Barriers and enablers of active surveillance for prostate cancer: a qualitive study of clinicians.

OBJECTIVES: To identify and explore barriers to, and enablers of, active surveillance (AS) in men with low-risk prostate cancer (LRPCa), as perceived by PCa clinicians. PATIENTS AND METHODS: Urologists and radiation oncologists in Australia and New Zealand were purposively sampled for a cross-section on gender and practice setting (metropolitan/regional; public/private). Using a grounded theory approach, semi-structed interviews were conducted with participants. Interviews were coded independently by two researchers using open, axial, and selective coding. A constant comparative approach was used to analyse data as it was collected. Thematic saturation was reached after 18 interviews, and a detailed model of barriers to, and enablers of, AS for LRPCa, as perceived by clinicians was developed. RESULTS: A model explaining what affects clinician decision making regarding AS in LRPCa emerged. It was underpinned by three broad themes: (i) clinician perception of patients' barriers and enablers; (ii) clinician perception of their own barriers and enablers; and (iii) engagement with healthcare team and resource availability. CONCLUSIONS: Clinicians unanimously agree that AS is an evidence-based approach for managing LRPCa. Despite this many men do not undergo AS for LRPCa, which is due to the interplay of patient and clinician factors, and their interaction with the wider healthcare system. This study identifies strategies to mitigate barriers and enhance enablers, which could increase access to AS by patients with LRPCa.

Comprehensive review of the use of hydrogel spacers prior to radiation therapy for prostate cancer.

OBJECTIVES: To provide a comprehensive narrative review of the published data on the impact of hydrogel spacers on rectal dosimetry and toxicity and to outline the practicalities of inserting hydrogel spacers. RESULTS: A growing body of evidence suggests that the administration of hydrogel spacers is safe and is associated with limited peri-operative morbidity. The impact on rectal dosimetry has been clearly established and use of hydrogel spacers is associated with reduced rectal morbidity. These results have been corroborated by several Phase II and III clinical trials and subsequent meta-analysis. There are several areas for future research, including the role of hydrogel spacers in prostate stereotactic beam radiotherapy and post-radiotherapy local recurrence. CONCLUSIONS: Hydrogel spacers provide a low-morbidity method to potential reduce rectal toxicity after radiation therapy in men with prostate cancer. Data outlining sexual function and oncological outcomes are limited to date. Future studies, currently being conducted, may provide further clarification of the role of hydrogel spacers in prostate cancer management.

The march toward single-fraction stereotactic body radiotherapy for localized prostate cancer-Quo Vadimus?

PURPOSE: Stereotactic body radiotherapy (SBRT) is an emerging treatment option for localized prostate cancer. There is increasing interest to reduce the number of fractions for prostate SBRT. METHODS: We provide a narrative review and summary of prospective trials of different fractionation schedules for prostate SBRT, focusing on efficacy, toxicities, and quality of life outcomes. RESULTS: There are two randomized phase 3 trials comparing standard external beam radiotherapy with ultra-hypofractionated radiotherapy. HYPO-RT-PC compared 78 Gy in 39 fractions vs 42.7 Gy in 7 fractions (3D-CRT or IMRT) showing non-inferiority in 5-year biochemical recurrence-free survival and equivalent tolerability. PACE-B trial compared 78 Gy in 39-fraction or 62 Gy in 20-fraction vs 36.25 Gy in 5-fraction prostate SBRT, with no significant differences in toxicity outcomes at 2 years. Five-year efficacy data for PACE-B are expected in 2024. Five-fraction prostate SBRT is currently the most common and well-established fractionation schedule with multiple prospective phase 2 trials published to date. There is more limited data on 1-4 fraction prostate SBRT. All fractionation schedules had acceptable toxicity outcomes. Experience from a high-dose-rate brachytherapy randomized trial showed inferior efficacy with single-fraction compared to two-fraction brachytherapy. Hence, caution should be applied in adopting single-fraction prostate SBRT. CONCLUSION: Two-fraction SBRT is likely the shortest fractionation schedule that maintains the therapeutic ratio. Several randomized trials currently recruiting will likely provide us with more definite answers about whether two-fraction prostate SBRT should become a standard-of-care option. Enrollment of eligible patients into these trials should be encouraged.

