Publications by authors named "Andrew Loblaw"

202 Publications

Gantry-based 5-fraction Elective Nodal Irradiation in Unfavorable-Risk Prostate Cancer: Outcomes from 2 Prospective Studies comparing SABR Boost with MR Dose Painted HDR Brachytherapy Boost.

Int J Radiat Oncol Biol Phys 2021 Oct 9. Epub 2021 Oct 9.

Odette Cancer Centre, Sunnybrook Health Sciences Centre; Department of Radiation Oncology, University of Toronto; Institute of Health Policy, Management and Evaluation. Electronic address:

Background: ASCO/CCO guidelines recommend brachytherapy boost for intermediate-risk (IR) or high-risk (HR) prostate cancer (PCa) patients. Stereotactic ablative body radiotherapy (SABR) is an emerging technique for PCa but its use in HR disease is limited. We compare efficacy, toxicity, and quality-of-life (QoL) in patients treated on 2 prospective protocols that used SABR boost or MR-guided HDR brachytherapy boost (MR-HDR) with 6-18 months of androgen deprivation therapy (ADT).

Methods: In XXXXXX study (study 1), patients received 40Gy to prostate and 25Gy to pelvis in 5 weekly fractions. In XXXXXX (study 2), patients received HDR-BT 15Gy x 1 to the prostate and ≤22.5Gy to the MRI nodule, followed by 25Gy in 5 weekly fractions to pelvis. All patients received between 6 and 18 months of androgen deprivation therapy.

Results: Thirty patients (NCCN 7% unfavorable IR, and 93% HR) completed study 1 while 31 patients (NCCN 3% favorable IR, 47% Unfavorable IR and 50% HR) completed treatment as per study 2. Median follow-up was 72 and 62 months, respectively. In study 2, 6 patients had BF and all 6 developed metastatic disease. Actuarial 5-year BF was 0% for study 1 and 18.2% for study 2 (p=0.005). There was no significant difference in worst acute or late GI or GU toxicity. Grade 3 late GU toxicity was noted in 3% of the patients in study 2 (HDR-BT boost). There was no significant difference in QoL or minimally clinical important change.

Conclusions: In the context of 5-fraction pelvic radiotherapy and ADT, there does not appear to be a significant difference in toxicity or QoL between SABR vs. HDR BT boost. While efficacy favored the SABR boost cohort, this should be viewed in the context of limitations and biases associated with comparing two sequential phase II studies.
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http://dx.doi.org/10.1016/j.ijrobp.2021.10.003DOI Listing
October 2021

Toxicity After Stereotactic Body Radiation Therapy for Prostate Cancer in Patients With Inflammatory Bowel Disease: A Multi-institutional Matched Case-Control Series.

Adv Radiat Oncol 2021 Nov-Dec;6(6):100759. Epub 2021 Aug 28.

Department of Radiation Oncology, UCLA Medical Center, Los Angeles, California.

Purpose: To evaluate the safety of stereotactic body radiation therapy (SBRT) for prostate cancer in men with inflammatory bowel disease (IBD).

Methods And Materials: We queried a consortium database for patients with IBD receiving SBRT for prostate cancer between 2006 and 2012. Identified patients were matched with patients without a history of IBD in a 3:1 fashion based on dose, fractionation, use of androgen deprivation therapy, and age distribution. Logistic regression was used to evaluate the association between having IBD and experiencing acute and late gastrointestinal (GI) and genitourinary (GU) toxicities as scored on the Common Terminology Criteria for Adverse Events scale. Time to late toxicity was evaluated using proportional hazard Cox models. Our study was limited by absence of data on prostate size, baseline International Prostate Symptom Score, and rectal dose-volume histogram parameters.

Results: Thirty-nine patients with flare-free IBD at time of treatment (median follow-up 83.9 months) and 117 matched controls (median follow-up 88.7 months) were identified. A diagnosis of IBD was associated with increased odds of developing any late grade GI toxicity (odds ratio [OR] 6.11, <.001) and GU toxicity (odds ratio 6.14, < .001), but not odds of developing late grade ≥2 GI ( = .08) or GU toxicity ( = .069). Acute GI and GU toxicity, both overall and for grade ≥2 toxicities, were more frequent in men with IBD ( < .05). Time to late GI and GU toxicity of any grade was significantly shorter in patients with IBD ( < .001). Time to late grade ≥2 GU, but not grade ≥2 GI toxicity, was also shorter in patients with IBD ( = .044 for GU and  = .144 for GI).

Conclusions: Patients with IBD who received SBRT for PCa had a higher likelihood of developing acute GI and GU toxicity, in addition to experiencing lower grade late toxicities that occurred earlier. However, patients with IBD did not have a higher likelihood for late grade ≥2 GI or GU toxicity after SBRT compared with the control cohort. Interpretation of this data are limited by the small sample size. Thus, men with IBD in remission should be properly counseled about these risks when considering SBRT.
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http://dx.doi.org/10.1016/j.adro.2021.100759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453194PMC
August 2021

Elective nodal ultra hypofractionated radiation for prostate cancer: Safety and efficacy from four prospective clinical trials.

Radiother Oncol 2021 Sep 4;163:159-164. Epub 2021 Sep 4.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Canada; Department of Radiation Oncology, University of Toronto, Canada; Institute of Health Policy, Management and Evaluation, Canada. Electronic address:

Background And Purpose: The role of elective nodal irradiation (ENI) in localized prostate cancer (PCa) is controversial. With increasing use of SBRT to the prostate, data is needed regarding the safety and efficacy of ENI using ultra-hypofractionated radiation (UHRT).

Materials And Methods: Between 2013-2020, 4 prospective clinical trials of intermediate or high-risk PCa receiving dose-escalated RT to the prostate (via HDR brachytherapy or SBRT boost) and ENI using UHRT (25 Gy in 5 weekly fractions) were conducted. Primary endpoints included acute genitourinary and gastrointestinal toxicities (CTCAE v3.0/4.0), and secondary endpoints included late genitourinary and gastrointestinal toxicities, patient-reported quality of life (EPIC) and biochemical failure (Phoenix definition).

Results: One-hundred sixty-five patients were enrolled, of whom 98 (59%) had high-risk disease. ADT was used in 141 (85%). Median follow-up was 38 months (IQR 10-63). The worst acute genitourinary and gastrointestinal toxicities respectively were 48% and 7.5% for grade 2, and 2.7% and 0% for grade 3. Cumulative incidence of late grade 2+ genitourinary and gastrointestinal toxicities at 36 months were 58% and 11.3% and for late grade 3+ toxicities were 1% and 0%, respectively. No grade 4+ acute or late toxicities were observed. Bowel and sexual toxicity significantly worsened up to 1-year compared to baseline. Over time, urinary (p < 0.0001), bowel (p = 0.0018) and sexual (p < 0.0001) scores significantly improved. The 3-year biochemical recurrence-free survival was 98%.

Conclusion: ENI using UHRT is associated with low incidence of grade 3+ toxicity, while grade 1-2 acute genitourinary and gastrointestinal toxicity is common. Randomized phase 3 trials are needed.
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http://dx.doi.org/10.1016/j.radonc.2021.08.017DOI Listing
September 2021

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

J Urol 2021 Aug 27:101097JU0000000000002187. Epub 2021 Aug 27.

