Radiotherapy For Prostate Cancer Research Articles

Early and repetitive novel-tracer PET-guided stereotactic body radiotherapy for nodal oligorecurrent prostate cancer after definitive first-line therapy.

Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) imaging can detect prostate cancer (PCa) nodal oligorecurrences (NOR) at very low prostate-specific antigen (PSA) levels. Prospective studies on oligorecurrent (OR) PCa have been hampered by either dated diagnostics or inhomogeneous cohorts and/or treatment approaches. We hypothesized that early and-if necessary and feasible-repetitive PSMA-PET-based metastasis-directed therapy (MDT) using stereotactic body radiotherapy (SBRT) would improve freedom from palliative (systemic) therapy at low toxicity. This study is aretrospective analysis of patients treated for OR PCa after definitive first-line therapy using PSMA-PET/CT-based SBRT. Endpoints were biochemical progression-free survival (bPFS), SBRT-free survival (SBRT-FS), androgen deprivation therapy (ADT)-free survival (ADT-FS), and toxicity. Atotal of 67patients and 248 metastases (211 nodal) were treated. Patients on concurrent ADT were excluded. Median PSA at inclusion was 2.175 ng/ml. bPFS, SBRT-FS, and ADT-FS for multiple-course SBRT were 9.5, 19.5, and 35.0 months, respectively; 32patients had ≥ 1course of SBRT. Median PSA nadir was 0.585 ng/ml. There was no ≥ grade2 toxicity. Modern-tracer PET/CT-based early and repetitive focal SBRT yields promising results with regard to bPFS, SBRT-FS, and ADT-FS with low toxicity. The ability of this approach to postpone initiation of palliative treatment with low toxicity should be re-evaluated prospectively.

Physician reported toxicities and patient reported quality of life of transperineal ultrasound-guided radiotherapy of prostate cancer

PurposeThis study aims to address therapy-related toxicities and quality of life in prostate cancer patients undergoing transperineal ultrasound (TPUS) guided radiotherapy (RT). MethodsAcute and late gastrointestinal (GI) and genitourinary (GU) toxicities were assessed by physicians using CTCAE v5.0. Patient-reported quality of life outcomes were evaluated using EORTC QLQ-C30, -PR25 and IPSS. We utilized Volumetric Modulated Arc Therapy (VMAT) or intensity modulated radiation therapy (IMRT) as the RT technique for this study. The assessments were carried out before RT, at RT end, 3 months after RT and subsequently at 1-year intervals. Prostate-specific antigen (PSA) was also evaluated at each follow-up. ResultsIn this study, a total of 164 patients were enrolled, while among them, 112 patients delivered quality-of-life data in a prospective evaluation. The median pre-treatment PSA was 7.9 ng/mL (range: 1.8–169 ng/ml). At the median follow-up of 19 months (3–82 months), the median PSA decreased to 0.22 ng/ml. Acute grade II GI and GU toxicities occurred in 8.6 % and 21.5 % patients at RT end. Regarding late toxicities, 2.2 % patients experienced grade II GI toxicities at 27 months and only one patient at 51 months, whereas no grade II GU late toxicities were reported at these time points. Quality of life scores also indicated a well-tolerated treatment. Patients mainly experienced acute clinically relevant symptoms of fatigue, pain, as well as deterioration in bowel and urinary symptoms. However, most symptoms normalized at 3 months and remained stable thereafter. Overall functioning showed a similar decline at RT end but improved over time. ConclusionThe outcomes of TPUS-guided RT demonstrated promising results in terms of minimal physician-reported toxicities and satisfactory patient-reported QoL.

A Machine Learning Approach for Predicting Biochemical Outcome After PSMA-PET-Guided Salvage Radiotherapy in Recurrent Prostate Cancer After Radical Prostatectomy: Retrospective Study.

