Trial Participation is Not Associated with Better Biochemical Recurrence-free Survival in a Large Cohort of External Beam Radiotherapy-Treated Intermediate- and High-Risk Prostate Cancer Patients.

AIMS: There is a widespread belief that outcomes of cancer patients treated within clinical trials might not be representative of the outcomes obtained within standard clinical settings. We sought to investigate the effect of trial participation on biochemical recurrence (BCR) in localised, D'Amico intermediate- and high-risk prostate cancer patients treated with external beam radiotherapy (EBRT). MATERIALS AND METHODS: We relied on a study population treated with EBRT between January 2001 and January 2021 at a single tertiary care centre, stratified according to trial enrolment. Separate Kaplan-Meier and multivariable Cox regression models tested BCR-free survival at 60 months within intermediate- and high-risk EBRT patients, after adjustment for covariables. Additionally, the analyses were refitted after inverse probability treatment weighting was performed separately for both risk subgroups. RESULTS: Of 932 eligible patients, 635 (68%) and 297 (32%) had intermediate- and high-risk prostate cancer, respectively. Overall, 53% of patients were trial participants. BCR rates were 11 versus 5% (P = 0.27) and 12 versus 14% (P = 0.08) in trial participants versus non-participants for intermediate- and high-risk subgroups, respectively. Differences in patient and clinical characteristics were recorded. Trial participation status failed to reach predictor status in multivariable Cox regression models for BCR in both intermediate-risk (hazard ratio 1.34; 95% confidence interval 0.71-2.49; P = 0.4) and high-risk patients (hazard ratio 1.03; 95% confidence interval 0.45-2.34; P = 0.9). Virtually the same results were recorded in inverse probability treatment weighting cohorts. CONCLUSIONS: Relying on a large cohort of EBRT-treated intermediate- and high-risk patients, no BCR differences were recorded between trial participants and non-participants after accounting for confounders.

Focal HDR brachytherapy boost to stereotactic radiotherapy (fBTsRT) for prostate cancer: a phase II randomized controlled trial.

BACKGROUND: For patients with a higher burden of localized prostate cancer, radiation dose escalation with brachytherapy boosts have improved cancer control outcomes at the cost of urinary toxicity. We hypothesize that a focal approach to brachytherapy boosts targeting only grossly visualized tumor volumes (GTV) combined with stereotactic radiotherapy will improve quality of life (QoL) outcomes without compromising cancer control. METHODS: 150 patients with intermediate or high-risk prostate cancer will be enrolled and randomized 1:1 in a cohort multiple randomized clinical trial phase 2 design. Patients are eligible if planned for standard-of-care (SOC) high dose rate (HDR) brachytherapy boost to radiotherapy (RT) with GTVs encompassing < 50% of the prostate gland. Those randomly selected will be offered the experimental treatment, consisting of focal HDR brachytherapy boost (fBT) of 13-15 Gy in 1 fraction followed by stereotactic radiotherapy (sRT) 36.25-40 Gy in 5 fractions to the prostate (+/- 25 Gy to the elective pelvis) delivered every other day. The primary endpoint is to determine if fBTsRT is superior to SOC by having fewer patients experience a minimally important decline (MID) in urinary function as measured by EPIC-26 at 1 and 2 years. Secondary endpoints include rates of toxicity measured by Common Terminology Criteria for Adverse Events (CTCAE), and failure-free survival outcomes. DISCUSSION: This study will determine whether a novel approach for the treatment of localized prostate cancer, fBTsRT, improves QoL and merits further evaluation. Trial registration This trial was prospectively registered in ClinicalTrials.gov as NCT04100174 as a companion to registry NCT03378856 on September 24, 2019.

Changes in periprostatic adipose tissue induced by 5α-reductase inhibitors.

