Background. ¹⁷⁷Lu-PSMA-617 (lutetium Lu 177 vipivotide tetraxetan) is FDA-approved for metastatic castration-resistant prostate cancer (mCRPC) and is routinely co-administered with androgen deprivation therapy (ADT). Sustained androgen suppression, however, drives lineage plasticity and progressive loss of prostate-specific membrane antigen (PSMA) expression-the very surface antigen on which the radioligand depends. Whether deep, durable response can be achieved with ¹⁷⁷Lu-PSMA-617 under maintained eugonadal androgen status has not, to our knowledge, been formally reported. Conclusion. Deep biochemical and imaging response to ¹⁷⁷Lu-PSMA-617 was achieved while preserving androgen status, mechanistically consistent with avoiding ADT-driven PSMA downregulation. The patientoriginated strategy, prospectively documented decision rule, and reproducible response trajectory warrant formal multi-site investigation, including within the Veterans Health Administration where prostate cancer is the most common solid tumor in male veterans.

PURPOSE:This guideline presents evidence-based consensus recommendations for high-dose-rate (HDR) brachytherapy boost in combination with external beam radiotherapy (EBRT) for the primary treatment of localized prostate cancer. METHODS AND MATERIALS:The American Brachytherapy Society convened a task force for addressing key questions concerning prostate HDR brachytherapy boost with EBRT for the primary treatment of localized prostate cancer. A comprehensive literature search was conducted to identify prospective and large retrospective studies involving HDR brachytherapy combined with EBRT. Outcomes of interest included biochemical and/or disease control, toxicity, patient-reported quality of life, and the role of androgen deprivation therapy. RESULTS:HDR brachytherapy using Ir-192 in combination with EBRT is an appropriate treatment option for men with intermediate- and high-risk prostate cancer. CT, ultrasound, and/or MRI are imaging platforms that may be utilized for treatment planning and delivery. A single implant/fraction of 15 Gy or 2 implants/fractions of 9.5-11 Gy each are acceptable regimens in combination with EBRT at a dose equivalent of 45-50.4 Gy in 1.8-2.0 Gy fractions. The addition of HDR brachytherapy is expected to improve biochemical control compared with dose escalated EBRT alone. HDR brachytherapy boost is expected to achieve similar biochemical control outcomes as a low dose rate (LDR) brachytherapy boost. Androgen deprivation therapy is recommended for men with unfavorable intermediate and high-risk disease, with varying duration dependent on cancer risk. Use of an HDR brachytherapy technique, as opposed to LDR permanent seeds, has been shown to have less acute genitourinary (GU) and gastrointestinal (GI) toxicity following treatment. CONCLUSIONS:For men with intermediate- and high-risk prostate cancer, HDR brachytherapy boost is a safe and effective technique for dose-escalation that can achieve superior biochemical control compared with EBRT alone, possibly with an improved GU and GI side effect profile compared with an LDR brachytherapy technique.

