Prostate Radiotherapy in Low-volume Metastatic Hormone-sensitive Prostate Cancer: A Network Meta-analysis.

BACKGROUND AND OBJECTIVE: The utility of prostate radiotherapy (RT) is unclear in men with metastatic hormone-sensitive prostate cancer (mHSPC) receiving intensified systemic therapy with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPIs). We performed a network meta-analysis of randomized controlled trials (RCTs) to investigate the role of prostate RT in low-volume mHSPC. METHODS: Bibliographic databases and conference proceedings were searched through July 2023 for RCTs evaluating the addition of ARPIs or prostate RT to standard of care (SOC) systemic therapy, defined as ADT or ADT plus docetaxel, for the initial treatment of mHSPC. We focused exclusively on aggregate data from the low-volume mHSPC subpopulation in these trials. We pooled the treatment arms into four groups: SOC, SOC plus ARPI, SOC plus RT, and SOC plus ARPI plus RT. The primary outcome was overall survival (OS). To compare treatment strategies, a fixed-effects Bayesian network meta-analysis was undertaken, while a Bayesian network meta-regression was performed to account for across-trial differences in docetaxel use as part of SOC and in proportions of patients with de novo presentation. KEY FINDINGS AND LIMITATIONS: Ten RCTs comprising 4423 patients were eligible. The Surface Under the Cumulative Ranking Curve scores were 0.0006, 0.45, 0.62, and 0.94 for SOC, SOC plus RT, SOC plus ARPI, and SOC plus ARPI plus RT, respectively. On a meta-regression, in a population with de novo mHSPC and no docetaxel use, we did not find sufficient evidence of a difference in OS between SOC plus ARPI plus RT versus SOC plus ARPI (hazard ratio [HR]: 0.76; 95% credible interval: 0.51-1.16) and SOC plus RT versus SOC plus ARPI (HR: 1.10; 95% credible interval: 0.92-1.42). CONCLUSIONS AND CLINICAL IMPLICATIONS: There was some evidence that SOC plus ARPI plus RT reduced mortality compared with the next best strategy of SOC plus ARPI in patients with low-volume de novo mHSPC. A meta-analysis with individual patient data or an RCT is needed to confirm these findings.

Variation in Access to Palliative Radiotherapy in Prostate Cancer: A Population-Based Study in Canada.

BACKGROUND: As a result of improvements in cancer therapies, patients with metastatic malignancies are living longer, and the role of palliative radiotherapy has become increasingly recognized. However, access to adequate palliative radiotherapy may continue to be a challenge, as is evident from the high proportion of patients dying of prostate cancer who never receive palliative radiotherapy. The main objective of this investigation is to identify and describe the factors associated with the receipt of palliative radiation treatment in a decedent cohort of prostate cancer patients in Ontario. METHODOLOGY:  Population-based administrative databases from Ontario, Canada, were used to identify prostate cancer decedents, 65 years or older who received androgen deprivation therapy between January 1, 2013, and December 31, 2018. Baseline and treatment characteristics were analyzed using univariate and multivariate logistic regression models for association with receipt of radiotherapy in a two-year observation period before death. RESULTS: We identified 3,788 prostate cancer decedents between 2013 and 2018; among these, 49.9% received radiotherapy in the two years preceding death. There were statistically significant positive associations between receipt of radiotherapy and younger age at diagnosis (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.1-2.3); higher stage at diagnosis (OR 1.3, 95% CI 1.1-1.7); receipt of care at a regional cancer center (OR 1.8, 95% CI 1.3-2.4); and involvement of radiation oncologists (OR 155.1, 95% CI 83.3-288.7) or medical oncologists (OR 1.4, 95% CI 1.1-1.8). However, there were no associations between receipt of radiotherapy and income, distance to the nearest cancer center, involvement of urologists in cancer care, healthcare administrative region, home-care involvement, or number of hospitalizations in the observation period. CONCLUSIONS: We found the utilization of palliative radiotherapy for prostate cancer patients in Ontario varies depending on age, stage at diagnosis, number of comorbidities, registration at regional cancer centers, and involvement of oncologists. There were no differences detected based on income or distance from a cancer center. The findings of this study represent an important opportunity to facilitate better access to palliative radiotherapy and referrals to multidisciplinary regional cancer centers, to improve the quality of life of this patient population.

