationClinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023.Trial SponsorIRAD/SEOR (Instituto de Investigación de Oncología Radioterápica / Sociedad Española de Oncología Radioterápica).Study settingClinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023.Trial statusProtocol version number and date: v. 5/ 17 May-2023. Date of recruitment start: August 8, 2023. Date of recruitment completion: July 1, 2024.

Clinical Outcomes of Prostate SBRT Using Non-adaptive MR-Guided Radiotherapy.

Stereotactic body radiotherapy (SBRT) is widely used for localized prostate cancer and implementation of MR-guided radiotherapy has the advantage of tighter margins and improved sparing of organs at risk. Here we evaluate outcomes and time required to treat using non-adaptive MR-guided SBRT (MRgSBRT) for localized prostate cancer at our institution. From 9/2019 to 11/2021 we conducted a retrospective review of 80 consecutive patients who were treated with MRgSBRT to the prostate. Patients included low (LR) (5%), favorable intermediate (FIR) (40%), unfavorable intermediate (UIR) (49%), and high risk (HR) (6%). Short-term androgen deprivation therapy was used in 32% of patients. Target volumes included prostate gland and proximal seminal vesicles with an isotropic 3mm margin. Treatment was prescribed to 36.25 Gy in 5 fractions every other day with urethral sparing. Hydrogel spacer was used in 18% of patients. Time on the linac was recorded as beam on time (BOT) plus total treatment time (TTT) including gating. Analyzed outcomes included PSA response and patient reported outcomes scored by the American Urological Association (AUA) questionnaire and toxicity per CTCAE v5. General linear regression model was used to analyze factors affecting PSA and AUA in longitudinal follow up, and chi-square test was used to assess factors affecting toxicity. Median follow up was 19.3months (3.8 - 36.6). Median BOT was 4.6min (2.6 - 7.2) with a median TTT of 11 min (7.6 - 15.8). Pre-treatment vs post-RT median PSA was 6.36 (2.20 - 19.6) vs 0.85 (0.19 - 3.6), respectively (P < 0.001). PSA decrease differed significantly when patients were stratified by risk category, favoring LR/FIR vs UIF/HR group (P = 0.019). Four (5%) patients experienced a biochemical failure (BCF), with a median time to BCF of 20.4months (7.9 - 34.5). Median biochemical failure free survival (BCFFS) was not reached, with 2-yr and 4-yr BCFFS of 97.1% and 72.1%, respectively. Patients with LR/FIR disease had 100% 2-yr and 4-yr BCFFS, whereas patients with UIF/HR had 95% and 41% 2-yr and 4-yr BCFFS (P = 0.05). Mean pre-treatment AUA was 7.3 (1 - 25) vs 11.3 (1 - 26) at first follow-up; however, AUA normalized to baseline over time. Urethral Dmax ≥35Gy trended to lower AUA score at all follow-ups (P = 0.07). Forty-one (51%) patients reported grade 1-2 genitourinary toxicities at the 1 month follow up. Grade 3 toxicity (proctitis) was noted in 1 patient. There was no decrease in any grade rectal toxicity with use of hydrogel spacer (3 vs 6, P = 0.2). No grade ≥4 toxicities was observed. MRgSBRT has the potential for treatment adaptation but this comes at the cost of increased resource utilization. Our experience with non-adaptive MRgSBRT of the prostate highlights its short treatment times as well as efficacy with good PSA control and low toxicity profile.

The Role of Proton Therapy for Prostate Cancer in the Setting of Hip Prosthesis.

Given that the current standard of proton therapy (PT) for prostate cancer is through bilateral beams, this modality is typically avoided when it comes to treatment of patients with hip prosthesis. The purpose of this study was to evaluate whether novel PT methods, i.e., anterior proton beams and proton arc therapy (PArc), could be feasible options to treat this patient subpopulation. We evaluate PT methods in the context of dosimetry and robustness and compare with standard of practice volumetric modulated arc therapy (VMAT) to explore any potential benefits. Two PT and one VMAT treatment plans were retrospectively created for 10 patients who participated in a clinical trial with a weekly repeat CT (rCT) imaging component. All plans were robustly optimized and featured: (1) combination anterior oblique and lateral proton beams (AoL), (2) PArc, and (3) VMAT. All patients had hydrogel spacers in place, which enabled safe application of anterior proton beams. The planned dose was 70 Gy (RBE) to the entire prostate gland and 50 Gy (RBE) to the proximal seminal vesicles in 28 fractions. Along with plan dose-volume metrics, robustness to setup and interfractional variations were evaluated using the weekly rCT images. The linear energy transfer (LET)-weighted dose was evaluated for PArc plans to ensure urethra sparing given the typical high-LET region at the end of range. Both PT methods were dosimetrically feasible and provided reduction of some key OAR metrics compared to VMAT except for penile bulb, while providing equally good target coverage. Significant differences in median rectum V35 (22-25%), penile bulb Dmean (5 Gy), rectum V61 (2%), right femoral head Dmean (5 Gy), and bladder V39 (4%) were found between PT and VMAT. All plans were equally robust to variations. LET-weighted dose in urethra was equivalent to the physical dose for PArc plans and hence no added urethral toxicity was expected. PT for treatment of prostate cancer patients with hip prosthesis is feasible and equivalent or potentially superior to VMAT in quality in some cases. The choice of radiotherapy regimen can be personalized based on patient characteristics to achieve the best treatment outcome.