Radiation myelopathy following stereotactic body radiation therapy for spine metastases.

PURPOSE: Stereotactic body radiation therapy (SBRT) is now considered a standard of care treatment option in the management of spine metastases. One of the most feared complications of spine SBRT is radiation myelopathy (RM). METHODS: We provided a narrative review of RM following spine SBRT based on review of the published literature, including data on spinal cord dose constraints associated with the risk of RM, strategies to mitigate the risk, and management options for RM. RESULTS: There are limited published data of cases of RM following spine SBRT with detailed spinal cord dosimetry. The HyTEC report provided recommendations for the point maximal dose (Dmax) for the spinal cord that is associated with a < 5% risk of RM for 1-5 fractions spine SBRT. In the setting of spine SBRT reirradiation after previous conventional external beam radiation therapy (cEBRT), factors associated with RM are: SBRT spinal cord Dmax, cumulative spinal cord Dmax, and the time interval between previous RT and SBRT reirradiation. There are various strategies to mitigate the risk of RM, including accurate delineation of the spinal cord (or thecal sac), strict adherence to the recommended spinal cord dose constraints, and robust treatment immobilisation set-up and delivery. Limited effective treatment options are available for patients who develop RM, and these include corticosteroids, hyperbaric oxygen, and bevacizumab; however, none have been supported by high quality evidence. CONCLUSION: RM is a rare but devastating complication following SBRT for spine metastases. There are strategies to minimise the risk of RM to ensure safe delivery of spine SBRT.

Prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA-PET/CT)-guided stereotactic ablative body radiotherapy for oligometastatic prostate cancer: a single-institution experience and review of the published literature.

OBJECTIVES: To report the outcomes of stereotactic ablative body radiotherapy (SABR) in men with oligometastatic prostate cancer (PCa) diagnosed on prostate-specific membrane antigen (PSMA)-positron emission tomography/computed tomography (PET/CT), based on a single-institution experience and the published literature. PATIENTS AND METHODS: This was a retrospective cohort study of the first 20 consecutive men with oligometastatic PCa, treated with SABR in a single institution, who had biochemical recurrence after previous curative treatment (surgery/radiotherapy), had no evidence of local recurrence, were not on palliative androgen deprivation therapy (ADT), and had PSMA-PET/CT-confirmed oligometastatic disease (≤3 lesions). These men were treated with SABR to a dose of 30 Gy in three fractions for bone metastases, and 35-40 Gy in five fractions for nodal metastases. The outcomes of interest were: PSA response; local progression-free survival (LPFS); distant progression-free survival (DPFS); and ADT-free survival (ADTFS). A literature review was performed to identify published studies reporting on outcomes of PSMA-PET/CT-guided SABR. RESULTS: In our institutional cohort, 12 men (60%) had a decline in PSA post-SABR. One man had local progression 9.6 months post-SABR, with 12-month LPFS of 93%. Ten men had distant progression outside of their SABR treatment field, confirmed on PSMA-PET/CT, with 12-month DPFS of 62%, of whom four were treated with palliative ADT, two received prostate bed radiotherapy for prostate bed progression (confirmed on magnetic resonance imaging), and four received a further course of SABR (of whom one had further progression and was treated with palliative ADT). At last follow-up, six men (one with local progression and five with distant progression) had received palliative ADT. The 12-month ADTFS was 70%. Men with longer intervals between local curative treatment and SABR had better DPFS (P = 0.03) and ADTFS (P = 0.005). Four additional studies reporting on PSMA-PET/CT-guided SABR for oligometastatic PCa were identified and included in the review, giving a total of 346 patients. PSA decline was reported in 60-70% of men post-SABR. The 2-year LPFS, DPFS and ADTFS rates were 76-100%, 27-52%, and 58-62%, respectively. CONCLUSION: Our results showed that PSMA-PET/CT could have an important role in identifying men with true oligometastatic PCa who would benefit the most from metastases-directed therapy with SABR.

Patient-reported outcome measures among breast cancer survivors: A cross-sectional comparison between Malaysia and high-income countries.