Purpose Accurate fusion of magnetic resonance images (MR) with transrectal ultrasound (US) is important for lesion localization during catheter placement and contouring during treatment planning. Accurate MR-fusion is challenging today because of the need for a separate post-implant MR. The current methods to circumvent post-implant MR are cognitive fusion or by fusing the preoperative MR to post-implant planning image. However, preoperative MR-fusion suffers from challenges with swelling deformation from placing needles. Registration Chaining is a method that utilizes intermediate US information by using needles as landmarks to guide the registration to allow the preoperative MR to be used on post-implant planning volume more accurately. This work hypothesizes that the Registration Chaining process more accurately transfers the pre-MR lesion center of mass (centroid) to ground truth post-MR/CT fusions than without Registration Chaining. Materials and Methods The Registration Chaining process begins with contouring the most recent preoperative MR. An initial registration is performed using Predictive Fusion (MIM Symphony), where the operator positions the US probe guided by the software to optimize the MR to US registration. An US volume reconstruction is acquired with only lesion-localized brachytherapy needles in place. A planning volume (CT or US) with the final needle configuration is also acquired immediately post-implant. A Registration Chaining workflow (MIM Symphony) is run to aid in the serial co-registration of the image volumes and to rigidly fuse the images allowing for translations and rotations. The workflow includes a mutual information algorithm that aligns needles on the intermediate US volume with the needles on the planning volume. Finally, the preoperative MR contours are transferred through the Registration Chain to the planning volume. For this study, Registration Chaining was compared to the conventional contour transfer method where pre-MR contours are rigidly fused directly to the final planning volume. To serve as the ground truth, a planning CT and MR were acquired together immediately post-implant and rigidly fused directly (GV). The transferred contours for both the conventional and Registration Chaining methods were evaluated to qualitatively confirm clinical acceptability by a board certified physician (PR) and a physicist (JS). The offset of the preoperative contours transferred to the post-implant CT between both methods was quantified as Euclidean distance between lesion centroids. Results The lesion centroid when transferred using the conventional method was displaced by 2.5 mm from the Registration Chaining method. The transferred contours from pre-MR to the post-implant MR using Registration Chaining were qualitatively superior to those from the conventional method and correctly included an additional needle which was not included within the conventionally transferred lesion contour (see Figure). Conclusions Whether for lesion-boosting or easing the clinical workflow, the Registration Chaining method was shown to accurately transfer the lesion contour from the pre-MR to the post-implant planning volume. Registration Chaining is a feasible solution to assist in fusing various planning volumes. Additional quantitative study should be performed in further clinical data to confirm the general accuracy of the method against ground truth post-implant MR.

Prostate cancer management is a critical component of men's health with ongoing controversies in screening and treatment. The purpose of this manuscript is to review contemporary evidence-based strategies in the management of localized prostate cancer to optimize patient outcomes, satisfaction, and shared decision making, to improve physician education and awareness, and to emphasize the importance of brachytherapy in the curative management of prostate cancer. The Bottom Line: 1. Selective screening and selective treatment reduces prostate cancer mortality rates. 2. Active surveillance is recommended for low risk prostate cancer. 3. Both radiation and surgery are appropriate options for patients with intermediate-risk and high-risk prostate cancer. 4. Quality of life and patient satisfaction favors brachytherapy for sexual function and urinary incontinence and surgery for urinary bother. 5. For patients with intermediate risk prostate cancer, brachytherapy achieves very high cure rates, acceptable sided effects, high patient satisfaction and is the most cost-effective treatment. 6. For patients with unfavorable intermediate-risk and high-risk prostate cancer, the combination of external beam radiation, brachytherapy, and ADT (Androgen Deprivation Therapy) achieves the highest rates of biochemical control and the lowest need for salvage therapies. 7. A collaborative shared decision making (SDM) process yields a well-informed, high-quality decision that is consistent with patients' preferences and value.

PURPOSE: The addition of a brachytherapy (BT) boost to external beam radiotherapy (EBRT) reduces recurrence risk in men with high-risk prostate cancer (PCa) and may reduce PCa-mortality for Gleason grade group 5 (GG5). Whether the extent of pattern five, a risk factor for distant metastases, impacts the benefit of a BT boost is unclear. METHODS: Men with localized GG5 PCa treated with (1) EBRT or (2) EBRT+BT between 2010 and 2016 were identified in the National Cancer Database. EBRT monotherapy group received conventionally fractionated (1.8 -2.0 Gy per fraction) >= 74 Gy or moderately hypofractionated (2.5-3.0 Gy per fraction) >= 60 Gy. EBRT + BT group received conventionally fractionated >= 45 Gy or moderately hypofractionated >= 37.5 Gy, and either LDR or HDR BT. All patients received concomitant ADT; none received chemotherapy, immunotherapy, or surgery. OS was compared using Kaplan-Meier, log-rank test, and multivariable Cox proportional hazards in the overall cohort, followed by subgroups based on primary versus secondary pattern 5. Propensity score- and exact-matching was used to corroborate results. RESULTS: A total of 8260 men were eligible: EBRT alone (89%) versus EBRT + BT (11%). 5-year OS for EBRT versus EBRT + BT was 76.3% and 85.0%, respectively (p = 0.002; multivariable adjusted HR 0.84, 95% CI 0.65-0.98; p = 0.04). These results remained consistent after propensity score and exact matching. The OS advantage of a BT boost was more prominent in men with Gleason 4 + 5 PCa (p = 0.001) and not observed in men with Gleason 5 + 5 or 5 + 4 PCa. CONCLUSIONS: Extent of pattern five may be useful in appropriately selecting men for EBRT+ BT and should be considered as a pre-randomization stratification variable for future clinical trial design. (c) 2022 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Background and Purpose: Local recurrences after previous radiotherapy (RT) are increasingly being iden-tified 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.Materials and Methods: 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%.Results: 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 system-atic 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 pre-ferred High Dose-Rate salvage BT, and indicated that both focal and whole gland techniques could be appropriate. There was no single preferred dose/fractionation. Conclusion: 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.(c) 2023 Elsevier B.V. All rights reserved. Radiotherapy and Oncology xxx (2023) xxx-xxx