Real-World Evaluation of Primary Versus Secondary Prevention of Skeletal-Related Events in Metastatic Castration-Resistant Prostate Cancer.

INTRODUCTION: Anti-osteoclast treatment with denosumab or zoledronate is known to effectively reduce the need for radiotherapy to bone and other skeletal-related events (SREs) in patients with metastatic castration-resistant prostate cancer (mCRPC). In this study, we analyze primary versus secondary initiation of bone-targeting agents (BTAs) relative to first palliative bone radiotherapy in patients dying of mCRPC. METHODS: Provincial administrative databases from Ontario, Canada identified patients with prostate cancer (2007-2018, n = 98 646) who received continuous androgen deprivation therapy (n = 29 453), died of prostate cancer (2013-2018, n = 3864), and received life-prolonging therapy for mCRPC (n = 1850). Variables were collected looking back 3 years from death. Multivariable analysis explored the relationship between clinical variables and BTAs. RESULTS: Of the 58% (1066/1850) patients with mCRPC who received BTA, only 289 (25.4%) started BTA prior to first palliative bone radiotherapy as primary prevention. Eight hundred and forty-eight (74.6%) patients either never received BTA before death (n = 447) or started BTA only after first bone radiotherapy (n = 401). More patients received denosumab (n = 825, 77%) than zoledronic acid (n = 241, 23%). 51.2% (582/1137) of palliative bone radiotherapy was initiated in the last 12 months of life. Factors associated with the use of BTA included elevated alkaline phosphatase (OR = 1.0, P = .023), de novo metastases (OR = 1.4, P = .005), medical oncologist involvement (OR = 2.0, P = .007), diagnosis 2012-2017 versus 2007-2011 (OR = 0.75, P = .034), and academic center (OR = 0.061, P = .007). CONCLUSION: A majority of patients with mCRPC never receive BTAs prior to first SRE, despite universal access and availability of these agents in Ontario. These results highlight an opportunity to improve outcomes by emphasizing early introduction of BTA in patients with mCRPC being started on systemic therapy.

Radiation Therapy Summary of the AUA/ASTRO Guideline on Clinically Localized Prostate Cancer.

PURPOSE: Our purpose was to develop a summary of recommendations regarding the management of patients with clinically localized prostate cancer based on the American Urologic Association/ ASTRO Guideline on Clinically Localized Prostate Cancer. METHODS: The American Urologic Association and ASTRO convened a multidisciplinary, expert panel to develop recommendations based on a systematic literature review using an a priori defined consensus-building methodology. The topics covered were risk assessment, staging, risk-based management, principles of management including active surveillance, surgery, radiation, and follow-up after treatment. Presented are recommendations from the guideline most pertinent to radiation oncologists with an additional statement on health equity, diversity, and inclusion related to guideline panel composition and the topic of clinically localized prostate cancer. SUMMARY: Staging, risk assessment, and management options in prostate cancer have advanced over the last decade and significantly affect shared decision-making for treatment management. Current advancements and controversies discussed to guide staging, risk assessment, and treatment recommendations include the use of advanced imaging and tumor genomic profiling. An essential active surveillance strategy includes prostate-specific antigen monitoring and periodic digital rectal examination with changes triggering magnetic resonance imaging and possible biopsy thereafter and histologic progression or greater tumor volume prompting consideration of definitive local treatment. The panel recommends against routine use of adjuvant radiation therapy (RT) for patients with prostate cancer after prostatectomy with negative nodes and an undetectable prostate-specific antigen, while acknowledging that patients at highest risk of recurrence were relatively poorly represented in the 3 largest randomized trials comparing adjuvant RT to early salvage and that a role may exist for adjuvant RT in selected patients at highest risk. RT for clinically localized prostate cancer has evolved rapidly, with new trial results, therapeutic combinations, and technological advances. The recommendation of moderately hypofractionated RT has not changed, and the updated guideline incorporates a conditional recommendation for the use of ultrahypofractionated treatment. Health disparities and inequities exist in the management of clinically localized prostate cancer across the continuum of care that can influence guideline concordance.