There is increasing interest in periprostatic fat and its influence on prostate cancer aggressiveness. In vitro data suggest that adipose stromal/stem cells (ASCs) can increase production of cytokines and growth factors resulting in invasive growth and metastasis in prostate cancer. The objective of the study was to determine the interaction between 5α-reductase inhibitors (5ARIs) and periprostatic adipose tissue (PPAT) and factors of prostate cancer aggressiveness. In this retrospective study, we identified 61 patients treated with 5ARIs for a period of ≥12 months before undergoing radiation therapy (brachytherapy or external beam radiotherapy). The control group consisted of 117 patients without any exposure to 5ARIs. Prior to being treated, all patients underwent abdominal computed tomography (CT). To measure PPAT, we defined the fat pad anteriorly to the prostate, as well as the intra-abdominal visceral adipose tissue (VAT) and subcutaneous tissue (SAT) at the level of L4/L5. All contours were performed manually. These adipose tissue measurements were correlated with the Cancer of the Prostate Risk Assessment (CAPRA) score using Pearson correlation coefficient. Differences in fat contents were evaluated using Student's t-test. Median time on 5ARIs for the 61 patients was 12 months (range 12-96). Patient on 5ARIs had a significantly (p < 0.001) smaller PPAT (0.4, SD 0.5) than patients without a 5ARI (0.6 cc, SD 0.4). There was no significant correlation between the CAPRA score and fat measurements when adjusted for 5ARI use (p = 0.18). In non-5ARI users, BMI was not correlated with PPAT but was correlated with SAT and VAT volume and its density. There were no significant differences in diabetics (p = 0.3), metformin users (p = 0.4) or statin users (p = 0.09) between both groups. 5ARIs taken for at least 12 months induce changes in PPAT volume. Whether these changes or the extent of changes will have an influence on outcome remains unknown.

Publication rates of abstracts presented at the 2007 and 2010 Canadian Association of Radiation Oncology meetings.

BACKGROUND: We set out to determine the rate, time-trend, and defining factors associated with publication of abstracts presented at two annual scientific meetings of the Canadian Association of Radiation Oncology (caro). METHODS: All abstracts accepted for oral presentation in 2007 and 2010 were obtained from the caro program archives and searched using the PubMed database. Variables in the dataset included the year of presentation at caro and of publication in a scientific journal, time to publication (in months), publishing journal, impact factor of publishing journal, abstract research type (clinical, technical, or basic science) and disease site, country of origin, and university of the first author. RESULTS: Overall, 88 of 172 abstracts from the 2007 (n = 102) and 2010 (n = 70) caro meetings were published in peer-reviewed journals (publication rate: 51.2%). Mean time to publication was 18.5 months. Among research types, clinical research (62.5%) and, among disease sites, prostate cancer (40.4%) were most likely to be published. Of all the abstracts, 50.1% were contributed by only 2 universities, a proportion that resembles the overall abstract publication rate of 51.2%. The conversion rate for those 2 universities (51.1%) is very similar to that for all abstracts presented at the two meetings. CONCLUSIONS: Half the abstracts presented at the 2007 and 2010 caro meetings were ultimately published in journals indexed in PubMed by about 1.5 years after presentation. Half the abstracts and publications came from just 2 universities; more must to be done to close the gap.

Using fiducial markers in the prostate bed in postprostatectomy external beam radiation therapy improves accuracy over surgical clips.

BACKGROUND AND PURPOSE: The purpose of this work was to assess the stability of fiducial markers in the prostate bed and compared their use to surgical clips. PATIENTS AND METHODS: In this study, 3-4 gold fiducial markers were transrectally implanted in the prostate bed of 14 patients. The stability of the fiducial markers position (fiducial markers fixity) over an EBRT course was assessed. Furthermore, the advantages of the fiducial markers compared to the surgical clips were assessed and the interobserver variation between the two technologies was compared. RESULTS: The mean fiducial marker migration during a course of EBRT was small with 1.2 mm (SD ± 0.8 mm). Compared to fiducial markers, the matches with surgical clips were mismatched ≥ 2 mm in 68% of treatments. This discrepancy of > 2 mm was on average 3.7 ± 1.3 mm. There was less interobserver variability for matching of fiducial markers (0.8 ± 0.7 mm) than for surgical clips (2.0 ± 1.6 mm). CONCLUSION: Fiducial markers showed less interobserver variability in matching and less variation in position than surgical clips. Fiducial markers could ultimately help in reducing treatment margins.