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Purpose: The use of magnetic resonance imaging (MRI) for radiation therapy simulation is growing because of its ability to provide excellent delineation of target tissue and organs at risk. With the use of hypofractionated schemes in prostate cancer, urethral sparing is essential; however, visualization of the prostatic urethra can be challenging because of the presence of benign prostatic hyperplasia as well as respiratory motion artifacts. The goal of this study was to compare the utility of 2 motion-insensitive, T2-weighted MRI pulse sequences for urethra visualization in the setting of MRI-based simulation., Methods and Materials: Twenty-two patients undergoing MRI simulation without Foley catheters were imaged on a 3 Tesla MRI scanner between October 2018 and January 2019. Sagittal multislice data were acquired using (1) MultiVane XD radial sampling with parallel imaging acceleration (MVXD) and (2) single-shot fast-spin-echo (SSFSE) sequences with acquisition times of 2 to 3 minutes per sequence. For each examination, 2 genitourinary radiologists scored prostatic urethra visibility on a 1-to-5 scale and rated the signal-to-noise ratio and the presence of artifacts in each series., Results: Urethral visibility was scored higher in the MVXD series than in the SSFSE series in 18 of 22 cases (Reader 1) and 17 of 22 cases (Reader 2). The differences in scores between MVXD and SSFSE were statistically significant for both readers (P < .0001 for both, paired Student's t-test) and interobserver agreement was high (Cohen's kappa = 0.67). Both readers found the signal-to-noise ratio of the MVXD sequence to be superior in all cases. The MVXD sequence was found to generate more artifacts than the SSFSE sequence, but these tended to appear in the periphery and did not affect the ability to visualize the urethra., Conclusions: A radial T2-weighted multislice pulse sequence was superior to an SSFSE sequence for visualization of the urethra in the setting of magnetic resonance simulation for prostate cancer., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: We determined the prognostic importance of a positive posttreatment biopsy after prostate radiotherapy., Materials and Methods: A total of 382 patients underwent a posttreatment biopsy after external beam radiotherapy for clinically localized prostate cancer. Posttreatment biopsies were classified as positive (prostatic adenocarcinoma without typical radiation induced changes), negative (no evidence of carcinoma) or adenocarcinoma with a severe treatment effect. Median followup in survivors was 9 years. Competing risks regression was used to assess relationships between prognostic predictors and cause specific mortality, distant metastasis and prostate specific antigen failure., Results: The prevalence of positive biopsy, treatment effect and negative biopsy was 30%, 22% and 48%, respectively. Androgen deprivation therapy omission and high risk disease were associated with a 2.6 and 1.8-fold increase, respectively, in the odds of positive posttreatment biopsy. The 15-year PSA relapse rate associated with negative, severe treatment effect and positive posttreatment biopsies was 34%, 36% and 79%, respectively (p <0.001). After controlling for known predictors the risk of distant metastasis was 2.6-fold higher in patients with a positive biopsy (p <0.001) and cause specific mortality was twice as high in patients with a positive biopsy compared to those with negative and severe treatment effect biopsy outcomes (HR 2.00, p = 0.022)., Conclusions: A positive posttreatment biopsy after external beam radiotherapy was associated with a higher risk of distant metastasis and prostate cancer related death. Patients with severe treatment effect classified biopsies have biological characteristics more like patients with a negative biopsy than a positive biopsy. Posttreatment biopsies were more often positive in the setting of external beam radiotherapy alone without androgen deprivation therapy or in the presence of high risk disease.