Division of Radiation Oncology, Department of Oncology, London Health Sciences Centre, London, Ontario, Canada.

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 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.
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http://dx.doi.org/10.1097/JU.0000000000002187DOI Listing
August 2021

Multipurpose ultrasound-based prostate phantom for use in interstitial brachytherapy.

Brachytherapy 2021 Aug 19. Epub 2021 Aug 19.

Department of Physics, Ryerson University, Toronto, ON, Canada; Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada. Electronic address:

Purpose: While brachytherapy is an effective treatment for localized prostate cancer, there has been a noticeable decline in its use. Training opportunity for prostate brachytherapy has been in steady decline, with some residents receiving little to no hands-on training. This work was developed to design a training environment that uses a phantom-based simulator to teach the process of TRUS-based prostate brachytherapy METHODS AND MATERIALS: A prostate phantom was fabricated from a representative prostate patient TRUS scan. Three materials were used: gelatin powder, graphite powder, and water. The prostate was developed using 9% gelatin and 0.3% graphite per 100 ml water. Five radiation oncologists were asked to qualitatively score the phantom according to image quality, haptic feedback, needle insertion quality, and its compatibility with operative tools. The contrast-to-noise ratio (CNR) was estimated using different concentrations of graphite. The elasticity of the phantom was evaluated based on ultrasound elastography measurements RESULTS: The prostate phantom had an average CNR of 3.94 ± 1.09 compared to real prostate images with a CNR of 2 ± 1.8. The average Young's modulus was computed to be 58.03 ± 6.24 kPa compared to real prostate tissue (58.8 ± 8.2 kPa). Oncologists ranked the phantom as "very good" for overall quality of the phantom. They reported that needle insertion quality was "very good" during a simulated brachytherapy procedure.

Conclusion: We have developed a 3D printing prostate phantom to be used for training purposes during prostate brachytherapy. The phantom has been evaluated for image quality and elasticity. The reconstructed phantom could be used as an anthropomorphic surrogate to train residents on prostate brachytherapy procedures.
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http://dx.doi.org/10.1016/j.brachy.2021.07.003DOI Listing
August 2021

Elective pelvic nodal irradiation with a simultaneous hypofractionated integrated prostate boost for localized high risk prostate cancer: Long term results from a prospective clinical trial.

Radiother Oncol 2021 Jul 26;163:21-31. Epub 2021 Jul 26.

Department of Radiation Oncology, University of Toronto, Canada; Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada. Electronic address:

Background: To report on long-term results of elective pelvic nodal irradiation (EPNI) and a simultaneous hypofractionated prostate boost for high-risk prostate cancer.

Materials And Methods: This was a prospective single-arm study. Patients with high-risk disease (cT3, PSA >20 ng/mL, or Gleason score 8-10) were eligible. Patients received 45 Gy in 25 fractions to the prostate and pelvic lymph nodes with a simultaneous intensity-modulated radiotherapy boost of 22.5 Gy to the prostate (total dose 67.5 Gy in 25 fractions), with androgen deprivation therapy (ADT) for 2-3 years. The primary endpoint was biochemical failure. Secondary endpoints included distant metastases and overall survival. Multivariable analysis was performed to look for predictive factors. Late toxicity was assessed using CTCAE v3.0.

Results: 230 patients enrolled. Median follow-up was 11.2 years (IQR 8.1-12.9). At 10 years, cumulative incidence of biochemical failure was 33.4%, distant metastasis was 16.5%, and overall survival was 76.3%. On multivariable analysis, PSA nadir ≥0.05 ng/mL was associated with biochemical failure (HR 6.8, 95% CI 4-11.8, p < 0.001) and distant metastases (HR 7.5, 95% CI 3.9-14.5, p < 0.0001). PSA nadir ≥0.1 ng/mL (HR 5.2, 95% 2.2-12, p = 0.0001) and ADT use ≤12 months (versus >24 months) (HR 2.3, 95% CI 1.3-3.9, p = 0.004) were associated with worse survival. The 5-year cumulative incidence of any late grade ≥3 gastrointestinal and genitourinary toxicity was 2.3% and 7.5%, respectively.

Conclusion: EPNI and a simultaneous hypofractionated prostate boost combined with long-term ADT for high-risk prostate cancer resulted in acceptable 10-year biochemical control and survival with low grade ≥3 toxicity.
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http://dx.doi.org/10.1016/j.radonc.2021.07.018DOI Listing
July 2021

Moving Unfavorable Small-Bowel Anatomy Away From the Prostate to Optimize Radiation Therapy Plans With the GU-Lok.

Pract Radiat Oncol 2021 Jul 5. Epub 2021 Jul 5.

Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. Electronic address:

Patients with localized prostate cancer comprise a large volume of treatments in radiation therapy centers. Occasionally, individual patient anatomy makes the safe delivery of an effective dose of radiation therapy challenging. We describe 2 cases of patients with a small bowel deep in the pelvis within the planning target volume with subsequent suboptimal radiation therapy treatment plans. We explore how we used the GU-Lok, a prostate immobilization device, to move the small bowel away from the prostate, and tighten target volume margins to help facilitate safe and effective treatment.
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http://dx.doi.org/10.1016/j.prro.2021.06.009DOI Listing
July 2021

Stereotactic pelvic radiotherapy with HDR boost for dose escalation in intermediate and high-risk prostate cancer (SPARE): Efficacy, toxicity and quality of life.

Radiother Oncol 2021 08 3;161:40-46. Epub 2021 Jun 3.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Canada; Department of Radiation Oncology, University of Toronto, Canada; Institute of Health Policy, Management and Evaluation, Canada. Electronic address:

Background: The ASCO/CCO guidelines recommend brachytherapy (BT) boost for eligible intermediate- (IR) or high-risk (HR) prostate cancer (PCa) patients. We present efficacy, toxicity and quality-of-life (QoL) outcomes in patients treated on a prospective protocol of MRI dose-painted high-dose-rate BT boost (HDR-BT) followed by 5-fraction pelvic radiotherapy (RT) and 6-18 months of androgen deprivation therapy (ADT).

Methods: In this phase I/II study, IR or HR PCa patients received HDR-BT 15 Gy × 1 to prostate and up to 22.5 Gy to MRI nodule, followed by 25 Gy in 5, weekly fractions to pelvis. Toxicity was assessed using CTCAEv3.0, and QoL was captured using EPIC questionnaire. Biochemical failure (BF; nadir + 2.0), and proportion of patients with PSA < 0.4 ng/ml at 4-years (4yPSARR) were evaluated. A minimally clinically important change (MCIC) was recorded if QoL score decreased >0.5 standard deviation of baseline scores.

Results: Thirty-one patients (NCCN 3.2% favorable IR, 48.4% unfavorable IR and 48.4% HR) completed treatment with a median follow-up of 61 months. Median D90 to MR nodule was 19.0 Gy and median prostate V100% was 96.5%. The actuarial 5-year BF rate was 18.2%, and the 4yPSARR was 71%. One patient died of PCa. Acute grade 2 and 3 toxicities: GU: 50%, 7%, and GI: 3%, none, respectively. Late grade 2 and 3 toxicities were: GU: 23%, 3%, and GI: 7%, none, respectively. Proportion of patients with MCIC was 7.7% for urinary domain and 32.0% for bowel domain.

