Faculty Bibliography

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.

INTRODUCTION/BACKGROUND:High-volume (≥ 50 %) biopsy core involvement (HVCI) is an independent risk factor for unfavorable intermediate-risk prostate cancer by NCCN guidelines. The studies demonstrating increased recurrence in high-volume disease were conducted in an era of conventional fractionation, often without dose-escalation. In the SBRT era, we explore the value of this pathologic criteria in intermediate-risk disease. METHODS:A large institutional database was reviewed to identify patients diagnosed with localized intermediate-risk (Gleason Grade [GG] 2 and 3) disease, who were treated with definitive five-fraction SBRT without ADT. HVCI was analyzed (1) traditionally with all positive cores given equal weight as well as weighted with a positive core of GG1 to GG3 given (2) linearly and (3) exponentially increased weight. Oncologic outcomes were analyzed using Cox and linear regression analysis. RESULTS:From 2009 to 2018, 888 patients with intermediate-risk prostate cancer were treated with five-fraction SBRT monotherapy to a median dose of 3500 cGy. The majority (68 %) had GG2 disease. HVCI was present in the 22 % and was inversely related to prostate volume and directly related to T-stage. Biochemical disease-free survival (BDFS) was not significantly associated with HVCI in the cohort (p = 0.47) nor in the GG2 (p = 0.85) and GG3 (p = 0.26) sub-cohorts. Similarly, when linear or exponential weight was given to a core with higher-grade disease, there was no association with BDFS. Finally, PSA nadir was not associated with HVCI; however, time to PSA nadir (TTN) was negatively associated with HVCI in the GG3 sub-cohort (p = 0.04). CONCLUSION/CONCLUSIONS:With a median follow-up of 4.1 years, HVCI was not associated with BDFS following SBRT monotherapy, particularly in patients with otherwise favorable intermediate-risk disease (GG2). TTN analysis suggests that HVCI may remain prognostic in GG3 disease (by definition unfavorable intermediate-risk). Further work should prospectively confirm whether HVCI is unnecessary in risk-stratifying GG2 disease in the SBRT era.

PURPOSE/OBJECTIVE:To evaluate the degree and rate of bladder filling during magnetic resonance imaging-guided linear accelerator (MRL) prostate stereotactic body radiotherapy (SBRT), and to determine the association of degree of bladder filling with intra-fractional prostatic motion requiring positional shifts during therapy. The impact of bladder filling on post-treatment target and normal tissue dosimetry was also evaluated. METHODS:Sixty-two consecutive prostate SBRT patients treated on the MRL with an empty bladder and a five-fraction regimen were evaluated. Bladder filling patterns during each treatment session and the frequency of required shifts to address intra-fractional prostate motion were studied. During each fraction, three MR image acquisitions were obtained: an immediate baseline T2-weighted sequence, a verification sequence after the plan was generated prior to treatment delivery, and a sequence post-treatment. Bladder filling rates were evaluated at these time points for each fraction and across the five treatment fractions. Multivariate analysis identified variables associated with increased bladder filling rates and the likelihood of positional target adjustments of the prostate during real-time adaptive planning. Post-treatment MR structures were used to recalculate plans for analysis of intra-fractional dosimetric variations in target and normal tissue doses. RESULTS:The median baseline bladder volume at fraction 1 was 88 cc (range 35-245), increasing to 138 cc (range 55-340) at verification MR and 156 cc (range 69-475) post-treatment. Bladder volume increases from baseline to verification MR and from verification MR to post-treatment MR were consistent across the cohort. Multivariate analysis identified the use of alpha receptor blockers during treatment (beta - 17.36 mL; 95 % CI - 32.97, -1.74; p = 0.030) and lower baseline bladder volume (beta 11.62 mL; 95 % CI 4.20, 19.05; p = 0.002) as significant factors in limiting both absolute bladder volume and the rate of bladder filling during adaptive SBRT fractions. Conversely, the need for a positional target shift at verification MR was associated with larger bladder volume (OR 1.20; 95 % CI 0.98, 1.46; p = 0.075) and high International Prostate Symptom Score (OR 5.42; 95 % CI 1.34, 21.89; p = 0.018). Post-treatment dosimetric analysis revealed no notable compromises to prostate target coverage (D95Gy median -0.19 Gy, IQR 0.49) or normal tissue constraints. CONCLUSIONS:This analysis of bladder filling dynamics in patients undergoing prostate SBRT with real-time adaptive planning demonstrated predictable bladder filling patterns using an empty bladder regimen. Dose-volume constraints were consistently achieved for both target volumes and normal tissues. The finding that alpha receptor blockers reduced the rate of bladder filling during treatment fractions may have implications for improving treatment consistency and patient comfort in real-time adaptive planning workflows.