The use of brachytherapy for the definitive treatment of localized prostate cancer has been established for over four decades (1). Therapy may be delivered using either permanent seed low dose rate (LDR) or high dose rate (HDR) technique. Both techniques are recommended in the ASCO/CCO joint guidelines (2), and data suggests comparable oncologic outcomes. Brachytherapy may be used as monotherapy for low risk and selected intermediate risk patients or in conjunction with external beam radiation therapy (EBRT) for unfavorable intermediate and high risk patients.

PurposeLocal recurrences after previous radiotherapy (RT) are increasingly being identified with increasing use of molecular imaging in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option for radiorecurrent prostate cancer. While supported by multiple prospective studies, limited comparative data exists to guide optimal patient selection and treatment technique. We sought to generate international consensus statements on the use and preferred technical considerations for salvage prostate BT.Materials and MethodsInternational 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 after salvage. An a priori threshold for consensus of ≥ 75% was set, with a majority opinion being set at ≥ 50%.ResultsThirty international experts agreed to participate, and the response rates were 100% (30/30), 93.3% (28/30) and 100% (30/30) for the first, second and third rounds of the survey respectively. Consensus was achieved for 56% (18 of 32) statements. Consensus was achieved in several areas of patient selection, including: 1) A minimum of 2-3 years from initial RT and consideration of salvage BT; 2) MRI and PSMA PET should be acquired prior to salvage; 3) Both a targeted and systematic prostate biopsy should be performed; 4) Salvage BT can be considered after any initial RT technique; and 5) Any Gleason Score at recurrence could be considered for salvage. Several areas did not reach consensus and were controversial: 1) Cut off for maximum T stage and PSA at time of salvage; 2) Whether ADT should be used with salvage BT (and duration); 3) Whether it was appropriate to combine local salvage with SBRT for oligometastatic disease and 4) Whether salvage BT may be repeated more than once. More than 50% of respondents preferred High Dose-Rate salvage BT, and indicated that both focal and whole gland salvage could be appropriate depending on the clinical situation. There was no single preferred dose fractionation for salvage prostate BT.ConclusionsThese findings will inform development of an international expert consensus statement for salvage prostate BT. Consensus was achieved on 56% of statements, though several controversial areas were identified. While our results highlight there is no single preferred approach for salvage BT, areas of controversy will be relevant for the design of future prospective studies and clinical trials of salvage BT.