OBJECTIVES: Patient-reported outcomes (PROs) in high-income countries (HICs) suggest that physical, emotional, and psychological needs are important in cancer care. To date, there have been few inconsistent descriptions of PROs in low-income and middle-income Asian countries. Using a standard questionnaire developed by the International Consortium for Health Outcomes Measurement (ICHOM), we compared the perceived importance of PROs between patients in Malaysia and those in HICs and between clusters of Malaysian women. METHODS: Breast cancer patients were recruited from three Malaysian hospitals between June and November 2017. We compared the proportion of patients who rated PROs as very important (scored 7-9 on a 9-point Likert scale) between Malaysian patients and data collected from patients in HICs via the ICHOM questionnaire development process, using logistic regression. A two-step cluster analysis explored differences in PROs among Malaysian patients. RESULTS: The most important PROs for both cohorts were survival, overall well-being, and physical functioning. Compared with HIC patients (n = 1177), Malaysian patients (n = 969) were less likely to rate emotional (78% vs 90%), cognitive (76% vs 84%), social (72% vs 81%), and sexual (30% vs 56%) functioning as very important outcomes (P < 0.001). Cluster analysis suggests that older, parous, Malaysian women, who were less likely to have received breast reconstructive surgery, were more likely to rate body image and satisfaction with the breast as very important outcomes. CONCLUSION: Taking into account the differences in PROs by cultural and socioeconomic settings could improve patient expectation of services and refine the assessment of cancer care outcomes.

Large institutional variations in use of androgen deprivation therapy with definitive radiotherapy in a population-based cohort of men with intermediate- and high-risk prostate cancer.

OBJECTIVE: To evaluate the pattern of use of androgen deprivation therapy (ADT) with definitive radiotherapy (RT) in men with prostate cancer (PCa) in a population-based study in Australia. PATIENTS AND METHODS: This is a prospective cohort of men with intermediate- and high-risk PCa, captured in the population-based Prostate Cancer Outcome Registry Victoria, who were treated with definitive prostate RT between January 2010 and December 2015. The primary outcome of interest was ADT utilization. Chi-squared test for trend was used to evaluate the temporal trend in the use of ADT over the study period. Multivariate logistic regressions were used to evaluate the effects of patient-, tumour- and treatment-related factors, and treatment institutions (public/ private and metropolitan/ regional) on the likelihood of ADT utilization. RESULTS: A total of 1806 men were included in the study, 199 of whom (11%) had favourable National Comprehensive Cancer Network (NCCN) intermediate-risk disease (i.e. only one intermediate-risk feature, primary Gleason grade 3, and <50% biopsy core involved), 687 (38%) had unfavourable NCCN intermediate-risk disease, and 920 (51%) had high-risk disease. Of the 1806 men, 1155 (64%) received ADT with RT. Men with NCCN high-risk PCa (84%) were more likely to have ADT than men with favourable NCCN intermediate-risk (32%) and unfavourable NCCN intermediate-risk (46%) PCa (P < 0.001). Men treated in public institutions (66%, vs 47% in private institutions; P < 0.001) and regional centres (78%, vs 59% in metropolitan institutions; P < 0.001) were more likely to receive ADT. There was a trend towards an increase in ADT utilization from 50% in 2010 to 64% in 2015 (P < 0.001). In multivariate analyses (adjusting for age, tumour-related factors, year of treatment and use of brachytherapy boost), treatment institution (public and regional) remained independently associated with increased likelihood of ADT utilization. Men with intermediate-risk PCa treated in regional and public institutions were 2.7 times (95% confidence interval [CI] 1.9-3.9; P < 0.001) and 2.8 times (95% CI 1.4-5.3; P = 0.002), more likely to receive ADT with RT, respectively, while men with high-risk PCa treated in regional and public institutions were 3.1 times (95% CI 1.7-5.7; P < 0.001) and 3.0 times (95% CI 1.7-5.4; P < 0.001), more likely to receive ADT with RT, respectively. CONCLUSION: This is the largest Australasian contemporary series reporting on the pattern of use of ADT with definitive prostate RT. While there was an increasing trend towards use of ADT over time, ADT still appeared to be underutilized in certain groups of patients who may benefit from ADT, with approximately one in five men with high-risk and one in two with unfavourable intermediate-risk PCa not receiving ADT with RT. There was notable variation in the use of ADT between public vs private and metropolitan vs regional institutions.