PURPOSE/UNASSIGNED:Screening colonoscopies (CS) performed before prostate stereotactic body radiation therapy (SBRT) allow for identifying synchronous malignancies and comorbid gastrointestinal (GI) conditions. Performing these procedures prior to radiation precludes the necessity of post-SBRT pelvic instrumentation, which may lead to severe toxicity and fistulization. We review compliance of CSs, incidence of GI pathology, and the impact of pretreatment CS findings on subsequent physician-reported toxicity and patient-reported quality of life (QoL). METHODS AND MATERIALS/UNASSIGNED:We reviewed an institutional database of patients treated for prostate cancer with SBRT including toxicity and QoL outcomes. A detailed review of pretreatment CS findings was reviewed including identification of diverticulosis, location of polyp resection, and presence of hemorrhoids. Pretreatment CS findings were then correlated with outcomes following SBRT. RESULTS/UNASSIGNED:Identification of comorbid GI conditions was a common event, with the presence of diverticulosis in 49.5% (n = 100), hemorrhoids in 67% (n = 136), and polyps in 48% (n = 98). More than half of patients with polyps removed had at least 1 removed from the rectosigmoid. Pretreatment CS did not introduce a delay in SBRT start date. Grade 1 toxicity was significantly lower in patients who underwent CS closer to the initiation of SBRT. There was no increased risk of physician-graded toxicity in the presence of diverticulosis, hemorrhoids, or polyps. Patient-reported GI QoL pattern in our screening cohort mimicked that seen in the previously published nonscreened population. There was no overt QoL detriment observed in patients who had GI pathology identified before SBRT. CONCLUSIONS/UNASSIGNED:GI pathology identified in our elderly patient population was commonly identified on pretreatment CS. Screening CS may optimize bowel health for patients heading into radiation therapy. Toxicity and QoL for patients with GI pathologies identified on pretreatment CS do not preclude the delivery of prostate SBRT. We advocate for pretreatment CS in patients eligible prior to SBRT.

PURPOSE/OBJECTIVE:To explore pragmatic approaches integrating MRI and PSMA-PET/CT for evaluating extraprostatic extension (EPE) of prostate cancer (PCa). METHODS:>12). Diagnostic performance was tested with receiver operating characteristic (ROC) curves and compared using DeLong and McNemar tests. RESULTS:>12 among which 87.5% (7/8) were corrected upgraded and had pathological EPE. CONCLUSION/CONCLUSIONS:Several pragmatic approaches were explored for integrating MRI and PSMA-PET/CT to assess EPE in PCa. Combining morphological information from MRI and PSMA expression on PET/CT demonstrated good diagnostic performance and may be a simple pragmatic integrated method that can be used.

PURPOSE/OBJECTIVE:This systematic review provides an overview of the available literature regarding the efficacy and safety of implantable rectal spacers (IRS) in reducing rectal dose and gastrointestinal (GI) toxicity during prostate cancer (PC) radiotherapy (RT). METHODS AND MATERIALS/METHODS:A comprehensive literature search was conducted in December 2024. Results included prospective research in humans and were limited to the English language. The 30 included studies, all published between 2007 and 2024, were randomized controlled trials (RCTs) or clinical trials which focused on adverse events (AEs), rectal dose reduction, GI toxicity, or bowel quality of life (QOL). Secondly, IRS implantation technique, safety, and spacing distance were assessed. RESULTS:RCT data was available for hydrogel (HG), hyaluronic acid (HA) and rectal balloon implant (RBI) spacers, while only one pilot study is available for HC. Prospective clinical research on IRS in brachytherapy is limited. One centimeter of spacing between rectum and prostate sufficed to spare the rectum, the primary dose-limiting organ. Findings indicate a favorable safety profile, with an overall complication rate of 0,96% when using hydrogel (HG) spacers. There was no grade 4-5 GI toxicity reported in clinical trials. The use of an IRS was associated with improved long-term bowel QOL. CONCLUSIONS:The integration of IRS into clinical practice offers potential to enhance the therapeutic landscape for PC patients. However, its use should be guided by careful consideration of individual patient needs to determine those who benefit most from IRS, as not all patients may benefit equally.

OBJECTIVES/UNASSIGNED:To evaluate the incidence and degree of rectal wall infiltration (RWI) of spacer gel used during prostate radiotherapy among two practitioners experienced in using rectal spacers. MATERIALS AND METHODS/UNASSIGNED:Consecutive patients with prostate cancer who received prostate radiotherapy after hydrogel rectal spacer insertion in August 2023-August 2024 by two experienced practitioners were retrospectively included. Post-implant magnetic resonance imaging examinations were evaluated by two radiologists for RWI: 0 (no abnormality), 1 (rectal wall edema), 2 (superficial RWI), and 3 (deep RWI). Scores 2-3 were considered positive for RWI and their location and degree of RWI (radial, longitudinal, and circumferential) were also categorized. Inter-reader agreement was assessed with Cohen's Kappa. RESULTS/UNASSIGNED:215 men were included. Agreement was substantial between the radiologists for RWI scores (Kappa, 0.697; 95% confidence interval, 0.594-0.800). RWI scores were 0 in 80.5% (173/215), 1 in 7.9% (17/215), 2 in 10.7% (23/215), and, 3 in 0.9% (2/215) of the men. Altogether, RWI was present (scores 2-3) in 11.6% (25/215), most commonly in the mid-gland and apex with median radial, longitudinal, and circumferential involvement of 3.2 mm, 8.6 mm, and 11.5%. None of these patients demonstrated any significant rectal toxicity. CONCLUSION/UNASSIGNED:RWI was very uncommon for experienced practitioners. The degree of RWI was focal and not associated with increased complications.