Radiation Oncologist Consultations Prior to Radical Prostatectomy: Disparities and Opportunities.

PURPOSE: In 2015, men undergoing radical prostatectomy in Ontario, Canada were recommended to undergo multidisciplinary care by seeing a radiation oncologist or discussion at multidisciplinary rounds before surgery. The a priori target rate was ≥76%. We used population-based data to explore factors associated with not receiving multidisciplinary care prior to radical prostatectomy. MATERIALS AND METHODS: Men who underwent radical prostatectomy for localized prostate cancer in Ontario between 2007 and 2017 were identified using administrative data. Physician billings identified patients who received multidisciplinary care. Multivariable logistic regression was used to predict receipt of multidisciplinary care. RESULTS: A total of 31,485 men underwent radical prostatectomy between 2007 and 2017. Of these patients 28.7% saw a radiation oncologist, 1.2% underwent multidisciplinary discussion and 1.9% had both before surgery. Multidisciplinary care receipt increased from 17.8% in 2007 to 47.8% in 2017 (p <0.001). The odds ratio between the highest and lowest geographic regions was 7.93 (95% CI 6.17-10.18, p <0.001). Lower odds of multidisciplinary care receipt were observed for men further from the nearest cancer center (OR 0.74 per 50 km, 95% CI 0.71-0.78, p <0.001) and higher odds for the highest versus lowest income quintile (OR 1.41, 95% CI 1.29-1.54, p <0.001). Of 128 urologists who performed ≥10 radical prostatectomies between 2016 and 2017, 29 (22.7%) met the target of having ≥76% of men seen for multidisciplinary care prior to surgery. CONCLUSIONS: Despite increasing utilization, many men do not receive multidisciplinary care prior to radical prostatectomy. While geography and the urologist appear to be the greatest factors predicting multidisciplinary care receipt, these factors are closely intertwined.

A personalized decision aid for prostate cancer shared decision making.

BACKGROUND: A shared decision-making model is preferred for engaging prostate cancer patients in treatment decisions. However, the process of assessing an individual's preferences and values is challenging and not formalized. The purpose of this study is to develop an automated decision aid for patient-centric treatment decision-making using decision analysis, preference thresholds and value elicitations to maximize the compatibility between a patient's treatment expectations and outcome. METHODS: A template for patient-centric medical decision-making was constructed. The inputs included prostate cancer risk group, pre-treatment health state, treatment alternatives (primarily focused on radiation in this model), side effects (erectile dysfunction, urinary incontinence, nocturia and bowel incontinence), and treatment success (5-year freedom from biochemical failure). A linear additive value function was used to combine the values for each attribute (side effects, success and the alternatives) into a value for all prospects. The patient-reported toxicity probabilities were derived from phase II and III trials. The probabilities are conditioned on the starting state for each of the side effects. Toxicity matrices for erectile dysfunction, urinary incontinence, nocturia and bowel incontinence were created for the treatment alternatives. Toxicity probability thresholds were obtained by identifying the patient's maximum acceptable threshold for each of the side effects. Results are represented as a visual. R and Rstudio were used to perform analyses, and R Shiny for application creation. RESULTS: We developed a web-based decision aid. Based on preliminary use of the application, every treatment alternative could be the best choice for a decision maker with a particular set of preferences. This result implies that no treatment has determinist dominance over the remaining treatments and that a preference-based approach can help patients through their decision-making process, potentially affecting compliance with treatment, tolerance of side effects and satisfaction with the decision. CONCLUSIONS: We present a unique patient-centric prostate cancer treatment decision aid that systematically assesses and incorporates a patient's preferences and values to rank treatment options by likelihood of achieving the preferred outcome. This application enables the practice and study of personalized medicine. This model can be expanded to include additional inputs, such as genomics, as well as competing, concurrent or sequential therapies.

Radiation Oncology Fellowship: a Value-Based Assessment Among Graduates of a Mature Program.

