Acute toxicity outcomes from salvage high-dose-rate brachytherapy for locally recurrent prostate cancer after prior radiotherapy.

Purpose: Isolated intra-prostatic recurrence of prostate adenocarcinoma after definitive radiotherapy presents a challenging clinical scenario. Salvage options require specialized expertise and pose risks of harm. This study aimed to present the acute toxicity results from using salvage high-dose-rate brachytherapy (sHDR-BT) as treatment in locally recurrent prostate cancer cases. Material and methods: Seventeen consecutive patients treated with sHDR-BT between 2019 and 2022 were evaluated retrospectively. Eligible patients had to have received curative intent prostate radiotherapy previously, and showed evidence of new biochemical failure. Evaluation with American Urological Association (AUA) and Common Terminology Criteria for Adverse Events (CTCAE) symptom assessments were performed for each case. Results: The median (inter-quartile range) age prior to salvage treatment was 68 (66-74) years. The median post-sHDR-BT follow-up time was 20 (13-24) months. At baseline prior to sHDR-BT, 8 (47%) patients had significant lower urinary tract symptoms. The median AUA score prior to sHDR-BT was 7 (3-18). Three (18%) patients reported irregular bowel function and 2 (12%) reported hematochezia prior to sHDR-BT. One-month post-treatment, the median AUA score was 13 (8-21, p = 0.21). Using CTCAE scoring, there were no cases of grade 2+ bowel or rectal toxicity, and no cases of grade 3+ urinary toxicity. Reported grade 2 urinary toxicities included 10 (59%) cases of bladder spasms, 2 (12%) cases of incontinence, 1 (6%) urinary obstruction, and 4 (24%) reports of urinary urgency. All these adverse events were temporary. Conclusions: This study adds to the existing literature by demonstrating that the acute toxicity profile of sHDR-BT is acceptable even without intra-operative magnetic resonance (MR) guidance or image registration. Further study is ongoing to determine long-term efficacy and toxicity of treatment.

Effects of Androgen Deprivation Therapy on Prostate Cancer Outcomes According to Competing Event Risk: Secondary Analysis of a Phase 3 Randomised Trial.

BACKGROUND: Previous studies indicate that the benefit of short-term androgen deprivation therapy (ADT) with radiotherapy (RT) for prostate cancer depends on competing risks. OBJECTIVE: To determine whether a quantitative method to stratify patients by risk for competing events (omega score) could identify subgroups that selectively benefit from ADT. DESIGN, SETTING, AND PARTICIPANTS: An ancillary analysis of NRG/RTOG 9408 phase 3 trial (NCT00002597) involving 1945 prostate cancer patients was conducted. INTERVENTION: Short-term ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We applied generalised competing event regression models incorporating age, performance status, comorbidity, T category, Gleason score (GS), and prostate-specific antigen (PSA), to stratify patients according to relative hazards for primary cancer-related events (distant metastasis or prostate cancer death) versus competing noncancer mortality. We tested interactions between ADT and subgroups defined by standard risk criteria versus relative risk (RR) using the omega score. RESULTS AND LIMITATIONS: T2b, higher GS, and higher PSA were associated with an increased RR for cancer-related versus competing mortality events (a higher omega score); increased age and comorbidity were associated with a decreased omega score. Of 996 patients with low-risk/favourable intermediate-risk (FIR) disease, 286 (28.7%) had a high omega score (≥0.314). Of 768 patients with unfavourable intermediate-risk disease, 175 (22.8%) had a low omega score. The overall discordance in risk classification was 26.1%. Both standard criteria and omega score identified significant interactions for the effect of ADT on cancer-related events and late mortality in low- versus high-risk subgroups. Within the low-risk/FIR subgroup, a higher omega score identified patients in whom ADT significantly reduced cancer events and improved event-free survival. Limitations are the need for external/prospective validation and lower RT doses than contemporary standards. CONCLUSIONS: Stratification based on competing event risk is useful for identifying prostate cancer patients who selectively benefit from ADT. PATIENT SUMMARY: We analysed the effectiveness of androgen deprivation therapy (ADT) for localised prostate cancer among patients, defined by the relative risk (RR) for cancer versus noncancer events. Among patients with traditional low-risk/favourable intermediate-risk disease, those with a higher RR benefitted from short-term ADT.