Purpose: Postprostatectomy radiation therapy planning with fluciclovine (F-18) positron emission tomography (PET)/computed tomography has demonstrated improved disease-free survival over conventional only (computed tomography- or magnetic resonance imaging-based) treatment planning. We hypothesized that incorporating PET would result in larger clinical target volumes (CTVs) without increasing patient-reported toxic effects. Methods and Materials: From 2012 to 2019, 165 postprostatectomy patients with detectable prostate-specific antigen were randomized (arm 1 [no PET]: 82; arm 2 [PET]: 83). Prostate bed target volumes with (CTV1: 45.0-50.4 Gy/1.8 Gy) or without (CTV2/CTV: 64.8-70.2 Gy/1.8 Gy) pelvic nodes, as well as organ-at-risk doses, were compared pre- versus post-PET (arm 2) using the paired t test and between arms using the t test. Patient-reported outcomes used International Prostate Symptom Score and Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP). Univariate and multivariable analyses were performed and linear mixed models were fitted. Results: Median follow-up of the whole cohort was 3.52 years. All patients had baseline patient-reported outcomes, 1 patient in arm 1 and 3 patients in arm 2 withdrew, and 4 arm 2 patients had extrapelvic uptake on PET with radiotherapy aborted, leaving 81 (arm 1) and 76 patients (arm 2) for analysis of toxic effects. Mean CTV1 (427.6 vs 452.2 mL; P = .462, arm 1 vs arm 2) and CTV2/CTV (137.18 vs 134.2 mL; P = .669) were similar before PET incorporation. CTV1 (454.57 vs 461.33 mL; P = .003) and CTV2/CTV (134.14 vs 135.61 mL; P < .001) were modestly larger after PET incorporation. Although V40 Gy (P = .402 and P = .522 for rectum and bladder, respectively) and V65 Gy (P = .157 and P = .182 for rectum and bladder, respectively) were not significantly different pre- versus post-PET, penile bulb dose significantly increased post-PET (P < .001 for both V40 Gy and V65 Gy). On univariate and multivariable analyses, arm was not significant for any EPIC-CP subdomain. International Prostate Symptom Score and EPIC-CP linear mixed models were not significantly different between arms. Conclusions: Despite larger CTVs after incorporation of fluciclovine (F-18) PET, we found no significant difference in patient-reported toxic effects with long-term follow-up. Published by Elsevier Inc.

Purpose Randomized data has shown a lower risk of recurrence with the addition of a brachytherapy (BT) boost in men with intermediate- and high-risk prostate cancer treated with external beam radiotherapy (EBRT) and concomitant androgen deprivation therapy (ADT). The inclusion of ADT with BT-based dose escalation is controversial, and professional guidelines support adding or excluding ADT for men with unfavorable intermediate risk prostate cancer treated with EBRT plus a BT boost. However, inclusion of ADT in men with intermediate risk prostate cancer may become more routine after results from RTOG 0815, and its impact on BT utilization in this population is unclear. Herein, we investigate the landscape of BT boost utilization in men with unfavorable intermediate risk prostate treated with EBRT and ADT in the United States. Materials and Methods Men ≥ 18 years diagnosed with clinical stage T1-2N0M0, PSA < 20, and Gleason grade group 3 prostate cancer between 2004-2017 were analyzed from the National Cancer Database. Those missing risk-stratification or treatment data were excluded. Eligible patients were grouped into the following cohorts based on primary radiation treatment modality: (i) EBRT alone or (ii) EBRT plus BT boost. EBRT monotherapy group received conventionally fractionated (1.8-2.0 Gy per fraction) ≥ 74 Gy or moderately hypofractionated (2.5-3.0 Gy per fraction) ≥ 60 Gy. EBRT plus BT boost group received conventionally fractionated ≥ 45 Gy or moderately hypofractionated ≥ 37.5 Gy, and either LDR or HDR BT. All patients received concomitant ADT. Cochran-Armitage was used to evaluate radiation modality treatment trends over time, and multivariable logistic regression was used to identify sociodemographic predictors of treatment. Results Among the eligible cohort, 46,490 (82%) were treated with EBRT alone and 10,236 (18%) were treated with EBRT plus BT boost. Median (range) age was 70 years (38-90). Between 2004 to 2017, there was a significant decline in annual use of a BT boost, from 24.5% in 2004 to 16.4% in 2017 (p<0.001). On MVA, Black race (adjusted OR 0.85, 95% CI 0.79-0.90, P<.0001), Medicaid insurance (aOR 0.67, 95% CI 0.57-0.78, P<.0001), and Charlson-Deyo comorbidity index > 1 (aOR 0.78, 95% CI 0.61-0.99, P=0.04) were associated with decreased odds of receiving a BT boost. Private insurance (aOR 1.11, 95% CI 1.05-1.18, P=.001), treatment at an academic institution (aOR 1.25, 95% CI 1.12-1.39, p<.0001), and Charlson-Deyo comorbidity index 0 (aOR 1.07, 95% CI 1.00-1.15, P=.04) were associated with increased odds of receiving a BT boost. Conclusions For men with unfavorable intermediate risk prostate cancer, utilization of a BT boost has significantly declined in the United States over the past two decades. Black and uninsured men have been at particularly high risk of undertreatment. Future studies aimed at identifying which men with intermediate-risk prostate cancer (e.g. based on genomic classifier or magnetic resonance imaging) derive the greatest oncologic benefit from a BT boost with EBRT and ADT is warranted to appropriately identify those who may be at risk of undertreatment with its exclusion. Additionally, future initiatives are needed to close the disparity gap in access and/or delivery of this efficacious treatment for Black and uninsured men, an overall undertreated population.