The University of Toronto - Department of Radiation Oncology (UTDRO) has had a well-established Fellowship Program for over 20 years. An assessment of its graduates was conducted to evaluate training experience and perceived impact on professional development. Graduates of the UTDRO Fellowship Program between 1991 and 2015 were the focus of our review. Current employment status was collected using online tools. A study-specific web-based questionnaire was distributed to 263/293 graduates for whom active e-mails were identified; questions focused on training experience, and impact on career progression and academic productivity. As a surrogate measure for the impact of UTDRO Fellowship training, a comparison of current employment and scholarly activities of individuals who obtained their Fellow of the Royal College of Physicians of Canada (FRCPC) designation in Radiation Oncology between 2000 and 2012, with (n = 57) or without (n = 230) UTDRO Fellowship training, was conducted. Almost all UTDRO Fellowship graduates were employed as staff radiation oncologists (291/293), and most of those employed were associated with additional academic (130/293), research (53/293), or leadership (68/293) appointments. Thirty-eight percent (101/263) of alumni responded to the online survey. The top two reasons for completing the Fellowship were to gain specific clinical expertise and exposure to research opportunities. Respondents were very satisfied with their training experience, and the vast majority (99%) would recommend the program to others. Most (96%) felt that completing the Fellowship was beneficial to their career development. University of Toronto, Department of Radiation Oncology Fellowship alumni were more likely to hold university, research, and leadership appointments, and author significantly more publications than those with FRCPC designation without fellowship training from UTDRO. The UTDRO Fellowship Program has been successful since its inception, with the majority of graduates reporting positive training experiences, benefits to scholarly output, and professional development for their post-fellowship careers. Key features that would optimize the fellowship experience and its long-term impact on trainees were also identified.

The effect of selection and referral biases for the treatment of localised prostate cancer with surgery or radiation.

BACKGROUND: Consultation with radiation oncologists, in addition to urologists, is advocated for patients diagnosed with prostate cancer. Treatment patterns for patients receiving consultation from radiation oncologists in addition to urologists have not previously been described. METHODS: We conducted a matched cohort study of men with newly diagnosed non-metastatic prostate cancer in Ontario, Canada. Patients who underwent consultation with a radiation oncologist prior to treatment were matched 1:1 with patients managed by a urologist alone based on tumour and patient characteristics. We examined rates of active treatment (surgery or radiotherapy) within one year following diagnosis. RESULTS: Among 5708 matched pairs (11,416 patients), those who received radiation oncology consultation were more likely to undergo active treatments whether they had intermediate or high-risk disease (88.6% vs. 65.9%, p < 0.0001; adjusted odds ratio 4.0, 95% CI: 3.6-4.4) or low-risk disease (56.1% vs. 13.3%, p < 0.0001; adjusted odds ratio 8.4, 95% CI: 6.7-10.6). This effect persisted after considering age, comorbidity, tumour volume and year of diagnosis. CONCLUSIONS: Patients newly diagnosed with prostate cancer who receive radiation oncology consultation are associated with a higher rate of active treatment, compared to patients managed by urologists only. Selection and referral biases, and unmeasured confounding such as patient preference must be considered as important factors attributing this association.

Developing and Evaluating Multimedia Patient Education Tools to Better Prepare Prostate-Cancer Patients for Radiotherapy Treatment (Randomized Study).

The purpose of this study is to determine the effectiveness of multimedia educational tools to improve CT planning preparation for intensity modulated radiotherapy (IMRT) for prostate cancer. Many patients are not prepared when given verbal preparation instructions to have a full bladder and empty rectum for their IMRT and require being rescanned, which results in additional costs for the patient and the hospital. A pamphlet and video outlining the proper preparation for prostate IMRT was created to decrease additional scans and the associated costs, while increasing patient satisfaction. A controlled, randomized experimental group study was conducted to examine the effectiveness of the multimedia tools (the video and the pamphlet), as compared to the pamphlet only, in preparing patients for their planning CT appointment. We found no statistical difference between the multimedia group and the pamphlet group in patients' preparedness for their appointments and the rescanning rate. However, patients in the multimedia group indicated that they felt more prepared about their treatment after watching the video and stated that they would recommend the video to other patients with prostate cancer. Furthermore, patients who had to wait longer for their planning CT appointment felt less prepared by the materials than those with a shorter wait time. We recommend reducing wait times between appointments as much as possible to increase patients' preparedness for the planning CT. We conclude that providing multimedia treatment information and minimizing wait times increases patients' feelings of preparedness leading to a more positive treatment experience and reducing costly rescans. TRIAL REGISTRATION: ClinicalTrials.gov NCT02410291.

MR-guided prostate biopsy for planning of focal salvage after radiation therapy.