Purpose: Rates of rectal toxicity after low-dose-rate (LDR) brachytherapy for prostate cancer are dependent on rectal dose, which is associated with rectal distance from prostate and implanted seeds. Placement of a hydrogel spacer between the prostate and rectum has proven to reduce the volume of the rectum exposed to higher radiation dose levels in the setting of external beam radiotherapy. We present our findings with placing a rectal hydrogel spacer in patients following LDR brachytherapy, and we further assess the impact of this placement on dosimetry and acute rectal toxicity., Methods and Materials: Between January 2016 and April 2017, 74 patients had placement of a hydrogel spacer, immediately following a Pd-103 seed-implant procedure. Brachytherapy was delivered as follows: as a monotherapy to 26 (35%) patients; as part of planned combination therapy with external beam radiotherapy to 40 (54%) patients; or as a salvage monotherapy to eight (11%) patients. Postoperative MRI was used to assess separation achieved with rectal spacer. Acute toxicity was assessed retrospectively using Radiation Oncology Therapy Group radiation toxicity grading system. Rectal dosimetry was compared with a consecutive cohort of 136 patients treated with seed implantation at our institution without a spacer, using a 2-tailed paired Student's t test (p < 0.05 for statistical significance)., Results: On average, 11.2-mm (SD 3.3) separation was achieved between the prostate and the rectum. The resultant mean rectal volume receiving 100% of prescribed dose (V 100% ), dose to 1 cc of rectum (D 1cc ), and dose to 2 cc of rectum (D 2cc ) were 0 (SD 0.05 cc), 25.3% (SD 12.7), and 20.5% (SD 9.9), respectively. All rectal dosimetric parameters improved significantly for the cohort with spacer placement as compared with the nonspacer cohort. Mean prostate volume, prostate V 100 and dose to 90% of gland (D 90 ) were 29.3 cc (SD 12.4), 94.0% (SD 3.81), and 112.4% (SD 12.0), respectively. Urethral D 20 , D 5cc , and D 1cc were 122.0% (SD 17.27), 133.8% (SD 22.8), and 144.0% (SD 25.4), respectively. After completing all treatments, at the time of first the followup, 7 patients reported acute rectal toxicity-6 experiencing Grade 1 rectal discomfort and 1 (with preexisting hemorrhoids) experiencing Grade 1 bleeding., Conclusions: Injection of rectal spacer is feasible in the post-LDR brachytherapy setting and reduces dose to the rectum with minimal toxicity. Prostate and urethral dosimetries do not appear to be affected by the placement of a spacer. Further studies with long-term followup are warranted to assess the impact on reduction of late rectal toxicity., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To analyze the effect of primary Gleason (pG) grade among a large cohort of Gleason 7 prostate cancer patients treated with external beam radiation therapy (EBRT)., Methods and Materials: From May 1989 to January 2011, 1190 Gleason 7 patients with localized prostate cancer were treated with EBRT at a single institution. Of these patients, 613 had a Gleason 7 with a minimum of a sextant biopsy with nonfragmented cores and full biopsy core details available, including number of cores of cancer involved, percentage individual core involvement, location of disease, bilaterality, and presence of perineural invasion. Median follow-up was 6 years (range, 1-16 years). The prognostic implication for the following outcomes was analyzed: biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific mortality (PCSM)., Results: The 8-year bRFS rate for pG3 versus pG4 was 77.6% versus 61.3% (P<.0001), DMFS was 96.8% versus 84.3% (P<.0001), and PCSM was 3.7% versus 8.1% (P=.002). On multivariate analysis, pG4 predicted for significantly worse outcome in all parameters. Location of disease (apex, base, mid-gland), perineural involvement, maximum individual core involvement, and the number of Gleason 3+3, 3+4, or 4+3 cores did not predict for distant metastases., Conclusions: Primary Gleason grade 4 independently predicts for worse bRFS, DMFS, and PCSM among Gleason 7 patients. Using complete core information can allow clinicians to utilize pG grade as a prognostic factor, despite not having the full pathologic details from a prostatectomy specimen. Future staging and risk grouping should investigate the incorporation of primary Gleason grade when complete biopsy core information is used., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Selecting the "optimal therapy" for the patient with localized prostate cancer may be one of the most challenging medical decisions facing the oncologist. Most patients will have a number of appropriate therapeutic options available to them. Before determining which therapy is most appropriate for a patient, a critical question which needs to be asked is whether any therapy is necessary, especially for those who present with early-stage, low-grade, low-volume disease. Furthermore, given the lack of randomized trials available to guide physicians regarding the superiority of one therapy over another, it is important to consider the different side-effect profiles relevant for each treatment modality. The potential toxicities of therapy impact quality-of-life outcomes and play an important role for most patients in their individual selection of a particular therapy. In addition, there are other important issues that need to be considered, which include the medical condition of the patient and emotional and psychological considerations, as well as family/peer viewpoints or perceived notions of a particular therapy. This review will discuss the relevant issues in the decision making and treatment selection for the patient., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: To determine the influence of rectal hydrogel spacer placement (HSP) on late rectal toxicity outcomes in prostate cancer patients treated with low‐dose‐rate (LDR) brachytherapy, with or without supplemental external beam radiotherapy (EBRT). Patients and Methods: A total of 224 patients underwent LDR brachytherapy with HSP, as monotherapy or combined with EBRT, between January 2016 and December 2019. Dosimetric variables reflecting the extent of rectal sparing and late rectal toxicity outcomes were evaluated. This spacer cohort was retrospectively compared to a similar patient group (n = 139) in whom HSP was not used. Results: Hydrogel spacer placement was associated with significantly reduced rectal doses for all dosimetric variables; the median percentage rectal dose to 1 cc of rectum and rectal dose to 2 cc of rectum of the spacer cohort were all significantly lower compared to the non‐spacer cohort. The incidence rates of overall (any grade) and grade ≥2 rectal toxicity were lower in patients with HSP compared to patients who did not undergo HSP: 12% and 1.8% vs 31% and 5.8%, respectively. The 3‐year cumulative incidence of overall rectal toxicity was significantly lower with HSP than without (15% vs 33%; P < 0.001), corresponding to an overall rectal toxicity reduction on univariable analysis (hazard ratio 0.45, 95% confidence interval 0.28–0.73; P = 0.001). In this patient cohort treated with prostate brachytherapy, none of the urethral dosimetric variables or the presence or absence of HSP was associated with late urinary toxicity. Conclusion: Hydrogel rectal spacer placement is a safe procedure, associated with significantly reduced rectal dose. HSP translates to a decrease in overall late rectal toxicity in patients receiving dose‐escalated brachytherapy‐based procedures. [ABSTRACT FROM AUTHOR]