Comparison of oncological and health-related quality of life outcomes between open and robot-assisted radical prostatectomy for localised prostate cancer - findings from the population-based Victorian Prostate Cancer Registry.

OBJECTIVE: To compare the short-term oncological and health-related quality of life (HRQOL) outcomes between open (ORP) and robot-assisted (RARP) radical prostatectomy in the population-based Victorian Prostate Cancer Registry. PATIENTS AND METHODS: This is a prospective cohort of patients with prostate cancer who had RP (1117 ORP and 885 RARP) between January 2009 and June 2012. The oncological outcomes of interest were: positive surgical margin (PSM) and biochemical recurrence (BCR), defined as postoperative PSA level of >0.2 ng/mL. The HRQOL outcomes were: sexual and urinary bother, assessed using the Expanded Prostate Cancer Index Composite at 1- and 2-years after diagnosis. For univariate comparison of continuous variables the Student's t-test or Mann-Whitney U-test were used, and the Pearson's chi-squared test was used for categorical variables. Bonferroni correction was applied to account for multiple testing, with a threshold for significance of P < 0.003 for univariate analyses. The inverse-probability-treatment-weighting (IPTW) approach was used to adjust for differences in baseline characteristics between ORP and RARP patients [including age, National Comprehensive Cancer Network (NCCN) risk categories, hospitals, and year of RP] in all multivariate analyses. Logistic regressions were used to analyse for PSM, Cox regressions for BCR, and ordinal logistic regressions for HRQOL outcomes. All multivariate analyses also adjusted for surgeons' average annual caseload, and employed the robust standard errors for clustering by surgeon. RESULTS: ORP and RARP patients were followed for a median of 19 and 17 months, respectively. The proportion of patients with NCCN low-risk prostate cancer was significantly higher among RARP patients (21% vs 26%; P = 0.002). Most RPs was done in private hospitals (77% ORP, and 85% RARP, P < 0.001). A higher proportion of RARP patients were operated by surgeons with higher annual caseloads (65% RARP and 53% ORP operated by surgeons with >20 case/year; P < 0.001). In the IPTW-adjusted multivariate analyses, RARP patients had a lower risk of PSM (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.38-0.81), and BCR (hazard ratio [HR] 0.73, 95% CI 0.55-0.99). In the sensitivity analyses (excluding public hospital patients), the lower PSM risk with RARP remained (OR 0.63, 95% CI 0.38-0.81), but the lower BCR risk with RARP was no longer statistically significant (HR 0.79, 95% CI 0.57-1.12). At 1-year follow-up, 61% of ORP and 59% of RARP patients reported 'moderate-big' sexual bother (P = 0.2), while 14% of ORP and 11% of RARP patients reported 'moderate-big' urinary bother (P = 0.08). The sexual and urinary bothers at 2 years were similar between ORP and RARP. In multivariate analyses, there were no statistically significant differences in the HRQOL outcomes between ORP and RARP. CONCLUSIONS: We report on a large population-based comparative study of ORP and RARP with better short-term oncological outcomes favouring RARP, but no significant differences in HRQOL outcomes. The results have to be interpreted taking into account significant surgeon heterogeneity in a population-based study.

Clinicopathological characteristics and management of prostate cancer in the human immunodeficiency virus (HIV)-positive population: experience in an Australian major HIV centre.