PURPOSE: To determine if the integration of diagnostic magnetic resonance (MR) imaging and MR-guided biopsy would improve target delineation for focal salvage therapy in men with prostate cancer. MATERIALS AND METHODS: Between September 2008 and March 2011, 30 men with biochemical failure after radiation therapy for prostate cancer provided written informed consent and were enrolled in a prospective clinical trial approved by the institutional research ethics board. An integrated diagnostic MR imaging and interventional biopsy procedure was performed with a 1.5-T MR imager by using a prototype table and stereotactic transperineal template. Multiparametric MR imaging (T2-weighted, dynamic contrast material-enhanced, and diffusion-weighted sequences) was followed by targeted biopsy of suspicious regions and systematic sextant sampling. Biopsy needle locations were imaged and registered to diagnostic images. Two observers blinded to clinical data and the results of prior imaging studies delineated tumor boundaries. Area under the receiver operating characteristic curve (Az) was calculated based on generalized linear models by using biopsy as the reference standard to distinguish benign from malignant lesions. RESULTS: Twenty-eight patients were analyzed. Most patients (n = 22) had local recurrence, with 82% (18 of 22) having unifocal disease. When multiparametric volumes from two observers were combined, it increased the apparent overall tumor volume by 30%; however, volumes remained small (mean, 2.9 mL; range, 0.5-8.3 mL). Tumor target boundaries differed between T2-weighted, dynamic contrast-enhanced, and diffusion-weighted sequences (mean Dice coefficient, 0.13-0.35). Diagnostic accuracy in the identification of tumors improved with a multiparametric approach versus a strictly T2-weighted or dynamic contrast-enhanced approach through an improvement in sensitivity (observer 1, 0.65 vs 0.35 and 0.44, respectively; observer 2, 0.82 vs 0.64 and 0.53, respectively; P < .05) and improved further with a 5-mm expansion margin (Az = 0.85 vs 0.91 for observer 2). After excluding three patients with fewer than six informative biopsy cores and six patients with inadequately stained margins, MR-guided biopsy enabled more accurate delineation of the tumor target volume be means of exclusion of false-positive results in 26% (five of 19 patients), false-negative results in 11% (two of 19 patients) and by guiding extension of tumor boundaries in 16% (three of 19 patients). CONCLUSION: The integration of guided biopsy with diagnostic MR imaging is feasible and alters delineation of the tumor target boundary in a substantial proportion of patients considering focal salvage.

Randomized Trial of Concomitant Hypofractionated Intensity Modulated Radiation Therapy Boost Versus Conventionally Fractionated Intensity Modulated Radiation Therapy Boost for Localized High-Risk Prostate Cancer (pHART2-RCT).

PURPOSE: The aim of this work is to report on the results of a phase 2 randomized trial of moderately hypofractionated (MH) versus conventionally fractionated (CF) radiation therapy to the prostate with elective nodal irradiation. METHODS AND MATERIALS: This was a single-center, prospective, phase 2 randomized study. Patients with high-risk disease (cT3, prostate-specific antigen level >20 ng/mL, or Gleason score 8-10) were eligible. Patients were randomized to either MH using a simultaneous integrated boost (68 Gy in 25 fractions to prostate; 48 Gy to pelvis) or CF (46 Gy in 23 fractions with a sequential boost to the prostate of 32 Gy in 16 fractions), with long-term androgen deprivation therapy. The primary endpoint was grade ≥2 acute gastrointestinal (GI) and genitourinary (GU) toxicity (Common Terminology Criteria for Adverse Events version 3.0). Secondary endpoints included late GI and GU toxicity, quality of life, and oncologic outcomes. RESULTS: One-hundred eighty patients were enrolled; 90 were randomized to and received MH and 90 to CF. The median follow-up was 67.4 months. Seventy-five patients (41.7%) experienced a grade ≥2 acute GI and/or GU toxicity, including 34 (37.8%) in the MH and 41 (45.6%) in the CF arms, respectively (P = .29). Late grade ≥2 GI (P = .07) and GU (P = .25) toxicity was not significantly different between arms; however, late grade ≥3 GI toxicity was worse in the MH group (P = .01). There were no statistically significant quality-of-life differences between the 2 treatments. There were no statistically significant differences observed in cumulative incidence of biochemical failure (P = .71) or distant metastasis (P = .31) and overall survival (P = .46). CONCLUSIONS: MH to the prostate and pelvis with androgen deprivation therapy for men with high-risk localized prostate cancer was not significantly different than CF with regard to acute toxicity, quality of life, and oncologic efficacy. However, late grade ≥3 GI toxicity was more common in the MH arm.

Prostate high dose-rate brachytherapy as monotherapy for low and intermediate-risk prostate cancer: Efficacy results from a randomized phase II clinical trial of one fraction of 19 Gy or two fractions of 13.5 Gy: A 9-year update.