To describe technical challenges and complications encountered during and after high-dose-rate prostate brachytherapy (HDR-BT) and review management of these complications. The authors performed a systematic review of the literature on toxicities encountered after prostate HDR-BT +/− external beam radiotherapy. A total of 397 studies were identified, of which 64 were included. A focused review of literature regarding the management of acute and late toxicities also performed. Most acute toxicities include grade 0–2 genitourinary and gastrointestinal toxicity. Overall, Grade 3+ Common Terminology Criteria for Adverse Events toxicity after HDR-BT was low [genitourinary: 0–1%; gastrointestinal 0–3%]. Rates of fistula formation were <1%, and radiation cystitis/proctitis were <14% and more commonly reported in cohorts treated with HDR-BT boost and external beam radiotherapy. HDR-BT both as monotherapy or combined with external beam radiotherapy for prostate cancer is well tolerated. Serious complications are rare. [ABSTRACT FROM AUTHOR]

Purpose: To report early toxicity and tumor control outcomes of Pd-103 brachytherapy with ultrahypofractionated stereotactic radiation therapy (RT) for intermediate-risk prostate cancer.Methods and Materials: This prospective trial included 40 patients with intermediate-risk prostate cancer who underwent low-dose-rate (Pd-103) brachytherapy (prescription dose, 100 Gy), followed 1 month later with ultrahypofractionated stereotactic RT (25 Gy in 5 fractions) to the prostate and seminal vesicles. The primary endpoint was the rate of grade 2+ genitourinary toxicity at 12 months using Common Terminology Criteria for Adverse Events v 4.0. Secondary endpoints included patient-reported quality-of-life metrics (International Prostate Scoring System [IPSS], International Index of Erectile Function, and Expanded Prostate Cancer Index Composite-bowel). Biochemical failure was defined as prostate-specific antigen nadir +2 ng/mL. Posttreatment biopsies were performed at between 24 and 36 months; median follow-up was 36 months.Results: The rate of grade 2 urinary toxicity at 12 months was 25% with no grade 3 urinary toxicity noted. Mean IPSS at baseline and 12 and 24 months was 5, 10, and 6.2, respectively. Mean change in IPSS from baseline at 12 months was +5.5 (interquartile range, 1-9.75) and +1.05 (interquartile range, -3 to 3.25) at 24 months. Grade 2 bowel toxicity was 5% at 12 months with no grade 3 bowel toxicity noted. Mean Expanded Prostate Cancer Index Composite-bowel domain scores at baseline and 12 months were 92.8 and 90.3, respectively. Of patients who were potent (International Index of Erectile Function ≥21) at baseline, 75% remained potent at 12 months. Of 40 patients, 28 underwent posttreatment prostate biopsy (PPB), which was negative (n = 20) or demonstrated severe treatment effect (n = 8). No patient had a positive PPB or developed biochemical failure during the follow-up period. One patient without a PPB developed osseous metastases at 18 months posttreatment in the absence of biochemical failure.Conclusion: Low-dose-rate brachytherapy in combination with ultrahypofractionated stereotactic RT was safe and effective for intermediate-risk prostate cancer in early results of this trial. [ABSTRACT FROM AUTHOR]

Brachytherapy is an ideal treatment approach for radiorecurrent prostate cancer given the highly conformal treatment. Increasingly, multiparametric magnetic resonance imaging is being utilized to enhance our ability to assess intraprostatic tumor characteristics. This article aims to review the current literature on whole gland salvage brachytherapy for radiorecurrent prostate cancer as well as the methodology and progress towards a focal approach to salvage brachytherapy. Particular emphasis is placed on the potential role of multiparametric MRI in achieving optimal outcomes with focal salvage brachytherapy. [ABSTRACT FROM AUTHOR]