Estimated absolute percentage of biopsied tissue positive for Gleason pattern 4 (eAPP4) in low dose rate prostate brachytherapy: Evaluation of prognostic utility in a large cohort.

PURPOSE: To determine whether a system to estimate Absolute Percentage of Biopsied Tissue Positive for Gleason Pattern 4 (eAPP4) is useful as a prognostication tool for patients with intermediate risk prostate cancer (IR-PCa) undergoing low dose rate prostate brachytherapy. METHODS: 497 patients with IR-PCa and known grade group 2 or 3 disease treated with low dose rate seed brachytherapy (LDR-BT) at a quaternary cancer centre were retrospectively reviewed. Prostate biopsies for each patient included Gleason grading with synoptic reporting that did not include percentage of pattern 4 disease found within the sample. Each core was assigned a grade grouping, however, and that was used with optimized estimates of percentage of pattern four disease to estimate eAPP4. Outcomes including cumulative incidence of recurrence (CIR), treatment of recurrent disease (RRX), and metastasis-free survival (MFS) were then reviewed and the prognostic value of eAPP4 evaluated. RESULTS: 428 (86%) patients had Gleason grade group 2 and 69 (14%) patients had Gleason grade group 3 disease. 230 (46%) patients had National Comprehensive Cancer Network (NCCN) favourable intermediate at baseline, while 267 (54%) of patients had NCCN unfavourable intermediate at baseline. Median follow-up was 7.3 (5.5-9.6) years. eAPP4 was predictive of CIR (p = 0.003), RRX (p = 0.003), or MFS (p = 0.001) events, while Gleason grade grouping alone was not. eAPP4 was strongest as a predictor for MFS when estimates of 30% (grade group 2) and 80% (grade group 3) were used [HR 1.07 (1.03-1.12); p = 0.001]. CONCLUSIONS: eAPP4 was strongly predictive of recurrence and metastasis-free survival in a large cohort of patients receiving LDR-BT treatment for IR-PCa. Treatment of future patients with IR-PCa could include the use of eAPP4 prognostication.

Clinical Outcomes from Dose-Reduced Radiotherapy to the Prostate in Elderly Patients with Localized Prostate Cancer.

Radical treatment of localized prostate cancer in elderly patients may lead to unacceptable treatment-associated toxicities that adversely impact quality of life without improving survival outcomes. This study reports on a cohort of 54 elderly (>70 years) patients that received 4000-5000 cGy of palliative external beam radiotherapy (EBRT) as an alternative to androgen deprivation therapy (ADT). The primary outcome of interest was the period of ADT-free survival, and secondary outcomes included overall survival (OS) and metastases-free survival (MFS). Kaplan-Meier regression was used to estimate survival outcomes. Thirty-six (67%) patients achieved a break in ADT post-radiotherapy, with a median time to ADT reinitiation of 20 months. Common Terminology Criteria for Adverse Events (CTCAE) were limited to low-grade gastrointestinal (GI) or genitourinary (GU) toxicities, with no skin toxicities observed. Grade 1 GI toxicity was observed in 9 (17%) patients, and grades 1 and 2 GU toxicities were observed in 13 (24%) and 3 (6%) patients, respectively, with no higher-grade toxicities reported. Five-year MFS and OS were 56% and 78%, respectively. In summary, the treatment regimen was well-tolerated and achieved durable ADT-free survival in most patients. Dose-reduced EBRT appears to be a viable alternative to ADT in elderly patients with localized prostate cancer.

MRI-TRUS registration methodology for TRUS-guided HDR prostate brachytherapy.