Aim/Objectives/Background: The American College of Radiology (ACR), American Brachytherapy Society (ABS), and American Society for Radiation Oncology (ASTRO) have jointly developed the following practice parameter for transperineal permanent brachytherapy of prostate cancer. Transperineal permanent brachytherapy of prostate cancer is the interstitial implantation of low-dose rate radioactive seeds into the prostate gland for the purpose of treating localized prostate cancer. Methods: This practice parameter was developed according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters—Radiation Oncology of the Commission on Radiation Oncology, in collaboration with ABS and ASTRO. Results: This practice parameter provides a framework for the appropriate use of low-dose rate brachytherapy in the treatment of prostate cancer either as monotherapy or as part of a treatment regimen combined with external-beam radiation therapy. The practice parameter defines the qualifications and responsibilities of all involved radiation oncology personnel, including the radiation oncologist, medical physicist, dosimetrist, radiation therapist, and nursing staff. Patient selection criteria and the utilization of supplemental therapies such as external-beam radiation therapy and androgen deprivation therapy are discussed. The logistics of the implant procedure, postimplant dosimetry assessment, and best practices with regard to safety and quality control are presented. Conclusions: Adherence to established standards can help to ensure that permanent prostate brachytherapy is delivered in a safe and efficacious manner.

PURPOSE:Brachytherapy is an essential technique to deliver radiation therapy and is involved in the treatment of multiple disease sites as monotherapy or as an adjunct to external beam radiation therapy. With a growing focus on the cost and value of cancer treatments as well as new payment models, it is essential that standardized quality measures and metrics exist to allow for straightforward assessment of brachytherapy quality and for the development of clinically significant and relevant clinical data elements. We present the American Brachytherapy Society consensus statement on quality measures and metrics for brachytherapy as well as suggested clinical data elements. METHODS AND MATERIALS:Members of the American Brachytherapy Society with expertise in disease site specific brachytherapy created a consensus statement based on a literature review and clinical experience. RESULTS:Key quality measures (ex. workup, clinical indications), dosimetric metrics, and clinical data elements for brachytherapy were evaluated for each modality including breast cancer, cervical cancer, endometrial cancer, prostate cancer, keratinocyte carcinoma, soft tissue sarcoma, and uveal melanoma. CONCLUSIONS:This consensus statement provides standardized quality measures and dosimetric quality metrics as well as clinical data elements for each disease site to allow for standardized assessments of brachytherapy quality. Moving forward, a similar paradigm can be considered for external beam radiation therapy as well, providing comprehensive radiation therapy quality measures, metrics, and clinical data elements that can be incorporated into new payment models.

A significant criticism of prostate brachytherapy has always been the relative lack of prospective, randomized trials investigating its optimal utilization. This is becoming more apparent in the context of progressive, external beam radiotherapy (EBRT) treatment techniques such as hypofractionation and stereotactic body radiotherapy (SBRT) which have undergone and continue to undergo vigorous clinical investigation ( 1 Lee W.R. Dignam J.J. Amin M.B. et al. Randomized phase III noninferiority study comparing two radiotherapy fraction schedules in patients with low-risk prostate cancer. J Clin Oncol. 2016; 34: 2325-2332 Crossref PubMed Scopus (327) Google Scholar , 2 Aluwini S. Pos F. Schimmel E. et al. Hypofractionated versus conventionally fractionated radiotherapy for patients with prostate cancer (HYPRO): Late toxicity results from a randomised, non-inferiority, phase 3 trial. Lancet Oncol. 2016; 17: 464-474 Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar , 3 Lukka H. Pugh S. Bruner D. et al. Patient reported outcomes in NRG Oncology RTOG 0938, evaluating two ultrahypofractionated regimens for prostate cancer. Int J Radiat Oncol Biol Phys. 2018; 102: 287-295 Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar ). Multiple prospective studies, including large-scale, cooperative group clinical trials, continue to accrue and lead to refinement and greater acceptance of SBRT for prostate cancer. This could pose a threat to future utilization of brachytherapy and the potential loss of this excellent treatment option for patients if this pattern does not change.