Salvage radiation therapy (sRT) is often the sole curative option in patients with biochemical recurrence after radical prostatectomy. After sRT, we developed and validated a nomogram to predict freedom from biochemical failure. This study aims to evaluate prostate-specific membrane antigen-positron emission tomography (PSMA-PET)-based sRT efficacy for postprostatectomy prostate-specific antigen (PSA) persistence or recurrence. Objectives include developing a random survival forest (RSF) model for predicting biochemical failure, comparing it with a Cox model, and assessing predictive accuracy over time. Multinational cohort data will validate the model's performance, aiming to improve clinical management of recurrent prostate cancer. This multicenter retrospective study collected data from 13 medical facilities across 5 countries: Germany, Cyprus, Australia, Italy, and Switzerland. A total of 1029 patients who underwent sRT following PSMA-PET-based assessment for PSA persistence or recurrence were included. Patients were treated between July 2013 and June 2020, with clinical decisions guided by PSMA-PET results and contemporary standards. The primary end point was freedom from biochemical failure, defined as 2 consecutive PSA rises >0.2 ng/mL after treatment. Data were divided into training (708 patients), testing (271 patients), and external validation (50 patients) sets for machine learning algorithm development and validation. RSF models were used, with 1000 trees per model, optimizing predictive performance using the Harrell concordance index and Brier score. Statistical analysis used R Statistical Software (R Foundation for Statistical Computing), and ethical approval was obtained from participating institutions. Baseline characteristics of 1029 patients undergoing sRT PSMA-PET-based assessment were analyzed. The median age at sRT was 70 (IQR 64-74) years. PSMA-PET scans revealed local recurrences in 43.9% (430/979) and nodal recurrences in 27.2% (266/979) of patients. Treatment included dose-escalated sRT to pelvic lymphatics in 35.6% (349/979) of cases. The external outlier validation set showed distinct features, including higher rates of positive lymph nodes (47/50, 94% vs 266/979, 27.2% in the learning cohort) and lower delivered sRT doses (<66 Gy in 57/979, 5.8% vs 46/50, 92% of patients; P<.001). The RSF model, validated internally and externally, demonstrated robust predictive performance (Harrell C-index range: 0.54-0.91) across training and validation datasets, outperforming a previously published nomogram. The developed RSF model demonstrates enhanced predictive accuracy, potentially improving patient outcomes and assisting clinicians in making treatment decisions.

Ejaculatory function after radiotherapy for prostate cancer: a systematic review and meta-analysis.

Scant data exists on the impacts of prostate radiation on ejaculatory function. We performed a systematic review and meta-analysis to assess ejaculatory outcomes in men after prostate radiation. We queried PubMed, Embase, and Web of Science to identify 17 articles assessing ejaculatory function post-radiation. The primary outcome was anejaculation rate and secondary outcomes included ejaculatory volume (EV), ejaculatory discomfort, and mean decline in ejaculatory function scores (EFS). We assessed study quality with the Newcastle-Ottawa scale. We calculated pooled proportions using inverse variance and random effects models. We identified 17 observational studies with 2156 patients reporting ejaculatory profiles post-radiation. Seven studies utilized external beam radiation therapy, 7 brachytherapy, 1 stereotactic RT and 2 utilized either external or brachytherapy. Ten studies reported an anejaculation rate. Pooled proportion of patients having anejaculation, decreased EV and EjD were 18% (95% CI, 11-36%), 85% (95% CI, 81-89%) and 24% (95% CI, 16-35%), respectively. Five studies reported decline in EFS post-radiation. Patients receiving radiation treatment may experience significant changes in their ejaculation, such as the absence of ejaculation, reduced EV, and EjD. It is important to counsel them about these potential side effects.

