PURPOSE:This single-center randomized trial compared health-related Quality of Life for men with unfavorable localized prostate cancer treated with combined pelvic external beam radiation therapy (EBRT) and prostate brachytherapy, randomly assigned to high-dose rate (HDR) or low-dose rate (LDR). We now report efficacy outcomes with a minimum 5-year follow-up. MATERIALS AND METHODS:Consenting patients receiving pelvic EBRT combined with prostate brachytherapy were randomized to either LDR (110 Gy) or HDR (15 Gy). Androgen deprivation was used in 76% of patients. EBRT delivered 46 Gy/23 using intensity modulated radiation therapy or volumetric-modulated arc therapy (68%) or 3-dimensional conformal radiotherapy (32%). Follow-up up was 1, 3, and 6 months, then every 6 months to 3 years, and then annually. Prostate-specific antigen (PSA) ≤0.2 ng/mL at 4 years defined cure. Biochemical failure-free survival (bFFS) and overall survival were calculated by Kaplan-Meier methods. All failures were investigated by imaging (computed tomography, bone scan, and/or Prostate Specific Membrane Antigen- Positron Emission Tomography (PET) ± biopsy if PET was not available. RESULTS:From January 2014 to December 2019, 195 men (42% intermediate risk/58% high risk) were randomly assigned: 108 to HDR and 87 to LDR. The median age was 71 years. Median PSA was 11.6 ng/mL (mean, 27.0 ng/mL). Median follow-up was 74 months (43-116 m). The median PSA nadirs were 0.07 and 0.08 in HDR and LDR (P = .16), and time to nadir was 13.8 and 14.1 months, respectively (P = .87). Four-year PSA ≤0.2 was maintained in 81% and 83% of HDR and LDR (P = .91). Eight-year bPFS (nadir + 2) was 86% and 85%, respectively. Eighteen of 22 biochemical failures have been identified; 3 are isolated local failures, whereas 14 are distant failures (isolated 11; 3 combined). CONCLUSIONS:In this small, randomized comparison, efficacy analysis shows no difference between LDR and HDR boost in bPFS at 5 and 8 years and confirms the excellent efficacy of dose escalation using prostate brachytherapy as documented in Ascende-RT for unfavorable localized prostate cancer.

Prostate cancer is characterized by an immunosuppressive tumour environment. This work combines Raman spectroscopy with group-and-bases-restricted non-negative matrix factorization (GBR-NMF) and machine learning to assemble models of immune cell densities within the needle-core biopsies of patients undergoing high-dose-rate brachytherapy (HDR-BT). Raman spectral acquisition, as well as immunohistochemistry staining of CD68[Formula: see text], CD3[Formula: see text], and [Formula: see text] cells, was completed for biopsies collected before and 2 weeks following the first fraction of HDR-BT. Regression techniques, constructed using GBR-NMF scores, that produced the most accurate predictions of immune cell density by metrics of root mean-squared error (RMSE) and R[Formula: see text] were the gradient-boosted trees model of [Formula: see text] density (RMSE: 163 counts[Formula: see text], [Formula: see text]: 0.65) and the elastic net model of [Formula: see text]/ [Formula: see text] (RMSE: 0.25, [Formula: see text]: 0.82). The accuracy of these models, herein defined as the fraction of patient predictions within [Formula: see text] standard deviation of their measured values was 11/16 and 12/16, for CD68[Formula: see text] CD3[Formula: see text] and CD68[Formula: see text]/ CD8[Formula: see text] models, respectively. To further delineate which metabolites were most important in the CD68[Formula: see text]/ CD8[Formula: see text] model, this ratio was further predicted in stromal and epithelial tissues within the biopsies, and resulting models utilized the GBR-NMF scores of glutathione, collagen, palmitic acid, and the pre- or post-HDR-BT label to produce an optimal performance level according to RMSE and R[Formula: see text]. In summary, this study illustrates a novel methodology in which supervised machine learning techniques are used to model immune cells, which are prognostic indicators of disease progression.

The detection of local radiorecurrence (LRR) of prostate cancer in the prostate or prostate bed after radiation therapy is increasingly common with the advent of advanced imaging modalities such as the PSMA PET/CT. Our aim is to review the literature and define the optimal workup for identifying LRR and discuss the key principals in management, with a focus on salvage re-irradiation. We performed a narrative review of the literature and ongoing studies centered on LRR workup and treatment. Workup for biochemical recurrence postradiation therapy includes PSMA PET/CT, multiparametric MRI, and systematic and targeted biopsy to confirm and define the extent of LRR. Historically, treatment options have included observation, palliative androgen deprivation therapy (ADT), or salvage local therapy to eradicate the LRR. Salvage local re-irradiation can be delivered using stereotactic body radiotherapy (SBRT), high dose rate (HDR) brachytherapy, or low dose rate (LDR) brachytherapy. Commonly used treatment regimens and practical considerations for the different salvage re-irradiation modalities based on the available literature are discussed. Salvage re-irradiation is a safe and effective treatment approach that offers a second chance to "cure" prostate cancer, while also delaying the need for palliative hormonal therapy. Salvage re-irradiation should be carefully considered in patients with LRR after weighing potential benefits against risks. Further data are needed to identify the optimal volume, dose and fractionation regimens.

