Faculty Bibliography

PURPOSE/OBJECTIVE:This study evaluated the extent of prostate displacement during SBRT on an MRI Linac using comprehensive motion management (CMM) and identified variables associated with intrafraction motion (IFM). METHODS:212 patients with clinically localized prostate cancer were treated with 5-fraction SBRT on a 1.5 T MR-Linac where IFM was continuously tracked and gated by CMM. Pre-beam positional shifts were identified from MRI registration prior to beam delivery. Intrafraction positional variability during beam delivery was evaluated, and multivariable analysis identified variables associated with IFM. RESULTS:In 614 fractions (62.7%), a > 1.5 mm pre-beam positional shift led to an adapt-to-position (ATP) plan correction. Mean anterior-posterior and superior-inferior pre-beam shifts were 2.2 mm and 2.1 mm, respectively. For 962 evaluable fractions, the median beam-on-time was 13.7 min with a mean duty cycle of 95.8%. Sustained > 3 mm displacement was observed in 520 fractions (54.1%) with a median cumulative duration of 24 s; >5 mm displacement was observed in 209 fractions (21.7%) with a median duration of 12.4 s. The ATS + ATP workflow was associated with reduced odds of sustained > 3 mm motion (p = 0.035), while older age was associated with increased odds (p = 0.011). CONCLUSIONS:Significant prostate shifts can occur immediately prior to and during radiation beam delivery, frequently exceeding applied margins and potentially leading to tumor underdosage. Continuous motion tracking and gating during prostate SBRT is an important tool in reducing IFM and enhance treatment delivery accuracy.

INTRODUCTION/BACKGROUND:Focal dose intensification strategies targeting the dominant intra-prostatic lesion (DIL) improve outcomes of patients with prostate cancer. The purpose was to determine whether the 6-month multiparametric (mp)MRI response of the DIL is associated with post-treatment prostate-specific antigen (PSA) kinetics after MRI linear accelerator (LINAC) guided stereotactic body radiotherapy (SBRT) with focal dose intensification. METHODS:), and PSA ≤ 1.0 ng/mL. RESULTS:(100.0% vs 82.9%, p = 0.010) and PSA ≤ 1.0 ng/mL (45.9% vs 11.4%, p = 0.001) compared to those without mpMRI CR. In 10 patients without 6-month mpMRI CR but had further MRI follow-up (median 13 months), DILs either further decreased in size (30.0%) or resolved (70.0%). CONCLUSION/CONCLUSIONS:Initial 6-month mpMRI response correlates with PSA kinetics, which is associated with important clinical outcomes. mpMRI can be used for post-SBRT evaluation to gauge local tumor response of the DIL, where most recurrences occur.

OBJECTIVE:Indeterminate lesions on prostate-specific membrane antigen (PSMA)-PET are challenging to address. We aimed to develop, implement, and evaluate a multidisciplinary consensus algorithm that integrates existing interpretation systems with multimodality imaging and clinicopathological information for interpreting indeterminate bone and lymph node lesions on PSMA-PET. MATERIALS AND METHODS/METHODS:This was a retrospective single-center study on a prospectively implemented algorithm. We included all consecutive prostate cancer patients whose PSMA-PET findings for indeterminate bone lesions or lymph nodes were discussed at a multidisciplinary tumor board (MDT) in 2024-2025. An algorithm determining the level of suspicion for metastasis was developed in a multidisciplinary fashion, incorporating lesion location, conventional imaging features, PSMA-PET characteristics, and clinicopathological information. The application of the algorithm and outcomes were documented, compared against a composite reference standard. Comparisons were made with PSMA-RADS and PROMISE V2 PSMA-expression scores. RESULTS:81 patients (median age 68, interquartile range 64-75) were included. Algorithm results were benign (48.1% [39/81]), equivocal (4.9% [4/81]), metastasis (40.7% [33/81]), and mixed (benign and metastatic lesions, 6.2% [5/81]). The algorithm was correct in 94.1% (64 of 68 patients with a sufficient reference standard). The algorithm was discordant with PSMA-RADS in 54.3% (44/81) and with PROMISE V2 PSMA-expression score in 71.6% (58/81). The frequency of equivocal lesions was lower using the algorithm (4.9% [4/81]) compared with PSMA-RADS (53.1% [43/81]) and PSMA-expression score (64.2% [52/81]). CONCLUSION/CONCLUSIONS:A multidisciplinary consensus algorithm for interpreting indeterminate bone lesions and lymph nodes on PSMA-PET was developed and implemented. Integrating clinicopathological information and multimodality imaging in an MDT setting reduced equivocal interpretations. KEY POINTS/CONCLUSIONS:Question While prostate-specific membrane antigen (PSMA)-PET has become essential in the management of prostate cancer, indeterminate bone lesions and lymph nodes remain challenging to address. Findings A multidisciplinary algorithm for interpreting indeterminate bone lesions and lymph nodes on PSMA-PET, incorporating clinicopathological information and multimodality imaging, reduced the frequency of equivocal interpretations. Clinical relevance An algorithm for interpreting indeterminate bone lesions and lymph nodes on PSMA-PET, incorporating clinicopathological information and multimodality imaging in a multidisciplinary tumor board setting, decreases the frequency of equivocal interpretations and can potentially help management decisions.