Conclusions: This novel treatment protocol incorporating MRI dose-painted HDR-BT boost and 5-fraction pelvic RT with ADT is well tolerated.
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http://dx.doi.org/10.1016/j.radonc.2021.05.024DOI Listing
August 2021

Comparison of Multiparametric Magnetic Resonance Imaging-Targeted Biopsy With Systematic Transrectal Ultrasonography Biopsy for Biopsy-Naive Men at Risk for Prostate Cancer: A Phase 3 Randomized Clinical Trial.

JAMA Oncol 2021 04;7(4):534-542

Toronto General Hospital, Department of Radiology, University of Toronto, Toronto, Ontario, Canada.

Importance: Magnetic resonance imaging (MRI) with targeted biopsy is an appealing alternative to systematic 12-core transrectal ultrasonography (TRUS) biopsy for prostate cancer diagnosis, but has yet to be widely adopted.

Objective: To determine whether MRI with only targeted biopsy was noninferior to systematic TRUS biopsies in the detection of International Society of Urological Pathology grade group (GG) 2 or greater prostate cancer.

Design, Setting, And Participants: This multicenter, prospective randomized clinical trial was conducted in 5 Canadian academic health sciences centers between January 2017 and November 2019, and data were analyzed between January and March 2020. Participants included biopsy-naive men with a clinical suspicion of prostate cancer who were advised to undergo a prostate biopsy. Clinical suspicion was defined as a 5% or greater chance of GG2 or greater prostate cancer using the Prostate Cancer Prevention Trial Risk Calculator, version 2. Additional criteria were serum prostate-specific antigen levels of 20 ng/mL or less (to convert to micrograms per liter, multiply by 1) and no contraindication to MRI.

Interventions: Magnetic resonance imaging-targeted biopsy (MRI-TB) only if a lesion with a Prostate Imaging Reporting and Data System (PI-RADS), v 2.0, score of 3 or greater was identified vs 12-core systematic TRUS biopsy.

Main Outcome And Measures: The proportion of men with a diagnosis of GG2 or greater cancer. Secondary outcomes included the proportion who received a diagnosis of GG1 prostate cancer; GG3 or greater cancer; no significant cancer but subsequent positive MRI results and/or GG2 or greater cancer detected on a repeated biopsy by 2 years; and adverse events.

Results: The intention-to-treat population comprised 453 patients (367 [81.0%] White, 19 [4.2%] African Canadian, 32 [7.1%] Asian, and 10 [2.2%] Hispanic) who were randomized to undergo TRUS biopsy (226 [49.9%]) or MRI-TB (227 [51.1%]), of which 421 (93.0%) were evaluable per protocol. A lesion with a PI-RADS score of 3 or greater was detected in 138 of 221 men (62.4%) who underwent MRI, with 26 (12.1%), 82 (38.1%), and 30 (14.0%) having maximum PI-RADS scores of 3, 4, and 5, respectively. Eighty-three of 221 men who underwent MRI-TB (37%) had a negative MRI result and avoided biopsy. Cancers GG2 and greater were identified in 67 of 225 men (30%) who underwent TRUS biopsy vs 79 of 227 (35%) allocated to MRI-TB (absolute difference, 5%, 97.5% 1-sided CI, -3.4% to ∞; noninferiority margin, -5%). Adverse events were less common in the MRI-TB arm. Grade group 1 cancer detection was reduced by more than half in the MRI arm (from 22% to 10%; risk difference, -11.6%; 95% CI, -18.2% to -4.9%).

Conclusions And Relevance: Magnetic resonance imaging followed by selected targeted biopsy is noninferior to initial systematic biopsy in men at risk for prostate cancer in detecting GG2 or greater cancers.

Trial Registration: ClinicalTrials.gov Identifier: NCT02936258.
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http://dx.doi.org/10.1001/jamaoncol.2020.7589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863017PMC
April 2021

Utilization of Salvage and Systemic Therapies for Recurrent Prostate Cancer as a Result of F-DCFPyL PET/CT Restaging.

Adv Radiat Oncol 2021 Jan-Feb;6(1):100553. Epub 2020 Sep 9.

Department of Oncology, Division of Radiation Oncology, London Health Sciences Centre and Western University, London, Canada.

Purpose: Our purpose was to investigate the effect of the addition of prostate-specific membrane antigen (PSMA)-targeted positron emission tomography/computed tomography (PET/CT) in patients with recurrent prostate cancer post-primary radiation therapy.

Methods And Materials: A prospective, multi-institutional clinical trial evaluated 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (F-DCFPyL) PET/CT restaging in 79 men with recurrent prostate cancer post-primary radiation therapy. We report actual patient management and compare this with proposed management both before and after PSMA-targeted PET/CT.

Results: Most patients (59%) had a major change in actual management compared with pre-PET/CT proposed management. The rate of major change was underestimated by immediately post-PET/CT surveys (32%). Eighteen patients with PSMA avidity in the prostate gland suspicious for malignancy had a prostate biopsy. Sensitivity, specificity, and positive predictive values of PSMA uptake in the prostate were 86%, 67%, and 92%, respectively. Thirty percent of patients had directed salvage therapy and 41% underwent systemic therapy. Eleven out of 79 patients (14%) had high-dose-rate brachytherapy alone for local recurrence, and 91% were free of recurrence at a median follow-up of 20 months.

Conclusions: Most patients had a major change in actual management compared with pre-PSMA-targeted PET/CT planned management, and this was underestimated by post-PET/CT questionnaires.
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http://dx.doi.org/10.1016/j.adro.2020.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820022PMC
September 2020

Initial Management of Noncastrate Advanced, Recurrent, or Metastatic Prostate Cancer: ASCO Guideline Update.

J Clin Oncol 2021 04 26;39(11):1274-1305. Epub 2021 Jan 26.

Nanhealth, Inc, Culver City, CA.

Purpose: Update all preceding ASCO guidelines on initial hormonal management of noncastrate advanced, recurrent, or metastatic prostate cancer.

Methods: The Expert Panel based recommendations on a systematic literature review. Recommendations were approved by the Expert Panel and the ASCO Clinical Practice Guidelines Committee.

Results: Four clinical practice guidelines, one clinical practice guidelines endorsement, 19 systematic reviews with or without meta-analyses, 47 phase III randomized controlled trials, nine cohort studies, and two review papers informed the guideline update.