Impact of daily plan adaptation on accumulated doses in ultra-hypofractionated magnetic resonance-guided radiation therapy of prostate cancer

Background and purposeUltra-hypofractionated online adaptive magnetic resonance-guided radiotherapy (MRgRT) is promising for prostate cancer. However, the impact of online adaptation on target coverage and organ-at-risk (OAR) sparing at the level of accumulated dose has not yet been reported. Using deformable image registration (DIR)-based accumulation, we compared the delivered adapted dose with the simulated non-adapted dose. Materials and methodsTwenty-three prostate cancer patients treated at two clinics with 0.35 T magnetic resonance-guided linear accelerator (MR-linac) following the same treatment protocol (5×7.5 Gy with urethral sparing and daily adaptation) were included. The fraction MR images were deformably registered to the planning MR image. Both non-adapted and adapted fraction doses were accumulated with the corresponding vector fields. Two DIR approaches were implemented. PTV* (planning target volume minus urethra+2mm) D95%, CTV* (clinical target volume minus urethra) D98%, and OARs (urethra+2mm, bladder, and rectum) D0.2cc, were evaluated. Statistical significance was inferred from a two-tailed Wilcoxon signed-rank test (p < 0.05). ResultsNormalized to the baseline, the accumulated PTV* D95% increased significantly by 2.7 % ([1.5, 4.3]%) through adaptation, and the CTV* D98% by 1.2 % ([0.1, 1.7]%). For the OARs after adaptation, accumulated bladder D0.2cc decreased by 0.4 % ([−1.2, 0.4]%), urethra+2mmD0.2cc by 0.8 % ([−1.6, −0.1]%), while rectum D0.2cc increased by 2.6 % ([1.2, 4.9]%). For all patients, rectum D0.2cc was still below the clinical constraint. Results of both DIR approaches differed on average by less than 0.2 %. ConclusionsOnline adaptation in MRgRT improved target coverage and OARs sparing at the level of accumulated dose.

Urethral Sparing versus Trans-Vesical Robot-Assisted Simple Prostatectomy: A Comparative Analysis of Perioperative, Postoperative Outcomes, and Ejaculation Preservation.

To compare the perioperative and postoperative outcomes between traditional trans-vesical robot-assisted simple prostatectomy (TV-RASP) and the newly introduced urethral-sparing (US) RASP. We retrospectively reviewed 42 patients who underwent TV-RASP (n=22) or US-RASP (n=20) performed by two experienced surgeons at two tertiary centers. Perioperative outcomes including operation time, estimated blood loss, length of hospital stay, and catheterization time were assessed. Postoperative outcomes were evaluated using the International Prostate Symptom Score (IPSS), quality of life (QoL), uroflowmetry parameters, Male Sexual Health Questionnaire-Ejaculation Dysfunction-Short Form (MSHQ-EjD-SF) scores, and maintenance of anterograde ejaculation. This study analyzed 22 and 20 patients who underwent TV-RASP and US-RASP, respectively. Except for the TV-RASP group being older (70.0 years) than the US-RASP group (64.5 years) (p=0.028), no differences among other baseline characteristics existed. Perioperative outcomes indicated that hospital stay and catheterization time were significantly shorter in the US-RASP group than in the TV-RASP group (p<0.001). At postoperative month 1, the median IPSS and QoL scores were significantly better in the US-RASP group than in the TV-RASP group (p=0.001 and p=0.002, respectively). However, at months 6 and 12, no significant differences were noted in IPSS, QoL, maximum flow rate, and postvoid residual urine between the two groups. Sexually active patients in the US-RASP group maintained postoperative MSHQ-EjD functional and bother scores, whereas the TV-RASP group experienced a decline. Notably, 75.0% of patients in the US-RASP group preserved antegrade ejaculation, compared to only 20.0% in the TV-RASP group (p<0.001). US-RASP is not inferior to TV-RASP in terms of functional outcomes. In addition, US-RASP yielded more rapid symptom improvements and preserved antegrade ejaculation than TV-RASP. However, larger prospective studies are required to confirm these findings and to further investigate the long-term efficacy and safety of US-RASP.

