Faculty Bibliography

BACKGROUND AND OBJECTIVE/OBJECTIVE:Most patients with high-risk localized prostate cancer (HRLPC) do not undergo stereotactic body radiotherapy (SBRT) in part because of the limited evidence of long-term outcomes. We report long-term efficacy and toxicity outcomes for men treated with SBRT for HRLPC. METHODS:Individual patient data from ten prospective clinical studies evaluating SBRT for HRLPC across nine institutions were pooled in the Stereotactic Body Radiotherapy for High-Risk Localized Carcinoma of the Prostate consortium. The Kaplan-Meier method was used to estimate 5-yr biochemical recurrence (BCR) and distant metastasis (DM), stratified by receipt of intensified treatment (≥12 mo of androgen deprivation therapy [ADT] with extremely dose-escalated [≥8 Gy/fraction] prostate-directed SBRT). The impact of intensified treatment on BCR-free survival and DM-free survival was evaluated using multivariable Cox proportional hazards models. Late Common Terminology Criteria for Adverse Events grade ≥2 gastrointestinal (GI) and genitourinary (GU) toxicity was analyzed using time-to-event models. KEY FINDINGS AND LIMITATIONS/UNASSIGNED:In 440 patients with a median follow-up time of 60.4 mo, 5-yr BCR and DM rates were 22% (95% confidence interval [CI] = 17-26%] and 9.2% (95% CI = 6.2-12%), respectively. In the 93 patients (21%) who received intensified treatment, 5-yr BCR and DM rates were 7.4% (95% CI = 1.7-13%) and 3.7% (95% CI = 0-7.9%), respectively. Receipt of intensified therapy was associated with a significant reduction in both BCR (hazard ratio [HR] = 0.38 [95% CI = 0.20-0.74], p = 0.005) and DM (HR = 0.43 [95% CI = 0.18-0.99], p = 0.049). For the overall cohort, 5-yr rates of grade ≥2 GU and GI toxicity were 23% (95% CI = 19-27%) and 10% (95% CI = 7-13%), respectively. Limitations include heterogeneous treatment techniques and the nonrandomized nature of the study. CONCLUSIONS AND CLINICAL IMPLICATIONS/CONCLUSIONS:The safety and efficacy profile of SBRT for HRLPC remains favorable at long-term follow-up, and SBRT should be integrated into shared decision-making for treatment of HRLPC.

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.

BACKGROUND AND PURPOSE/UNASSIGNED:To evaluate the dosimetric and toxicity profiles of stereotactic body radiotherapy (SBRT) for prostate cancer, comparing cohorts with and without intraprostatic boost (IPB) to assess feasibility and safety of IPB, with particular attention to urethral and bladder dose and toxicity. MATERIALS AND METHODS/UNASSIGNED:This retrospective cohort study analyzed 349 patients with localized prostate cancer treated between 2018 and 2023. Of these, 266 received SBRT with IPB, and 83 received SBRT without IPB. Patients were treated using a robotic SBRT platform with fiducial tracking. Dosimetric parameters for the urethra, including D0.03cc, D0.3cc, and V40Gy, and for the bladder, including D0.03cc, D5cc, D10cc, and V37Gy, were evaluated. Acute and late toxicities were assessed using CTCAE criteria. RESULTS/UNASSIGNED:For the urethra, median values for D0.03cc, D0.3cc, and V40Gy, and for the bladder, median values D0.03cc, D5cc, D10cc, and V37Gy were compared and no statistically significant differences were observed between the two cohorts. Late urinary toxicity of grade 3 or higher occurred in 2.25 % of patients in the IPB group and 2.47 % in the no IPB group, with no grade 3 acute toxicities reported. DISCUSSION/UNASSIGNED:These findings support the use of SBRT using an IPB as a feasible and safe approach to achieve focal dose escalation to dominant intra-prostatic lesions (DILs) without significantly increasing urethra or bladder dose or toxicity. Future research should focus on standardizing DIL contouring, exploring adaptive planning techniques to increase accuracy, and prospectively studying toxicity and quality of life in patients treated with IPB with SBRT.

PURPOSE/OBJECTIVES/UNASSIGNED:SBRT is a standard of care treatment for localized prostate cancer. Whole gland dose escalation remains controversial. Concomitant intraprostatic boost (IPB) may offer an acceptable compromise for dose escalation. In this series, we report changes in International Prostate Symptom Scores (IPSS) over a 12-month period following SBRT with IPB in patients treated in a large academic institution. MATERIALS/METHODS/UNASSIGNED:Seventy-four patients treated from October 2018 to March 2022 with robotic stereotactic body radiotherapy completed IPSS questionnaires. IPSS were evaluated for patients at three timepoints: pre-treatment, post-treatment (defined as 3 months after SBRT completion), and at follow-up (defined as within 12 months after SBRT completion). The patients were stratified into two cohorts: patients who experienced minimally important difference (MID) in their post-treatment IPSS and those who did not. Urethral and bladder doses were retrospectively extracted from the treatment planning software and compared between the two cohorts using Wilcoxon rank sum test. RESULTS/UNASSIGNED:Of the 74 patients, 46 (62%) experienced MID in scores (cohort A), while 28 (38%) did not (cohort B). Patient characteristics in the two cohorts such as risk stratification and initial PSA were well-balanced. Median IPSS for cohort A were 5 (range: 0-21) pre-treatment, 12 (range: 3-28) post-treatment, and 8 (range: 1-32) at 12 months. For cohort B, the scores were 9.5 (range: 0-29), 7 (range: 1-19), and 8.5 (range: 0-32), respectively. In addition, there was a statistically significant difference in D0.03cc to the bladder in cohort A compared to cohort B (41.9 Gy vs 40.2 Gy; p < 0.001). CONCLUSION/UNASSIGNED:IPB is well tolerated with acceptable change in urinary quality of life metrics as measured by IPSS. Max dose to the bladder remains the only significant difference in patients who experienced MID in their urinary quality of life.