Recommendations: Docetaxel, abiraterone, enzalutamide, or apalutamide, each when administered with androgen deprivation therapy (ADT), represent four separate standards of care for noncastrate metastatic prostate cancer. Currently, the use of any of these agents in any particular combination or series cannot be recommended. ADT plus docetaxel, abiraterone, enzalutamide, or apalutamide should be offered to men with metastatic noncastrate prostate cancer, including those who received prior therapies, but have not yet progressed. The combination of ADT plus abiraterone and prednisolone should be considered for men with noncastrate locally advanced nonmetastatic prostate cancer who have undergone radiotherapy, rather than castration monotherapy. Immediate ADT may be offered to men who initially present with noncastrate locally advanced nonmetastatic disease who have not undergone previous local treatment and are unwilling or unable to undergo radiotherapy. Intermittent ADT may be offered to men with high-risk biochemically recurrent nonmetastatic prostate cancer. Active surveillance may be offered to men with low-risk biochemically recurrent nonmetastatic prostate cancer. The panel does not support use of either micronized abiraterone acetate or the 250 mg dose of abiraterone with a low-fat breakfast in the noncastrate setting at this time.Additional information is available at www.asco.org/genitourinary-cancer-guidelines.
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http://dx.doi.org/10.1200/JCO.20.03256DOI Listing
April 2021

Stereotactic Body Radiotherapy for High-Risk Localized Carcinoma of the Prostate (SHARP) Consortium: Analysis of 344 Prospectively Treated Patients.

Int J Radiat Oncol Biol Phys 2021 07 23;110(3):731-737. Epub 2021 Jan 23.

Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, California. Electronic address:

Purpose: To explore the efficacy and toxicity of stereotactic body radiation therapy (SBRT) in high-risk prostate cancer (HRPCa) in a consortium of 7 institutional phase 2 trials and prospective registries.

Methods And Materials: Individual patient data were pooled for 344 patients with a minimum follow-up of 24 months. Biochemical recurrence-free survival (BCRFS) and distant metastasis-free survival (DMFS) were estimated using a Kaplan-Meier framework. Fine and Gray competing risk and Cox proportional hazards regression models were developed to assess the association between time to BCR and time to distant metastasis and prespecified variables of interest. Logistic regression models were developed to evaluate associations between acute and late grade ≥2 genitourinary and gastrointestinal and the following a priori-specified variables: age, dose per fraction, ADT use, and nodal radiation therapy.

Results: Median follow-up was 49.5 months. Seventy-two percent of patients received ADT, with a median duration of 9 months, and 19% received elective nodal radiation therapy. Estimated 4-year BCRFS and DMFS rates were 81.7% (95% CI, 77.2%-86.5%) and 89.1% (95% CI, 85.3%-93.1%). The crude incidences of late grade ≥3 genitourinary and gastrointestinal toxicity were 2.3% and 0.9%.

Conclusions: These data support a favorable toxicity and efficacy profile for SBRT for HRPCa. Further prospective studies are needed to evaluate the optimal dose and target volume in the context of SBRT for HRPCa.
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http://dx.doi.org/10.1016/j.ijrobp.2021.01.016DOI Listing
July 2021

Prostate high dose-rate brachytherapy as monotherapy for prostate cancer: Late toxicity and patient reported outcomes from a randomized phase II clinical trial.

Radiother Oncol 2021 03 4;156:160-165. Epub 2021 Jan 4.

Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Canada. Electronic address:

Background And Purpose: Long-term toxicity of high dose-rate brachytherapy as monotherapy for prostate cancer is not well defined. We report late toxicity and health related quality of life (HRQOL) changes from a randomized phase II clinical trial of two different fractionation schemes.

Materials And Methods: Eligible patients had NCCN low or intermediate risk prostate cancer. 170 patients were randomized to receive either a single 19 Gy or two-fractions of 13.5 Gy one week apart. Toxicity was measured using Common Terminology for Adverse Events (CTCAE) v4.0, and HRQOL was measured using the Expanded Prostate Index Composite (EPIC).

Results: Median follow-up was 63 months. The 5-year cumulative incidence of Grade 2 or higher genitourinary (GU) and gastrointestinal (GI) toxicity was 62% and 12% in the single-fraction arm, and 47% and 9% in the two-fraction arm, respectively. Grade 3 GU toxicity was only seen in the single fraction arm with a cumulative incidence of 2%. The 5-year prevalence of Grade 2 GU toxicity was 29% and 21%, in the single- and two-fraction arms, respectively, with Grade 2 GI toxicity of 1% and 2%. Beyond the first year, no significant differences in mean urinary HRQOL were seen compared to baseline in the two-fraction arm, in contrast to the single-fraction arm where a decline in urinary HRQOL was seen at 4 and 5 years. Sexual HRQOL was significantly reduced in both treatment arms at all timepoints, with no changes in the bowel domain.

Conclusions: HDR monotherapy is well tolerated with minimal impact on HRQOL.
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http://dx.doi.org/10.1016/j.radonc.2020.12.021DOI Listing
March 2021

Estimating acute urinary retention risk post prostate high dose-rate (HDR) brachytherapy: A clinical-based recursive partitioning analysis.

Radiother Oncol 2021 01 20;154:118-122. Epub 2020 Sep 20.

Department of Radiation Oncology, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Purpose: To determine factors associated with need for post-procedural catheterization in prostate cancer patients treated with 15 Gy high dose-rate brachytherapy boost (HDR-BT).

Material And Methods: Patients treated with 15 Gy HDR-BT followed by EBRT were retrospectively evaluated for development of urinary retention and hematuria requiring catheterization in the first 30 days post procedure. Clinical characteristics and treatment details were obtained and used as independent variables under study. Univariable and multivariable logistic regression analysis were used to determine predictors of post brachytherapy complications and a classification tree for risk of urinary retention was created using recursive partitioning analysis (RPA).

Results: A total of 425 patients treated with 15 Gy HDR-BT were included in this analysis. 27 patients (6.3%) required catheter placement due to acute urinary retention and thirteen other patients (3%) developed hematuria requiring urinary catheter insertion ± continuous bladder irrigation. Number of needles, prostate volume and prior use of ADT, alpha-blockers or 5α-reductase inhibitors were statistically associated with urinary retention in the univariable logistic regression analysis. In multivariable analysis, prostate volume, previous use of alpha-blocker, and use of ADT remained significant. In the RPA, populations were identified in which the rate of urinary retention ranged from 2% to 50% depending on presence of one or more of these risk factors.

Conclusion: The overall rate of acute urinary complications post HDR brachytherapy is low, but the individual risk of urinary retention can increase depending on the number of risk factors present. A more patient-directed retention risk estimation can be performed by using the classification risk tree presented here.
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http://dx.doi.org/10.1016/j.radonc.2020.09.023DOI Listing
January 2021

Hospital-level Effects Contribute to Variations in Prostate Cancer Quality of Care.

Eur Urol Oncol 2021 Jun 13;4(3):494-497. Epub 2020 Sep 13.

Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre-University Health Network, Toronto, ON, Canada; Division of Urology, Department of Surgery, University of Toronto, Toronto, ON, Canada. Electronic address:

A paucity of real-world data exists highlighting whether variations in prostate cancer quality of care occur at a hospital level, independent of differences in case mix. To overcome this knowledge gap, we benchmarked hospital-level quality (n = 1245 hospitals) across a broad multidisciplinary panel of previously reported disease-specific, expert-defined quality indicators (QIs), adjusting for differences in patient case mix by indirect standardization. A composite measure of prostate cancer quality-the prostate cancer quality score (PC-QS)-was derived, and associations between PC-QS and hospital volume, academic status, and location as well as patient all-cause mortality were determined. After adjusting for the case mix, of the total of 1245 hospitals evaluated, 2-37% were identified as those performing significantly below the national average for a given QI. Hospitals with a higher PC-QS displayed larger patient volumes, were more commonly academic affiliated, and had lower overall mortality. Collectively, our data-driven benchmarking analysis reveals that widespread hospital-level variations exist in prostate cancer quality of care after adjusting for differences in case mix, with the PC-QS serving as a novel, validated, quality benchmarking tool. PATIENT SUMMARY: Our statistical benchmarking method shows that the quality of prostate cancer care varies between hospitals, after accounting for differences in patient characteristics. The prostate cancer quality score is a novel, validated, quality benchmarking tool.
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http://dx.doi.org/10.1016/j.euo.2020.08.010DOI Listing
June 2021

Single-fraction HDR brachytherapy as monotherapy in low and intermediate risk prostate cancer: Outcomes from two clinical trials with and without an MRI-guided boost.

Radiother Oncol 2021 01 10;154:29-35. Epub 2020 Sep 10.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Canada. Electronic address:

Purpose: Single-fraction HDR monotherapy for the treatment of localized prostate cancer is appealing, but published outcomes are discouraging. An approach to improve local control is MRI-guided focal dose-escalation to the dominant intraprostatic lesion (DIL). Here we report a comparison of outcomes from two phase II clinical trials with and without a focal boost.

Methods: Patients had low or intermediate-risk disease. Patients in Trial1 received a single 19 Gy HDR implant to the whole prostate. Trial2 incorporated an additional MRI-guided focal DIL boost to at least 23 Gy. ADT was not allowed. Toxicities (CTCAEv4.0) and quality of life (EPIC) were collected. Biochemical failure (BF) was defined as nadir +2. Univariate and multivariate logistic regression analysis was conducted to search for predictors of BF.

Results: Trial1 had 87 patients with a median follow-up of 62 months, while Trial2 had 60 patients with a median follow-up of 50 months. The five-year cumulative BF rate was 32.6% and 31.3%, respectively (p = 0.9). 77.5% of failures were biopsy-confirmed local failures, all of which underwent local salvage therapy. The addition of a DIL boost was not associated with worse toxicity or QOL. Baseline PSA and Gleason score correlated with BF, but none of the dosimetric parameters was a significant predictor of BF.

Conclusions: MRI-guided focal boost was safe and well tolerated, but did not improve local control after 19 Gy single-fraction HDR monotherapy, and the control rates were unacceptable. Single-fraction HDR monotherapy for prostate cancer should not be offered outside of clinical trials.
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http://dx.doi.org/10.1016/j.radonc.2020.09.007DOI Listing
January 2021

Dosimetric evaluation of MRI-to-ultrasound automated image registration algorithms for prostate brachytherapy.

Brachytherapy 2020 Sep - Oct;19(5):599-606. Epub 2020 Jul 22.

Department of Medical Physics, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. Electronic address:

Purpose: Identifying dominant intraprostatic lesions (DILs) on transrectal ultrasound (TRUS) images during prostate high-dose-rate brachytherapy treatment planning remains a significant challenge. Multiparametric MRI (mpMRI) is the tool of choice for DIL identification; however, the geometry of the prostate on mpMRI and on the TRUS may differ significantly, requiring image registration. This study assesses the dosimetric impact attributed to differences in DIL contours generated using commonly available MRI to TRUS automated registration: rigid, semi-rigid, and deformable image registration, respectively.

Methods And Materials: Ten patients, each with mpMRI and TRUS data sets, were included in this study. Five radiation oncologists with expertise in TRUS-based high-dose-rate brachytherapy were asked cognitively to transfer the DIL from the mpMRI images of each patient to the TRUS image. The contours were analyzed for concordance using simultaneous truth and performance level estimation (STAPLE) algorithm. The impact of DIL contour differences due to registration variability was evaluated by comparing the STAPLE-DIL dosimetry from the reference (STAPLE) plan with that from the evaluation plans (manual and automated registration) for each patient. The dosimetric impact of the automatic registration approach was also validated using a margin expansion that normalizes the volume of the autoregistered DILs to the volumes of the STAPLE-DILs. Dose metrics including D, D, V, and V to the prostate and DIL were reported. For urethra and rectum, D and V were reported.

Results: Significant differences in DIL coverage between reference and evaluation plans were found regardless of the algorithm methodology. No statistical difference was reported in STAPLE-DIL dosimetry when manual registration was used. A margin of 1.5 ± 0.8 mm, 1.1 ± 0.8 mm, and 2.5 ± 1.6 mm was required to be added for rigid, semi-rigid, and deformable registration, respectively, to mitigate the difference in STAPLE-DIL coverage between the evaluation and reference plans.

Conclusion: The dosimetric impact of integrating an MRI-delineated DIL into a TRUS-based brachytherapy workflow has been validated in this study. The results show that rigid, semi-rigid, and deformable registration algorithms lead to a significant undercoverage of the DIL D and D. A margin of at least 1.5 ± 0.8 mm, 1.1 ± 0.8 mm, and 2.5 ± 1.6 mm is required to be added to the rigid, semi-rigid, and deformable DIL registration to be suitable for DIL-boosting during prostate brachytherapy.
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http://dx.doi.org/10.1016/j.brachy.2020.06.014DOI Listing
May 2021

Does ADT benefit unfavourable intermediate risk prostate cancer patients treated with brachytherapy boost and external beam radiotherapy? A propensity-score matched analysis.

Radiother Oncol 2020 09 30;150:195-200. Epub 2020 Jun 30.

Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada. Electronic address:

Purpose: To investigate the role of androgen deprivation therapy (ADT) in unfavorable intermediate risk (UIR) prostate cancer patients treated with high-dose rate (HDR) brachytherapy (BT) boost.

Material And Methods: Data from 326 consecutive NCCN UIR prostate cancer patients treated in a single institution from 2009 to 2016 with 15 Gy HDR-BT boost plus 37.5 Gy external beam radiotherapy (EBRT) in 15 fractions to prostate and proximal seminal vesicles were retrospectively collected. Baseline information was collected and patients receiving vs. not receiving ADT were matched using a propensity-score model. Primary endpoint was biochemical-failure-free survival (BFFS). Kaplan-Meier estimates and stratified log-rank tests (adjusting for matched design) were used to compare BFFS, castration-resistance (CRFS) and metastasis free survival (MFS) outcomes between both groups.

Results: A total of 326 patients were included in the analysis of which 52 ADT patients were matched to 104 non-ADT patients in a 1:2 ratio. Median follow-up was 3.4 years and 5.5 years for ADT and non-ADT respectively. No significant baseline differences were observed. ADT was used for a median total time of 6 months (interquartile range [IQR]: 4-6) and delivered a median time of 2.7 months (IQR: 1.7-4.3) prior to HDR-BT. BFFS was significantly improved in the ADT group (stratified log-rank: p = 0.043) with 3-year and 6-year BFFS of 98% and 90% for the ADT group and 92% and 82% for the non-ADT group, respectively. No significant differences were detected for CRFS or MFS.