Redefining bladder neck dose in low-dose-rate prostate brachytherapy–Can we improve urinary toxicity without impacting disease control?

We sought to assess the impact of bladder neck dose (BND) on patient reported urinary toxicity, and feasibility of relative urethral sparing technique in prostate brachytherapy (PB). We retrospectively identified bladder neck as a point dose on post-implant CT scans in patients treated with 131Cs PB. Urinary symptoms were assessed through EPIC questionnaires. Patient cohorts were identified based on mean BND as a percentage of prescription dose with toxicity assessment at each time point. In our cohort of 542 patients, BND was associated with clinically significant acute urinary symptoms and chronic symptoms, as patients receiving >70% of the prescription dose had significantly worse overall EPIC scores than patients receiving ≤70% of prescription dose. There was no difference in bDFS between patients receiving BND ≤70% (96% bDFS) and >70% (94% bDFS) at a median follow up of 57 months. BND has a significant impact on both acute and chronic urinary symptoms, with reduced symptoms reported with BND <70% of prescription dose. With a median follow up of 4.7 years, excellent bDFS has thus far been achieved with relative urethral and bladder neck sparing. Utilizing this constraint should improve urinary symptoms without impacting disease control.

Dosimetric Impact of Intrafraction Prostate Motion and Interfraction Anatomical Changes in Dose-Escalated Linac-Based SBRT

The aim of this study was to investigate the impact of intrafraction prostate motion and interfraction anatomical changes on dose metrics and the effect of beam gating and motion correction in dose-escalated Linac-based SBRT. Thirteen patients (56 fractions) with organ-confined prostate cancer underwent dose-escalated FFF-VMAT SBRT. Accurate patient setup was ensured by CBCT, and real-time 3D prostate motion data were obtained using a novel electromagnetic tracking device. Treatment was interrupted when the signals exceeded a 2 mm threshold in any of the three spatial directions and couch position was corrected unless the offset was transient. Prostate trajectories with and without beam gating and motion correction events were reconstructed and analyzed. Rectum and bladder volumes on each daily CBCT were recorded and compared with volumes at simulation. The prostate motion observed for each fraction was incorporated into the patient original treatment plan with an isocenter shift method. Actually, delivered treatments were then obtained by recalculating the reconstructed motion-encoded plan on deformed CTs reflecting the patient CBCT-anatomy of the day. Non-gated treatments were also simulated using the prostate motion data assuming that no treatment interruptions have occurred. Treatment interruptions because of target motion trespassing the predefined threshold occurred in 25 fractions (45%). Rectum and bladder volume changes were relevant in most patients. The mean relative dose differences between actually delivered and planned treatments were -3.0% [-18.5 - 2.8] for CTV D99% and -2.6% [-17.8 - 1.0] for PTV D95% over all 56 fractions. However, the median cumulative CTV coverage with 93% of the prescribed dose turned out to be satisfactory. Urethra sparing was slightly degraded and a mean reduction of rectum and bladder dose was seen in all but two dose metrics: the maximum dose to rectum mucosa and the bladder D40%. Nevertheless, only 2 major deviations in rectum mucosa D0.035cc were observed at the end of the treatment. The greatest contribution to target missing and OARs doses came from the interfraction anatomical variations, while intrafraction prostate motion marginally contributed in gated treatments. In non-gated treatments, further deteriorations by 2.4 - 2.8% in minimum target coverage metrics and by 3.1 - 11.6% in bladder dose parameters would have occurred on average. The implemented motion management strategy and the strict patient preparation regimen, along with current PTV margins, robustness of original treatment plans, and fast FFF beam delivery, ensured no significant degradations of dose metrics due to both intrafraction motion and interfraction anatomical changes. Non-gated treatments would have more widely deteriorated the dosimetry of some individual fractions. Thus, continuous monitoring, beam gating and motion correction are recommended to safely deliver dose-escalated prostate SBRT.

Knowledge Based Planning Evolution: Multi-Criteria Optimization of Prostates. Is There Always a Better Model?