The use of multiparametric MRI (mp-MRI) can reliably identify dominant intra-prostatic lesions (DILs) within prostate cancer. Dose escalation to DILs using high-dose-rate (HDR) brachytherapy may improve tumor control probability. In this study, we retrospectively investigated a total of 17 patients treated by HDR prostate brachytherapy, each of whom has mp-MRI and CT images acquired pre-treatment. 21 DILs were contoured based on mp-MRI and propagated to CT images after registration using a newly developed deformable image registration method. A boost plan was created for each patient and optimized on the original needle pattern. In addition, separate plans were generated using a virtually implanted needle around the DIL in order to simulate mp-MRI guided needle placement. Both plans were optimized to maximize DIL V150 coverage while meeting OAR sparing constraints. DIL V150, prostate coverage, and OAR sparing were compared with original plan results. Overall, optimized boost plans significantly escalate dose to DILs while meeting OAR constraints. The addition of mp-MRI guided virtual needles facilitate increased coverage of DIL volumes, achieving a V150 >90% in 85% of DILs compared with 57% of boost plan without an additional needle. These results strongly indicate that the proposed mp-MRI guided DIL boost in HDR brachytherapy is feasible without violating OAR constraints. This retrospective study suggests the use of mp-MRI-defined DIL to optimize needle placement through the deformable MRI-ultrasound registration in the operating room may represent a strategy to personalize treatment delivery and improve tumor control.

PURPOSE: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. METHODS AND MATERIALS: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. RESULTS: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. CONCLUSIONS:LDR brachytherapy is a convenient, effective, and well-tolerated treatment for prostate cancer.

