Faculty Bibliography

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.

Our purpose was to evaluate the performance of ¹¹C-choline PET/CT in detecting biochemically recurrent prostate cancer (PCa) in a large non-European cohort (in the context of emerging evidence for prostate-specific membrane antigen PET in this setting) and to map patterns of PCa recurrence. Methods: We retrospectively analyzed ¹¹C-choline PET/CT scans from 287 patients who were enrolled in an imaging protocol based on rising prostate-specific antigen (PSA) levels (mean, 3.43 ng/mL; median, 0.94 ng/mL; range, 0.15-89.91 ng/mL) and suspected recurrent PCa. A total of 187 patients had undergone primary radical prostatectomy (RP) (79/187 had secondary radiotherapy), 30 had undergone primary radiotherapy, and 70 had a persistent PSA elevation after receiving initial treatment (69 after RP, 1 after radiotherapy). The level of suspicion for recurrence on ¹¹C-choline PET/CT was scored (0, negative; 1, equivocal; 2, positive) by 2 readers. The correlation between ¹¹C-choline PET/CT positivity and initial treatment, Gleason score, National Comprehensive Cancer Network stage, PSA level, PSA doubling time, PSA velocity, and time between initial treatment and PET imaging was evaluated. Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria were used to map ¹¹C-choline recurrence patterns. Results: Considering scores 1 and 2 as positives, consensus between the 2 readers deemed 66% of the ¹¹C-choline PET/CT scans as positive. When sorted by PSA level, 45% of patients with a PSA of less than 0.5 ng/mL, 56% of patients with a PSA of 0.5-0.99 ng/mL, 70% of patients with a PSA of 1.0-1.99 ng/mL, and 90% of patients with a PSA of at least 2.0 ng/mL scored either 1 or 2 on ¹¹C-choline PET/CT scans. When considering scores of 2 only, ¹¹C-choline PET/CT positivity was 54% (28%, 46%, 62%, and 81%, respectively, for patients with PSA < 0.5 ng/mL, 0.5-0.99 ng/mL, 1.0-1.99 ng/mL, and ≥ 2.0 ng/mL). In multivariate analysis, only PSA level was significantly associated with scan positivity. Pattern analysis showed that pelvic lymph nodes were the most common site of recurrence, and 28% of patients had ¹¹C-choline-positive suspected recurrences outside the initial treatment field. Conclusion:

PURPOSE:We sought to develop a quality surveillance program for approximately 15,000 US veterans treated at the 40 radiation oncology facilities at the Veterans Affairs (VA) hospitals each year. METHODS AND MATERIALS:State-of-the-art technologies were used with the goal to improve clinical outcomes while providing the best possible care to veterans. To measure quality of care and service rendered to veterans, the Veterans Health Administration established the VA Radiation Oncology Quality Surveillance program. The program carries forward the American College of Radiology Quality Research in Radiation Oncology project methodology of assessing the wide variation in practice pattern and quality of care in radiation therapy by developing clinical quality measures (QM) used as quality indices. These QM data provide feedback to physicians by identifying areas for improvement in the process of care and identifying the adoption of evidence-based recommendations for radiation therapy. RESULTS:Disease-site expert panels organized by the American Society for Radiation Oncology (ASTRO) defined quality measures and established scoring criteria for prostate cancer (intermediate and high risk), non-small cell lung cancer (IIIA/B stage), and small cell lung cancer (limited stage) case presentations. Data elements for 1567 patients from the 40 VA radiation oncology practices were abstracted from the electronic medical records and treatment management and planning systems. Overall, the 1567 assessed cases passed 82.4% of all QM. Pass rates for QM for the 773 lung and 794 prostate cases were 78.0% and 87.2%, respectively. Marked variations, however, were noted in the pass rates for QM when tumor site, clinical pathway, or performing centers were separately examined. CONCLUSIONS:The peer-review protected VA-Radiation Oncology Surveillance program based on clinical quality measures allows providers to compare their clinical practice to peers and to make meaningful adjustments in their personal patterns of care unobtrusively.