PURPOSE:This study aims to clinically implement eb_gui, a user-friendly toolkit for Monte Carlo simulations utilizing egs_brachy, in the context of low-dose-rate (LDR) brachytherapy for prostate and breast cancers. METHODS:A set of test cases, ranging from simple to complex scenarios including single- and multi-seed patient models, was developed for LDR brachytherapy of both breast (103Pd) and prostate (125I). Utilizing Digital Imaging and Communications in Medicine (DICOM) files, the open-source interface eb_gui was employed to compute doses. The commissioning process involved comparing eb_gui results against clinical TG-43 treatment planning system (TG43-TPS) calculations, encompassing point-by-point differences across 3D dose distributions, dose volume histograms, and dose metrics. Additionally, patient-specific dose distributions were computed using eb_gui's full-tissue models (TG186-MC) and compared against TG-43 Monte Carlo calculations (TG43-MC) across multiple cancer centers. RESULTS:Excellent agreement was observed between TG43-TPS and TG43-MC calculated doses, with point-to-point differences of less than 1 Gy (∼1% of prescription dose) for breast and prostate cases. Comparisons between multicenter TG186-MC and TG43-MC doses highlighted discrepancies that underscore the limitations of the TG-43 formalism and affirming the necessity for a model-based dose calculation algorithm (MBDCA). CONCLUSION:This study successfully developed a series of test cases and a commissioning workflow for implementing eb_gui in LDR brachytherapy across multiple centers. The findings underscore the potential of TG-186 MBDCA to enhance the precision of patient dosimetry and improve the accuracy of treatment outcome predictions in LDR brachytherapy. This work represents a significant step toward broader adoption of advanced dose calculation methodologies in clinical practice.

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:High dose rate (HDR) brachytherapy is increasingly adopted for dose escalation in prostate cancer treatment. We report the clinical efficacy and toxicity of HDR prostate brachytherapy combined with external beam radiotherapy (EBRT) and evaluate the predictability of the biochemical definition of cure of 4-year PSA ≤0.2 ng/mL for failure free survival (FFS). METHODS:A single centre retrospective study was conducted, including all patients with high-tier intermediate risk and high-risk prostate cancer treated with HDR brachytherapy combined with EBRT from 2011 to 2019. Patient and prostate cancer characteristics, treatment, clinical endpoints, and follow up were collected. RESULTS:Total 319 patients were analyzed. The median age was 68 with median follow up of 77.1 months. Total 142 had high-tier intermediate and 177 had high-risk disease. Brachytherapy doses were initially 20 Gy/2 fractions, and subsequently 15 Gy/1 fraction. All patients received 46 Gy/23 fractions of EBRT. Overall survival at 5 and 9 years was 92.2% and 77.0%, respectively. Failure-free survival (FFS) was 86.0% at 5 years and 76.1% at 9 years. PSA ≤ 0.2 ng/mL at 4 years was seen in 79.3% of patients and was associated with FFS of 94.1% at 9 years. Grade 3 urethral stricture, hematuria, or proctitis occurred in 2.8%, 0%, and 0%, respectively. CONCLUSION:HDR brachytherapy in addition to EBRT is effective treatment for unfavourable localized prostate cancer with a very acceptable toxicity profile. The biochemical definition of cure of PSA < 0.2 ng/mL at 4 years was predictive for FFS at 9 years.

Brachytherapy is an essential skill in the practice of radiation oncology and is an important component of high-quality, full-service radiation oncology departments. With rapidly changing technology, the role of brachytherapy is constantly evolving, but it remains critically important for optimal patient care in several disease sites. As a procedural aspect of radiation oncology practice, brachytherapy requires a fundamentally different and more focused training approach, with specific training objectives, a unique knowledge base, and specialized training environment. The existing gap in brachytherapy training and experience is compounded with a lack of standardized training objectives. Consensus statement objectives were in part adapted with permission from the Royal College of Physician and Surgeons of Canada, and then further reviewed, modified and enriched with expert knowledge by all authors. Training objectives were further synchronized with the US Accreditation Council for Graduate Medical Education (ACGME). This ABS/GEC-ESTRO Consensus Statement of training objectives will facilitate brachytherapy training by outlining the necessary knowledge and procedural skills for successful practice in brachytherapy. The final brachytherapy curriculum development for any individual program, country and regions, is the responsibility of the individual programs and licensing jurisdictions and should be tailored to their patient population, available equipment and facilities.