PURPOSE: High-dose-rate (HDR) prostate brachytherapy is an established technique for whole-gland treatment. For transrectal ultrasound (TRUS)-guided HDR prostate brachytherapy, image fusion with a magnetic resonance image (MRI) can be performed to make use of its soft-tissue contrast. The MIM treatment planning system has recently introduced image registration specifically for HDR prostate brachytherapy and has incorporated a Predictive Fusion workflow, which allows clinicians to attempt to compensate for differences in patient positioning between imaging modalities. In this study, we investigate the accuracy of the MIM algorithms for MRI-TRUS fusion, including the Predictive Fusion workflow. MATERIALS AND METHODS: A radiation oncologist contoured the prostate gland on both TRUS and MRI. Four registration methodologies to fuse the MRI and the TRUS images were considered: rigid registration (RR), contour-based (CB) deformable registration, Predictive Fusion followed by RR (pfRR), and Predictive Fusion followed by CB deformable registration (pfCB). Registrations were compared using the mean distance to agreement and the Dice similarity coefficient for the prostate as contoured on TRUS and the registered MRI prostate contour. RESULTS: Twenty patients treated with HDR prostate brachytherapy at our center were included in this retrospective evaluation. For the cohort, mean distance to agreement was 2.1 ± 0.8 mm, 0.60 ± 0.08 mm, 2.0 ± 0.5 mm, and 0.59 ± 0.06 mm for RR, CB, pfRR, and pfCB, respectively. Dice similarity coefficients were 0.80 ± 0.05, 0.93 ± 0.02, 0.81 ± 0.03, and 0.93 ± 0.01 for RR, CB, pfRR, and pfCB, respectively. The inclusion of the Predictive Fusion workflow did not significantly improve the quality of the registration. CONCLUSIONS: The CB deformable registration algorithm in the MIM treatment planning system yielded the best geometric registration indices. MIM offers a commercial platform allowing for easier access and integration into clinical departments with the potential to play an integral role in future focal therapy applications for prostate cancer.

Excessive waitlists and delays to treatment with low-dose-rate brachytherapy predict an increased risk of recurrence and metastases in intermediate-risk prostatic carcinoma.

PURPOSE: It has previously been shown that increased wait times for prostatectomy are associated with poorer outcomes in intermediate-risk prostatic carcinoma (PCa). However, the impact of wait times on PCa outcomes following low-dose-rate brachytherapy (LDR-BT) are unknown. METHODS AND MATERIALS: We retrospectively reviewed 466 intermediate-risk PCa patients that underwent LDR-BT at a single comprehensive cancer center between 2003 and 2016. Wait times were defined as the time from biopsy to LDR-BT. The association of wait times with outcomes was evaluated using Cox and Fine-Gray regression in both univariate and multivariate models. RESULTS: Median (interquartile range) follow-up and wait time for all patients were 8.1 (6.3-10.4) years and 5.1 (3.9-6.9) months, respectively. Among NCCN unfavourable intermediate-risk (UIR) patients (n = 170; 36%), increased wait times predicted both a greater cumulative incidence of recurrence [MHR = 1.01/month of wait time (95% CI: 1.00-1.03); P = 0.044] and metastases [MHR = 1.04/month of wait time (95% CI: 1.02-1.06); P < 0.001] in multivariate modeling. In NCCN favourable intermediate-risk (FIR) patients, there was no significant association between wait time and recurrence or metastases risk. Among all intermediate-risk patients, wait time was associated with an increase in the incidence of metastases [MHR = 1.03/month of wait time (95% CI: 1.02-1.05); P < 0.001], but not recurrence in multivariate models. There was no association between wait time and overall survival in the UIR, FIR, or all intermediate-risk cohorts. CONCLUSIONS: Resource constraints within this center's public healthcare system have contributed to waitlists exceeding 5-months in length. This study finds that patients with UIR PCa experience a 1% increase in the risk of recurrence and 4% increase in the risk of metastases with each additional month of delay in definitive disease management. Preventing such extended management delays in LDR-BT may improve disease-related outcomes in patients with PCa.

Intraoperative optimization of seed implantation plan in breast brachytherapy.

PURPOSE: Low-dose-rate permanent-seed (LDR-PS) brachytherapy has shown a great potential for treating breast cancer. An implantation scheme indicating the template pose and needle trajectories is determined before the operation. However, when performing the pre-planned scheme intraoperatively, a change of the patient's posture will cause seed placements away from the desired locations. Hence, the implantation scheme should update based on the current patient's posture. METHODS: A numerical method of optimizing the implantation scheme for the LDR-PS breast brachytherapy is presented here. The proposed algorithm determines the fewest needle trajectories and template poses for delivering the seeds to the intraoperative desired locations. The clinical demand, such as the minimum distance between the chest wall and the needle, is considered in the optimization process. RESULTS: The method was simulated for a given LDR-PS brachytherapy procedure to evaluate the optimal scheme as the number of the template poses changing. The optimization parameters of the needles' number and the implantation errors are used to adjust the algorithm outcome. The results show that the implantation schemes obtained by our method have a satisfactory accuracy in the cases of 2 or 3 template poses. The computation time is about 76s to 150s according to the number of the template poses from 1 to 3. CONCLUSION: The proposed method can find the optimal implantation scheme corresponding to the current desired seed locations immediately once there is a change of patient's posture. This work can be applied to the robot-assisted LDR-PS breast brachytherapy for improving the operation accuracy and efficiency.