Machine learning automated treatment planning for online magnetic resonance guided adaptive radiotherapy of prostate cancer

Background and purposeNo best practices currently exist for achieving high quality radiation therapy (RT) treatment plan adaptation during magnetic resonance (MR) guided RT of prostate cancer. This study validates the use of machine learning (ML) automated RT treatment plan adaptation and benchmarks it against current clinical RT plan adaptation methods. Materials and methodsWe trained an atlas-based ML automated treatment planning model using reference MR RT treatment plans (42.7 Gy in 7 fractions) from 46 patients with prostate cancer previously treated at our institution. For a held-out test set of 38 patients, retrospectively generated ML RT plans were compared to clinical human-generated adaptive RT plans for all 266 fractions. Differences in dose-volume metrics and clinical objective pass rates were evaluated using Wilcoxon tests (p < 0.05) and Exact McNemar tests (p < 0.05), respectively. ResultsCompared to clinical RT plans, ML RT plans significantly increased sparing and objective pass rates of the rectum, bladder, and left femur. The mean ± standard deviation of rectum D20 and D50 in ML RT plans were 2.5 ± 2.2 Gy and 1.6 ± 1.3 Gy lower than clinical RT plans, respectively, with 14 % higher pass rates; bladder D40 was 4.6 ± 2.9 Gy lower with a 20 % higher pass rate; and the left femur D5 was 0.8 ± 1.8 Gy lower with a 7 % higher pass rate. ConclusionsML automated RT treatment plan adaptation increases robustness to interfractional anatomical changes compared to current clinical adaptive RT practices by increasing compliance to treatment objectives.

Depth of Hydrogel Spacer Rectal Wall Infiltration Was Not Associated With Rectal Toxicity: Results From a Randomized Prospective Trial

Rectal spacers have gained popularity as a dose-sparing material for prostate cancer radiation therapy (RT). However, the procedure can be associated with unintended rectal wall infiltration (RWI) of the spacer gel. We therefore classified RWI severity as a function of depth and explored its association with rectal toxicity using a data set from prostate cancer patients treated with RT on a prospective randomized clinical trial (RCT). Postimplant T2-weighted magnetic resonance images of 149 subjects randomized to the hydrogel spacer arm of a published multicenter RCT were assessed for the presence and depth of RWI. All implants were assigned a score of 0 (no rectal wall signal changes), 1 (rectal wall edema/signal change), 2 (partial RWI), or 3 (full-thickness RWI); RWI was defined as a score of 2 or 3. Correlations were made between RWI score and physician-reported procedure, acute, and late rectal toxicity. Although 62.4% of implants had no rectal wall signal abnormalities, 24% [scores of 2 (20.1%) and 3 (4.0%)] of procedures exhibited radiographic evidence of RWI. Full-thickness RWI was associated with both a longer length (22.8 ± 7.0 mm, P = .008) and a larger circumferential percentage (35.8% ± 9.2%, P = .045) of rectal infiltration. Although 7 subjects (5%) experienced transient procedure-related rectal toxicities (most commonly perineal/rectal pain), only one had RWI (score of 2, National Cancer Institute's Common Terminology Criteria for Adverse Events grade 1). Consequently, no correlation was observed between procedural rectal toxicity and the presence/extent of RWI (P = .64). Similarly, no difference in acute (P = .64) or late (P = .85) rectal toxicity incidence or grade was detected between RWI categories; none of the 6 men with a RWI score of 3 developed late rectal toxicity by 15 months. Based on data from an RCT, RWI did not contribute to increased rectal toxicity prior and up to 15 months after conventional prostate cancer RT.

Biology-guided radiotherapy in metastatic prostate cancer: time to push the envelope?

The therapeutic landscape of metastatic prostate cancer has undergone a profound revolution in recent years. In addition to the introduction of novel molecules in the clinics, the field has witnessed a tremendous development of functional imaging modalities adding new biological insights which can ultimately inform tailored treatment strategies, including local therapies. The evolution and rise of Stereotactic Body Radiotherapy (SBRT) have been particularly notable in patients with oligometastatic disease, where it has been demonstrated to be a safe and effective treatment strategy yielding favorable results in terms of disease control and improved oncological outcomes. The possibility of debulking all sites of disease, matched with the ambition of potentially extending this treatment paradigm to polymetastatic patients in the not-too-distant future, makes Biology-guided Radiotherapy (BgRT) an attractive paradigm which can be used in conjunction with systemic therapy in the management of patients with metastatic prostate cancer.