Purpose/Objective(s) Brachytherapy (BT) boost is recommended for optimal dose escalation in radiation management of unfavorable organ-confined prostate cancer. High dose rate (HDR) BT is associated with faster symptom recovery than low dose rate BT. We report the clinical efficacy and toxicity of HDR prostate BT combined with external beam radiotherapy (EBRT) and evaluate the ability to achieve a 4-year PSA ≤0.2 ng/mL to predict freedom from prostate cancer recurrence long-term. Materials/Methods All patients treated with HDR BT from program initiation 06/2011 until 08/2019 at one institution were identified. Baseline patient and prostate cancer characteristics, treatment details, and clinical endpoints including clinical failure, toxicity, and PSA response were collected. Results Three hundred twenty-five patients with localized prostate cancer treated with HDR prostate BT combined with EBRT were identified. Disease stratification was 179 high risk, 145 high tier intermediate, and 1 low tier intermediate. Grade group (GG) distribution was 21% GG 2, 39% GG 3, 11% GG 4, and 29% GG 5. Clinical T stage was 34% T1c/T2a, 48% T2b/T2c, 17% T3a/b, 0.3% T4, and 1.2% Tx. Baseline PSA was <10 ng/mL in 41%, 10 to 20 ng/mL in 39%, and >20 ng/mL in 20 % of patients. Androgen deprivation was used in 72% with duration <6 mo in 7%, 6 to12 mo in 18%, 12 mo in 64%, and > 12 mo in 10%. HDR BT was 20 Gy/2 fractions for first 50 patients, a single 13.5 Gy for 1 patient, and 15 Gy/1 for the remaining patients. EBRT was delivered as 46 Gy/23 fractions in 98% of cases; using 3D conformal RT in 38%, intensity modulated RT in 5%, and volumetric modulated arc therapy in 57% of cases. EBRT targets were 68% whole pelvis, 20% mini pelvis, and 12% prostate and seminal vesicles. Median follow up is 77 months (range = 25-139). 17% of patients had biochemical failure. 11% were identified as distant and 3% as regional lymph node failure by conventional imaging or PSMA PET. 4% had local failure diagnosed by PSMA PET or biopsy. 82% of patients had no evidence of disease at last follow up. 4-year PSA is available for 274 patients, 79% of whom have a PSA ≤0.2 ng/mL. For these patients, at most recent follow up (median 76 mo, range = 46-139 mo), the median current PSA was 0.04 ng/mL and 97% were free of prostate cancer recurrence. CTCAE V5 late grade 2 urethral strictures were seen in 5% and grade 3 in 3%. CTCAE V5 late grade 2 genitourinary and gastrointestinal bleeding was 0.6% and 3.4%, respectively, with no grade 3 toxicity. Conclusion HDR brachytherapy added to EBRT is an effective form of dose escalation for unfavorable localized prostate cancer. The very low rates of regional lymph node and prostate failure and minimal grade 3 toxicity have accelerated its rise to standard of care in our center.

The extent to which PSA screening is related to prostate cancer mortality reduction in the United States (US) is controversial. US Surveillance, Epidemiology, and End Results Program (SEER) data from 1980 to 2016 were examined to assess the relationship between prostate cancer mortality and cumulative excess incidence (CEI) in the PSA screening era and to clarify the impact of race on this relationship. CEI was considered as a surrogate for the intensity of prostate cancer screening with PSA testing and subsequent biopsy as appropriate. Data from 163,982,733 person-years diagnosed with 544,058 prostate cancers (9 registries, 9% of US population) were examined. Strong inverse linear relationships were noted between CEI and prostate cancer mortality, and 317,356 prostate cancer deaths were avoided. Eight regions of the US demonstrated prostate cancer mortality reduction of 46.0–63.7%. On a per population basis, the lives of more black men than white men were saved in three of four registries with sufficient black populations for comparison. Factor(s) independent of CEI (potential effects of treatment advances) explained 14.6% of the mortality benefit (p-value = 0.3357) while there was a significant main effect of CEI (effect = −0.0064; CI: [−0.0088, −0.0040]; p-value < 0.0001). Therefore, there is a strong relationship between CEI and prostate cancer mortality reduction that was not related to factors independent of screening utilization. Minority populations have experienced large mortality reductions in the context of PSA mass utilization.