Effect of Concomitant Medications on Treatment Response and Survival in De Novo Metastatic Prostate Cancer: Secondary Analysis of the LATITUDE Study.

PURPOSE: It is unclear whether exposure to commonly prescribed medications influences survival and treatment response in patients with de novo high-risk metastatic prostate cancer (mPCa) treated with androgen receptor pathway inhibitors (ARPIs). METHODS: We performed a secondary analysis of the LATITUDE trial to determine whether receipt of concomitant medications influenced the effect of abiraterone acetate and prednisone, in addition to androgen deprivation therapy (ADT), on overall survival (OS) and prostate cancer-specific mortality (PCSM) in patients with de novo mPCa. We focused on 7 commonly prescribed classes of medications: metformin, statins, proton pump inhibitors (PPIs), cyclooxygenase 2 (COX-2) inhibitors, aspirin, acetaminophen, and NSAIDs (nonselective COX inhibitors). To account for multiple testing, a two-sided p < 0.0024 was set as the threshold for statistical significance. RESULTS: Overall, 1135 patients were eligible. There was some evidence of a differential treatment effect from abiraterone among patients who received concomitant NSAIDs (hazard ratio [HR] for OS: 0.54; 95% CI: 0.42-0.70) versus those who did not (HR: 0.74; 95% CI: 0.60-0.91), though this did not reach significance (interaction p = 0.05). A similar non-significant finding of heterogeneity of effect from abiraterone was noted among patients who received concomitant aspirin (HR for OS: 0.93 [0.63-1.36]) versus those who did not (HR: 0.61 [0.51-0.73]) (interaction p = 0.04). Receipt of NSAIDs was independently associated with a significantly inferior OS (HR: 1.37 [1.15-1.62]; p < 0.001) and higher relative incidence of PCSM (sHR: 1.47 [1.21-1.78]; p < 0.001). CONCLUSIONS: This exploratory analysis did not find statistically significant evidence of differences in treatment effects from ADT plus abiraterone in de novo high-risk mPCa based on the receipt of concurrent medications. The receipt of NSAIDs was independently associated with increased PCSM and inferior OS.

Emergent radiotherapy for pelvic malignancies: a narrative review.

BACKGROUND AND OBJECTIVE: Patients with primary genitourinary (GU), gynecologic (GYN) and gastrointestinal (GI) cancers can develop life-threatening or critical function-threatening symptoms that necessitate emergent intervention with palliative radiotherapy (RT). Unfortunately, research describing the use of RT in this critical setting is lacking. We aimed to review literature describing emergent palliative RT for primary pelvic malignancies and provide a narrative synthesis of relevant studies. METHODS: A medical librarian searched Ovid MEDLINE, Embase Classic, and Embase databases for relevant English language references from 1946-2022. No restrictions were placed on study type, publication type or date. References for GU, GYN and GI cancers were grouped and synthesized separately. KEY CONTENT AND FINDINGS: The treatment of bleeding from primary pelvic tumors was the only indication for emergent RT identified, however, no references reported dedicated cohorts of patients treated for bleeding in the emergent setting. Most references were retrospective single institution studies describing various dose fractionation schemes for non-emergent palliative RT. Outcome measures and response assessment times varied. The latency to hemostasis after RT commencement was not well described; most studies reported outcomes captured weeks or months following treatment. In general, high rates of hemostasis for GU, GYN and GI tumors have been reported following RT schedules ranging from a single fraction to many weeks of fractionated treatments. Bleeding seems to respond more favorably than other symptoms including pain and obstruction. CONCLUSIONS: Managing bleeding was the only indication for emergent RT identified in our search. Scant data exist that describe the latency to a hemostatic response following RT. This is an important knowledge gap in the literature given how commonly patients are affected by this complication of primary pelvic malignancies.