Conclusion: Short-term ADT increased BFFS in UIR prostate cancer patients treated with HDR-BT boost plus EBRT.
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http://dx.doi.org/10.1016/j.radonc.2020.06.039DOI Listing
September 2020

Gantry-Mounted Linear Accelerator-Based Stereotactic Body Radiation Therapy for Low- and Intermediate-Risk Prostate Cancer.

Adv Radiat Oncol 2020 May-Jun;5(3):404-411. Epub 2019 Oct 14.

Department of Radiation Oncology, University of California, Los Angeles, California.

Purpose: To establish the safety and efficacy of gantry-mounted linear accelerator-based stereotactic body radiation therapy (SBRT) for low- and intermediate-risk prostate cancer.

Methods: We pooled 921 patients enrolled on 7 single-institution prospective phase II trials of gantry-based SBRT from 2006 to 2017. The cumulative incidences of biochemical recurrence (defined by the Phoenix definition) and physician-scored genitourinary (GU) and gastrointestinal (GI) toxicities (defined per the original trials using Common Terminology Criteria for Adverse Events) were estimated using a competing risk framework. Multivariable logistic regression was used to evaluate the relationship between late toxicity and prespecified covariates: biologically effective dose, every other day versus weekly fractionation, intrafractional motion monitoring, and acute toxicity.

Results: Median follow-up was 3.1 years (range, 0.5-10.8 years). In addition, 505 (54.8%) patients had low-risk disease, 236 (25.6%) had favorable intermediate-risk disease, and 180 (19.5%) had unfavorable intermediate-risk disease. Intrafractional motion monitoring was performed in 78.0% of patients. The 3-year cumulative incidence of biochemical recurrence was 0.8% (95% confidence interval [CI], 0-1.7%), 2.2% (95% CI, 0-4.3%), and 5.1% (95% CI, 1.0-9.2%) for low-, favorable intermediate-, and unfavorable intermediate-risk disease. Acute grade ≥2 GU and GI toxicity occurred in 14.5% and 4.6% of patients, respectively. Three-year cumulative incidence estimates of late grade 2 GU and GI toxicity were 4.1% (95% CI, 2.6-5.5%) and 1.3% (95% CI, 0.5-2.1%), respectively, with late grade ≥3 GU and GI toxicity estimates of 0.7% (95% CI, 0.1-1.3%) and 0.4% (95% CI, 0-0.8%), respectively. The only identified significant predictors of late grade ≥2 toxicity were acute grade ≥2 toxicity ( < .001) and weekly fractionation ( < .01), although only 12.4% of patients were treated weekly.

Conclusions: Gantry-based SBRT for prostate cancer is associated with a favorable safety and efficacy profile, despite variable intrafractional motion management techniques. These findings suggest that multiple treatment platforms can be used to safely deliver prostate SBRT.
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http://dx.doi.org/10.1016/j.adro.2019.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276661PMC
October 2019

Accelerating prostate stereotactic ablative body radiotherapy: Efficacy and toxicity of a randomized phase II study of 11 versus 29 days overall treatment time (PATRIOT).

Radiother Oncol 2020 08 27;149:8-13. Epub 2020 Apr 27.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Canada; Institute of Health Policy Management and Evaluation, University of Toronto, Canada. Electronic address:

Background: Prostate stereotactic ablative radiotherapy (SABR) regimens differ in time, dose, and fractionation. We report an update of a multicentre, Canadian randomized phase II study to investigate the impact of overall treatment time on quality of life (QOL), efficacy, and toxicity.

Methods: Men with intermediate risk prostate cancer were randomized to 40 Gy in 5 fractions delivered every other day (EOD) versus once per week (QW). Primary outcome was proportion of patients experiencing a minimally clinically important change (MCIC) in acute bowel QOL using EPIC. Secondary outcomes were toxicity, biochemical failure (BF), other QOL domains, and the rate of salvage therapy.

Findings: 152 men from 3 centers were randomized; the median follow-up was 62 months. Results are described for EOD versus QW. Acute bowel and urinary QOL was reported previously. Late changes in QOL were not significantly different between the two arms. There were 1 (1.3%) vs 3 (2.7%) late grade 3 + GI toxicities (p = 0.36) and 5 (6.7%) vs 2 (2.7%) late grade 3 GU toxicities (p = 0.44). Two and 5 patients had BF (5-year failure rate 3.0 vs 7.2%, p = 0.22); 0 and 4 patients received salvage therapy (p = 0.04). 5-Year OS and CSS was 95.8% and 98.6% with no difference between arms (p = 0.49, p = 0.15). 3 patients in the QW arm developed metastases.

Interpretation: Although we previously reported that weekly prostate SABR had better bowel and urinary QOL compared to EOD, the updated results show no difference in late toxicity, QOL, BF, or PSA kinetics. Patients should be counseled that QW SABR reduces short-term toxicity compared to QW SABR.
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http://dx.doi.org/10.1016/j.radonc.2020.04.039DOI Listing
August 2020

Impact of Biopsy Compliance on Outcomes for Patients on Active Surveillance for Prostate Cancer.

J Urol 2020 11 24;204(5):934-940. Epub 2020 Apr 24.

Department of Radiation Oncology, Odette Cancer Center, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Purpose: Active surveillance for prostate cancer relies on regular prostate specific antigen tests and surveillance biopsies. Compliance rates with biopsies vary but the subsequent impact on oncologic outcomes is not known. The objective of this study was to determine whether noncompliance with the confirmatory biopsy negatively impacts prostate cancer specific outcomes.

Materials And Methods: A retrospective analysis was performed on a prospective single-arm cohort of men enrolled in active surveillance for prostate cancer between 1995 and 2018 with a median followup of 9.1 years. A total of 1,275 patients were enrolled and 1,043 had a minimum of 3 years of followup and were included in the analysis. Patients were stratified by compliance with a confirmatory biopsy within 24 months of enrollment in active surveillance. The primary outcome was recurrence-free survival. Secondary outcomes included metastatic-free survival and cause specific survival.

Results: A total of 1,275 patients were enrolled, and 1,043 had a minimum of 3 years of followup and were included in the analysis, of whom 425 were treated for localized prostate cancer. Patients noncompliant with the confirmatory biopsy had higher rates of recurrence after treatment (19% vs 12%, HR 1.64, 95% CI 1.19-2.26, p=0.003) and metastases (7% vs 2%, HR 3.56, 95% CI 1.8-7.0, p=0.0003) even after accounting for age, prostate specific antigen and Grade Group. Cause specific survival was not significantly different between the 2 groups. The results were consistent even in the subset of patients with Grade Group 1 disease at study entry.

Conclusions: Noncompliance with a confirmatory biopsy compromises the control of prostate cancer in men followed on active surveillance. Patients and physicians should be aware of the importance of adhering to protocol for men on active surveillance.
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http://dx.doi.org/10.1097/JU.0000000000001091DOI Listing
November 2020

Conventional vs machine learning-based treatment planning in prostate brachytherapy: Results of a Phase I randomized controlled trial.