Implementation of high-dose-rate brachytherapy for prostatic carcinoma in an unshielded operating room facility.

PURPOSE: The purpose of the study was to describe our approach towards safe delivery of single-fraction high-dose-rate (HDR) brachytherapy (BT) boost in patients with prostate cancer in the setting of an unshielded operating room (OR). METHODS AND MATERIALS: A total of 95 patients received 15 Gy HDR BT boost. The procedure involved transrectal ultrasound-based catheter insertion and planning in the OR, after which the patient was moved to a shielded treatment room for radiation. This required three vital components: (1) an OR table capable of transporting the patient in lithotomy position, (2) robust motion management checks to ensure reproducibility of prostate and catheter positions in the treatment room before radiation delivery, (3) remote monitoring of patient vitals while under anesthesia, during the radiation. Initial viability of this approach was confirmed by assessing acute toxicities using the Common Terminology Criteria for Adverse Events v4.0 and American Urologic Association symptom scores. RESULTS: We found good stability in prostate and catheter position, with less than 1 mm shifts in each direction due to patient transfer. The median baseline American Urologic Association score was 7 (3-11), which increased to 12 (7-17) at 4 weeks and 9 (5-14) at 3 months (p = 0.003). Common Terminology Criteria for Adverse Events ≥ grade 2 genitourinary and gastrointestinal toxicities were experienced by 7% and 0% patients, respectively, at 3 months posttreatment completion. CONCLUSIONS: Single-fraction HDR prostate BT can be delivered safely in an unshielded OR facility with a distant shielded treatment room using rigorous motion management checks and supplementary procedural equipment.

Analysis of outcomes after non-contour-based dose painting of dominant intra-epithelial lesion in intra-operative low-dose rate brachytherapy.

PURPOSE: To compare the outcomes of patients with intermediate risk prostate cancer (IR-PCa) treated with low-dose rate I-125 seed brachytherapy (LDR-BT) and targeted dose painting of a histologic dominant intra-epithelial lesion (DIL) to those without a DIL. METHODS: 455 patients with IR-PCa were treated at a single center with intra-operatively planned LDR-BT, each following the same in-house dose constraints. Patients with a DIL on pathology had hot spots localized to that region but no specific contouring during the procedure. RESULTS: 396 (87%) patients had a DIL. Baseline tumor characteristics and overall prostate dosimetry were similar between patients with and without DIL except the median number of biopsy cores taken: 10 (10-12) vs 12 (10-12) (p = 0.002).19 (5%) and 18 (5%) of patients with and 1 (2%) and 0 (0%) of those without DIL experienced CTCAE grade 2 and 3 toxicity respectively. Overall, toxicity grade did not significantly correlate with presence of DIL (p = 0.10).Estimated 7-year freedom from biochemical failure (FFBF) was 84% (95% confidence interval: 79-89) and 70% (54-89) in patients with and without a DIL (log-rank p = 0.315). In DIL patients, cox regression revealed location of DIL ("Base" vs "Apex" HR: 1.03; 1.00-1.06; p = 0.03) and older age (70 vs 60 HR: 1.62; 1.06-2.49; p = 0.03) was associated with poor FFBF. CONCLUSIONS: Targeting DIL through dose painting during intraoperatively planned LDR-BT provided no statistically significant change in FFBF. Patients with DILs in the prostate base had slightly lower FFBF despite DIL boost.

Peer-based credentialing for brachytherapy: Application in permanent seed implant.