Background: Molecular imaging is increasingly used to guide prostate cancer decisions and treatment planning. The specific aim was to evaluate the role of fluciclovine (18F) PET/CT [PET] in improving cancer control over conventional imaging for post-prostatectomy radiotherapy. Methods: Patients with prostate cancer with detectable PSA post-prostatectomy and negative conventional imaging were randomized to radiotherapy directed by conventional imaging (Arm 1) vs conventional imaging+PET (Arm 2). The treatment setting was an academic medical center with community affiliates. In Arm 2, radiotherapy decisions were rigidly determined by PET, which was also used for target delineation. Using a standard post-radiotherapy failure definition, failure rates at 3 years (primary study endpoint) were compared. Univariate and multivariable analyses were performed for demographic, disease, and treatment factors. Secondary endpoints included provider-reported gastrointestinal and genitourinary toxicities. Findings: From September 18, 2012 to March 4, 2019, 165 patients were randomized. PET findings resulted in a 35·4% rate of decision changes, including 4 patients having radiotherapy aborted. Median follow-up was 3·52 years. Three-year failure-free survival rate for Arm 1 vs Arm 2 was 63·0 vs 75·5% (difference,12·5; 95% CI:4·3-20·8; p=0·0028) and at 4-years was 51·2 vs 75·5% (difference,24·3; 95% CI:15·6-33·0; p<0·0001). On univariate analysis, Arm achieved a statistical trend(p=0·0540); Gleason sum, extracapsular extension, seminal vesicle invasion, pelvic field, and PSA reached significance. On multivariable analysis, Arm (HR=2·04[95%CI: 1·06-3·93], p=0·0327), extracapsular extension, pelvic field, and PSA reached significance. Toxicity was similar in both Arms. Interpretation: Inclusion of fluciclovine (18F) PET into post-prostatectomy radiotherapy decisions and planning resulted in a significant improvement in failure rate. Integration of novel PET radiotracers into radiotherapy decisions and planning for prostate cancer patients warrants further study. Trial Registration: Enrollment was done under ClinicalTrials.gov registration (NCT 01666808) which is closed to new participants. Funding: NIH R01 CA169188 [major source]; Blue Earth Diagnostics, Ltd. [cassette arrangement with Emory]. Declaration of Interests: ABJ reports personal fees from Blue Earth Diagnostics, Ltd. in the role of advisory board service outside the submitted work. ES - none. SG - none. RH - none. BH - none. PJR - none. JWS - none. PRP - none. KMX - none. MG discloses he is entitled to a royalty derived from sale of products related to the research described in this manuscript. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policies. For human research studies the consent forms it is stated that he is entitled to a share of sales royalty received by the University from Nihon under that agreement. The terms of this arrangement have been reviewed and approved by the University in accordance with its conflict of interest policies. VAM - none. SSJ - none. OK - none. BCC - none. MAB - none. OAA - none. AAA - none. VRD - none. DMS participates through the Emory Office of Sponsored Projects in sponsored grants including those funded or partially funded by Blue Earth Diagnostics, Ltd; Nihon MediPhysics Co, Ltd.; Telix Pharmaceuticals (US) Inc.; Advanced Accelerator Applications; FUJIFILM Pharmaceuticals U.S.A., Inc; Amgen Inc. Also reports consultant fees outside the submitted work from: Syncona; AIM Specialty Health; Global Medical Solutions Taiwan; Progenics Pharmaceuticals, Inc. Ethics Approval Statement: Signed informed consent was obtained from every trial participant. The treatment setting was at Winship Cancer Center of Emory University (academic medical center with community affiliates); institution review board approval was through Emory University.

PURPOSE:Addition of a brachytherapy boost to external beam radiation therapy (EBRT) reduces prostate cancer (PCa) recurrence at the expense of genitourinary (GU) toxicity. Whether brachytherapy boost technique, specifically low-dose-rate (LDR-BT) versus high-dose-rate (HDR-BT), impacts treatment-related toxicity is unclear. METHODS:Between 2012-2018, 106 men with intermediate/high risk PCa underwent EBRT (37.5-45 Gy in 1.8-2.5 Gy/fraction) plus brachytherapy boost, either with LDR-BT (110 Gy I-125 or 100 Gy Pd-103; n = 51) or HDR-BT (15 Gy x1 Ir-192; n = 55). Patient-reported outcomes (PRO) were assessed by International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index Composite (EPIC-CP) surveys at 3-6-month intervals for up to three years following treatment, with higher scores indicating more severe toxicity. Provider-reported GU and gastrointestinal (GI) toxicity was graded per CTCAE v5.0 at each follow-up. Linear mixed models comparing PROs between LDR-BT versus HDR-BT were fitted. Stepwise multivariable analysis (MVA) was performed to account for age, gland size, androgen deprivation therapy use, and alpha-blocker medication use. Incidence rates of grade 2+ GU/GI toxicity was compared using Fisher's exact test. RESULTS:Use of LDR-BT was associated with greater change in IPSS (p=0.003) and EPIC-CP urinary irritative score (p = 0.002) compared with HDR-BT, but effect size diminished over time (LDR-BT versus HDR-BT: baseline to 6-/24-month mean IPSS change, +6.4/+1.4 versus +2.7/-3.0, respectively; mean EPIC-CP irritative/obstructive change, +2.5/+0.1 versus +0.9/+0.1, respectively). Results remained significant on MVA. Post-treatment grade 2+ GU toxicity was significantly higher in the LDR-BT group (67.5% versus 42.9% for LDR-BT and HDR-BT, respectively; p <0.001). There were no differences between groups in incontinence, bowel function, and erectile function, or grade 2+ GI toxicity. CONCLUSION:Compared with LDR-BT, HDR-BT was associated with lower acute patient- and provider-reported GU toxicity.