Purpose We studied adjuvant daily sildenafil citrate during and after radiotherapy for prostate cancer for erectile function preservation. Materials and Methods We performed a randomized, prospective trial of 279 patients with localized prostate cancer treated with radiotherapy who received sildenafil citrate (50 mg daily) or placebo (2:1 randomization). Medication/placebo was initiated 3 days before treatment and continued daily for 6 months. Before therapy and 3, 6, 9, 12, 18 and 24 months after radiotherapy patients completed the IIEF questionnaire, including the erectile function domain, the I-PSS questionnaire and the RAND SF-36®. All IIEF domains were scored. Results At 12 months erectile function scores were better for sildenafil citrate than placebo (p = 0.018), 73% of patients on sildenafil citrate vs 50% on placebo had mild/no erectile dysfunction (p = 0.024) and the sildenafil citrate arm had superior overall satisfaction (p = 0.027) and IIEF total scores (p = 0.043). At 24 months erectile function and IIEF scores were no longer significantly better for sildenafil citrate (p = 0.172 and 0.09, respectively) and yet overall satisfaction scores were higher (p = 0.033). Sexual desire scores in patients who received sildenafil citrate were higher at 24 months although they had completed drug therapy 18 months previously (p = 0.049). At 24 months 81.6% of patients on sildenafil citrate and 56.0% of those on placebo achieved functional erection with or without erectile dysfunction medication (p = 0.045). Conclusions Daily sildenafil citrate during and after radiotherapy for prostate cancer was associated with improved overall sexual function compared with placebo for various sexual function domains. To our knowledge this is the largest randomized, prospective, controlled trial to show the usefulness of a phosphodiesterase-5 inhibitor as a rehabilitation strategy in patients with prostate cancer who received radiation therapy. [ABSTRACT FROM AUTHOR]

: PurposeA prostate brachytherapy program was initiated in 1990, when comparatively little was known of the relative importance of disease- and treatment-related factors on outcome. Patients treated during the first 6 years of the program were analyzed to determine the value of patient selection and implant quality on biochemical control.: Methods and materialsWe treated 243 patients with clinically localized prostate cancer with radioactive seed implantation and underwent 1-month CT-based dosimetric analysis. Follow-up ranged from 61 to 135 months (median 75). The Gleason score was ≤6 in 78% (n = 189), 7 in 14% (n = 35), and 8–10 in 8% (n = 19). The initial prostate-specific antigen (PSA) level was ≤10 ng/mL in 61% (n = 149), 10.1–20 ng/mL in 26% (n = 63), and >20 ng/mL in 13% (n = 31). The disease stage was T2a or less in 49% (n = 120), and Stage T2b-T2c in 51% (n = 123). A real-time ultrasound-guided technique was used with 125I (n = 138) and 103Pd (n = 105) isotopes. No patient underwent external beam radiotherapy as part of their primary treatment. Of the 243 patients, 60% also received hormonal ablation for at least 3 months before and 2–3 months after seed implantation. All patients included underwent a 1-month CT-based dosimetric analysis. The implant dose was defined as the dose delivered to 90% of the prostate volume on postimplant dosimetry (D90). On the basis of prior dose–response analyses, patients were retrospectively grouped into optimal D90 (125I ≥140 Gy Task Group 43 or 103Pd ≥100 Gy) and suboptimal D90 ( 125I <140 Gy or 103Pd <100 Gy) dose groups. Biochemical failure was defined using the American Society for Therapeutic Radiology Oncology definition.: ResultsDisease-related factors, including initial PSA level, Gleason score, and stage, were significant predictors of biochemical failure. The actuarial 8-year freedom from biochemical failure (bFFF) rate was 80% for those with a PSA level ≤10 ng/mL, 86% for PSA 10.1–20 ng/mL, and 45% for PSA >20 ng/mL (p = 0.0019). Patients with a Gleason score of ≤6 had an 8-year bFFF rate of 81% vs. 67% for those with Gleason score 7 and 53% for those with Gleason score 8–10 (p = 0.0003). Patients with Stage T2a or less had an 8-year bFFF rate of 85% compared with 69% for those with Stage T2b-T2c (p = 0.013). The 8-year bFFF rate was 88% for low-risk patients (Stage T2a or less, Gleason score ≤6, and initial PSA level ≤10 ng/mL; n = 75), 81% for moderate-risk patients (Stage T2b or Gleason score 7 or initial PSA level >10.1–20 ng/mL; n = 70), and 65% for high-risk patients (two or more moderate-risk features or Gleason score ≥8 or initial PSA level >20 ng/mL; n = 98; p = 0.0009). Patients with optimal dose implants (n = 145) had an 8-year bFFF rate of 82% compared with 68% for those with suboptimal dose implants (n = 98; p = 0.007). Hormonal therapy did not significantly affect biochemical failure (p = 0.27). In multivariate analysis, the statistically significant variables included initial PSA level (p <0.0001), Gleason score (p = 0.024), and dose group (p = 0.046). Because our current practice limits implantation alone to low-risk patients, an analysis of this subgroup was undertaken to validate the importance of dose. In the optimal dose group, low-risk patients had an 8-year bFFF rate of 94% vs. 75% for the low-risk patients in the suboptimal dose group (p = 0.02).: ConclusionWith minimal follow-up of 5 years, these data continue to support the use of implantation alone in low-risk prostate cancer patients and demonstrate the importance of implant quality (dose) in achieving optimal outcomes. Low-risk patients who receive an optimal dose implant have a 94% bFFF rate at 8 years. [Copyright &y& Elsevier]