A patient-specific auto-planning method for MRI-guided adaptive radiotherapy in prostate cancer

Background and purposeFast and automated generation of treatment plans is desirable for magnetic resonance imaging (MRI)-guided adaptive radiotherapy (MRIgART). This study proposed a novel patient-specific auto-planning method and validated its feasibility in improving the existing online planning workflow. Materials and methodsData from 40 patients with prostate cancer were collected retrospectively. A patient-specific auto-planning method was proposed to generate adaptive treatment plans. First, a population dose-prediction model (M0) was trained using data from previous patients. Second, a patient-specific model (Mps) was created for each new patient by fine-tuning M0 with the patient’s data. Finally, an auto plan was optimized using the parameters derived from the predicted dose distribution by Mps. The auto plans were compared with manual plans in terms of plan quality, efficiency, dosimetric verification, and clinical evaluation. ResultsThe auto plans improved target coverage, reduced irradiation to the rectum, and provided comparable protection to other organs-at-risk. Target coverage for the planning target volume (+0.61 %, P = 0.023) and clinical target volume 4000 (+1.60 %, P < 0.001) increased. V2900cGy (−1.06 %, P = 0.004) and V1810cGy (−2.49 %, P < 0.001) to the rectal wall and V1810cGy (−2.82 %, P = 0.012) to the rectum were significantly reduced. The auto plans required less planning time (−3.92 min, P = 0.001), monitor units (−46.48, P = 0.003), and delivery time (−0.26 min, P = 0.004), and their gamma pass rates (3 %/2 mm) were higher (+0.47 %, P = 0.014). ConclusionThe proposed patient-specific auto-planning method demonstrated a robust level of automation and was able to generate high-quality treatment plans in less time for MRIgART in prostate cancer.

Multi-scale anatomical regularization for domain-adaptive segmentation of pelvic CBCT images.

Cone beam computed tomography (CBCT) image segmentation is crucial in prostate cancer radiotherapy, enabling precise delineation of the prostate gland for accurate treatment planning and delivery. However, the poor quality of CBCT images poses challenges in clinical practice, making annotation difficult due to factors such as image noise, low contrast, and organdeformation. The objective of this study is to create a segmentation model for the label-free target domain (CBCT), leveraging valuable insights derived from the label-rich source domain (CT). This goal is achieved by addressing the domain gap across diverse domains through the implementation of a cross-modality medical image segmentationframework. Our approach introduces a multi-scale domain adaptive segmentation method, performing domain adaptation simultaneously at both the image and feature levels. The primary innovation lies in a novel multi-scale anatomical regularization approach, which (i) aligns the target domain feature space with the source domain feature space at multiple spatial scales simultaneously, and (ii) exchanges information across different scales to fuse knowledge from multi-scaleperspectives. Quantitative and qualitative experiments were conducted on pelvic CBCT segmentation tasks. The training dataset comprises 40 unpaired CBCT-CT images with only CT images annotated. The validation and testing datasets consist of 5 and 10 CT images, respectively, all with annotations. The experimental results demonstrate the superior performance of our method compared to other state-of-the-art cross-modality medical image segmentation methods. The Dice similarity coefficients (DSC) for CBCT image segmentation results is %, and the average symmetric surface distance (ASSD) is . Statistical analysis confirms the statistical significance of the improvements achieved by ourmethod. Our method exhibits superiority in pelvic CBCT image segmentation compared to its counterparts.