The current paradigm of radiotherapy Knowledge Based Planning (KBP) utilizes dose volume relationships on previously treated plans and may be insensitive to clinician plan preferences. To improve KBP models, incorporation of plan quality metrics and optimization weightings can be achieved using Clinical Scoring Metrics (CSM) and Multi-Criteria Optimization (MCO) respectively. A combination of KBP, MCO and CSM may result in higher quality plan output with potential to improve all prospective clinical plans. This study assesses the benefit of MCO, using CSM, and its application in the evolution of the KBP model. A retrospective Dose Volume Histogram (DVH) parameter review was undertaken for 40 intact prostate radiotherapy cases. Following analysis, these cases were used to develop the CSM system to reflect clinician preferences and departmental protocol. Hypofractionated plans containing simultaneous integrated boost (SIB) and urethral sparing were originally planned using a clinically approved KBP model (Model A). Model A was then refined using MCO, improving the 40 individual model plans to form Model B. A further 20 prostate patients, who were excluded from KBP development, were planned using both models to compare plan quality using the CSM system. Using a single optimization, Model A resulted in a median plan score of 134.1 (92.4-151.5), compared to the median Model B score of 145.1 (114.5-175.1) out of a possible score of 200 points. A Wilcoxon rank sum test was conducted and found the model score difference was significant (p = 0.014). Organ At Risk (OAR) doses, including Rectum V30 Gy, were found to significantly (p = 0.019) decrease, with Model A resulting in a median of 22.1 Gy (9.3-39.0), compared to the Model B median of 16.3 Gy (6.8-35.7). PTV coverage metric V57 Gy, resulted in no significant differences (p = 0.47) with a median score of 98.4% (97.2% - 99.9%) and 98.4% (96.9% - 99.2%) for model A and B, respectively. The application of MCO was used to influence and produce higher quality KBP models, as supported by a CSM system. OAR doses were found to significantly decrease, with no effect on target coverage. As a result, existing plan objectives were tightened through the utilization of KBP models, even with a single optimization resulting in higher scoring plans. The future development of this work may increase the efficiency of planning operations and allow the clinician to accurately anticipate planning goals for not only prostate, but all disease sites.

PO66: A Novel Direction Modulated Brachytherapy Solution for the Urethra Sparing in Prostate HDR Brachytherapy

PO66: A Novel Direction Modulated Brachytherapy Solution for the Urethra Sparing in Prostate HDR Brachytherapy

Analytical HDR prostate brachytherapy planning with automatic catheter and isotope selection.

High dose rate (HDR) brachytherapy is commonly used to treat prostate cancer. Existing HDR planning systems solve the dwell time problem for predetermined catheters and a single energy source. Additional degrees of freedom can be obtained by relaxing the catheters' pre-designation and introducing more source types, and may have a dosimetric benefit, particularly in improving conformality to spare the urethra. This study presents a novel analytical approach to solving the corresponding HDR planning problem. The catheter and dual-energy source selection problem was formulated as a constrained optimization problem with a non-convex group sparsity regularization. The optimization problem was solved using the fast-iterative shrinkage-thresholding algorithm (FISTA). Two isotopes were considered. The dose rates for the HDR 4140 Ytterbium (Yb-169) source and the Elekta Iridium (Ir-192) HDR Flexisource were modeled according to the TG-43U1 formalism and benchmarked accordingly. Twenty-two retrospective HDR prostate brachytherapy patients treated with Ir-192 were considered. An Ir-192 only (IRO), Yb-169 only (YBO), and dual-source (DS) plan with optimized catheter location was created for each patient with N catheters, where N is the number of catheters used in the clinically delivered plans. The DS plans jointly optimized Yb-169 and Ir-192 dwell times. All plans and the clinical plans were normalized to deliver a 15Gy prescription (Rx) dose to 95% of the clinical treatment volume (CTV) and evaluated for the CTV D90%, V150%, and V200%, urethra D0.1cc and D1cc, bladder V75%, and rectum V75%. Dose-volume histograms (DVHs) were generated for each structure. The DS plans ubiquitously selected Ir-192 as the only treatment source. IRO outperformed YBO in organ at risk (OARs) OAR sparing, reducing the urethra D0.1cc and D1cc by 0.98% ( ) and 1.09% ( ) of the Rx dose, respectively, and reducing the bladder and rectum V75% by 0.09 ( ) and 0.13 cubic centimeters (cc) ( ), respectively. The YBO plans delivered a more homogenous dose to the CTV, with a smaller V150% and V200% by 3.20 ( ) and 1.91 cc ( ), respectively, and a lower CTV D90% by 0.49% ( ) of the prescription dose. The IRO plans reduce the urethral D1cc by 2.82% ( ) of the Rx dose compared to the clinical plans, at the cost of increased bladder and rectal V75% by 0.57 ( ) and 0.21 cc ( ), respectively, and increased CTV V150% by a mean of 1.46 cc ( ) and CTV D90% by an average of 1.40% of the Rx dose ( ). While these differences are statistically significant, the clinical differences between the plans are minimal. The proposed analytical HDR planning algorithm integrates catheter and isotope selection with dwell time optimization for varying clinical goals, including urethra sparing. The planning method can guide HDR implants and identify promising isotopes for specific HDR clinical goals, such as target conformality or OAR sparing.