Effect of Pelvic External Beam Radiation Therapy on Bone Mineral Density: A Secondary Analysis of a Phase 3 Randomized Controlled Trial.

PURPOSE: Pelvic radiation therapy may lead to decreased bone mineral density (BMD) and increased risk of fracture that could be of particular concern in patients with prostate cancer who also receive androgen deprivation therapy (ADT). We performed an exploratory analysis of a randomized, double-masked, placebo-controlled trial to determine whether exposure to prior pelvic external beam radiation therapy (XRT) affects BMD and risk of fracture in patients with prostate cancer treated with ADT. METHODS AND MATERIALS: Patients with nonmetastatic prostate cancer aged ≥70 years or <70 years with low BMD (T-score < -1) or osteoporotic fracture who had been receiving ADT for ≥12 months were randomly assigned to receive densoumab or placebo every 6 months for 3 years. BMD was measured at baseline and at months 1, 3, 6, 12, 24, and 36. We applied multivariable linear mixed-effects models with an interaction term between the treatment arm and exposure to prior pelvic XRT to evaluate differential XRT effect on percent BMD change between the 2 treatment arms. RESULTS: Among 1407 eligible patients, 31% (n = 447) received prior pelvic XRT. There was no significant difference in any clinical fractures among patients with (5.8%, 26 of 447) or without (5.2%, 50 of 960) prior pelvic XRT (P = .42). Prior pelvic XRT was associated with a significant (0.54%) improvement in BMD (95% CI, 0.05-1.02) in the placebo group and a nonsignificant (0.04%) decline in BMD (95% CI, -0.47 to -0.35) in the denosumab group (interaction P = .007). There was no significant difference in pelvic XRT effect on percent BMD change in the lumbar spine (P = .65) or total hip (P = .39) between the 2 treatment groups. CONCLUSIONS: We did not find sufficient evidence to suggest any detrimental effect of pelvic XRT on the treatment effect from denosumab on percent BMD change, with only an approximately 5% incidence of clinical fractures.

Association of PSA kinetics after testosterone recovery with subsequent recurrence: secondary analysis of a phase III randomized controlled trial.

PURPOSE: After cessation of androgen deprivation therapy (ADT), testosterone gradually recovers to supracastrate levels (> 50 ng/dL). After this, rises in prostate-specific antigen (PSA) are often seen. However, it remains unknown whether early PSA kinetics after testosterone recovery are associated with subsequent biochemical recurrence (BCR). METHODS: We performed a secondary analysis of a phase III randomized controlled trial in which newly diagnosed localized prostate cancer patients were randomly allocated to ADT for 6 months starting 4 months prior to or simultaneously with prostate RT. We calculated the PSA doubling time (PSADT) based on PSA values up to 18 months after supracastrate testosterone recovery. Competing risk regression was used to evaluate the association of PSADT with relative incidence of BCR, considering deaths as competing events. RESULTS: Overall, 313 patients were eligible. Median PSADT was 8 months. Cumulative incidence of BCR at 10 years from supracastrate testosterone recovery was 19% and 11% in patients with PSADT < 8 months and ≥ 8 months (p = 0.03). Compared to patients with PSADT of < 4 months, patients with higher PSADT (sHR for PSADT 4 to < 8 months: 0.36 [95% CI 0.16-0.82]; 8 to < 12 months: 0.26 [0.08-0.91]; ≥ 12 months: 0.20 [0.07-0.56]) had lower risk of relative incidence of BCR. CONCLUSIONS: Early PSA kinetics, within 18 months of recovery of testosterone to a supracastrate level, can predict for subsequent BCR. Taking account of early changes in PSA after testosterone recovery may allow for recognition of potential failures earlier in the disease course and thereby permit superior personalization of treatment.

Prognostic Role of Dynamic Changes in Serological Markers in Metastatic Hormone Naïve Prostate Cancer.