Enhancing Visualization of Gold Markers in Prostate Cancer Radiation Therapy Planning Through MRI Pulse Sequence Optimization

Prostate cancer treatment often involves the use of gold markers to enhance the accuracy of radiation therapy. However, the visualization of these markers using MRI remains a challenge due to their small size and susceptibility to artifacts. This study investigates the optimization of MRI pulse sequences to improve the visibility of gold markers in the context of radiation therapy simulation for prostate cancer patients. By comparing various pulse sequences and their parameters, we aim to identify the optimal configuration that provides the best contrast and minimal artifacts.

116 Factors Associated with Successful CT Simulation in Prostate Cancer Radiotherapy

116 Factors Associated with Successful CT Simulation in Prostate Cancer Radiotherapy

Stereotactic Radiation Therapy for Localized Prostate Cancer: 10-Year Outcomes From Three Prospective Trials

Background and purposeStereotactic ablative radiotherapy (SABR) is growingly accepted for the treatment of localized prostate cancer with recent randomized trials showing non-inferiority compared to conventional or moderately hypofractionated radiotherapy. The natural history of prostate cancer necessitates extended surveillance for recurrence; however, there are few prospective studies reporting long-term outcomes. Materials and methodsThis study included patients with low and intermediate risk localized prostate cancer from three Canadian clinical trials enrolled from 2006-2013. All patients received SABR to the prostate consisting of 35-40 Gy in 5 fractions over 11-29 days. PSA, distant metastasis, and vital status were prospectively recorded. Occurrence of second malignancy after treatment was assessed by chart review and classified using modified Cahan's criteria. Results267 patients were included. Median follow up was 10.3 years (IQR 7.8 – 12.7). 10-year BF (95% CI) was 7.7% (3.9-11.5). 10-year OS, PCSS, and FFM were 84.1% (79.3 – 89.1%), 99.2% (98.1 – 100), and 98.8% (97.5-100), respectively. 27/267 (10.1%) patients experienced a SM, with 6/27 patients (22.2%) classified as having a SM likely (n=3) or possibly (n=3) related to prior radiotherapy. 10-year freedom from SM was 89.2%. ConclusionSABR shows excellent long-term disease control for low and intermediate risk localized prostate cancer. Patients treated for prostate cancer have a moderate risk of second malignancy, consistent with background rates for the population.

Hypofractionated Dose Escalation Radiotherapy for High-Risk Prostate Cancer: the survival analysis of the Prostate Cancer Study-5 (PCS-5), a GROUQ-led phase III trial

Background and objectiveProstate Cancer Study 5 (PCS5) compared conventional fractionated radiotherapy (CFRT) with hypofractionated radiotherapy (HFRT) in high-risk prostate cancer (PCa) patients, hypothesizing similar toxicity and survival outcomes. This report presents the efficacy analysis. MethodsPCS5 is a Canadian multicenter, open-label, phase 3 randomized control trial. Men with histologically proven, clinically localized PCa with one or more high-risk features (T3/T4, Gleason score ≥8, and prostate-specific antigen >20) were eligible. Patients were randomized 1:1 to CFRT (76 Gy/38 fractions [Fx] to the prostate and 46 Gy/23 Fx to the pelvic lymph nodes [PLNs]) or HFRT (68 Gy/25 Fx to the prostate and 45 Gy/25 Fx to the PLNs) and 28 mo of androgen suppression. The primary endpoint was toxicity; secondary endpoints included survival outcomes. Key findings and limitationsOf 329 patients, 164 were randomized to HFRT and 165 to CFRT, with 159 in the HFRT arm and 160 in the CFRT arm included in survival analyses. At the 5-yr median follow-up, there were no significant differences in overall survival (OS; 90.3% vs 89.7%; risk ratio [RR]: 1.01; 95% confidence interval [CI]: 0.93–1.09), PCa-specific survival (PCSS; 97.4% vs 97.5%; RR: 1.00; 95% CI: 0.93–1.07), biochemical recurrence–free survival (BCRFS; 85.2% vs 85.2%; RR: 1.00; 95% CI: 0.91–1.10), or distant metastasis–free survival (DMFS; 87.1% vs 87.1%; RR: 1.00; 95% CI: 0.92–1.09). Hazard ratios were 0.92 (95% CI: 0.56–1.53) for OS, 1.31 (95% CI: 0.46–3.78) for PCSS, 0.85 (95% CI: 0.56–1.30) for BCRFS, and 0.90 (95% CI: 0.56–1.43) for DMFS. Sample size was a limiting factor. Conclusions and clinical implicationsThere were no differences in survival outcomes between HFRT (68 Gy/25 Fx) and CFRT (76 Gy/38 Fx). HFRT, including PLN radiotherapy and long-term androgen deprivation therapy, should be considered a new standard of care for high-risk PCa patients undergoing external beam radiotherapy.