OBJECTIVES: To characterise clinicopathological characteristics of prostate cancer among human immunodeficiency virus (HIV)-positive men and to evaluate the current practice patterns in the management of prostate cancer in these men. PATIENTS AND METHODS: We retrospectively reviewed all patients with HIV in the State-wide HIV referral centre in Victoria, who were diagnosed with prostate cancer from 2000 onwards. In all, 12 patients were identified, and the medical records were reviewed to collect data on HIV parameters at the time of prostate cancer diagnosis, as well as prostate cancer clinicopathological characteristics, treatment details and outcomes. RESULTS: At the time of prostate cancer diagnosis, eight patients had undetectable viral load, and the median cluster of differentiation 4 (CD4) count was 485 cells/µL. The average age at diagnosis of prostate cancer was 63 years and the median prostate-specific antigen (PSA) level of 11.1 ng/mL. Four patients had Gleason 6 prostate cancer, four Gleason 7, one Gleason 8 and three Gleason 9. Seven of the 12 patients had a positive family history for prostate cancer. Of the patients with clinically localised prostate cancer (10), most were treated with radiotherapy (RT): one permanent seed brachytherapy (BT), five external beam RT (EBRT), two open radical prostatectomies (RP), one active surveillance (AS), and one on watchful waiting (WW). For the two patients with metastatic disease, one had androgen-deprivation therapy and EBRT, while the other had a combination of EBRT and chemo-hormonal therapy with doxetacel. All patients were followed for a median of 46 months, with three deaths reported, none of which was a prostate cancer-specific death. CONCLUSIONS: This is the first Australasian series on prostate cancer management in a HIV population. With the prolonged survival among HIV-positive men in the highly active anti-retroviral therapy era, PSA testing should be offered to this group of patients, especially those with a positive family history. HIV-positive men should also be offered all treatment options in the same manner as men in the general population.

Transperineal biopsy prostate cancer detection in first biopsy and repeat biopsy after negative transrectal ultrasound-guided biopsy: the Victorian Transperineal Biopsy Collaboration experience.

OBJECTIVES: To present the Victorian Transperineal Biopsy Collaboration (VTBC) experience in patients with no prior prostate cancer diagnosis, assessing the cancer detection rate, pathological outcomes and anatomical distribution of cancer within the prostate. PATIENTS AND METHODS: VTBC was established through partnership between urologists performing transperineal biopsies of the prostate (TPB) at three institutions in Melbourne. Consecutive patients who had TPB, as first biopsy or repeat biopsy after previous negative transrectal ultrasound-guided (TRUS) biopsy, between September 2009 and September 2013 in the VTBC database were included. Data for each patient were collected prospectively (except for TPB before 2011 in one institution), based on the minimum dataset published by the Ginsburg Study Group. Univariate and multivariate analyses were used to identify factors predictive of cancer detection on TPB. RESULTS: In all, 160 patients were included in the study, of whom 57 had TPB as first biopsy and 103 had TPB as repeat biopsy after previous negative TRUS biopsies. The median patient age at TPB was 63 years, with the repeat-biopsy patients having a higher median serum PSA level (5.8 ng/mL for first biopsy and 9.6 ng/mL for repeat biopsy) and larger prostate volumes (40 mL for first biopsy, and 51 mL for repeat biopsy). Prostate cancer was detected in 53% of first-biopsy patients and 36% of repeat-biopsy patients, of which 87% and 81%, respectively, were clinically significant cancers, defined as a Gleason score of ≥7, or more than three positive cores of Gleason 6. Of the cancers detected in repeat biopsies, 75% involved the anterior region (based on the Ginsburg Study Group's recommended biopsy map), while 25% were confined exclusively within the anterior region; a lower proportion of only 5% of cancers detected in first biopsies were confined exclusively within the anterior region. Age, serum PSA level and prostate volume were predictive of cancer detection in repeat biopsies, while only age was predictive in first biopsies. CONCLUSIONS: TPB is an alternative approach to TRUS biopsy of the prostate, offering a high rate of detection of clinically significant prostate cancer. It provides excellent sampling of the anterior region of the prostate, which is often under-sampled using the TRUS approach, and should be considered as an option for all men in whom a prostate biopsy is indicated.

Prevalence of Baseline Erectile Dysfunction (ED) in an Australian Cohort of Men with Localized Prostate Cancer.