Background: To evaluate inter-fractional variations in bladder and rectum during prostate stereotactic body radiation therapy (SBRT) and determine dosimetric and clinical consequences.Methods: Eighty-five patients with 510 computed tomography (CT) images were analyzed. Median prescription dose was 40 Gy in 5 fractions. Patients were instructed to maintain a full bladder and empty rectum prior to simulation and each treatment. A single reviewer delineated organs at risk (OARs) on the simulation (Sim-CT) and Cone Beam CTs (CBCT) for analyses.Results: Bladder and rectum volume reductions were observed throughout the course of SBRT, with largest mean reductions of 86.9 mL (19.0%) for bladder and 6.4 mL (8.7%) for rectum noted at fraction #5 compared to Sim-CT (P < 0.01). Higher initial Sim-CT bladder volumes were predictive for greater reduction in absolute bladder volume during treatment (ρ = - 0.69; P < 0.01). Over the course of SBRT, there was a small but significant increase in bladder mean dose (+ 4.5 ± 12.8%; P < 0.01) but no significant change in the D2cc (+ 0.8 ± 4.0%; P = 0.28). The mean bladder trigone displacement was in the anterior direction (+ 4.02 ± 6.59 mm) with a corresponding decrease in mean trigone dose (- 3.6 ± 9.6%; P < 0.01) and D2cc (- 6.2 ± 15.6%; P < 0.01). There was a small but significant increase in mean rectal dose (+ 7.0 ± 12.9%, P < 0.01) but a decrease in rectal D2cc (- 2.2 ± 10.1%; P = 0.04). No significant correlations were found between relative bladder volume changes, bladder trigone displacements, or rectum volume changes with rates of genitourinary or rectal toxicities.Conclusions: Despite smaller than expected bladder and rectal volumes at the time of treatment compared to the planning scans, dosimetric impact was minimal and not predictive of detrimental clinical outcomes. These results cast doubt on the need for excessively strict bladder filling and rectal emptying protocols in the context of image guided prostate SBRT and prospective studies are needed to determine its necessity. [ABSTRACT FROM AUTHOR]

Promising results have been demonstrated using single fraction external beam for treatment of prostate cancer. Due to inherent differences of delivery between external beam and brachytherapy, the feasibility of replicating the external beam dosimetry in brachytherapy is investigated. A retrospective study was performed using datasets of 120 HDR prostate patients from 6 different physicians in a single institution. The original plans were prescribed to 15Gy (with EBRT to follow). No changes were made to catheter placement, dwell positions, or contours. An in-house software, a linear optimizer with bounded and unbounded constraints, was used to elevate the dose to the entire gland to 24 Gy with no manual manipulation of the optimized plan/dwell times. The resulting plans were compared with published results of single fraction external beam plans to a dose of 24Gy, using the same dosimetric constraints [1]. Prostate D50%, Dmean, D95%, D2%, V24Gy, and V21.6Gy were reported, as well as OAR constraints D1cc for the rectum and urethra. Brachytherapy vs external beam prostate median metrics were 31.4 vs 24.5 Gy for Dmean; 22.1 vs 22.1 Gy for D95%; 79.8 vs 84.8% for V24Gy; 96.2 vs 96.2% for V21.6Gy. D1cc median metrics were 10.6 vs 18.5Gy for urethra and 18.2 vs 18.8Gy for rectum. Dose escalation to the prostate was feasible and achieved similar results to external beam single fraction radiotherapy in terms of target coverage and OAR constraints. Due to the inherent differences of radiation delivery, the dose distributions differ primarily in hotspots and non-homogeneity that could lead to clinical differences. Delivery uncertainty is believed to be lower in brachytherapy, resulting in shrinking of margins and more accurate placement and delivery of hotspots, if desired. The retrospective study was based upon fixed prior implant geometries, therefore further work to investigate the placement of needles to further optimize dose conformality is ongoing. [1] Greco C et al. Safety and Efficacy of Virtual Prostatectomy With Single-Dose Radiotherapy in Patients With Intermediate-Risk Prostate Cancer: Results From the PROSINT Phase 2 Randomized Clinical Trial. JAMA Oncol. 2021 May 1;7(5):700-708. [ABSTRACT FROM AUTHOR]