We investigated whether inter-patient variation in the dynamic trajectory of hemoglobin (Hb), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and prostate-specific antigen (PSA) can prognosticate overall survival (OS) in de novo mHSPC. This is a secondary analysis of the LATITUDE trial in which high-risk de novo mHSPC patients were randomly assigned to receive either androgen deprivation therapy (ADT) plus abiraterone or ADT plus placebo. We used a five-fold cross-validated joint model approach to determine the association of temporal changes in the serological markers with OS. Decision curve analysis was applied to determine the net benefit. When dynamic changes in Hb, LMR, NLR, PLR, and PSA were included in a multivariate joint model, an increase in the log of the current value of PSA (HR: 1.24 [1.20-1.28]) was associated with inferior OS. A multivariate joint model that captured dynamic trajectory of Hb, NLR, PLR, LMR, and PSA up to 24 months, showed a net benefit over the "treat all" strategy at a threshold of probability of approximately ≥30% while no net benefit was seen when dynamic change in PSA was omitted. Our joint model could be used for designing future adaptive trials investigating sequential treatment personalization.

Adjuvant therapy for renal cell carcinoma: 2023 Canadian Kidney Cancer Forum consensus statement.

INTRODUCTION: Several recent randomized trials evaluated the impact of adjuvant immune checkpoint inhibitor (ICI)-based therapy on post-surgical outcomes in renal cell carcinoma (RCC), with disparate results. The objective of this consensus statement is to provide data-driven guidance regarding the use of ICIs after complete resection of clear-cell RCC in a Canadian context. METHODS: An expert panel of genitourinary medical oncologists, urologic oncologists, and radiation oncologists with expertise in RCC management was convened in a dedicated session during the 2022 Canadian Kidney Cancer Forum in Toronto, Canada. Topic statements on the management of patients after surgery for RCC, including counselling, risk stratification, indications for medical oncology referral, appropriate followup, eligibility and management for adjuvant ICIs, as well as treatment options for patients with recurrence who received adjuvant immunotherapy, were discussed. Participants were asked to vote if they agreed or disagreed with each statement. Consensus was achieved if greater than 75% of participants agreed with the topic statement. RESULTS: A total of 22 RCC experts voted on 14 statements. Consensus was achieved on all topic statements. The panel felt patients with clear-cell RCC at increased risk of recurrence after surgery, as per the Keynote-564 group definitions, should be counselled about recurrence risk by a urologist, should be informed about the potential role of adjuvant ICI systemic therapy, and be offered referral to discuss risks and benefits with a medical oncologist. The panel felt that one year of pembrolizumab is currently the only regimen that should be considered if adjuvant therapy is selected. Panelists emphasized current opinions are based on disease-free survival given the available results. Significant uncertainty regarding the benefit and harms of adjuvant therapy remains, primarily due to a lack of consistent benefit observed across similar trials of adjuvant ICI-based therapies and immature overall survival (OS) data. CONCLUSIONS: This consensus document provides guidance from Canadian RCC experts regarding the potential role of ICI-based adjuvant systemic therapy after surgery. This rapidly evolving field requires frequent evidence-based re-evaluation.

Implications of metastatic stage at presentation in docetaxel naïve metastatic castrate resistant prostate cancer.