INTRODUCTION: Erectile dysfunction (ED) is a common complication following prostate cancer treatment. Post-treatment erectile function (EF) preservation is strongly dependent on the baseline EF prior to treatment. AIM: To assess the baseline EF among patients with localized prostate cancer, and the factors associated with baseline EF. METHODS: All men with clinically localized prostate cancer had their baseline EF assessed prior to brachytherapy at our institution. Six hundred ninety-nine men who completed the International Index of Erectile Function five-item questionnaires pre-treatment between 2001 and 2013 were included in the study. Data on patient factors (medical comorbidities and smoking history) and prostate cancer clinicopathological characteristics were recorded. Ordinal logistic regressions were used to estimate the effects of each variable on the severity of ED. MAIN OUTCOME MEASURES: Baseline EF among men with localized prostate cancer, and factors associated with ED. RESULTS: Prior to permanent seed brachytherapy, 335 (48%) patients reported no ED, 129 (17%) mild ED, 42 (6%) mild-moderate ED, 37 (5%) moderate ED, and 165 (24%) severe ED. In multivariate analyses, age, diabetes, and hypertension remained to be independently associated with ED, with diabetes most strongly associated with worse ED (odds ratio = 2.6; 95% confidence interval = 1.3-5.3). CONCLUSIONS: ED is common among patients with localized prostate cancer prior to any curative treatment. Assessment of baseline ED is important prior to curative treatment of prostate cancer in order to offer appropriate advise on likelihood of EF preservation post-treatment and avoid patient dissatisfaction with treatment outcomes due to unrealistic expectations.

Management and outcomes of glioblastoma: 20-year experience in a single Australian institution.

INTRODUCTION: We aimed to evaluate the changing patterns in the management of glioblastoma (GBM) and impact on survival outcomes over a 20-year period. METHODS: This is a retrospective study of patients diagnosed with GBM between 2001 and 2020, who had radiation therapy (RT) in an Australian institution. The primary outcomes were changes in treatment modalities (including surgery, RT, and chemotherapy) over time and overall survival (OS). Multivariable Cox regressions were used to evaluate factors associated with OS, including age, sex, ECOG performance status, treatment modalities, treatment facility, and year of treatment. RESULTS: 1079 patients were included in this study. Thirty-five per cent of patients had gross total resection, increasing from 31% in 2001-2005 to 45% in 2016-2020 (P < 0.001). Sixty-four per cent of patients had ≥60 Gy RT, increasing from 57% in 2001-2005 to 66% in 2016-2020 (P < 0.001). Seventy-five per cent of patients had chemotherapy, increasing from 22% in 2001-2005 to 89% in 2016-2020 (P < 0.001). Treatment received varied based on patients' age and ECOG performance status. The median OS for the entire cohort was 13.0 months (95% CI = 12.0-13.7). Median OS in patients who had maximal treatment (i.e., gross total resection, ≥60 Gy RT and chemotherapy) was 20.6 months (95% CI = 17.3-22.8). In multivariable analyses, age, sex, treatment facility, extent of surgical resection, RT dose, and chemotherapy use were associated with OS. CONCLUSION: This is one of the largest Australian series on the management and outcomes of GBM spanning a 20-year period. We observed improvement in OS over time, which is likely associated with evolving treatment options over the study period.

Urethra contouring on computed tomography urethrogram versus magnetic resonance imaging for stereotactic body radiotherapy in prostate cancer.

Accurate urethra contouring is critical in prostate SBRT. We compared urethra contouring on CT-urethrogram and T2-weighted MRI. The dice similarity coefficient, Jaccard index, Hausdorff distance and mean distance to agreement were evaluated. All four metrics indicate better agreement and less variability in urethra contouring on CT-urethrogram, compared to T2-weighted MRI.

Prostate-Specific Antigen Response to Androgen Deprivation Therapy in the Neoadjuvant Setting for High-Risk Prostate Adenocarcinoma (PIRANHA): Pooled Analysis of Two Randomized Clinical Trials.