PURPOSE/OBJECTIVE:Optimizing radiotherapy delivery for higher-risk prostate cancer often requires dose escalation while minimizing dose to surrounding normal tissues. We report on the feasibility of combining high-dose-rate (HDR) brachytherapy with dose intensification to the dominant intra-prostatic lesion (DIL) followed by magnetic resonance-guided stereotactic body radiotherapy (MRgSBRT). METHODS AND MATERIALS/METHODS:Eighty-eight patients were treated with a single fraction of 15-Gy HDR brachytherapy boost followed by MRgSBRT to prostate, or prostate and pelvic lymph nodes, to a dose of 25 Gy in five fractions. The DIL noted on multi-parametric MR imaging was defined as a PIRADS-4/-5 lesion with an associated diffusion-weighted abnormality(s), and was intraoperatively boosted during brachytherapy to 120% of the prescription dose. Dosimetric objectives included D99% >120% to the DIL, D1% <120% for the urethra and D1cc <80% for the rectum. Real-time adaptive SBRT was delivered with a 1.5-T Unity MR Linac. RESULTS:For the HDR procedure, the mean prostate and DIL D90% were 108.3% ± 2.7% and 135.9% ± 12.2%, respectively. Mean urethra Dmax and D20% were 116.5% ± 4.5% and 108.2% ± 3.8%, respectively. Mean rectal V100 and D1cc were 0.0 ± 0.0cc and 73.6% ± 7.0%, respectively. DIL objective was not met in two lesions owing to proximity of the urethra and bladder neck. At a median follow-up of 6.8 months, Grade 2 genitourinary acute toxicity was observed in 33% of patients and Grade 2 acute gastrointestinal toxicity was observed in 1%. CONCLUSIONS:HDR boost with dose escalation to the DIL in combination with MRgSBRT is a feasible and effective treatment protocol. No significant genitourinary or gastrointestinal acute toxicity was observed.

Post-radiotherapy erectile dysfunction (ED) can significantly impact the quality of life of patients with prostate cancer (PCa). Critical anatomical structures, such as the neurovascular bundle (NVB), internal pudendal arteries (IPA), penile bulb, and corporal tissues track in close proximity to the prostate, making them susceptible to radiation-related damage. This study aimed to evaluate the anatomical patterns of these structures and their relationship with the prostate, and to provide comprehensive illustrative examples on MRI. Consecutive patients with PCa who underwent MRI-linear accelerator (LINAC)-based stereotactic body radiotherapy (SBRT) in January-December 2024 were included. NVB patterns were classified into 3 categories: (1) "classical" with discrete NVB elements, (2) "adherent", dispersed and adherent to prostatic capsule, and (3) "absent". The smallest distance between the IPA and the prostate capsule and membranous urethral length (MUL), serving as a surrogate for distance between corporal tissue and prostatic apex, were also measured. These MRI findings were compared between prostate volumes >40 and <40 ml and between MRI/pathological features of the dominant intraprostatic lesion. A total of 160 men (median age 70 years, interquartile range [IQR] 64-76) were included. The most common NVB pattern was "classic" (80.0-85.0%), followed by the "adherent" NVB pattern (13.8-18.1%). The median smallest distance between the IPA and prostate was 2.3 cm (IQR 1.8-2.8 cm), with 3.1-3.8% less than 1.0 cm. The median MUL was 1.5 cm (IQR, 1.2-1.8 cm), with 2.5% of patients less than 1.0 cm. No significant association was found between these MRI features and prostate volume or other variables (p = 0.09-0.99). In conclusion, most PCa patients demonstrated favorable anatomy for potential dose sparing of critical structures. Comprehensive MRI illustrations are provided to help radiation oncologists recognize the location, trajectory, and relationship of these structures, facilitating their contouring and ultimately aiding in achieving meaningful dose reductions to these erectile function structures.