The purpose of this guideline is to present evidence-based consensus recommendations for low dose rate (LDR) permanent seed brachytherapy for the primary treatment of prostate cancer. The American Brachytherapy Society convened a task force for addressing key questions concerning ultrasound-based LDR prostate brachytherapy for the primary treatment of prostate cancer. A comprehensive literature search was conducted to identify prospective and multi-institutional retrospective studies involving LDR brachytherapy as monotherapy or boost in combination with external beam radiation therapy with or without adjuvant androgen deprivation therapy. Outcomes included disease control, toxicity, and quality of life. LDR prostate brachytherapy monotherapy is an appropriate treatment option for low risk and favorable intermediate risk disease. LDR brachytherapy boost in combination with external beam radiation therapy is appropriate for unfavorable intermediate risk and high-risk disease. Androgen deprivation therapy is recommended in unfavorable intermediate risk and high-risk disease. Acceptable radionuclides for LDR brachytherapy include iodine-125, palladium-103, and cesium-131. Although brachytherapy monotherapy is associated with increased urinary obstructive and irritative symptoms that peak within the first 3 months after treatment, the median time toward symptom resolution is approximately 1 year for iodine-125 and 6 months for palladium-103. Such symptoms can be mitigated with short-term use of alpha blockers. Combination therapy is associated with worse urinary, bowel, and sexual symptoms than monotherapy. A prostate specific antigen <= 0.2 ng/mL at 4 years after LDR brachytherapy may be considered a biochemical definition of cure. LDR brachytherapy is a convenient, effective, and well-tolerated treatment for prostate cancer. [ABSTRACT FROM AUTHOR]

To quantitatively evaluate through automated simulations the clinical significance of potential high-dose rate (HDR) prostate brachytherapy (HDRPB) physics errors selected from our internal failure-modes and effect analysis (FMEA). A list of failure modes was compiled and scored independently by 8 brachytherapy physicists on a one-to-ten scale for severity (S), occurrence (O), and detectability (D), with risk priority number (RPN) = SxOxD. Variability of RPNs across observers (standard deviation/average) was calculated. Six idealized HDRPB plans were generated, and error simulations were performed: single (N = 1722) and systematic (N = 126) catheter shifts (craniocaudal; -1cm:1 cm); single catheter digitization errors (tip and connector needle-tips displaced independently in random directions; 0.1 cm:0.5 cm; N = 44,318); and swaps (two catheters swapped during digitization or connection; N = 528). The deviations due to each error in prostate D90%, urethra D20%, and rectum D1cm3 were analyzed using two thresholds: 5–20% (possible clinical impact) and >20% (potentially reportable events). Twenty-nine relevant failure modes were described. Overall, RPNs ranged from 6 to 108 (average ± 1 standard deviation, 46 ± 23), with responder variability ranging from 19% to 184% (average 75% ± 30%). Potentially reportable events were observed in the simulations for systematic shifts >0.4 cm for prostate and digitization errors >0.3 cm for the urethra and >0.4 cm for rectum. Possible clinical impact was observed for catheter swaps (all organs), systematic shifts >0.2 cm for prostate and >0.4 cm for rectum, and digitization errors >0.2 cm for prostate and >0.1 cm for urethra and rectum. A high variability in RPN scores was observed. Systematic simulations can provide insight in the severity scoring of multiple failure modes, supplementing typical FMEA approaches. [ABSTRACT FROM AUTHOR]