A novel direction modulated brachytherapy technique for urethra sparing in high-dose-rate brachytherapy of prostate cancer

PurposeImage-guided high-dose-rate (HDR) prostate brachytherapy is a safe and effective treatment option for prostate cancer patients; however, some patients still experience acute and late genitourinary (GU) toxicity. Studies have shown that urethral dose is associated with the incidence and severity of GU toxicity. Therefore, a technique that can further spare the urethra while ensuring adequate target coverage is highly desirable. Intensity modulated brachytherapy (IMBT) designs, such as rotating shield brachytherapy (RSBT), offer ideal dosimetry theoretically but are challenging to implement clinically due to the need for high precision in moving the treatment delivery mechanisms synchronized with the source loading. In this study, we propose a novel relatively easy-to-implement solution based on the direction modulated brachytherapy (DMBT) design concept, which does not involve moving parts and works effectively with the ubiquitous 192Ir source. Materials and MethodsThe popular Varian VS2000 (VS) and GammaMedPlus (GMP) 192Ir sources, with outer diameters of 0.6 mm and 0.9 mm, respectively, were simulated using the GEANT4 Monte Carlo (MC) simulation code. The novel DMBT needle concept consists of a 14-gauge nitinol needle, which houses a platinum shield inside. A single groove, consistent with the outer diameter of each source, was incorporated inside the platinum shield to accommodate the HDR source. The maximum thickness of the shield was 1.1 mm (0.8 mm) for the VS (GMP) source. To evaluate the effectiveness of the DMBT needle concept in reducing urethral dose, 6 patient cases were studied and DMBT plans were created by replacing two needles close to the urethra with the DMBT needles. The dosimetric comparisons between the DMBT and reference clinical plans were done by assessing the dose-volume histogram (DVH) planning criteria for the target coverage and organs-at-risk. ResultsThe MC results showed that the use of the novel DMBT needle design with the VS source (GMP source) could reduce the dose by 49.6% (39.2%) at 1 cm from the needle behind the platinum shield, as compared to the unshielded side. Additionally, when using the same DVH planning criteria as the original plan, the DMBT plan with the VS (GMP) source reduced the maximum urethral dose by 10.3% ± 5.6% (8.1% ± 5.0%) and 17.7% ± 14.2% (16.6% ± 13.3%) for 0 mm and 2 mm margins, respectively, while maintaining equivalent V90% and D100 target coverage. ConclusionThe novel DMBT technique offers a promising clinically implementable solution for sparing urethra, particularly in pre-apical region, without compromising the target coverage or increasing treatment time.

MP73-09 A RETROSPECTIVE CLINICAL SERVICE EVALUATION OF LESION-TARGETED MRI-GUIDED TRANSURETHRAL ULTRASOUND ABLATION (TULSA) FOR THE TREATMENT OF LOCALIZED PROSTATE CANCER

You have accessJournal of UrologyCME1 Apr 2023MP73-09 A RETROSPECTIVE CLINICAL SERVICE EVALUATION OF LESION-TARGETED MRI-GUIDED TRANSURETHRAL ULTRASOUND ABLATION (TULSA) FOR THE TREATMENT OF LOCALIZED PROSTATE CANCER Rolf Muschter, Leonhard Steinmeister, and Agron Lumiani Rolf MuschterRolf Muschter More articles by this author , Leonhard SteinmeisterLeonhard Steinmeister More articles by this author , and Agron LumianiAgron Lumiani More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003341.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: MR-guided transurethral ultrasound ablation (TULSA) is a novel minimally-invasive therapy option for the treatment of organ-confined prostate cancer (PCa) through a whole-gland or lesion-targeted approach. TULSA has shown promising safety and oncological outcomes with minimum side-effect on patients urinary, bowel, and sexual functions. The objective of this retrospective single-center study was to perform a clinical service evaluation of lesion-targeted TULSA for patients with localized PCa. METHODS: Men with organ-confined PCa (proved by MRI and biopsy) received lesion-targeted TULSA with sparing of sphincter, urethra, and rectum. A customized treatment was planned for every patient based on his expectations and PCa characteristics. For a subset of men with concurrent PCa and benign prostate hyperplasia (BPH), TULSA was applied as a combined therapy. Repeat TULSA was allowed and a suprapubic catheter was used. The Clavien-Dindo stratification was used to assess the frequency and severity of all adverse events (AEs). Mid-term oncological outcomes were evaluated using multi-parametric MRI (mpMRI) and prostate-specific antigen (PSA). Surgeon-assessed functional outcomes were recorded. RESULTS: 180 patients (150 primary and 30 salvage) with median [IQR] age, baseline PSA, and follow-up availability of 67 [63-76], 8.0 ng/ml [5.2-13], and 12-mon (max 48), respectively, were treated. 40 patients experienced Grade 1 and 2 AEs, resolving within 4 weeks using antibiotics or relevant medication. Grade 3 AEs (urinary retention requiring surgical intervention) occurred in two patients, resolving within 3 months. No grade 4 or higher events and no bowel-related complications occurred. 98% of men preserved pad-free continence. 94/94 men, who were previously potent, maintained erectile potency. 85% of men with concurrent BPH and PCa experienced symptom relief. The mid-term oncological success rate was 88%. A single repeat TULSA was performed on 13 patients. CONCLUSIONS: Lesion-targeted TULSA is a safe and customizable prostate ablation therapy with promising mid-term oncological outcomes and minimal side-effect profile on patients erectile, bowel, and urinary functions. TULSA offers the flexibility to treat localized prostate cancer in a primary, salvage, or concurrent setting of BPH through a patient-tailored whole-gland or lesion-targeted approach. Source of Funding: No funding was received © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1038 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rolf Muschter More articles by this author Leonhard Steinmeister More articles by this author Agron Lumiani More articles by this author Expand All Advertisement PDF downloadLoading ...