PURPOSE: The purpose of the study was to establish a quantitative method for implant quality evaluation in permanent seed implant brachytherapy for credentialing. Delivery-based credentialing will promote consistency in brachytherapy seed delivery and improve patient outcomes. METHODS: A workflow for delivery-based credentialing was outlined and applied to permanent breast seed implant brachytherapy. Delivery simulations were performed on implantable anthropomorphic breast phantoms. Two institutions experienced in permanent seed implant brachytherapy demonstrated the peer credentialing process. Each delivery was evaluated for seed placement accuracy as the measure of implant quality, both for implant accuracy and across five simulations to assess implant variation. Initial credentialing criteria are set based on two factors; the mean seed placement accuracy (implant accuracy) and the mean standard deviation (seed variation) with the threshold for each set with the addition of two standard deviations. RESULTS: Across two institutions, seed placement accuracy (±standard deviation) was calculated for all five delivery simulations to yield 6.1 (±2.6) mm. To set credentialing criteria, the implant accuracy (6.1 mm) plus two standard deviations (2.0 mm) and the seed variation (2.6 mm) plus two standard deviations (0.8) mm yield a threshold of 8.1 ± 3.4 mm. It is expected that 95% of experienced institutions would perform the phantom simulation within this threshold. CONCLUSION: Brachytherapy programs should validate delivery accuracy by formal credentialing, which is standard in external beam programs. This quantitative implant evaluation should be combined with current credentialing standards for permanent seed brachytherapy to form a comprehensive validation of institutional brachytherapy program quality.

Establishing a simulation-based education program for radiation oncology learners in permanent seed implant brachytherapy: Building validation evidence.

PURPOSE: The purpose of this study was to establish a simulation-based education program for radiation oncology learners in permanent seed implant brachytherapy. The first step in formalizing any education program is a validation process that builds evidence-based verification that the learning environment is appropriate. METHODS AND MATERIALS: The primary education task allowed practitioners to use an anthropomorphic breast phantom to simulate a permanent seed implant brachytherapy delivery. Validation evidence is built by generating data to assess learner and expert cohorts according to their proficiency. Each practitioner's performance during the simulation was evaluated by seed placement accuracy, procedural time-to-complete, and two qualitative evaluation tools-a global rating scale and procedural checklist. RESULTS: The average seed placement accuracy (±SD) was 8.1 ± 3.5 mm compared to 6.1 ± 2.6 mm for the learner and expert cohort, respectively. The median (range) procedural time-to-complete was 64 (60-77) minutes and 43 (41-50) minutes for the learner and expert cohort, respectively. Seed placement accuracy (student t-test, p < 0.05) and procedural time-to-complete (Mann-Whitney U-test, p < 0.05) were statistically different between the cohorts. In both the global rating scale and procedural checklist, the expert cohort demonstrated improved proficiency compared to the learner cohort. CONCLUSIONS: This validation evidence supports the utilization of this simulation environment toward appropriately capturing the delivery experience of practitioners. The results demonstrate that, in all areas of evaluation, expert cohort proficiency was superior to learner cohort proficiency. This methodology will be used to establish a simulation-based education program for radiation oncology learners in permanent seed implant brachytherapy.

Prostate-Specific Antigen After Neoadjuvant Androgen Suppression in Prostate Cancer Patients Receiving Short-Term Androgen Suppression and External Beam Radiation Therapy: Pooled Analysis of Four NRG Oncology Radiation Therapy Oncology Group Randomized Clinical Trials.