BACKGROUND: We performed a secondary analysis of ACIS study to determine if synchronous versus metachronous metastatic presentation has any association with survival and treatment response to dual androgen receptor axis-targeted therapy (ARAT) in docetaxel naïve metastatic castrate resistant prostate cancer (mCRPC). METHODOLOGY: In this phase III randomized controlled trial, docetaxel naïve mCRPC patients were randomized to either apalutamide or placebo combined with abiraterone and prednisone. Multivariable Cox regression models were applied to determine the adjusted association of M-stage with radiographic progression-free survival (rPFS) and overall survival (OS). To determine the heterogeneity of treatment effect based on metastatic stage (M-stage) at presentation, Cox regression was applied with interaction terms between M-stage and treatment. RESULTS: Among 972 patients, 432 had M0, 334 had M1, while M-stage at presentation was unknown in 206. There was no association of M-stage at presentation with rPFS in patients with prior local therapy (LT) (hazard ratio for M1-stage: 1.22 [95% confidence interval: 0.82-1.82]; unknown: 1.03 [0.77-1.38]) or without prior LT (M1-stage: 0.87 [0.64-1.19]; unknown: 1.15 [0.77-1.72]) with no significant heterogeneity. Similarly, there was no association of M-stage with OS in patients with prior LT (M1-stage: 1.04 [0.81-1.33]; unknown: 0.98 [0.79-1.21]) or without prior LT (M1-stage: 0.95 [0.70-1.29]; unknown: 1.17 [0.80-1.71]) with no significant heterogeneity. Based on M-stage at presentation, we did not find any significant heterogeneity in treatment effect on rPFS (interaction p = 0.13), and OS (interaction p = 0.87). CONCLUSION: M-stage at presentation had no association with survival in chemotherapy-naïve mCRPC. We did not find any statistically significant heterogeneity in efficacy of dual ARAT based on synchronous versus metachronous presentation.

Effect of Prior Local Therapy on Response to First-line Androgen Receptor Axis Targeted Therapy in Metastatic Castrate-resistant Prostate Cancer: A Secondary Analysis of the COU-AA-302 Trial.

BACKGROUND: Men with localized prostate cancer are often treated with local therapy (LT). However, a proportion of these patients will eventually develop recurrence and progression requiring systemic therapy. Whether primary LT affects the response to this subsequent systemic treatment is unclear. OBJECTIVE: We investigated whether the receipt of prior prostate-directed LT influenced the response to first-line systemic therapy and survival in docetaxel-naïve metastatic castrate-resistant prostate cancer (mCRPC) patients. DESIGN, SETTING, AND PARTICIPANTS: This is an exploratory analysis of the COU-AA-302 trial, a multicentric double-blinded phase 3 randomized controlled trial in which mCRPC patients with no to mild symptoms were randomized to receive abiraterone plus prednisone or placebo plus prednisone. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We compared the time-varying effects of first-line abiraterone in patients with and without prior LT using a Cox proportional hazard model. The cut points were chosen using grid search, and were 6 and 36 mo for radiographic progression-free survival (rPFS) and overall survival (OS), respectively. We also investigated whether there was any difference in treatment effect on score change (relative to baseline) in various patient-reported outcomes (measured by Functional Assessment of Cancer Therapy-Prostate [FACT-P]) over time depending on the receipt of prior LT. The adjusted association of prior LT with survival was determined using weighted Cox regression models. RESULTS AND LIMITATIONS: Among 1053 eligible patients, 64% (n = 669) received prior LT. We did not find any statistically significant heterogeneity of time-dependent treatment effect from abiraterone on rPFS in patients with (hazard ratio [HR]: 0.36 [95% confidence interval: 0.27-0.49] at ≤6 mo; 0.64 [0.49-0.83] at >6 mo) or without (HR: 0.37 [0.26-0.55] at ≤6 mo; 0.72 [0.50-1.03] at >6 mo) prior LT. Similarly, there was no significant heterogeneity in time-dependent treatment effect on OS with (HR: 0.88 [0.71-1.10] at ≤36 mo; 0.76 [0.52-1.11] at >36 mo) or without (0.78 [0.60-1.01] at ≤36 mo; 0.55 [0.30-0.99] at >36 mo) prior LT. We did not find sufficient evidence of a difference in treatment effect from abiraterone on score change over time in prostate cancer subscale (interaction p = 0.4), trial outcome index (interaction p = 0.8), and FACT-P total score (interaction p = 0.6) depending on the receipt of prior LT. Receipt of prior LT was associated with a significant improvement in OS (average HR: 0.72 [0.59-0.89]). CONCLUSIONS: This study demonstrates that the efficacy of first-line abiraterone and prednisone in docetaxel-naïve mCRPC do not vary significantly based on the receipt of prior prostate-directed LT. Further studies are needed to explore the plausible mechanisms of the association of prior LT with superior OS. PATIENT SUMMARY: This secondary analysis of the COU-AA-302 trial suggests that survival benefits and temporal changes in quality of life with first-line abiraterone in docetaxel-naïve mCRPC do not differ significantly among patients who received versus those who did not receive prior prostate-directed local therapy.