44 Ultrahypofractionated Versus Moderately Hypofractionated and Conventionally Fractionated Pelvic Radiotherapy for Prostate Cancer: Outcomes from 3 Prospective Clinical Trials

44 Ultrahypofractionated Versus Moderately Hypofractionated and Conventionally Fractionated Pelvic Radiotherapy for Prostate Cancer: Outcomes from 3 Prospective Clinical Trials

Pretreatment plasma osteopontin level as a marker of response to curative radiotherapy and hormonal treatment for prostate cancer

Background and purposeOsteopontin is a known marker for tumour hypoxia with relevance for the outcome of radiotherapy. We analysed the plasma concentration of OPN in prostate cancer patients receiving RT with or without ADT to evaluate OPN as a potential marker of treatment response. Materials and methodsBetween 2012 and 2014, 274 patients with prostate cancer qualifying for RT were enrolled to the study. SCADT received 34.3 % of patients, LCADT 46.3 %. The median OPN concentration was 83.9 ng/mL. We analysed the groups by OPN level: group A with OPN below and group B with OPN above the median. ResultsThere was a significant difference in OPN between the Gleason score (p = 0.005), the D’Amico risk (p = 0.002), the ADT (p < 0.001) and the RT (p = 0.019) groups. We found a positive correlation between OPN and clinical stage (p = 0.042).There were no significant effect of OPN on bRFS, RFS and MFS. The 10-year OS rate for group A was 81 % and for group B 60 % (p < 0.001). Cox analysis showed that low OPN level (p < 0.001), low age (p = 0.002) and low Gleason score (p = 0.038) were associated with higher OS. The prognostic influence of OPN on survival decreased with duration of ADT with the strongest effect of OPN (HR=3.93) observed when RT alone was used, weakest effect (HR=2.48) for SCADT and the smallest effect (HR=2.09) for LCADT. ConclusionsBased on the obtained results, we assume that the level of OPN measured before the start of radiotherapy may be an independent predictor of OS of patients with prostate cancer treated with radiotherapy with and without ADT.

910: Comparison of Eclipse and RayStation in Multi-Criteria Optimization in Prostate Cancer Radiotherapy

910: Comparison of Eclipse and RayStation in Multi-Criteria Optimization in Prostate Cancer Radiotherapy

2943: Ultra hypofractionated radiotherapy in high risk prostate cancer: a real world experience

2943: Ultra hypofractionated radiotherapy in high risk prostate cancer: a real world experience

2592: Early Results of Curative Intent Radiotherapy in Low Burden Metastatic Prostate Cancer

2592: Early Results of Curative Intent Radiotherapy in Low Burden Metastatic Prostate Cancer

1280: Stereotactic Radiotherapy and ARTA in metastatic Castration-Resistant Prostate Cancer

1280: Stereotactic Radiotherapy and ARTA in metastatic Castration-Resistant Prostate Cancer

2802: Ultra-hypofractionated radiotherapy in High risk localised prostate cancer

2802: Ultra-hypofractionated radiotherapy in High risk localised prostate cancer