PURPOSE: To validate whether prostate-specific antigen (PSA) level after neoadjuvant androgen suppression (neoAS) is associated with long-term outcome after neoAS and external beam radiation therapy (RT) with concurrent short-term androgen suppression (AS) in patients with prostate cancer. METHODS AND MATERIALS: This study included 2404 patients. The patients were treated with neoAS before RT and concurrent AS (without post-RT AS) and were pooled from NRG Oncology/RTOG trials 9202, 9408, 9413, and 9910. Multivariable models were used to test associations between the prespecified dichotomized post-neoAS, pre-RT PSA level (≤0.1 vs >0.1 ng/mL) groupings, and clinical outcomes. RESULTS: The median follow-up for surviving patients was 9.4 years. The median post-neoAS, pre-RT PSA level was 0.3 ng/mL, with 32% of patients having levels ≤0.1 ng/mL. Race, Gleason score, tumor stage, node stage, pretreatment PSA level, and duration of neoAS were associated with the groups of patients with PSA levels ≤0.1 and >0.1 ng/mL. In univariate analyses, post-neoAS, pre-RT PSA level >0.1 ng/mL was associated with increased risks of biochemical failure (hazard ratio [HR], 2.04; P < .0001); local failure (HR, 2.51; P < .0001); distant metastases (HR, 1.73; P = .0006); cause-specific mortality (HR, 2.36; P < .0001); and all-cause mortality (HR, 1.24; P = .005). In multivariable models that also included baseline and treatment variables, post-neoAS, pre-RT PSA level >0.1 ng/mL was independently associated with increased risk of biochemical failure (HR, 2.00; P < .0001); local failure (HR, 2.33; P < .0001); and cause-specific mortality (HR, 1.75; P = .03). CONCLUSIONS: Patients with a PSA level >0.1 ng/mL after neoAS and before the start of RT had less favorable clinical outcomes than patients whose PSA level was ≤0.1 ng/mL. The role of post-neoAS, pre-RT PSA level relative to PSA levels obtained along the continuum of medical care is not presently defined but could be tested in future clinical trials.

Exposure to radiation and medical oncology training: A survey of Canadian urology residents and fellows.

INTRODUCTION: Residency experiences and teaching in oncology among urology residents are variable across Canada. We sought to identify how radiation and medical oncology concepts, as they pertain to genitourinary malignancies, are taught to urology residents. METHODS: A total of 190 trainees enrolled in Canadian urology residency training programs were invited to participate in the study from January 2016 to June 2016. Participants completed an online questionnaire addressing the training they received. RESULTS: The overall response rate was 32%. Twenty-three percent of respondents were in their fellowship year; 17%, 20%, 10%, 17%, and 12% were first-, second-, third-, fourth-, and fifth-year residents, respectively, with a median of four (range 1-9) respondents from each training program. Ninety-five percent of respondents had academic half-day (AHD) as part of their training that included radiotherapy (61%) and chemotherapy (51%) teaching. Most respondents indicated their main exposure to chemotherapy and radiation came from informal teaching in urology clinics. Twenty-nine percent and 41%, of participants had mandatory rotations in radiation and medical oncology, respectively. Only 6% of respondents used their voluntary elective time in these disciplines and most voluntary electives were of 1-2-week duration. Despite this, 90% of respondents preferred some mandatory radiation and medical oncology training. CONCLUSIONS: Most of the limited exposure that urology residents have to medical and radiation oncology is through AHD or informal urology clinics, despite a desire among current urology trainees to have clinical exposure in these areas. Moving forward, urology residency programs should consider integrating medical and radiation oncology rotations into the residency program curriculum.

Appropriate timing for postimplant imaging in permanent breast seed implant: Results from a serial CT study.

PURPOSE: Postimplant analysis in permanent breast seed implant (PBSI) is performed at inconsistent times subsequent to seed implantation across cancer centers, creating challenges in the interpretation of dosimetric data and ultimately the correlation with clinical outcomes. The purpose of this study is to determine the most appropriate time postimplant to perform this analysis. METHODS AND MATERIALS: Nine patients treated at our institution with PBSI were included in this analysis. Each underwent 4 postimplant CT scans: 0, 15, 30, and 60 days postimplant. A model of the accumulated dose was created by deformably registering the Day 15, 30, and 60 postimplant CT scans and dose matrices to the Day 0 scan, scaling for seed decay. The results from this model were compared to each individual postplan by integral comparison of dose-volume histogram curves for a dose evaluation volume. RESULTS: The Day 30 postplan showed the best agreement with the accumulated dose model and the smallest interpatient variability across the patient cohort. The mean (±SD) for the dose evaluation volume V90, V100, V150, and V200 for the accumulated dose model was 90 ± 7%, 86 ± 8%, 66 ± 14%, and 41 ± 16%, respectively. CONCLUSIONS: Based on the results of this patient cohort, we recommend that postimplant dosimetric analysis for PBSI be performed approximately 30 days following the implant.

Does Seed Migration Increase the Risk of Second Malignancies in Prostate Cancer Patients Treated With Iodine-125 Loose Seeds Brachytherapy?