Brachytherapy 2020 Jul - Aug;19(4):470-476. Epub 2020 Apr 19.

Department of Medical Physics, Sunnybrook Odette Cancer Centre, Toronto, ON, Canada. Electronic address:

Purpose: The purpose of this study was to evaluate the noninferiority of Day 30 dosimetry between a machine learning-based treatment planning system for prostate low-dose-rate (LDR) brachytherapy and the conventional, manual planning technique. As a secondary objective, the impact of planning technique on clinical workflow efficiency was also evaluated.

Materials And Methods: 41 consecutive patients who underwent I-125 LDR monotherapy for low- and intermediate-risk prostate cancer were accrued into this single-institution study between 2017 and 2018. Patients were 1:1 randomized to receive treatment planning using a machine learning-based prostate implant planning algorithm (PIPA system) or conventional, manual technique. Treatment plan modifications by the radiation oncologist were evaluated by computing the Dice coefficient of the prostate V isodose volume between either the PIPA-or conventional-and final approved plans. Additional evaluations between groups evaluated the total planning time and dosimetric outcomes at preimplant and Day 30.

Results: 21 and 20 patients were treated using the PIPA and conventional techniques, respectively. No significant differences were observed in preimplant or Day 30 prostate D, V, rectum V, or rectum D between PIPA and conventional techniques. Although the PIPA group had a larger proportion of patients with plans requiring no modifications (Dice = 1.00), there was no significant difference between the magnitude of modifications between each arm. There was a large significant advantage in mean planning time for the PIPA arm (2.38 ± 0.96 min) compared with the conventional (43.13 ± 58.70 min) technique (p >> 0.05).

Conclusions: A machine learning-based planning workflow for prostate LDR brachytherapy has the potential to offer significant time savings and operational efficiencies, while producing noninferior postoperative dosimetry to that of expert, conventional treatment planners.
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http://dx.doi.org/10.1016/j.brachy.2020.03.004DOI Listing
April 2021

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.

Radiother Oncol 2020 05 5;146:90-96. Epub 2020 Mar 5.

Sunnybrook Odette Cancer Centre, University of Toronto, Canada.

Background And Purpose: High dose-rate (HDR) brachytherapy as monotherapy is a treatment option for localized prostate cancer, but optimal dose and fractionation is unknown. We report efficacy results of a randomized phase II trial of HDR monotherapy delivered as either one or two fractions.

Materials And Methods: Eligible patients had low or intermediate risk prostate cancer, prostate volume <60 cc, and no androgen deprivation use. 170 patients were randomized to receive HDR as either a single fraction of 19 Gy or as two fractions of 13.5 Gy one week apart. Median age was 65 years, median PSA was 6.33 ng/ml, and Grade Group 1, 2 and 3 was present in 28%, 60%, and 12%, respectively. There was no difference in baseline factors between arms and 19%, 51% and 30% had low risk, favourable intermediate and unfavourable intermediate risk disease, respectively. The Phoenix definition was used to define biochemical failure, all local failures were confirmed by biopsy and toxicity was assessed using CTCAE v.4.

Results: Median follow-up was 60 months. PSA decreased more quickly in the 2-fraction arm (p = 0.009). Median PSA at 5-years was 0.65 ng/ml in the single fraction and 0.16 ng/ml in the 2-fraction arm. The 5-year biochemical disease-free survival and cumulative incidence of local failure was 73.5% and 29% in the single fraction arm and 95% (p = 0.001) and 3% (p < 0.001) in the 2-fraction arm, respectively. Recurrence was not associated with initial stage, grade group, or risk group. Grade 2 late rectal toxicity occurred in 1% while the incidence of grade 2 and 3 urinary toxicity was 45% and 1%, respectively, with no difference between arms.

Conclusions: HDR monotherapy delivered as two fraction of 13.5 Gy is well tolerated with a high cancer control rate at 5 years. Single fraction monotherapy is inferior and should not be used.
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http://dx.doi.org/10.1016/j.radonc.2020.02.009DOI Listing
May 2020

Evaluating the Tolerability of a Simultaneous Focal Boost to the Gross Tumor in Prostate SABR: A Toxicity and Quality-of-Life Comparison of Two Prospective Trials.

Int J Radiat Oncol Biol Phys 2020 05 25;107(1):136-142. Epub 2020 Jan 25.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Purpose: Dose-escalated stereotactic ablative radiotherapy (SABR) to the whole prostate may be associated with better outcomes but has a risk of increased toxicity. An alternative approach is to focally boost the dominant intraprostatic lesion (DIL) seen on magnetic resonance imaging. We report the toxicity and quality-of-life (QOL) outcomes of 2 phase 2 trials of prostate and pelvic SABR, with or without a simultaneous DIL boost.

Methods And Materials: The first trial treated patients with high-risk prostate cancer to a dose of 40 Gy to the prostate and 25 Gy to the pelvis in 5 fractions. The second trial treated patients with intermediate-risk and high-risk prostate cancer to a dose of 35 Gy to the prostate, 25 Gy to the pelvis, and a DIL boost up to 50 Gy in 5 fractions. Acute toxicities, late toxicities, and QOL were assessed.

Results: Thirty patients were enrolled in each trial. In the focal boost cohort, the median DIL D90% was 48.3 Gy. There was no significant difference in acute grade ≥2 gastrointestinal or genitourinary toxicity between the 2 trials or in cumulative worst late gastrointestinal or genitourinary toxicity up to 24 months. There was no significant difference in QOL domain scores or minimally clinical important change between the 2 trials.

Conclusions: Prostate and pelvic SABR with a simultaneous DIL boost was feasible. Acute grade ≥2 toxicity, late toxicity, and QOL seemed to be comparable to a cohort that did not receive a focal boost. Further follow-up will be required to assess long-term outcomes, and randomized data are required to confirm these findings.
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http://dx.doi.org/10.1016/j.ijrobp.2019.12.044DOI Listing
May 2020

Stereotactic Ablative Body Radiotherapy for Intermediate- or High-Risk Prostate Cancer.

Authors:
Andrew Loblaw

Cancer J 2020 Jan/Feb;26(1):38-42

From the Odette Cancer Centre, Sunnybrook Health Sciences Centre; and Department of Radiation Oncology, and Institute of Health Care Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.

Stereotactic ablative radiotherapy (SABR) is a relatively novel form of high precision radiotherapy. For low- and intermediate risk patients, ultrahypofractionation (UHF - more than 5 Gy per day) has been compared to conventionally fractionated or moderately hypofractionated radiotherapy in two large randomized studies. A third smaller randomized study examined the question of the optimal frequency of treatments. The results of these studies will be reviewed. SABR for high risk prostate cancer has been shown to be feasible and is well tolerated with careful planning and setup techniques. However, there is currently insufficient data supporting its use for high-risk patients to offer SABR outside of a clinical trial. SABR costs less to the radiotherapydepartments and, the patient, as well as increasing system capacity. Therefore, it has the potential to be widely adopted in the next few years.
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http://dx.doi.org/10.1097/PPO.0000000000000425DOI Listing
April 2021

Dosimetric predictors of toxicity and quality of life following prostate stereotactic ablative radiotherapy.