Implementation of a Web-Based Communication System for Primary Care Providers and Cancer Specialists.

Healthcare providers have reported challenges with coordinating care for patients with cancer. Digital technology tools have brought new possibilities for improving care coordination. A web- and text-based asynchronous system (eOncoNote) was implemented in Ottawa, Canada for cancer specialists and primary care providers (PCPs). This study aimed to examine PCPs' experiences of implementing eOncoNote and how access to the system influenced communication between PCPs and cancer specialists. As part of a larger study, we collected and analyzed system usage data and administered an end-of-discussion survey to understand the perceived value of using eOncoNote. eOncoNote data were analyzed for 76 shared patients (33 patients receiving treatment and 43 patients in the survivorship phase). Thirty-nine percent of the PCPs responded to the cancer specialist's initial eOncoNote message and nearly all of those sent only one message. Forty-five percent of the PCPs completed the survey. Most PCPs reported no additional benefits of using eOncoNote and emphasized the need for electronic medical record (EMR) integration. Over half of the PCPs indicated that eOncoNote could be a helpful service if they had questions about a patient. Future research should examine opportunities for EMR integration and whether additional interventions could support communication between PCPs and cancer specialists.

Web-Based Asynchronous Tool to Facilitate Communication Between Primary Care Providers and Cancer Specialists: Pragmatic Randomized Controlled Trial.

BACKGROUND: Cancer poses a significant global health burden. With advances in screening and treatment, there are now a growing number of cancer survivors with complex needs, requiring the involvement of multiple health care providers. Previous studies have identified problems related to communication and care coordination between primary care providers (PCPs) and cancer specialists. OBJECTIVE: This study aimed to examine whether a web- and text-based asynchronous system (eOncoNote) could facilitate communication between PCPs and cancer specialists (oncologists and oncology nurses) to improve patient-reported continuity of care among patients receiving treatment or posttreatment survivorship care. METHODS: In this pragmatic randomized controlled trial, a total of 173 patients were randomly assigned to either the intervention group (eOncoNote plus usual methods of communication between PCPs and cancer specialists) or a control group (usual communication only), including 104 (60.1%) patients in the survivorship phase (breast and colorectal cancer) and 69 (39.9%) patients in the treatment phase (breast and prostate cancer). The primary outcome was patient-reported team and cross-boundary continuity (Nijmegen Continuity Questionnaire). Secondary outcome measures included the Generalized Anxiety Disorder Screener (GAD-7), Patient Health Questionnaire on Major Depression, and Picker Patient Experience Questionnaire. Patients completed the questionnaires at baseline and at 2 points following randomization. Patients in the treatment phase completed follow-up questionnaires at 1 month and at either 4 months (patients with prostate cancer) or 6 months following randomization (patients with breast cancer). Patients in the survivorship phase completed follow-up questionnaires at 6 months and at 12 months following randomization. RESULTS: The results did not show an intervention effect on the primary outcome of team and cross-boundary continuity of care or on the secondary outcomes of depression and patient experience with their health care. However, there was an intervention effect on anxiety. In the treatment phase, there was a statistically significant difference in the change score from baseline to the 1-month follow-up for GAD-7 (mean difference -2.3; P=.03). In the survivorship phase, there was a statistically significant difference in the change score for GAD-7 between baseline and the 6-month follow-up (mean difference -1.7; P=.03) and between baseline and the 12-month follow-up (mean difference -2.4; P=.004). CONCLUSIONS: PCPs' and cancer specialists' access to eOncoNote is not significantly associated with patient-reported continuity of care. However, PCPs' and cancer specialists' access to the eOncoNote intervention may be a factor in reducing patient anxiety. TRIAL REGISTRATION: ClinicalTrials.gov NCT03333785; https://clinicaltrials.gov/ct2/show/NCT03333785.