PURPOSE: A suboptimal prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) among men who go on to receive definitive radiation therapy for prostate cancer might suggest the existence of castration-resistant disease or altered androgen receptor signaling. This in turn may portend worse long-term clinical outcomes, especially in men with high-risk disease. We set out to evaluate the prognostic impact of poor PSA response to neoadjuvant ADT in men with high-risk prostate cancer. METHODS AND MATERIALS: This was a post hoc analysis of the multicenter TROG 03.04 RADAR and PCS IV randomized clinical trials. Inclusion criteria for this analysis were patients with high-risk prostate cancer (defined as Gleason score ≥8, initial PSA ≥20 ng/mL, or cT3a disease or higher) who received definitive radiation therapy, at least 18 months of ADT, and had a preradiation therapy PSA level drawn after at least 3 months of neoadjuvant ADT. Poor PSA response was defined as PSA >0.5 ng/mL. Cox regression and Fine-Gray models were used to test whether poor PSA response was associated with metastasis-free survival, biochemical recurrence, prostate-cancer specific mortality, and overall survival. RESULTS: Nine hundred thirty men met inclusion criteria for this analysis. Median follow-up was 130 months (interquartile range [IQR], 89-154 months). After a median of 3 months (IQR, 3-4.2 months) of neoadjuvant ADT, the median PSA was 0.60 ng/mL (IQR, 0.29-1.59). Overall, 535 men (57%) had a PSA >0.5 ng/mL. Poor PSA response was associated with significantly worse metastasis-free survival (hazard ratio [HR], 3.93; P = .02), worse biochemical recurrence (subdistribution HR, 2.39; P = .003), worse prostate-cancer specific mortality (subdistribution HR, 1.50; P = .005), and worse overall survival (HR, 4.51; P = .05). CONCLUSIONS: Patients with PSA >0.5 mg/mL after at least 3 months of neoadjuvant ADT had worse long-term clinical outcomes and should be considered for treatment intensification.

Predictors of Tumor Dynamics Over a 6-Week Course of Concurrent Chemoradiotherapy for Glioblastoma and the Effect on Survival.

PURPOSE: We present the final analyses of tumor dynamics and their prognostic significance during a 6-week course of concurrent chemoradiotherapy for glioblastoma in the Glioblastoma Longitudinal Imaging Observational study. METHODS AND MATERIALS: This is a prospective serial magnetic resonance imaging study in 129 patients with glioblastoma who had magnetic resonance imaging obtained at radiation therapy (RT) planning (F0), fraction 10 (F10), fraction 20 (F20), and 1-month post-RT. Tumor dynamics assessed included gross tumor volume relative to F0 (Vrel) and tumor migration distance (dmigration). Covariables evaluated included: corpus callosum involvement, extent of surgery, O6-methylguanine-DNA-methyltransferase methylation, and isocitrate dehydrogenase mutation status. RESULTS: The median Vrel were 0.85 (range, 0.25-2.29) at F10, 0.79 (range, 0.09-2.22) at F20, and 0.78 (range, 0.13-4.27) at 1 month after completion of RT. The median dmigration were 4.7 mm (range, 1.1-20.4 mm) at F10, 4.7 mm (range, 0.8-20.7 mm) at F20, and 6.1 mm (range, 0.0-45.5 mm) at 1 month after completion of RT. Compared with patients who had corpus callosum involvement (n = 26), those without corpus callosum involvement (n = 103) had significant Vrel reduction at F20 (P = .03) and smaller dmigration at F20 (P = .007). Compared with patients who had biopsy alone (n = 19) and subtotal resection (n = 71), those who had gross total resection (n = 38) had significant Vrel reduction at F10 (P = .001) and F20 (P = .001) and a smaller dmigration at F10 (P = .03) and F20 (P = .002). O6-Methylguanine-DNA-methyltransferase methylation and isocitrate dehydrogenase mutation status were not significantly associated with tumor dynamics. The median progression-free survival and overall survival (OS) were 8.5 months (95% CI, 6.9-9.9) and 20.4 months (95% CI, 17.6-25.2). In multivariable analyses, patients with Vrel ≥ 1.33 at F10 had worse OS (hazard ratio [HR], 4.6; 95% CI, 1.8-11.4; P = .001), and patients with dmigration ≥ 5 mm at 1-month post-RT had worse progression-free survival (HR, 1.76; 95% CI, 1.08-2.87) and OS (HR, 2.2; 95% CI, 1.2-4.0; P = .007). CONCLUSIONS: Corpus callosum involvement and extent of surgery are independent predictors of tumor dynamics during RT and can enable patient selection for adaptive RT strategies. Significant tumor enlargement at F10 and tumor migration 1-month post-RT were associated with poorer OS.