PURPOSE/OBJECTIVE:Genomic classifiers are endorsed by guidelines and commonly used to inform prognosis in prostate cancer. We aimed to understand the distribution of genomic risk within the validated staging collaboration for cancer of the prostate (STAR-CAP) and propose a system integrating genomic and clinicopathologic risk. We hypothesized that genomic heterogeneity would have implications on risk estimates and may inform treatment decisions. MATERIALS AND METHODS/METHODS:Genomic risk was assessed using the Decipher genomic classifier in two separate multi-institutional, prospectively collected population-based registries: (1) Decipher Genomics Resource for Intelligent Discovery (GRID) [n = 50,891] and (2) Michigan Urological Surgery Improvement Collaborative (MUSIC-Decipher) [n = 1602]. The primary endpoint was estimated prostate cancer-specific mortality (PCSM), and secondary endpoint was distant metastasis (DM). Marginal risk estimates provided by STAR-CAP were combined with hazard ratios of Decipher to calculate integrated risk estimates. RESULTS:Median age and PSA was 68 years and 6.2 ng/mL in GRID, and 66 years and 10.5 ng/mL in MUSIC. The GRID population had 50.2%, 18.5%, and 31.4% with low-, intermediate-, and high-Decipher risk, compared to 48.0%, 16.2%, and 35.8% in MUSIC. Decipher-based genomic risk varied across STAR-CAP stages in both registries. Estimates of 10-year PCSM (0.1% to 48.8%) and DM (0.3%-72.9%) varied widely after integration of clinical-genomic risk. Use of an integrated Decipher-STAR-CAP system led to significant stage reclassification, including 23.4% upstaging and 45.6% downstaging at least one stage. CONCLUSIONS:These findings suggest integration of genomic and clinicopathologic risk may lead to more nuanced risk assessment in prostate cancer and may help individualize treatment consideration.

PURPOSE/UNASSIGNED:This study aims to evaluate the feasibility of delivering escalated doses to the dominant intraprostatic lesion (DIL) as noted on T2-weighted magnetic resonance imaging and diffusion-weighted imaging while maintaining dose to the surrounding normal tissue structures within dose-volume constraints. METHODS AND MATERIALS/UNASSIGNED:A total of 50 consecutive patients were treated with prostate stereotactic body radiation therapy (SBRT), via a simultaneous integrated boost to the DIL, on a 1.5-Tesla magnetic resonance imaging linear accelerator platform. These patients were treated with SBRT to 40 Gy in 5 fractions every other day, and the DIL was simultaneously boosted to 45 Gy in 5 fractions. No patient was treated with androgen deprivation therapy. The normal tissue structures and the prostate and DIL were recontoured, and a postfraction plan was generated to retrospectively generate the doses delivered to the prostate and the DIL boost target for each of these 250 therapy sessions. RESULTS/UNASSIGNED:< .05). Despite excellent target coverage, the rectum, urethra, and bladder dose constraints were generally maintained. At 6 months from completion of therapy, the median prostate-specific antigen result was 1.1 ng/mL (range, 0-5.6 ng/mL) compared to the median pre-SBRT prostate-specific antigen of 6.8 ng/mL (range, 3.45-31 ng/mL). No patient developed late grade 3 or higher urinary or rectal toxicities at median follow-up of 10.8 months (range, 6.4-15.7 months). CONCLUSIONS/UNASSIGNED:With real-time adaptive planning on a magnetic resonance imaging linear accelerator, dose escalation was achieved in most cases with the intended doses without significantly compromising the dose-volume constraints of the surrounding normal tissue structures. These dosimetric findings were associated with an excellent tolerance profile at 12 months and a low incidence of urinary or rectal toxicity.

PURPOSE/OBJECTIVE: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/METHODS: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/UNASSIGNED:We evaluated prostate volume changes during stereotactic body radiation therapy (SBRT) using serial MRI, identifying variables associated with prostatic swelling and their correlation with acute toxicity. METHODS/UNASSIGNED:Fifty-two patients with localized prostate cancer, androgen deprivation therapy naive, underwent SBRT to 40 Gy in five fractions on an MRI-Linear Accelerator with dominant intraprostatic lesion boosts to 45 Gy when present. Whole prostate (WP) and transition zone (TZ) measurements were assessed on the pre-treatment T2 MRI obtained for daily adaptation. Volumes were calculated using the ellipsoid formula. Non-transition zone (nonTZ) measures = WP values - TZ values. Transition zone index (TZI) = TZ volume/WP volume. Acute toxicity and International Prostate Symptom Scores (IPSS) were recorded. RESULTS/UNASSIGNED:Prostate volume increased significantly over the first four fractions, peaking at fraction 4 with mean percent and absolute changes of 21 % and 7.8 cc, respectively. Standardized TZ measures were strongly associated with WP volume (β per SD 10.60-12.78; all p < 0.001), whereas the only nonTZ dimension weakly associated was anteroposterior (β per SD 1.78). Each standard deviation increase in baseline TZ parameters doubled to tripled the odds of significant swelling (≥10 cc) (all p ≤ 0.011). The interaction of baseline TZI with later fractions was significantly associated with swelling (fraction 4: β = 12.06, p = 0.020; fraction 5: β = 10.96, p = 0.036), but not baseline TZI alone. Neither Grade 2+ genitourinary toxicity nor IPSS changes were associated with prostate measures or TZI. CONCLUSIONS/UNASSIGNED:Prostate volume significantly increases during SBRT, primarily corresponding with TZ volumetric changes. Baseline TZ measurements most strongly predict high-volume swelling. Acute toxicity was not associated with volumetric change.