Extreme hypofractionated stereotactic radiotherapy for elderly prostate cancer patients: side effects preliminary analysis of a phase II trial.

Aim of this study is to evaluate safety and efficacy of SBRT in elderly patients affected by localized prostate cancer (PC). Men aged 70years or older were enrolled and analyzed. The SBRT schedule was 35Gy in 5 fractions administered in 1-2weeks. According to risk group, androgen deprivation therapy (ADT) was prescribed. Urinary symptoms were evaluated at baseline using the International Prostate Symptom Score (IPSS). Genitourinary (GU) and gastrointestinal (GI) toxicities were assessed at the end of treatment, 2weeks after SBRT and during follow-up using the Common Terminology Criteria for Adverse Events (CTCAE). PSA values were recorded before treatment and during follow-up as biochemical response criteria. Between 07/2019 and 09/2021, 111 patients were enrolled. Median age was 77years. At the end of treatment, no acute GU/GI toxicities ≥ G2 were observed. At 2-3weeks after treatment, 3 patients reported G2 GU toxicity, while 14 patients referred G2 GI toxicity. During the last follow up, 26 and 2 patients reported, respectively, G1 and G2 GU toxicity, while 22 and 1 cases described, respectively, G1 and G2 GI toxicity. No late toxicities ≥ G3 were recorded. GU toxicity is related to absence of urethra sparing, increasing PTV volume, Dmax PTV and IPSS; GI toxicity is related to RT schedule (each other day is better than consecutive day), Dmax rectum and IPSS, At a median follow-up of 24months, excellent biochemical disease control was achieved in all cases with median PSA of 0.5ng/ml. SBRT in elderly patients affected by PC is feasible and well tolerated with excellent biochemical disease control. Longer follow-up is needed to assess late toxicity profile and long-term clinical outcome.

Genitourinary Quality-of-Life Comparison Between Urethral Sparing Prostate Stereotactic Body Radiation Therapy Monotherapy and Virtual High-Dose-Rate Brachytherapy Boost

Although radiation dose escalation improves prostate cancer disease control, it can cause increased toxicity. Genitourinary (GU) symptoms after prostate radiation therapy affect patient health-related quality of life (QoL). We compared patient-reported GU QoL outcomes following 2 alternative urethral sparing stereotactic body radiation therapy regimens. Expanded Prostate Cancer Index Composite (EPIC)-26 GU scores were compared between 2 urethral sparing stereotactic body radiation therapy trials. The SPARK trial prescribed a "Monotherapy" dose of 36.25 Gy in 5 fractions to the prostate. The PROMETHEUS trial prescribed 2 phases: a 19- to 21-Gy in 2 fractions "Boost" to the prostate, followed by 46 Gy in 23 fractions or 36 Gy in 12 fractions. The biological effective dose (BED) for urethral toxicity was 123.9 Gy for Monotherapy and 155.8 to 171.2 Gy for Boost. Mixed effects logistic regression models were utilized to estimate the difference in the odds of a minimal clinically important change from baseline EPIC-26 GU score between regimens at each follow-up. 46 Monotherapy and 149 Boost patients completed baseline EPIC-26 scoring. Mean EPIC-26 GU scores revealed statistically superior urinary incontinence outcomes for Monotherapy at 12 months (mean difference, 6.9; 95% confidence interval [CI], 1.6-12.1; P=.01) and 36 months (mean difference, 9.6; 95% CI, 4.1-15.1; P < .01). Monotherapy also revealed superior mean urinary irritative/obstructive outcomes at 12 months (mean difference, 6.9; 95% CI, 2.0-12.9; P < .01) and 36 months (mean difference, 6.3; 95% CI, 1.9-10.8; P < .01). For both domains and at all time points, the absolute differences were <10%. There were no significant differences in the odds of reporting a minimal clinically important change between regimens at any time point. Even in the presence of urethral sparing, the higher BED delivered in the Boost schedule may have a small adverse effect on GU QoL compared with Monotherapy. However, this did not translate to statistically significant differences in minimal clinically important changes. Whether the higher BED of the boost arm offers an efficacy advantage is being investigated in the Trans Tasman Radiation Oncology Group 18.01 NINJA randomized trial.