BACKGROUND AND PURPOSE: High dose-rate (HDR) brachytherapy as a monotherapy is an accepted treatment for localized prostate cancer, but the optimal dose and fractionation schedule remain unknown. We report on the efficacy of a randomized Phase II trial comparing HDR monotherapy delivered as 27 Gy in 2 fractions vs. 19 Gy in 1 fraction with a median follow-up of 9 years. MATERIALS AND METHODS: Enrolled patients had low or intermediate-risk disease, <60 cc prostate volume and no androgen deprivation use. Patients were randomized to 27 Gy in 2 fractions delivered one week apart vs a single fraction of 19 Gy. RESULTS: 170 patients were randomized: median age 65 years, median follow-up 107 months and median baseline PSA 6.35 ng/ml. NCCN risk categories comprised low (19 %), favourable (51 %), and unfavourable intermediate risk (30 %). The median PSA at 8 years was 0.08 ng/ml in the 2-fraction arm vs. 0.89 ng/ml in the single-fraction arm. The cumulative incidence of local failure at 8 years was 11.2 % in the 2-fraction arm vs. 35.9 % in the single-fraction arm (p < 0.001). The incidence of distant failure at 8 years was 3.8 % in the 2-fraction arm and 2.5 % in the single-fraction arm (p = 0.6). CONCLUSIONS: HDR monotherapy delivered in two fractions of 13.5 Gy demonstrated a persistent cancer control rate at 8 years and was well-tolerated. Single-fraction monotherapy yielded poor oncologic control and is not recommended. These findings contribute to the ongoing discourse on optimal HDR monotherapy strategies for low and intermediate-risk prostate cancer.

Treatment options for localized prostate cancer.

OBJECTIVE: To describe treatment options for clinically localized prostate cancer: radical prostatectomy, prostate brachytherapy, external beam radiation, and active surveillance. QUALITY OF EVIDENCE: Prostate-specific antigen (PSA) outcomes presented are from non-randomized, cohort, and other comparisons trials (level II evidence). We describe PSA outcomes from Canadian centres when they are available. One small randomized controlled trial (level I evidence) in localized prostate cancer is available to compare radical prostatectomy with brachytherapy. MAIN MESSAGE: Treatment choice in prostate cancer is based on initial PSA level, clinical stage of disease, and Gleason score, together with baseline urinary function, comorbidities, and patient age. In this article, we describe patients' eligibility for and the common side effects of all treatment options. Prostate brachytherapy and active surveillance have evolved as new standard treatments of localized prostate cancer. We give a brief overview of the brachytherapy procedure, side effects, and PSA outcomes across Canada, as well as active surveillance guidelines. CONCLUSION: Prostate cancer treatment requires a multidisciplinary approach, with input from both urology and radiation oncology. Input from family physicians is often as important in helping guide patients through the treatment decision process.

Radiation therapy after radical surgery in prostate cancer.

Radiation therapy plays a key role in the treatment of prostate cancer on its own. For higher risk diseases, the risk of recurrence following single modality therapy increases and a combination of treatment modalities may be necessary to achieve optimal results. We review clinical outcomes of adjuvant and salvage radiotherapy following radical prostatectomy, including disease-free survival, cancer-specific survival and overall survival. We also discuss when best to intervene with post-prostatectomy radiotherapy.

An Updated Analysis of the Survival Endpoints of ASCENDE-RT.

PURPOSE: Using the primary endpoint of time to biochemical progression (TTP), Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (ASCENDE-RT) randomized National Comprehensive Cancer Network patients with intermediate and high-risk prostate cancer to low-dose-rate brachytherapy boost (LDR-PB) or dose-escalated external beam boost (DE-EBRT). Randomization to the LDR-PB arm resulted in a 2-fold reduction in biochemical progression compared with the DE-EBRT group at a median follow-up of 6.5 years (P < .001). Herein, the primary endpoint and secondary survival endpoints of the ASCENDE-RT trial are updated at a 10-year median follow-up. METHODS: Patients were randomly assigned to either the LDR-PB or the DE-EBRT arm (1:1). All patients received 1 year of androgen deprivation therapy and 46 Gy in 23 fractions of pelvic RT. Patients in the DE-EBRT arm received an additional 32 Gy in 16 fractions, and those in the LDR-PB arm received an 125I implant prescribed to a minimum peripheral dose of 115 Gy. Two hundred patients were randomized to the DE-EBRT arm and 198 to the LDR-PB arm. RESULTS: The 10-year Kaplan-Meier TTP estimate was 85% ± 5% for LDR-PB compared with 67% ± 7% for DE-EBRT (log rank P < .001). Ten-year time to distant metastasis (DM) was 88% ± 5% for the LDR-PB arm and 86% ± 6% for the DE-EBRT arm (P = .56). There were 117 (29%) deaths. Ten-year overall survival (OS) estimates were 80% ± 6% for the LDR-PB arm and 75% ± 7% for the DE-EBRT arm (P = .51). There were 30 (8%) patients who died of prostate cancer: 12 (6%) in the LDR-PB arm, including 2 treatment-related deaths, and 18 (9%) in the DE-EBRT arm. CONCLUSIONS: Men randomized to the LDR-PB boost arm of the ASCENDE-RT trial continue to experience a large advantage in TTP compared with those randomized to the DE-EBRT arm. ASCENDE-RT was not powered to detect differences in its secondary survival endpoints (OS, DM, and time to prostate cancer-specific death) and none are apparent.

