Faculty Bibliography

PURPOSE/OBJECTIVE:There are limited data regarding high-dose stereotactic body radiation therapy (SBRT) for prostate cancer in patients with poor baseline urinary function. The purpose of this study was to evaluate genitourinary (GU) toxicity and changes in patient-reported symptom severity scores after prostate SBRT in men with a high pretreatment International Prostate Symptom Score (IPSS). METHODS AND MATERIALS/METHODS:Seven hundred fifty-three patients treated with prostate SBRT at our institution from 2012 to 2019 were identified, of whom 72 consecutive patients with baseline IPSS ≥15 were selected for this study. GU toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and IPSS were prospectively documented at each follow-up visit. Univariable logistic regression was used to evaluate for potential predictors of GU toxicity. RESULTS:= .001). CONCLUSIONS:In men with baseline IPSS ≥15 managed with prostate SBRT, the rate of severe GU toxicity was low and patient-reported symptoms generally improved over time. Thus, high pretreatment IPSS should not deter clinicians from offering prostate SBRT.

IMPORTANCE:In 2016, the American Joint Committee on Cancer (AJCC) established criteria to evaluate prediction models for staging. No localized prostate cancer models were endorsed by the Precision Medicine Core committee, and 8th edition staging was based on expert consensus. OBJECTIVE:To develop and validate a pretreatment clinical prognostic stage group system for nonmetastatic prostate cancer. DESIGN, SETTING, AND PARTICIPANTS:This multinational cohort study included 7 centers from the United States, Canada, and Europe, the Shared Equal Access Regional Cancer Hospital (SEARCH) Veterans Affairs Medical Centers collaborative (5 centers), and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry (43 centers) (the STAR-CAP cohort). Patients with cT1-4N0-1M0 prostate adenocarcinoma treated from January 1, 1992, to December 31, 2013 (follow-up completed December 31, 2017). The STAR-CAP cohort was randomly divided into training and validation data sets; statisticians were blinded to the validation data until the model was locked. A Surveillance, Epidemiology, and End Results (SEER) cohort was used as a second validation set. Analysis was performed from January 1, 2018, to November 30, 2019. EXPOSURES:Curative intent radical prostatectomy (RP) or radiotherapy with or without androgen deprivation therapy. MAIN OUTCOMES AND MEASURES:Prostate cancer-specific mortality (PCSM). Based on a competing-risk regression model, a points-based Score staging system was developed. Model discrimination (C index), calibration, and overall performance were assessed in the validation cohorts. RESULTS:Of 19 684 patients included in the analysis (median age, 64.0 [interquartile range (IQR), 59.0-70.0] years), 12 421 were treated with RP and 7263 with radiotherapy. Median follow-up was 71.8 (IQR, 34.3-124.3) months; 4078 (20.7%) were followed up for at least 10 years. Age, T category, N category, Gleason grade, pretreatment serum prostate-specific antigen level, and the percentage of positive core biopsy results among biopsies performed were included as variables. In the validation set, predicted 10-year PCSM for the 9 Score groups ranged from 0.3% to 40.0%. The 10-year C index (0.796; 95% CI, 0.760-0.828) exceeded that of the AJCC 8th edition (0.757; 95% CI, 0.719-0.792), which was improved across age, race, and treatment modality and within the SEER validation cohort. The Score system performed similarly to individualized random survival forest and interaction models and outperformed National Comprehensive Cancer Network (NCCN) and Cancer of the Prostate Risk Assessment (CAPRA) risk grouping 3- and 4-tier classification systems (10-year C index for NCCN 3-tier, 0.729; for NCCN 4-tier, 0.746; for Score, 0.794) as well as CAPRA (10-year C index for CAPRA, 0.760; for Score, 0.782). CONCLUSIONS AND RELEVANCE:Using a large, diverse international cohort treated with standard curative treatment options, a proposed AJCC-compliant clinical prognostic stage group system for prostate cancer has been developed. This system may allow consistency of reporting and interpretation of results and clinical trial design.