PURPOSE: To evaluate the risk of second malignancies after migration of seeds (MS) in prostate cancer patients treated with 125I loose seeds brachytherapy. METHODS AND MATERIALS: Data from 2802 prostate cancer patients treated with 125I loose seeds brachytherapy in 3 Canadian centers were reviewed. After seeds implant, all patients underwent postimplant pelvic radiography and computed tomography scan for postimplant dosimetry. These images were used to assess whether seed migration occurred. The incidence of second malignancies was determined through the review of patient charts. The 7- and 10-year cumulative incidences of second malignancies and their 95% confidence intervals (CIs) were calculated. Fine and Gray competing risk regression analysis was used to assess the factors associated with the development of second malignancies. RESULTS: Mean age and median follow-up were 63.5 years and 74 (range, 12-246) months, respectively. Migration of seeds occurred in 263 of 2802 patients (9.4%). Second malignancy occurred in 87 patients (3.1%) for the entire cohort and was not different between patients who experienced MS (9, 3.4%) and those who did not (78, 3.1%) (P = .755). The 7-year cumulative incidence rates of second malignancies were 2.95% (95% CI 1.20%-6.00%) (with MS) versus 2.82% (2.10%-3.70%) (without MS) (P = .756). The corresponding values at 10 years were 6.16% (2.20%-12.3%) versus 4.51% (3.20%-5.50%) (P = .570). Migration of seeds did not seem to be a significant predictive factor for second malignancies development (adjusted hazard ratio 1.27 [95% CI 0.63-2.55]; P = .510). In both models, only advanced age was significantly associated with second malignancies development. CONCLUSIONS: These results did not show an increased risk of second malignancies associated with MS after 125I loose seeds brachytherapy for prostate cancer patients. Longer follow-up and more events are required to better correlate MS and second malignancies.

Multicenter Evaluation of Biochemical Relapse-Free Survival Outcomes for Intraoperatively Planned Prostate Brachytherapy Using an Automated Delivery System.

PURPOSE: To report biochemical recurrence in prostate cancer treated with intraoperatively planned low-dose-rate prostate brachytherapy using an automated delivery system (IO-LDRB). METHODS AND MATERIALS: Between 2003 and 2013, 2608 patients from 3 centers were treated with IO-LDRB as single-modality treatment for low or low-tier intermediate-risk prostate cancer. Databases from the 3 centers have been analyzed. These independent databases were collected prospectively. Patient, tumor, and treatment characteristics were then compared, Kaplan-Meier survival estimates of biochemical relapse-free survival (bRFS) were generated, and the Cox proportional hazards model was used to determine factors predicting for relapse. RESULTS: A total of 2608 patients with a median follow-up of 4.7 (interquartile range, 3.1-6.9) years were analyzed. Median age was 64 (range, 42-84) years. In these patients, median initial prostate-specific antigen was 5.5 ng/mL, 74% were T1, and 26% were T2; 73% were Gleason 6, and 25% Gleason 7. Median percentage of biopsy cores positive was 33%, and median gland volume was 34.2 cm3. Eleven percent of patients received hormones for a median of 3.0 months before implantation. Median seed activity was 0.437 mCi, D90 (dose covering 90% of the prostate volume) was 186.7 Gy, and V100 was 99.37%. Biochemical relapse was observed in 124 patients (4.8%), and median time to failure was 4.0 years. Predicted bRFS was 93% at 7 years. On Cox regression bRFS was dependent only on D90 at the time of implantation and prostate-specific antigen density. CONCLUSIONS: This study demonstrates that IO-LDRB is an effective treatment option for patients with low and low-tier intermediate-risk prostate cancer. Rates of biochemical relapse remain low several years after treatment. These results compared favorably to published manual preplan technique results.

Institutional long-term outcomes at the first Canadian center performing intraoperatively planned low-dose-rate brachytherapy alone in low- and intermediate-risk prostate cancer.