Two-fraction stereotactic ablative radiotherapy with simultaneous boost to MRI-defined dominant intra-prostatic lesion - Results from the 2SMART phase 2 trial.

PURPOSE: This is the first report of the 2SMART Phase II trial evaluating the safety of two-fraction stereotactic ablative radiotherapy (SABR) with focal boost to magnetic resonance imaging (MRI) defined dominant intra-prostatic lesion (DIL) for localised prostate cancer. MATERIALS AND METHODS: Men with low or intermediate risk prostate cancer were eligible for the study. The gross tumour volume (GTV) was MRI-defined DIL, and the clinical target volume (CTV) was entire prostate gland. The planning target volume (PTV) was a 2 mm expansion anteroposterior and lateral, and 2.5 mm superoinferior. The prescribed dose was 32 Gy to GTV, and 26 Gy to CTV. Primary endpoint was minimal clinically important change (MCIC) in quality of life (QOL) within 3-months of SABR, assessed using the EPIC-26 questionnaire. Secondary endpoints were acute and late toxicities (assessed using CTCAEv4), PSA nadir, and biochemical failure (based on Phoenix criteria). RESULTS: Thirty men were enrolled in the study - 2 (7%) had low-risk and 28 (93%) had intermediate risk prostate cancer. The median follow-up was 44 months (range:39-49 months). The median PSA nadir was 0.25 ng/mL, with median time to nadir of 37 months. One patient (3%) had biochemical failure at 44 months post-treatment. Ten (33%), six (20%), and three (10%) men had acute MCIC in urinary, bowel, and sexual QOL domains respectively. No acute or late grade ≥ 3 urinary or bowel toxicities were observed. CONCLUSION: This novel protocol of two-fraction prostate SABR with MRI-defined DIL boost is a safe approach for dose-escalation, with minimal impact on acute QOL and no grade ≥ 3 toxicities.

Dosimetric correlates of toxicities and quality of life following two-fraction stereotactic ablative radiotherapy (SABR) for prostate cancer.

PURPOSE: There is no evidence-based data to guide dose constraints in two-fraction prostate stereotactic ablative radiotherapy (SABR). Using individual patient-data from two prospective trials, we aimed to correlate dosimetric parameters with toxicities and quality of life (QoL) outcomes. MATERIALS AND METHODS: We included 60 patients who had two-fraction prostate SABR in the 2STAR (NCT02031328) and 2SMART (NCT03588819) trials. The prescribed dose was 26 Gy to the prostate+/-32 Gy boost to the dominant intraprostatic lesions. Toxicities and QoL data were prospectively collected using CTCAEv4 and EPIC-26 questionnaire. The outcomes evaluated were acute and late grade ≥ 2 toxicities, and late minimal clinical important changes (MCIC) in QoL domains. Dosimetric parameters for bladder, urethra, rectum, and penile bulb were evaluated. RESULTS: The median follow-up was 56 months (range: 39-78 months). The cumulative incidence of grade ≥ 2 genitourinary (GU), gastrointestinal (GI), and sexual toxicities were 62%, 3%, and 17% respectively in the acute setting (<3 months), and 57%, 15%, and 52% respectively in late setting (>6 months). There were 36%, 28%, and 29% patients who had late MCIC in urinary, bowel and sexual QoL outcomes respectively. Bladder 0.5 cc was significant predictor for late grade ≥ 2 GU toxicities, with optimal cut-off of 25.5 Gy. Penile bulb D5cc was associated of late grade ≥ 2 sexual toxicities (no optimal cut-off was identified). No dosimetric parameters were identified to be associated with other outcomes. CONCLUSION: Using real-life patient data from prospective trials with medium-term follow-up, we identified additional dose constraints that may mitigate the risk of late treatment-related toxicities for two-fraction prostate SABR.