Purpose/Objective(s) This single center randomized trial compared health-related QOL for men with unfavorable localized prostate cancer treated with combined pelvic external beam radiation (EBRT) and prostate brachytherapy (BT), randomly selected for either High Dose Rate (HDR) or Low Dose Rate (LDR). We now report the efficacy outcomes with a minimum 5 year follow up. Materials/Methods Consenting patients receiving pelvic EBRT (46 Gy/23) combined with prostate BT were randomized to either LDR (110 Gy) or HDR (15 Gy) boost. HDRBT preceded EBRT by one week, while LDRBT followed. Androgen deprivation was used in 76%, beginning with 3 months neoadjuvant and continued for median 12 months. EBRT delivered 46 Gy/23 fractions using IMRT or VMAT in 68% and 3DcRT in 32%. Image guidance was either daily cone beam CT or implanted fiducials. All patients were followed up at 1-, 3-, and 6-mo, every 6 mo to 3 years, then annually. PSA ≤ 0.2 at 4 years defined cure. Biochemical failure-free survival (bFFS), and overall survival (OS) were calculated by Kaplan Meier methods. Results From January 2014 to December 2019, a random number generator assigned 191 men (42% IR/ 58% HR): 108 to HDR and 87 to LDR. Median age was 71. Clinical stage was T1c in 15%, T2a/b in 48%, T2c/T3a in 35% and T3b in 2%. 43% had Gleason 8 or 9. Median PSA was 11.6 ng/mL, mean 27.0 ng/mL, max 145 ng/mL. The median follow up was 73 months (43 m – 116 m). The median PSA nadir was 0.07 in HDR and 0.08 in LDR (P = 0.16). The median time to PSA nadir was 13.8 mo in HDR and 14.1 in LDR (P = 0.87). At four years, 81% of HDR and 83% of LDR had a PSA ≤ 0.2 (P = 0.91). At five years, bFFS (nadir+2) for HDR and LDR were 94% and 90% respectively, and at 8 years 86% and 85% respectively. The 8-year OS for HDR and LDR was 73% and 70%. One patient in each arm had intraprostatic local failure. All failures were identified by imaging (CT, bone scan, and/or PSMA PET) +/- biopsy if conventional staging negative and PET not available. Twelve failures were distant, 3 regional and 2 combined regional and distant. Conclusion Previously reported primary QOL endpoint (ASTRO 2022) confirmed faster symptom recovery for HDR patients. In this small, randomized comparison, efficacy analysis shows no difference between LDR and HDR boost in biochemical disease-free survival at 5 and 8 years and confirms the excellent efficacy of dose escalation using a prostate brachytherapy boost as documented in the Ascende-RT trial for unfavorable localized prostate cancer.

Purpose This single-center randomized trial compared health-related QOL for men with unfavorable localized prostate cancer treated with combined pelvic external beam radiation (EBRT) and prostate brachytherapy (BT), randomly selected for either High Dose Rate (HDR) or Low Dose Rate (LDR). We now report the efficacy outcomes. Materials and Methods Consenting patients receiving pelvic EBRT (46Gy/23) combined with prostate BT were randomized to either LDR (110Gy) or HDR (15Gy) boost. HDRBT preceded EBRT by one week, while LDRBT followed. Androgen deprivation was used in 76%, beginning with three months neoadjuvant and continued for median 12 months. EBRT delivered 46 Gy/23 fractions using IMRT or VMAT in 68% and 3DcRT in 32%. Image guidance was either daily cone beam CT or implanted fiducials. All patients were followed up at 1-, 3-, and 6-mo, every 6 mo to 3 years, then annually. PSA ≤ 0.2 at 4 years defined cure. Biochemical failure-free survival (bFFS), and overall survival (OS) were calculated by Kaplan Meier methods. Results From 01/2014 to 12/2019, a random number generator assigned 191 men (42% IR/ 58% HR): 108 to HDR and 87 to LDR. Median age was 71. Clinical stage was T1c in 15%, T2a/b in 48%, T2c/T3a in 35% and T3b in 2%. 43% had Gleason 8 or 9. Median PSA was 11.6 ng/ml, mean 27.0 ng/ml, max 145 ng/ml. The median follow up was 73 months (43m - 116m). The median PSA nadir was 0.07 in HDR and 0.08 in LDR (p=0.16). The median time to PSA nadir was 13.8 mo in HDR and 14.1 in LDR (p=0.87). At four years, 81% of HDR and 83% of LDR had a PSA ≤ 0.2 (p=0.91). At five years, bFFS (nadir+2) for HDR and LDR were 94% and 90% respectively, and at 8 years 86% and 85% respectively. The 8-year OS for HDR and LDR was 73% and 70%. One patient in each arm had intraprostatic local failure. All failures were identified by imaging (CT, bone scan and/or PET) ± biopsy. 12 failures were distant, 3 regional and 2 combined regional and distant. Conclusions Previously reported primary QOL endpoint confirmed faster symptom recovery for HDR patients. In this small, randomized comparison, efficacy analysis shows no difference between LDR and HDR boost in biochemical disease-free survival at 5 and 8 years.