PURPOSE: The aim of this study is to report the long-term outcomes and toxicities from a large cohort of patients with localized prostate cancer treated with low-dose-rate intraoperatively planned brachytherapy. METHODS AND MATERIALS: Prostate-specific antigen levels, urinary symptoms, and erectile function were recorded at baseline, and each followup visit was then entered into a prospective database. Urinary toxicity requiring procedural intervention was retrospectively verified using an integrated electronic medical system. A separate cross-sectional survey was performed to measure postimplant sexual function. RESULTS: A total of 822 patients with low and favorable intermediate-risk prostate cancer were treated at our institution between 2003 and 2013. The Kaplan-Meier estimates for biochemical recurrence for our cohort were 95% and 87% at 5 and 10 years, respectively. Cystoscopy, transurethral resection of prostate, or dilatation was required for 7.1% of 720 patients with more than 2 years of followup. At a median followup of 3.7 years, 64.4% of patients retained adequate erectile function for intercourse, with 54% of patients who were no longer sexually active postimplant reporting social factors as the primary reason. CONCLUSIONS: Our institutional experience with intraoperative low-dose-rate prostate brachytherapy yielded excellent long-term results with a low incidence of urinary and sexual toxicity.

Parameters predicting for prostate specific antigen response rates at one year post low-dose-rate intraoperative prostate brachytherapy.

PURPOSE: To develop a model for prostate specific antigen (PSA) values at one year among patients treated with intraoperatively planned 125I prostate brachytherapy (IOPB). MATERIAL AND METHODS: Four hundred and deven patients treated with IOPB for prostate adenocarcinoma were divided into four groups: those with PSA values ≥ 3 ng/ml; < 3 and ≥ 2; < 2 and ≥ 1 or PSA < 1 between 10.5 and 14.5 months post implantation (1yPSA). Ordinal regression analysis was then performed between patient, tumor, and treatment characteristics. 1yPSA values were also compared with toxicity outcomes. RESULTS: Median 1yPSA was 0.77 (0.04-17.36). Thirty-two patients (8%) had a PSA ≥ 3; 35 (9%) had PSA < 3, ≥ 2; 87 (21%) had PSA < 2, ≥ 1, and most patients 254 (62%) had PSA < 1. PSA response was independent of gland volume, Gleason score, clinical stage, seed activity, V90, V200, D90, or number of needles and seeds used. Older patients had significantly lower 1yPSA; median ages 65.1 (46.5-81.0), 62.1 (50.4-79.5), 60.5 (47.1-80.3), and 58.1 (45.1-74.2) years for each of the 1yPSA groups respectively (p < 0.001). Also, both implant V150 (p < 0.001) and initial PSA values (p = 0.04) were predictive of 1yPSA values. There was no correlation between 1yPSA values and toxicity encountered. CONCLUSIONS: PSA response at 1 year post IOPB appears to be dependent on patient age, initial PSA, and implant V150. Our results provide reassurance that parameters other than biochemical failure influence 1yPSA values.

Assessing guideline impact on referral patterns of post-prostatectomy patients to radiation oncologists.

INTRODUCTION: Adjuvant radiotherapy (aRT) can improve biochemical progression-free survival in patients with high-risk features (HRF) after radical prostatectomy (RP). Guidelines from Alberta and the Genitourinary Radiation Oncologists of Canada (GUROC) recommend that patients with HRF be referred to radiation oncologists (RO) based on the findings from three randomized, controlled trials (RCT). Our study examines the impact of these recommendations both pre- (2005) and post- (2012) publication of RCT and GUROC guideline establishment. METHODS: Patients undergoing RP during 2005 and 2012 were identified from the provincial cancer registry. Charts were retrospectively reviewed and variables of interest were linked to the registry data. RO referral patterns for each year were determined and variables influencing referral (extracapsular extension, positive margin, seminal vesicle invasion, and post-RP prostate-specific antigen [PSA]) were compared. RESULTS: Median time to referral was 26.4 months in 2005 compared to 3.7 months 2012 (p<0.001). Among patients referred post-RP, a higher proportion was referred within six months in 2012 (21%) as compared to 2005 (13%) (p=0.003). Among eligible patients in 2012, 30% were referred for discussion of aRT compared to 24% in 2005 (p=0.003). There was a marked drop in patients referred for salvage radiation therapy beyond six months and a rise in the number of patients who are never referred. CONCLUSIONS: Despite an increase in referral rates to RO post-RP from 2005-2012, more than 50% of those patients with HRF did not receive a referral. Initiatives aimed at improving multidisciplinary care and guideline adherence should be undertaken.