To Boost or Not to Boost: Pooled Analyses From 2-Fraction SABR Trials for Localized Prostate Cancer.

PURPOSE: Focal boost to dominant intraprostatic lesion (DIL) is an approach for dose escalation in prostate radiation therapy. In this study, we aimed to report the outcomes of 2-fraction SABR ± DIL boost. METHODS AND MATERIALS: We included 60 patients with low- to intermediate-risk prostate cancer enrolled in 2 phase 2 trials (30 patients in each trial). In the 2STAR trial (NCT02031328), 26 Gy (equivalent dose in 2-Gy fractions = 105.4 Gy) was delivered to the prostate. In the 2SMART trial (NCT03588819), 26 Gy was delivered to the prostate, with up to 32 Gy boost to magnetic resonance imaging-defined DIL (equivalent dose in 2-Gy fractions = 156.4 Gy). The reported outcomes included prostate-specific antigen (PSA) response (ie, <0.4 ng/mL) at 4 years (4yrPSARR), biochemical failure (BF), acute and late toxicities, and quality of life (QOL). RESULTS: In 2SMART, median DIL D99% of 32.3 Gy was delivered. Median follow-up was 72.7 months (range, 69.1-75.) in 2STAR and 43.6 months (range, 38.7-49.5) in 2SMART. The 4yrPSARR was 57% (17/30) in 2STAR and 63% (15/24) in 2SMART (P = 0.7). The 4-year cumulative BF was 0% in 2STAR and 8.3% in 2SMART (P = 0.1). The 6-year BF in 2STAR was 3.5%. For genitourinary toxicities, there were differences in grade ≥1 urinary urgency in the acute (0% vs 47%; P < .001) and late settings (10% vs 67%; P < .001) favoring 2STAR. For urinary QOL, no difference was observed in the acute setting, but lower proportion in 2STAR had minimal clinically important changes in urinary QOL score in the late setting (21% vs 50%; P = .03). There were no significant differences in gastrointestinal and sexual toxicities and QOL in both acute and late settings between the 2 trials. CONCLUSIONS: This study presents the first prospective data comparing 2-fraction prostate SABR ± DIL boost. The addition of DIL boost resulted in similar medium-term efficacy (in 4yrPSARR and BF), with impact on late urinary QOL outcomes.

Dose-Escalated Radiation Alone or in Combination With Short-Term Total Androgen Suppression for Intermediate-Risk Prostate Cancer: Patient-Reported Outcomes From NRG/Radiation Therapy Oncology Group 0815 Randomized Trial.

PURPOSE: To report patient-reported outcomes (PROs) of a phase III trial evaluating total androgen suppression (TAS) combined with dose-escalated radiation therapy (RT) for patients with intermediate-risk prostate cancer. METHODS: Patients with intermediate-risk prostate cancer were randomly assigned to dose-escalated RT alone (arm 1) or RT plus TAS (arm 2) consisting of luteinizing hormone-releasing hormone agonist/antagonist with oral antiandrogen for 6 months. The primary PRO was the validated Expanded Prostate Cancer Index Composite (EPIC-50). Secondary PROs included Patient-Reported Outcome Measurement Information System (PROMIS)-fatigue and EuroQOL five-dimensions scale questionnaire (EQ-5D). PRO change scores, calculated for each patient as the follow-up score minus baseline score (at the end of RT and at 6, 12, and 60 months), were compared between treatment arms using a two-sample t test. An effect size of 0.50 standard deviation was considered clinically meaningful. RESULTS: For the primary PRO instrument (EPIC), the completion rates were ≥86% through the first year of follow-up and 70%-75% at 5 years. For the EPIC hormonal and sexual domains, there were clinically meaningful (P < .0001) deficits in the RT + TAS arm. However, there were no clinically meaningful differences by 1 year between arms. There were also no clinically meaningful differences at any time points between arms for PROMIS-fatigue, EQ-5D, and EPIC bowel/urinary scores. CONCLUSION: Compared with dose-escalated RT alone, adding TAS demonstrated clinically meaningful declines only in EPIC hormonal and sexual domains. However, even these PRO differences were transient, and there were no clinically meaningful differences between arms by 1 year.

Dose-Escalated Radiotherapy Alone or in Combination With Short-Term Androgen Deprivation for Intermediate-Risk Prostate Cancer: Results of a Phase III Multi-Institutional Trial.