BACKGROUND:Studies using stereotactic body radiotherapy (SBRT) dose escalation in in low- and intermediate-risk prostate cancer patients have indicated favorable outcomes. OBJECTIVE:To evaluate tolerance and tumor control outcomes in low- and intermediate-risk prostate cancer patients treated with high-dose SBRT following our phase 1 trial. DESIGN, SETTING, AND PARTICIPANTS:A total of 551 patients with low- or intermediate-risk prostate cancer were treated with SBRT. INTERVENTION:Treatment with 37.5-40Gy SBRT in five fractions directed to the prostate and seminal vesicles. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Outcome measurements included acute toxicities (<3 mo after radiotherapy [RT]) and late toxicities (>3 mo after RT) and tumor control evaluation (prostate-specific antigen [PSA] levels at 3-6-mo intervals and post-treatment prostate biopsy at 2yr). RESULTS AND LIMITATIONS:Acute grade 2 gastrointestinal (GI) toxicities occurred in 1.8% of patients, and late grade 2 and 3 GI toxicities were observed in 3.4% and 0.4% of patients, respectively. Acute grade 2 genitourinary (GU) toxicities occurred in 10% of patients, and grade 3 acute GU toxicities were observed in 0.7% of patients. Late grade 2 and 3 GU toxicities were observed in 21.1% and 2.5% of patients, respectively. The use of a hydrogel rectal spacer was significantly associated with reduced late GI toxicity and lower odds of developing late GU toxicity. The median follow-up was 17 mo, and 53% of those with at least 2yr of follow-up (103/193) had a biopsy performed. The 5-yr cumulative incidence of PSA failure was 2.1%, and the incidence of a positive 2-yr treatment biopsy was 12%. Limitations to this report include its retrospective nature and short follow-up time. CONCLUSIONS:Favorable short-term outcomes were achieved with high-dose SBRT for low- and intermediate-risk disease. Severe late toxicities were observed and favorable tumor control was found. PATIENT SUMMARY:We utilized stereotactic body radiotherapy, a form of external beam radiotherapy that delivers highly targeted high-dose treatment to the prostate, to treat over 500 localized prostate cancer patients in five sessions over 1.5 wk. Treatments were well tolerated without significant urinary or rectal side effects. Nearly 90% of those who underwent biopsies after treatment did not demonstrate residual active disease.

PURPOSE:To report early toxicity and tumor control outcomes of Pd-103 brachytherapy with ultrahypofractionated stereotactic radiation therapy (RT) for intermediate-risk prostate cancer. METHODS AND MATERIALS:This prospective trial included 40 patients with intermediate-risk prostate cancer who underwent low-dose-rate (Pd-103) brachytherapy (prescription dose, 100 Gy), followed 1 month later with ultrahypofractionated stereotactic RT (25 Gy in 5 fractions) to the prostate and seminal vesicles. The primary endpoint was the rate of grade 2+ genitourinary toxicity at 12 months using Common Terminology Criteria for Adverse Events v 4.0. Secondary endpoints included patient-reported quality-of-life metrics (International Prostate Scoring System [IPSS], International Index of Erectile Function, and Expanded Prostate Cancer Index Composite-bowel). Biochemical failure was defined as prostate-specific antigen nadir +2 ng/mL. Posttreatment biopsies were performed at between 24 and 36 months; median follow-up was 36 months. RESULTS:The rate of grade 2 urinary toxicity at 12 months was 25% with no grade 3 urinary toxicity noted. Mean IPSS at baseline and 12 and 24 months was 5, 10, and 6.2, respectively. Mean change in IPSS from baseline at 12 months was +5.5 (interquartile range, 1-9.75) and +1.05 (interquartile range, -3 to 3.25) at 24 months. Grade 2 bowel toxicity was 5% at 12 months with no grade 3 bowel toxicity noted. Mean Expanded Prostate Cancer Index Composite-bowel domain scores at baseline and 12 months were 92.8 and 90.3, respectively. Of patients who were potent (International Index of Erectile Function ≥21) at baseline, 75% remained potent at 12 months. Of 40 patients, 28 underwent posttreatment prostate biopsy (PPB), which was negative (n = 20) or demonstrated severe treatment effect (n = 8). No patient had a positive PPB or developed biochemical failure during the follow-up period. One patient without a PPB developed osseous metastases at 18 months posttreatment in the absence of biochemical failure. CONCLUSION:Low-dose-rate brachytherapy in combination with ultrahypofractionated stereotactic RT was safe and effective for intermediate-risk prostate cancer in early results of this trial.