Dosimetric Impact of Intrafraction Prostate Motion and Interfraction Anatomical Changes in Dose-Escalated Linac-Based SBRT

The dosimetric impact of intrafraction prostate motion and interfraction anatomical changes and the effect of beam gating and motion correction were investigated in dose-escalated linac-based SBRT. Fifty-six gated fractions were delivered using a novel electromagnetic tracking device with a 2 mm threshold. Real-time prostate motion data were incorporated into the patient's original plan with an isocenter shift method. Delivered dose distributions were obtained by recalculating these motion-encoded plans on deformed CTs reflecting the patient's CBCT daily anatomy. Non-gated treatments were simulated using the prostate motion data assuming that no treatment interruptions have occurred. The mean relative dose differences between delivered and planned treatments were -3.0% [-18.5-2.8] for CTV D99% and -2.6% [-17.8-1.0] for PTV D95%. The median cumulative CTV coverage with 93% of the prescribed dose was satisfactory. Urethra sparing was slightly degraded, with the maximum dose increased by only 1.0% on average, and a mean reduction in the rectum and bladder doses was seen in almost all dose metrics. Intrafraction prostate motion marginally contributed in gated treatments, while in non-gated treatments, further deteriorations in the minimum target coverage and bladder dose metrics would have occurred on average. The implemented motion management strategy and the strict patient preparation regimen, along with other treatment optimization strategies, ensured no significant degradations of dose metrics in delivered treatments.

Mechanisms, mitigation, and management of urinary toxicity from prostate radiotherapy.

Urinary toxicity is common following pelvic radiotherapy and can have a substantial negative effect on survivorship. Due to its prevalence and the increasing number of related clinical trials, localised prostate cancer radiotherapy is a useful illustrative tool to explore urinary toxicity. A good understanding of the interplay between anatomy, radiation-sensitive cell populations, and treatment sequencing is necessary for optimal outcomes. Emerging evidence suggests that the prostatic urethra is a radiation-sensitive structure, not only for stricture development, but also chronic irritative symptoms. Tools now exist not only to identify the urethra, but also to direct radiation dose away from the urethra, with early data suggesting that this reduces moderate-to-severe late urinary toxicity. Coupled with new evidence supporting dominant nodule microboosting and ultrahypofractionation as emerging standards of care, urethral sparing radiotherapy is a powerful tool against radiation induced urinary toxicity while also maximising disease control.

Clinical Outcomes of Prostate SBRT Using Non-Adaptive MR-Guided Radiotherapy (MRgRT)