Background Molecular imaging is increasingly used to guide treatment decisions and planning in prostate cancer. We aimed to evaluate the role of F-18-fluciclovine-PET/CT in improving cancer control compared with conventional imaging (bone scan and either CT or MRI) alone for salvage postprostatectomy radiotherapy. Methods In EMPIRE-1, a single-centre, open-label, phase 2/3 randomised controlled trial, patients with prostate cancer with detectable PSA after prostatectomy and negative conventional imaging (no extrapelvic or bone findings) were randomly assigned in a 1:1 ratio to radiotherapy directed by conventional imaging alone or to conventional imaging plus F-18-fluciclovine-PET/CT. Computer-generated randomisation was stratified by PSA concentration, adverse pathology indicators, and androgen deprivation therapy intent. In the F-18-fluciclovine-PET/CT group, radiotherapy decisions were rigidly determined by PET findings, which were also used for target delineation. The primary endpoint was 3 year event-free survival, with events defined as biochemical or clinical recurrence or progression, or initiation of systemic therapy, using univariate and multivariable analyses in patients who received radiotherapy. This trial is registered with ClinicalTrials.gov, NCT01666808 and is closed to new participants. Findings From Sept 18, 2012, to March 4, 2019, 165 patients were randomly assigned, with median follow-up of 3.52 years (95% CI 2.98-3.95). PET findings resulted in four patients in the F-18-fluciclovine-PET/CT group having radiotherapy aborted; these patients were excluded from survival analyses. Median survival was not reached (95% CI 35.2-not reached; 33% of 81 patients had events) in the conventional imaging group compared with not reached (95% CI not reached-not reached; 20% of 76 patients) in the F-18-fluciclovine-PET/CT group, and 3 year event-free survival was 63.0% (95% CI 49.2-74.0) in the conventional imaging group versus 75.5% (95% CI 62.5-84.6) for F-18-fluciclovine-PET/CT (difference 12.5; 95% CI 4.3-20.8; p=0.0028). In adjusted analyses, study group (hazard ratio 2.04 [95% CI 1.06-3.93], p=0.0327) was significantly associated with event-free survival. Toxicity was similar in both study groups, with the most common adverse events being late urinary frequency or urgency (37 [46%] of 81 patients in the conventional imaging group and 31 [41%] of 76 in the PET group), and acute diarrhoea (11 [14%] in the conventional imaging group and 16 [21%] in the PET group). Interpretation Inclusion of F-18-fluciclovine-PET into postprostatectomy radiotherapy decision making and planning significantly improved survival free from biochemical recurrence or persistence. Integration of novel PET radiotracers into radiotherapy decisions and planning for prostate cancer patients warrants further study.

PURPOSE: Education and training on prostate brachytherapy for radiation oncology and medical physics residents in the United States is inadequate, resulting in fewer competent radiation oncology personnel to perform implants, and is a factor in the subsequent decline of an important, potentially curative cancer treatment modality for patients with cancer. The American Brachytherapy Society (ABS) leadership has recognized the need to establish a sustainable medical simulation low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy workshop program that includes physician-physicist teams to rapidly translate knowledge to establish high-quality brachytherapy programs. METHODS: The ABS, in partnership with industry and academia, has held three radiation oncology team-based LDR/HDR workshops composed of physician-physicist teams in Chicago in 2017, in Houston in 2018, and in Denver in 2019. The predefined key metric of success is the number of attendees who returned to their respective institutions and were actively performing brachytherapy within 6 months of the prostate brachytherapy workshop. RESULTS: Of the 111 physician/physicist teams participating in the Chicago, Houston, and Denver prostate brachytherapy workshops, 87 (78%) were actively performing prostate brachytherapy (51 [59%] HDR and 65 [75%] LDR). CONCLUSIONS: The ABS prostate brachytherapy LDR/HDR simulation workshop has provided a successful education and training structure for medical simulation of the critical procedural steps in quality assurance to shorten the learning curve for delivering consistently high-quality brachytherapy implants for patients with prostate cancer. An ABS initiative, intended to bend the negative slope of the brachytherapy curve, is currently underway to train 300 new competent brachytherapy teams over the next 10 years. (C) 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.