PURPOSE: It remains unknown whether or not short-term androgen deprivation (STAD) improves survival among men with intermediate-risk prostate cancer (IRPC) treated with dose-escalated radiotherapy (RT). METHODS: The NRG Oncology/Radiation Therapy Oncology Group 0815 study randomly assigned 1,492 patients with stage T2b-T2c, Gleason score 7, or prostate-specific antigen (PSA) value >10 and ≤20 ng/mL to dose-escalated RT alone (arm 1) or with STAD (arm 2). STAD was 6 months of luteinizing hormone-releasing hormone agonist/antagonist therapy plus antiandrogen. RT modalities were external-beam RT alone to 79.2 Gy or external beam (45 Gy) with brachytherapy boost. The primary end point was overall survival (OS). Secondary end points included prostate cancer-specific mortality (PCSM), non-PCSM, distant metastases (DMs), PSA failure, and rates of salvage therapy. RESULTS: Median follow-up was 6.3 years. Two hundred nineteen deaths occurred, 119 in arm 1 and 100 in arm 2. Five-year OS estimates were 90% versus 91%, respectively (hazard ratio [HR], 0.85; 95% CI, 0.65 to 1.11]; P = .22). STAD resulted in reduced PSA failure (HR, 0.52; P <.001), DM (HR, 0.25; P <.001), PCSM (HR, 0.10; P = .007), and salvage therapy use (HR, 0.62; P = .025). Other-cause deaths were not significantly different (P = .56). Acute grade ≥3 adverse events (AEs) occurred in 2% of patients in arm 1 and in 12% for arm 2 (P <.001). Cumulative incidence of late grade ≥3 AEs was 14% in arm 1 and 15% in arm 2 (P = .29). CONCLUSION: STAD did not improve OS rates for men with IRPC treated with dose-escalated RT. Improvements in metastases rates, prostate cancer deaths, and PSA failures should be weighed against the risk of adverse events and the impact of STAD on quality of life.

Salvage prostate brachytherapy in radiorecurrent prostate cancer: An international Delphi consensus study.

BACKGROUND AND PURPOSE: Local recurrences after previous radiotherapy (RT) are increasingly being identified in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option. We sought to generate international consensus statements on the use and preferred technical considerations for salvage prostate BT. MATERIALS AND METHODS: International experts in salvage prostate BT were invited (n = 34) to participate. A three-round modified Delphi technique was utilized, with questions focused on patient- and cancer-specific criteria, type and technique of BT, and follow-up. An a priori threshold for consensus of ≥ 75% was set, with a majority opinion being ≥ 50%. RESULTS: Thirty international experts agreed to participate. Consensus was achieved for 56% (18/32) of statements. Consensus was achieved in several areas of patient selection: 1) A minimum of 2-3 years from initial RT to salvage BT; 2) MRI and PSMA PET should be obtained; and 3) Both targeted and systematic biopsies should be performed. Several areas did not reach consensus: 1) Maximum T stage/PSA at time of salvage; 2) Utilization/duration of ADT; 3) Appropriateness of combining local salvage with SABR for oligometastatic disease and 4) Repeating a second course of salvage BT. A majority opinion preferred High Dose-Rate salvage BT, and indicated that both focal and whole gland techniques could be appropriate. There was no single preferred dose/fractionation. CONCLUSION: Areas of consensus within our Delphi study may serve as practical advice for salvage prostate BT. Future research in salvage BT should address areas of controversy identified in our study.

Patient costs associated with external beam radiotherapy treatment for localized prostate cancer: the benefits of hypofractionated over conventionally fractionated radiotherapy.

INTRODUCTION: To estimate the out-of-pocket costs for patients undergoing external beam radiotherapy (EBRT) for prostate cancer and calculate the patient-related savings of being treated with a 5-fraction versus a standard 39-fraction approach. MATERIALS AND METHODS: Seventy patients accrued to the pHART3 (n = 84) study were analyzed for out-of-pocket patient costs as a result of undergoing treatment. All costs are in Canadian dollars. Using the postal code of the patient's residence, the distance between the hospital and patient home was found using Google Maps. The Canada Revenue Agency automobile allowance rate was then applied to determine the cost per kilometer driven. RESULTS: The average cost of travel from the hospital and pHART3 patient's residence was $246 per person after five trips. In a standard fractionation regimen, pHART3 patients would have incurred an average cost of $1921 after 39 visits. The patients receiving hypofractionated radiotherapy would have paid an average of $38 in parking while those receiving conventional treatment would have paid $293. The difference in out-of-pocket costs for the patients receiving a standard versus hypofractionated treatment was $1930. CONCLUSIONS: Medium term prospective data shows that hypofractionated radiotherapy is an effective treatment method for localized prostate cancer. Compared to standard EBRT, hypofractionated radiotherapy requires significantly fewer visits. Due to the long distance patients may have to travel to the cancer center and the expense of parking, the short course treatment saves each patient an average of $1900. A randomized study of standard versus hypofractionated accelerated radiotherapy should be conducted to confirm a favorable efficacy and tolerability profile of the shorter fractionation scheme.