Sildenafil citrate has been shown to be protective of sexual function when given concurrently and following prostate radiation therapy (RT), but some evidence suggests an increased biochemical recurrence (BCR) risk in patients taking sildenafil after radical prostatectomy. To evaluate whether sildenafil use is associated with increased risk of BCR in patients receiving prostate RT, we performed a secondary analysis of a randomized placebo-controlled trial (RPCT) that compared sildenafil citrate to placebo during and after prostate RT. The study population consisted of prostate cancer patients who initiated radiation treatment at our institution and participated in our multi-institutional RPCT that compared 6 months of sildenafil 50 mg once a day to placebo with a 24-month follow-up. Androgen deprivation therapy (ADT) was allowed. Prostate cancer prognostic risk grouping was not an exclusion criterion, but most study participants had low- or intermediate-risk prostate cancer. Statistical analysis was performed using Kaplan-Meier plots and log-rank testing. The primary outcomes of this report were biochemical recurrence and overall survival rates, where BCR was defined according to the Phoenix definition. Data of 162 men were analyzed. Nine men had inadequate PSA follow-up and the remaining 153 men were included in the final report. Median age was 61 years. At a median follow-up of 8.3 years (range: 3.0–12.2), 5/94 (5.3%) and 2/59 (3.4%) patients developed BCR in the sildenafil and placebo groups, respectively. The 6-year BCR-free survival was 98.8% for all patients, 98.1% for the sildenafil cohort, and 100% for the placebo cohort. The 10-year BCR-free survival was 94.4% for all patients, 95.6% for the sildenafil cohort, and 92.9% for the placebo cohort. There was no difference in BCR-free survival between the sildenafil and placebo groups by log-rank comparison (p = 0.36). This analysis informs clinical decision making about the safety of using sildenafil during and after prostate RT. This study included patients who were treated in the setting of a prospective, randomized placebo-controlled trial, and who attained high medication compliance. However, the study was limited by the post-hoc nature of the analysis, use of ADT in some patients, inadequate study power to detect a difference in BCR between sildenafil and placebo groups. Prophylactic sildenafil citrate was not associated with biochemical recurrence risk in prostate cancer patients treated with radiation. However, the study was inadequately powered to definitively conclude a negative finding. Haseltine JM, Hopkins M, Schofield E, et al. Sildenafil Citrate and Risk of Biochemical Recurrence in Prostate Cancer Patients Treated With Radiation Therapy: Post-Hoc Analysis of a Randomized Controlled Trial. J Sex Med 2021;18:1467–1472. [ABSTRACT FROM AUTHOR]

• SBRT dose levels of 40 Gy associated with improved post-treatment biopsy outcomes. • Two-year positive post-treatment biopsies pre-dated PSA failure in majority of patients. • PSA level at time of 2-year biopsy was <1 in majority of those with positive biopsies. • Positive biopsy pts had higher 5-year BCR compared to negative pts (57% vs 7%; p < 0.001). To investigate predictors associated with post-treatment biopsy outcomes after stereotactic body radiotherapy (SBRT) for localized prostate cancer. 257 patients treated with prostate SBRT to dose levels of 32.5 Gy to >40 Gy in 5–6 fractions underwent a post-treatment biopsy performed approximately two years after treatment to evaluate local control status. 73 had% intermediate-risk disease (n = 187) and the remaining 17% (n = 43) and 10% (n = 27) had low-risk and high-risk disease, respectively. The incidence of positive, negative, and treatment-effect post-treatment biopsies were 15.6%, 57.6%, and 26.8%, respectively. The incidence of a positive biopsy according to dose was 37.5% (n = 9/24), 21.4% (n = 6/28), 19.4% (n = 6/31), and 10.9% (n = 19/174) for 32.5 Gy, 35 Gy, 37.5 Gy, and >40 Gy, respectively. In a multivariable model, patients treated with SBRT doses of <40 Gy and those with unfavorable-intermediate-risk or high-risk disease had higher likelihood of a positive post-treatment biopsy. A positive post-SBRT biopsy was associated with a significantly higher likelihood of subsequent PSA relapse at five years (Positive biopsy: 57%, 95% CI: 29–77% compared to negative biopsy: 7%, 95% CI: 3–14%; p < 0.001). Based on two-year post-SBRT biopsies, excellent tumor control was achieved when dose levels of 40 Gy or higher were used. Standard SBRT dose levels of 35–37.5 Gy were associated with a higher likelihood of a positive post-treatment biopsy. Two-year positive post-treatment biopsies pre-dated the development of PSA failure in the majority of patients. [ABSTRACT FROM AUTHOR]