Development and validation of a multivariable prognostic model in de novo metastatic castrate sensitive prostate cancer.

BACKGROUND: Metastatic castrate sensitive prostate cancer (mCSPC) is a heterogeneous disease state with variable prognosis. Although several life-prolonging systemic agents are available, there is no robust multivariable model to predict prognosis and improve risk stratification in mCSPC. The objective of this study was to build and validate a multivariable prognostic model to predict overall survival (OS) in mCSPC. METHODS: We used data from LATITUDE, a phase III randomized controlled trial in which men with de novo mCSPC were randomly allocated to either ADT plus abiraterone or ADT with placebo. Patients with non-missing data (n = 1,058) were randomly split in a 70:30 ratio to training (n = 743) and testing (n = 315) sets. Elastic net regression was used for variable selection. A multivariable Cox regression model for OS was then fitted using the selected variables. The predictive accuracy of the model was assessed on the testing set using the time-dependent area under curve (tAUC) with bootstrapped confidence intervals [CI] primarily for OS and secondarily for radiographic progression-free survival (rPFS). RESULTS: The 11 prognostic variables in the final model were performance status, number of skeletal metastases, Gleason score, presence of liver metastasis, worst pain score, albumin, lactate dehydrogenase, prostate-specific antigen, hemoglobin, and treatment regimen. The tAUC for predicting OS at 2- and 3-years was 0.74 (95% CI, 0.67-0.80) and 0.72 (95% CI, 0.65-0.77), respectively. The tAUC for rPFS at 2- and 3-years was 0.72 (95% CI, 0.65-0.77) and 0.77 (95% CI, 0.70-0.82), respectively. CONCLUSIONS: A prognostic model for men with de novo mCSPC was developed and validated in an independent testing set. Our model had high accuracy for predicting OS and rPFS. The model includes commonly used clinical and laboratory parameters and can guide risk stratification of these patients for participation in future trials.

Real-world utilization and outcomes of docetaxel among older men with metastatic prostate cancer: a retrospective population-based cohort study in Canada.

BACKGROUND: The adoption of docetaxel for systemic treatment of metastatic prostate cancer (PCa), in both castration-sensitive (mCSPC) and castration-resistant (mCRPC) settings, is poorly understood. This study examined the real-world utilization of docetaxel in these patients and their outcomes. METHODS: A retrospective population-based study used administrative data from Ontario, Canada, to identify men aged ≥66 years who were diagnosed with de novo mCSPC or mCRPC between 2014 and 2019 and received docetaxel. The study assessed treatment tolerability and toxicity, and survival in both cohorts. Descriptive and comparative statistical analysis were conducted. RESULTS: The study identified 11.2% (399/3556) and 13.2% (203/1534) patients diagnosed with de novo mCSPC and with mCRPC who received docetaxel respectively. The median age in both cohorts was 72 years (IQR: 68-76). Overall, 43.9% (n = 175) patients with de novo mCSPC and 52.1% (n = 85) with mCRPC completed ≥6 cycles of docetaxel. Over two-fifth also needed dose adjustments in both cohorts. Hospitalization or emergency department visit for febrile neutropenia were noted in 15.8% (n = 63) of de novo mCSPC patients and similarly in 19% (n = 31) of mCRPC cohort. The median survival of PCa patients who completed ≥6 cycles of docetaxel was significantly longer relative to those who completed <4 cycles: 32.7 vs. 23.5 months (p < 0.001) for mCSPC and 20.5 vs. 10.7 (p = 0.012) for mCRPC respectively. CONCLUSIONS: In this population-based study of elderly patients with metastatic PCa, treatment with docetaxel was associated with poor tolerability and higher toxicity compared with clinical trials. Receipt of limited cycles and reduced overall dose of docetaxel were associated with inferior overall survival.