A comparative study of patient-reported outcomes after contemporary radiation techniques for prostate cancer.

PURPOSE: We aim to compare health-related quality of life (HRQoL) deterioration at 12 months in low-and intermediate-risk prostate cancer (PCa) patients treated with stereotactic ablative radiotherapy (SABR), high dose-rate brachytherapy (HDR) monotherapy and HDR boost. MATERIAL AND METHODS: Patients treated as part of 7 prospective clinical trials were included. All patients had low-or intermediate-risk PCa. Three strategies were considered: SABR, HDR monotherapy and HDR boost. HRQoL was prospectively measured at baseline and 12 months in all trials, using the Expanded Prostate Index Composite (EPIC). A minimally important difference (MID) was defined as a deterioration of HRQoL scores at 12 months compared to baseline ≥0.5 standard deviation of baseline score. Univariate and multivariable logistic regression using generalized estimating equations were used to compare the proportion of patients having MID between groups. A set of sensitivity analyses was conducted. RESULTS: 648 patients were included: 288, 173 and 187 respectively in the SABR, HDR monotherapy and HDR boost group. On univariate and multivariable analyses, SABR and HDR monotherapy compared to HDR boost, were associated with less deterioration in the urinary (38%, 40% vs. 55%; OR:0.543, 95%CI:0.320-0.922, p = 0.024; OR:0.468, 95%CI:0.432-0.507, p < 0.001) and sexual domains (38%, 42% vs. 47%; OR:0.762, 95%CI:0.645-0.900, p = 0.001; OR: 0.786, 95%CI:0.650-0.949, p = 0.012). These findings wererobust to a variety ofsensitivity analyses. CONCLUSION: Recent monotherapeutic approaches for low- and intermediate-risk PCa are associated with the preservation of patients HRQoL. Ultimately, the questions of efficacy, toxicity, and HRQoL will be best answered by a randomized clinical trial.

Success of targeted transperineal biopsy in patients on surveillance for grade group 1 prostate cancer.

INTRODUCTION: We aimed to determine the minimum cross-sectional ellipsoid area on magnetic resonance (MR) of intraprostatic nodules that best predicts for subsequent targeted biopsies revealing ≥ grade group (GG) 2 disease. METHODS: Forty-six patients previously diagnosed with GG 1 prostate adenocarcinoma who received cognitively fused, MR-guided, transperineal targeted biopsies in addition to six random biopsies were included in this analysis. A Youden cutpoint analysis was used to determine the ellipsoid area in the axial plane best predicting for ≥GG 2 disease within the targeted biopsy cores and logistic regression used to assess the result. RESULTS: Median time from MR imaging to targeted biopsy was 2.4 (1.4-5.5) months. Forty of 46 (87%) patients had one nodule and 6/46 (13%) had two separate nodules on MR that received targeted biopsy. Of the 52 nodules, five (10%), 33 (63%), and 14 (27%) were Prostate Imaging-Reporting and Data System (PI-RADS) 3, 4, and 5, respectively. Thirteen (25%), six (12%), and 33 (64%) were in the anterior, medial, and posterior regions of the prostate, respectively. Median area was 0.72 (0.49-1.29) cm2 (average diameter 9.5 mm). Fifteen of 46 (33%) patients had ≥1 random biopsy and 20/52 (38%) nodules had ≥1 targeted biopsy revealing ≥GG 2 disease. The optimal area cutpoint was ≥0.7 cm2, with an area under the curve of 0.671 (0.510-0.832). On logistic regression, area ≥0.7 cm2 was solely predictive of targeted biopsy revealing ≥GG 2 disease (odds ratio 6.5, 1.3-32.4, p=0.022). CONCLUSIONS: Nodule area ≥0.7 cm2 may predict for transperineal-based targeted biopsies being positive for ≥GG 2 disease when 1-2 cores are taken.