<h3>Purpose/Objective(s)</h3> Stereotactic body radiation therapy (SBRT) is widely used for localized prostate cancer and implementation of MR-guided radiotherapy (MRgRT) has the advantage of smaller target margins and improved sparing of organs at risk. Here we evaluate outcomes and time required to treat using non-adaptive MRgRT for prostate SBRT at our institution. <h3>Materials/Methods</h3> From 9/2019 to 10/2021, 77 consecutive patients were treated with MRgRT prostate SBRT. Patients included low (4%), favorable intermediate (40%), unfavorable intermediate (49%) and high risk (7%). Short-term ADT was used in 32% of patients. Our clinical pathway allowed maximum prostate gland volume of 60cc. Target volumes included prostate gland and proximal seminal vesicles with an isotropic 3mm margin. Treatment was prescribed to 36.25 Gy in 5 fractions every other day with urethral sparing to maximum dose of 35 Gy. SpaceOAR gel was used in 17% of patients Time on the Linac was recorded as beam on time (BOT) plus total treatment time (TTT) including gating. Analyzed outcomes included PSA response and patient reported outcomes scored by the American Urological Association (AUA) questionnaire and toxicity per CTCAE v5. Repeated-measure analysis and Bonferroni correction were used to test changes in PSA and toxicity. <h3>Results</h3> Median follow up was 9.5 months (range 1.1 – 23.1). Median pre-treatment PSA was 6.5 (range 2.2 – 19.6) and median AUA score was 6 (1 – 25) with a median prostate size of 32.6 cc (range 17 – 70). At first follow up, median change in PSA was -5.23 ng/mL (Delta range +0.02– -19.3ng/ml) with a median AUA of 10 (range 1 – 26). At second follow up, median change in PSA was -6.33 ng/mL (range +1.48– -19.31ng/mL) and median AUA of 7 (range 0 – 33). At third follow up, median change in PSA was -6.09ng/mL (range -1.84 – -14.9ng/mL) and median AUA was 6.5 (1 – 25). There was a significant decrease in PSA between pre-treatment and first through fourth follow up (p=0.003). The greatest difference was between pretreatment PSA and PSA at 4^thfollow-up (decrease in PSA by 5.9 ng/ml, p<.001). Toxicity as measured by CTCAE v5 decreased from 53% at first follow up to 23% at second follow up and 1% at third follow up. Common toxicities included grade 2 urethritis, tenesmus and one grade 3 proctitis. No grade ≥4 toxicity was seen. Our MR-Linac underwent an upgrade in 11/2020 allowing for faster treatment times. For patients treated prior to the upgrade, mean BOT was 4.89 min with a TTT of 12.50 min whereas for those treated after mean BOT was 4.52 min with a TTT of 10.68 min. <h3>Conclusion</h3> A benefit of MRgRT is the potential for treatment adaptation, however it comes at the cost of increased resource utilization and reduced clinical efficiency. Our experience with non-adaptive MRgRT prostate SBRT maintains clinical efficiency as well as efficacy. Taken together these results suggest a non-adaptive approach may allow more patients to access an effective and safe treatment, while also maximizing resource utilization.

OC-0765 Genitourinary hrQoL following Urethral sparing prostate SBRT compared with virtual HDR boost.

OC-0765 Genitourinary hrQoL following Urethral sparing prostate SBRT compared with virtual HDR boost.

Urethra Sparing With Target Motion Mitigation in Dose-Escalated Extreme Hypofractionated Prostate Cancer Radiotherapy: 7-Year Results From a Phase II Study.

PurposeTo explore whether the rectal distension-mediated technique, harnessing human physiology to achieve intrafractional prostate motion mitigation, enables urethra sparing by inverse dose painting, thus promoting dose escalation with extreme hypofractionated stereotactic ablative radiotherapy (SABR) in prostate cancer.Materials and MethodsBetween June 2013 and December 2018, 444 patients received 5 × 9 Gy SABR over 5 consecutive days. Rectal distension-mediated SABR was employed via insertion of a 150-cm3 air-inflated endorectal balloon. A Foley catheter loaded with 3 beacon transponders was used for urethra visualization and online tracking. MRI-based planning using Volumetric Modulated Arc Therapy - Image Guided Radiotherapy (VMAT-IGRT) with inverse dose painting was employed in delivering the planning target volume (PTV) dose and in sculpting exposure of organs at risk (OARs). A 2-mm margin was used for PTV expansion, reduced to 0 mm at the interface with critical OARs. All plans fulfilled Dmean ≥45 Gy. Target motion ≥2 mm/5 s motions mandated treatment interruption and target realignment prior to completion of the planned dose delivery.ResultsPatient compliance to the rectal distension-mediated immobilization protocol was excellent, achieving reproducible daily prostate localization at a patient-specific retropubic niche. Online tracking recorded ≤1-mm intrafractional target deviations in 95% of treatment sessions, while target realignment in ≥2-mm deviations enabled treatment completion as scheduled in all cases. The cumulative incidence rates of late grade ≥2 genitourinary (GU) and gastrointestinal (GI) toxicities were 5.3% and 1.1%, respectively. The favorable toxicity profile was corroborated by patient-reported quality of life (QOL) outcomes. Median prostate-specific antigen (PSA) nadir by 5 years was 0.19 ng/ml. The cumulative incidence rate of biochemical failure using the Phoenix definition was 2%, 16.6%, and 27.2% for the combined low/favorable–intermediate, unfavorable intermediate, and high-risk categories, respectively. Patients with a PSA failure underwent a 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA) scan showing a 20.2% cumulative incidence of intraprostatic relapses in biopsy International Society of Urological Pathology (ISUP) grade ≥3.ConclusionThe rectal distension-mediated technique is feasible and well tolerated. Dose escalation to 45 Gy with urethra-sparing results in excellent toxicity profiles and PSA relapse rates similar to those reported by other dose-escalated regimens. The existence of intraprostatic recurrences in patients with high-risk features confirms the notion of a high α/β ratio in these phenotypes resulting in diminished effectiveness with hypofractionated dose escalation.