Radiother Oncol 2020 03 3;144:135-140. Epub 2019 Dec 3.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Canada; Institute of Health Policy Management and Evaluation, University of Toronto, Canada. Electronic address:

Purpose: SABR offers an effective treatment option for clinically localized prostate cancer. Here we report the dosimetric predictors of late toxicity and quality of life (QOL) in a pooled cohort of patients from four phase II trials.

Methods: The combined cohort included all three prostate cancer risk groups. The prescription dose was 35-40 Gy in 5 fractions. Toxicity (CTCAE) and QOL (EPIC) were collected. Multiple dosimetric parameters for the bladder, rectum and penile bulb were collected. Univariate (UVA) followed by multivariate (MVA) logistic regression analysis was conducted to search for significant dosimetric predictors of late GI/GU toxicity, or minimal clinically important change in the relevant QOL domain.

Results: 258 patients were included with median follow up of 6.1 years. For QOL, bladder Dmax, V38, D1cc, D2cc, D5cc and rectal V35 were predictors of urinary and bowel MCIC on UVA. On MVA, only bladder V38 remained significant. For late toxicity, various parameters were significant on UVA but only rectal Dmax, V38 and bladder D2cc were significant predictors on MVA.

Conclusions: This report confirms that the high-dose regions in the bladder and rectum are more significant predictors of late toxicity and QOL after prostate SABR compared to low-dose regions. Caution must be taken to avoid high doses and hotspots in those organs.
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http://dx.doi.org/10.1016/j.radonc.2019.11.017DOI Listing
March 2020

A Prospective Study of 18F-DCFPyL PSMA PET/CT Restaging in Recurrent Prostate Cancer following Primary External Beam Radiotherapy or Brachytherapy.

Int J Radiat Oncol Biol Phys 2020 03 12;106(3):546-555. Epub 2019 Nov 12.

Division of Radiation Oncology, Department of Oncology, London Health Sciences Centre and Western University, London, Canada. Electronic address:

Purpose: Radio-recurrent prostate cancer is typically detected by a rising prostate-specific antigen and may reflect local or distant disease. Positron emission tomography (PET) radiotracers targeting prostate-specific membrane antigen, such as 18F-DCFPyL have shown promise in restaging men with recurrent disease postprostatectomy but are less well characterized in the setting of radio-recurrent disease.

Methods And Materials: A prospective, multi-institutional study was conducted to evaluate the effect of 18F-DCFPyL PET/computed tomography (CT) when added to diagnostic imaging (DI; CT abdomen and pelvis, bone scan, multiparametric magnetic resonance imaging pelvis) for men with radio-recurrent prostate cancer. All men were imaged with DI and subsequently underwent 18F-DCFPyL PET/CT with local and central reads. Tie break reads were performed as required. Management questionnaires were completed after DI and again after 18F-DCFPyL PET/CT. Discordance in patterns of disease detected with 18F-DCFPyL PET/CT versus DI and changes in management were characterized.

Results: Seventy-nine men completed the study. Most men had T1 disease (62%) and Gleason score <7 (95%). Median prostate-specific antigen at diagnosis was 7.4 ng/mL and at relapse was 4.8 ng/mL. DI detected isolated intraprostatic recurrence in 38 out of 79 men (48%), regional nodal recurrence in 9 out of 79 (11%), distant disease in 12 out of 79 (15%), and no disease in 26 out of 79 (33%). 18F-DCFPyL PET/CT detected isolated intraprostatic recurrence in 38 out of 79 men (48%), regional nodal recurrence in 21 out of 79 (27%), distant disease in 24 out of 79 (30%), and no disease in 10 out of 79 (13%). DI identified 8 out of 79 (10%) patients to have oligometastatic disease, compared with 21 out of 79 (27%) with 18F-DCFPyL PET/CT. 18F-DCFPyL PET/CT changed proposed management in 34 out of 79 (43%) patients.

Conclusions: 18F-DCFPyL PET/CT identified extraprostatic disease in twice as many men with radio-recurrent prostate cancer compared with DI and detected a site of recurrence in 87% of men compared with 67% with DI. Furthermore, 18F-DCFPyL PET/CT identified potentially actionable disease (prostate only recurrence or oligometastatic disease) in 75% of men and changed proposed management in 43% of men.
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http://dx.doi.org/10.1016/j.ijrobp.2019.11.001DOI Listing
March 2020

Randomized Study of Systematic Biopsy Versus Magnetic Resonance Imaging and Targeted and Systematic Biopsy in Men on Active Surveillance (ASIST): 2-year Postbiopsy Follow-up.

Eur Urol 2020 03 8;77(3):311-317. Epub 2019 Nov 8.

Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.

Background: The initial report from the ASIST trial showed little benefit from targeted biopsy for men on active surveillance (AS) for prostate cancer. Data after 2-yr follow-up are now available for analysis.

Objective: To determine if there was a difference in the AS failure rate in a 2-yr follow-up period among men undergoing magnetic resonance imaging (MRI) before initial confirmatory biopsy (CBx) compared to those who did not.

Design, Setting, And Participants: This is the 2-yr post-CBx follow-up for the ASIST trial, a prospective, randomized, multicenter, open-label study for men with Gleason grade group (GG) 1 cancer eligible for AS. Patients were randomized to CBx with 12-core systematic sampling or MRI with systematic and targeted sampling.

Outcome Measurements And Statistical Analysis: Patients with GG ≤ 1 on CBx were followed for 2 yr and had MRI and biopsy at that time point. Patients failed AS if they were no longer under AS because of grade progression, clinical progression, subject choice, clinical judgment, treatment, or lost to follow-up. Clinically significant cancer (CSC) was defined as GG ≥ 2.

Results And Limitations: In total, 259 men underwent CBx, 132 in the non-MRI and 127 in the MRI arm. After biopsy, 101 men in the non-MRI arm (76%) and 98 in the MRI arm (77%) continued AS. There were fewer men with AS failures in the MRI (19/98, 19%) compared to the non-MRI group (35/101, 35%; p =  0.017). At 2-yr biopsy there were fewer men with CSC in the MRI arm (9.9%, 8/81) than in the non-MRI arm (23%, 17/75; p =  0.048). Significant differences in AS failure rates were detected across the three centers in the MRI arm only (4.2% [2/48] vs 17% [4/24] vs 27% [7/26]; p =  0.019).

Conclusions: Baseline MRI before CBx during AS results in 50% fewer AS failures and less grade progression over 2 yr. The center where MRI and targeted biopsy is performed may influence AS failure rates.

Patient Summary: The ASIST trial randomized 273 men on active surveillance with low-grade prostate cancer diagnosed within the last year to systematic biopsy or magnetic resonance imaging (MRI) with systematic and targeted biopsy. The initial report showed little benefit from targeted biopsy. However, after 2 yr of follow-up we found that baseline MRI before confirmatory biopsy resulted in 50% fewer failures of surveillance and less progression to higher-grade cancer. This confirms the value of MRI in men on surveillance. This study is registered at ClinicalTrials.gov (NCT01354171).
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http://dx.doi.org/10.1016/j.eururo.2019.10.007DOI Listing
March 2020
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