• Salvage brachytherapy is safe and effective for radiorecurrent prostate cancer. • Thirty international experts completed a Delphi consensus study. • Consensus was achieved in 18 of 30 statements. • No single preferred dose, fractionation, or technique was found. Local recurrences after previous radiotherapy (RT) are increasingly being identified in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option. We sought to generate international consensus statements on the use and preferred technical considerations for salvage prostate BT. International experts in salvage prostate BT were invited (n = 34) to participate. A three-round modified Delphi technique was utilized, with questions focused on patient- and cancer-specific criteria, type and technique of BT, and follow-up. An a priori threshold for consensus of ≥ 75% was set, with a majority opinion being ≥ 50%. Thirty international experts agreed to participate. Consensus was achieved for 56% (18/32) of statements. Consensus was achieved in several areas of patient selection: 1) A minimum of 2–3 years from initial RT to salvage BT; 2) MRI and PSMA PET should be obtained; and 3) Both targeted and systematic biopsies should be performed. Several areas did not reach consensus: 1) Maximum T stage/PSA at time of salvage; 2) Utilization/duration of ADT; 3) Appropriateness of combining local salvage with SABR for oligometastatic disease and 4) Repeating a second course of salvage BT. A majority opinion preferred High Dose-Rate salvage BT, and indicated that both focal and whole gland techniques could be appropriate. There was no single preferred dose/fractionation. Areas of consensus within our Delphi study may serve as practical advice for salvage prostate BT. Future research in salvage BT should address areas of controversy identified in our study. [ABSTRACT FROM AUTHOR]

Purpose To report the long-term control and toxicity outcomes of patients with clinically localized prostate cancer, who underwent low-dose-rate prostate brachytherapy with magnetic resonance spectroscopic image (MRSI)–directed dose escalation to intraprostatic regions. Methods and Materials Forty-seven consecutive patients between May 2000 and December 2003 were analyzed retrospectively. Each patient underwent a preprocedural MRSI, and MRS-positive voxels suspicious for malignancy were identified. Intraoperative planning was used to determine the optimal seed distribution to deliver a standard prescription dose to the entire prostate, while escalating the dose to MRS-positive voxels to 150% of prescription. Each patient underwent transperineal implantation of radioactive seeds followed by same-day CT for postimplant dosimetry. Results The median prostate D 90 (minimum dose received by 90% of the prostate) was 125.7% (interquartile range [IQR], 110.3–136.5%) of prescription. The median value for the MRS-positive mean dose was 229.9% (IQR, 200.0–251.9%). Median urethra D 30 and rectal D 30 values were 142.2% (137.5–168.2%) and 56.1% (40.1–63.4%), respectively. Median followup was 86.4 months (IQR, 49.8–117.6). The 10-year actuarial prostate-specific antigen relapse–free survival was 98% (95% confidence interval, 93–100%). Five patients (11%) experienced late Grade 3 urinary toxicity (e.g., urethral stricture), which improved after operative intervention. Four of these patients had dose-escalated voxels less than 1.0 cm from the urethra. Conclusions Low-dose-rate brachytherapy with MRSI-directed dose escalation to suspicious intraprostatic regions exhibits excellent long-term biochemical control. Patients with dose-escalated voxels close to the urethra were at higher risk of late urinary stricture. [ABSTRACT FROM AUTHOR]

To develop ABCD, an HDR brachytherapy prostate optimizer with mixed bound and unbound functionalities and evaluate its performance. ABCD utilized linear optimization with iterative constraint refinement. ABCD aims to maximize (unbounded) dose to voxels within the prostate while achieving bounded constraints on organs-at-risk (urethra and rectum D max). 20 HDR prostate plans were retrospectively optimized using ABCD and with a commercial optimizer (VEGO, Varian Medical Systems) with constraints of rectum D max < 17.1Gy and urethra D max < 22.8Gy. These constraints were chosen to mimic potential dose constraints for monotherapy prostate HDR patients. For VEGO, a prostate D 90 objective iteratively increased by the user until rectum and urethra limits were reached was used. Prostate V 19Gy , D 90 , D 98 and D min were reported. Statistical comparison was performed using a paired T-test (p < 0.05 for significance). ABCD vs VEGO prostate metrics were (median with range): V 19Gy = 98.3 (85.8 - 100) % vs 95.9 (87.5 - 99.6, p = 0.008 < 0.05) %; D 90 = 20.8 (18.3 - 22.3) Gy vs 21.0 (18.2 - 23.2, p = 0.1 > 0.05) Gy; D 98 = 19.1 (16.6 - 21.1) Gy vs 17.7 (14.1 - 20.0, p = 8 × 10−5 < 0.05) Gy; D min = 16.5 (15.2 - 18.7) Gy vs 12.5 (10.5 - 16.4, p = 4 × 10−10 < 0.05) Gy. ABCD respected rectum and urethral constraints; commercial optimizer plans had to be rescaled to meet the constraints. Dose escalation to the prostate was possible with ABCD without iterative optimization by the user. While ABCD did not specifically aim to escalate D 90 dose, it achieved similar results compared to specific D 90 escalation strategies with a commercial optimizer while at the same time permitting statistically significant dose escalation of all other metrics investigated. Further work is ongoing to investigate the utility in DIL boosts, as well as integrating needle suggestions within the optimization step to provide superior dose coverage. [ABSTRACT FROM AUTHOR]