BACKGROUND:To evaluate inter-fractional variations in bladder and rectum during prostate stereotactic body radiation therapy (SBRT) and determine dosimetric and clinical consequences. METHODS:Eighty-five patients with 510 computed tomography (CT) images were analyzed. Median prescription dose was 40 Gy in 5 fractions. Patients were instructed to maintain a full bladder and empty rectum prior to simulation and each treatment. A single reviewer delineated organs at risk (OARs) on the simulation (Sim-CT) and Cone Beam CTs (CBCT) for analyses. RESULTS:Bladder and rectum volume reductions were observed throughout the course of SBRT, with largest mean reductions of 86.9 mL (19.0%) for bladder and 6.4 mL (8.7%) for rectum noted at fraction #5 compared to Sim-CT (P < 0.01). Higher initial Sim-CT bladder volumes were predictive for greater reduction in absolute bladder volume during treatment (ρ = - 0.69; P < 0.01). Over the course of SBRT, there was a small but significant increase in bladder mean dose (+ 4.5 ± 12.8%; P < 0.01) but no significant change in the D2cc (+ 0.8 ± 4.0%; P = 0.28). The mean bladder trigone displacement was in the anterior direction (+ 4.02 ± 6.59 mm) with a corresponding decrease in mean trigone dose (- 3.6 ± 9.6%; P < 0.01) and D2cc (- 6.2 ± 15.6%; P < 0.01). There was a small but significant increase in mean rectal dose (+ 7.0 ± 12.9%, P < 0.01) but a decrease in rectal D2cc (- 2.2 ± 10.1%; P = 0.04). No significant correlations were found between relative bladder volume changes, bladder trigone displacements, or rectum volume changes with rates of genitourinary or rectal toxicities. CONCLUSIONS:Despite smaller than expected bladder and rectal volumes at the time of treatment compared to the planning scans, dosimetric impact was minimal and not predictive of detrimental clinical outcomes. These results cast doubt on the need for excessively strict bladder filling and rectal emptying protocols in the context of image guided prostate SBRT and prospective studies are needed to determine its necessity.

BACKGROUND AND PURPOSE/OBJECTIVE:Magnetic Resonance (MR)-only planning has been implemented clinically for radiotherapy of prostate cancer. However, fewer studies exist regarding the overall success rate of MR-only workflows. We report on successes and challenges of implementing MR-only workflows for prostate. MATERIALS AND METHODS/METHODS:A total of 585 patients with prostate cancer underwent an MR-only simulation and planning between 06/2016-06/2018. MR simulation included images for contouring, synthetic-CT generation and fiducial identification. Workflow interruptions occurred that required a backup CT, a re-simulation or an update to our current quality assurance (QA) process. The challenges were prospectively evaluated and classified into syn-CT generation, motion/artifacts in the MRs, fiducial QA and bowel preparation guidelines. RESULTS:MR-only simulation was successful in 544 (93.2 %) patients. . In seventeen patients (2.9%), reconstruction of synthetic-CT failed due to patient size, femur angulation, or failure to determine the body contour. Twenty-four patients (4.1%) underwent a repeat/backup CT scan because of artifacts on the MR such as image blur due to patient motion or biopsy/surgical artifacts that hampered identification of the implanted fiducial markers. In patients requiring large coverage due to nodal involvement, inhomogeneity artifacts were resolved by using a two-stack acquisition and adaptive inhomogeneity correction. Bowel preparation guidelines were modified to address frequent rectum/gas issues due to longer MR scan time. CONCLUSIONS:MR-only simulation has been successfully implemented for a majority of patients in the clinic. However, MR-CT or CT-only pathway may still be needed for patients where MR-only solution fails or patients with MR contraindications.

Patients who receive pelvic radiation are at risk for both local recurrences of their primary malignancy or for the development of a new malignancy in the irradiated pelvic structures. The management of postirradiation pelvic tumor is complicated and can be associated with both poor prognosis and significant morbidity. Historically, reirradiation within the pelvis was never entertained as part of treatment management due to concern for severe toxicity and exceeding of normal-tissue tolerances. However, it may play a role with modern techniques and careful patient selection. The following case and accompanying expert opinions demonstrate some of the key considerations for pelvic reirradiation as a treatment option.