Why is a small sample size not enough?

BACKGROUND: Clinical studies are often limited by resources available, which results in constraints on sample size. We use simulated data to illustrate study implications when the sample size is too small. METHODS AND RESULTS: Using 2 theoretical populations each with N = 1000, we randomly sample 10 from each population and conduct a statistical comparison, to help make a conclusion about whether the 2 populations are different. This exercise is repeated for a total of 4 studies: 2 concluded that the 2 populations are statistically significantly different, while 2 showed no statistically significant difference. CONCLUSIONS: Our simulated examples demonstrate that sample sizes play important roles in clinical research. The results and conclusions, in terms of estimates of means, medians, Pearson correlations, chi-square test, and P values, are unreliable with small samples.

Bladder Cancer Survivors Who Do Not Smoke Have Better Longitudinal Health-Related Quality of Life Measures: An Assessment of the Comparative Effectiveness and Survivorship Health in Bladder Cancer (CEASE-BC) Study.

PURPOSE: Cigarette smoking is the most common risk factor for the development of bladder cancer (BC), yet there is a paucity of data characterizing the relationship between smoking status and longitudinal health-related quality of life (HRQoL) outcomes in patients with BC. We examined the association between smoking status and HRQoL among patients with BC. MATERIALS AND METHODS: Data were sourced from a prospective, longitudinal study open between 2014 and 2017, which examined HRQoL in patients aged ≥ 18 years old diagnosed with BC across North Carolina. The QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core instrument) was administered at 3, 12, and 24 months after BC diagnosis. Our primary exposure of interest was current smoking status. Linear regression using generalized estimating equations was used to analyze the relationship between smoking status and various domains of the QLQ-C30. RESULTS: A total of 154 patients enrolled in the study. Eighteen percent were classified as smoking at 3 months from diagnosis, and packs per day ranged from < 0.5 to 2. When controlling for time from diagnosis, demographic covariates, cancer stage, and treatment type, mean differences for physical function (7.4), emotional function (5.6), and fatigue measures (-8.2) were significantly better for patients with BC who did not smoke. CONCLUSIONS: Patients with BC who do not smoke have significantly better HRQoL scores in the domains of physical function, emotional function, and fatigue. These results underscore the need to treat smoking as an essential component of BC care.

Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part III: Salvage Therapy After Radiotherapy or Focal Therapy, Pelvic Nodal Recurrence and Oligometastasis, and Future Directions.

PURPOSE: The summary presented herein covers recommendations on salvage therapy for recurrent prostate cancer intended to facilitate care decisions and aid clinicians in caring for patients who have experienced a recurrence following prior treatment with curative intent. This is Part III of a three-part series focusing on evaluation and management of suspected non-metastatic recurrence after radiotherapy (RT) and focal therapy, evaluation and management of regional recurrence, management for molecular imaging metastatic recurrence, and future directions. Please refer to Part I for discussion of treatment decision-making and Part II for discussion of treatment delivery for non-metastatic biochemical recurrence (BCR) after radical prostatectomy (RP). MATERIALS AND METHODS: The systematic review that informs this Guideline was based on searches in Ovid MEDLINE (1946 to July 21, 2022), Cochrane Central Register of Controlled Trials (through August 2022), and Cochrane Database of Systematic Reviews (through August 2022). Update searches were conducted on July 26, 2023. Searches were supplemented by reviewing electronic database reference lists of relevant articles. RESULTS: In a collaborative effort between AUA, ASTRO, and SUO, the Salvage Therapy for Prostate Cancer Guideline Panel developed evidence- and consensus-based guideline statements to provide guidance for the care of patients who experience BCR after initial definitive local therapy for clinically localized disease. CONCLUSIONS: Continuous and deliberate efforts for multidisciplinary care in prostate cancer will be required to optimize and improve the oncologic and functional outcomes of patients treated with salvage therapies in the future.

Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part I: Introduction and Treatment Decision-Making at the Time of Suspected Biochemical Recurrence after Radical Prostatectomy.

PURPOSE: The summary presented herein covers recommendations on salvage therapy for recurrent prostate cancer intended to facilitate care decisions and aid clinicians in caring for patients who have experienced a recurrence following prior treatment with curative intent. This is Part I of a three-part series focusing on treatment decision-making at the time of suspected biochemical recurrence (BCR) after radical prostatectomy (RP). Please refer to Part II for discussion of treatment delivery for non-metastatic BCR after RP and Part III for discussion of evaluation and management of recurrence after radiotherapy (RT) and focal therapy, regional recurrence, and oligometastasis. MATERIALS AND METHODS: The systematic review that informs this Guideline was based on searches in Ovid MEDLINE (1946 to July 21, 2022), Cochrane Central Register of Controlled Trials (through August 2022), and Cochrane Database of Systematic Reviews (through August 2022). Update searches were conducted on July 26, 2023. Searches were supplemented by reviewing electronic database reference lists of relevant articles. RESULTS: In a collaborative effort between AUA, ASTRO, and SUO, the Salvage Therapy for Prostate Cancer Panel developed evidence- and consensus-based statements to provide guidance for the care of patients who experience BCR after initial definitive local therapy for clinically localized disease. CONCLUSIONS: Advancing work in the area of diagnostic tools (particularly imaging), biomarkers, radiation delivery, and biological manipulation with the evolving armamentarium of therapeutic agents will undoubtedly present new opportunities for patients to experience long-term control of their cancer while minimizing toxicity.

Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part II: Treatment Delivery for Non-metastatic Biochemical Recurrence After Primary Radical Prostatectomy.

PURPOSE: The summary presented herein covers recommendations on salvage therapy for recurrent prostate cancer intended to facilitate care decisions and aid clinicians in caring for patients who have experienced a recurrence following prior treatment with curative intent. This is Part II of a three-part series focusing on treatment delivery for non-metastatic biochemical recurrence (BCR) after primary radical prostatectomy (RP). Please refer to Part I for discussion of treatment decision-making and Part III for discussion of evaluation and management of recurrence after radiotherapy (RT) and focal therapy, regional recurrence, and oligometastasis. MATERIALS AND METHODS: The systematic review that informs this Guideline was based on searches in Ovid MEDLINE (1946 to July 21, 2022), Cochrane Central Register of Controlled Trials (through August 2022), and Cochrane Database of Systematic Reviews (through August 2022). Update searches were conducted on July 26, 2023. Searches were supplemented by reviewing electronic database reference lists of relevant articles. RESULTS: In a collaborative effort between AUA, ASTRO, and SUO, the Salvage Therapy for Prostate Cancer Panel developed evidence- and consensus-based guideline statements to provide guidance for the care of patients who experience BCR after initial definitive local therapy for clinically localized disease. CONCLUSIONS: Optimizing and personalizing the approach to salvage therapy remains an ongoing area of work in the field of genitourinary oncology and represents an area of research and clinical care that requires well-coordinated, multi-disciplinary efforts.

EGFR as a potent CAR T target in triple negative breast cancer brain metastases.

PURPOSE: There is currently no curative treatment for patients diagnosed with triple-negative breast cancer brain metastases (TNBC-BM). CAR T cells hold potential for curative treatment given they retain the cytolytic activity of a T cell combined with the specificity of an antibody. In this proposal we evaluated the potential of EGFR re-directed CAR T cells as a therapeutic treatment against TNBC cells in vitro and in vivo. METHODS: We leveraged a TNBC-BM tissue microarray and a large panel of TNBC cell lines and identified elevated epidermal growth factor receptor (EGFR) expression. Next, we designed a second-generation anti-EGFR CAR T construct incorporating a clinically relevant mAb806 tumor specific single-chain variable fragment (scFv) and intracellular 4-1BB costimulatory domain and CD3ζ using a lentivirus system and evaluated in vitro and in vivo anti-tumor activity. RESULTS: We demonstrate EGFR is enriched in TNBC-BM patient tissue after neurosurgical resection, with six of 13 brain metastases demonstrating both membranous and cytoplasmic EGFR. Eleven of 13 TNBC cell lines have EGFR surface expression ≥ 85% by flow cytometry. EGFR806 CAR T treated mice effectively eradicated TNBC-BM and enhanced mouse survival (log rank p < 0.004). CONCLUSION: Our results demonstrates anti-tumor activity of EGFR806 CAR T cells against TNBC cells in vitro and in vivo. Given EGFR806 CAR T cells are currently undergoing clinical trials in primary brain tumor patients without obvious toxicity, our results are immediately actionable against the TNBC-BM patient population.

A community engagement training program for basic and translational cancer researchers.

PURPOSE: There is an increasing awareness of the importance of patient engagement in cancer research, but many basic and translational researchers have never been trained to do so. To address this unmet need, a 1-year patient engagement training program for researchers was developed. METHODS: Eleven researchers and eleven paired research advocates participated. This program, designed for virtual delivery, included 3 didactic modules focused on (1) Community Outreach and Engagement principles and methods, (2) Communication skills, and (3) Team Science. This was followed by longitudinal projects to be completed by the researcher/advocate pairs, including learning about the research project, and co-authoring abstracts, manuscripts and grant proposals. Monthly group meetings allowed pairs to share their experiences. The program culminated in the pairs creating and presenting oral abstracts for the University of Kansas Cancer Center's Annual Research Symposium. RESULTS: All participants indicated that the modules had a positive impact on their ability to collaborate in research. Both researcher self-evaluations and patient advocate evaluations of their researcher partner showed an improvement in researcher communication competency. Results from the Patient Engagement in Research Scale showed that advocates were highly engaged. Within 1 year after program completion, participating pairs have completed four abstracts and 9 grant proposals. CONCLUSION: The program will be modified based on participant feedback, and can be adapted for future cohorts if an increased number of sessions per month and shortened program duration are desired. The program's virtual format allows scalability across institutions to potentially benefit large cohorts of researchers.

Use of Monitoring Tests Among Patients With Localized Prostate Cancer Managed With Observation.

PURPOSE: It is unknown whether compliance with recommended monitoring tests during observation of localized prostate cancer has changed over time. MATERIALS AND METHODS: We performed a retrospective cohort study of Medicare beneficiaries diagnosed with low- or intermediate-risk prostate cancer in 2004-2016 who were initially managed with observation for a minimum of 12 months. The primary objective was to examine rates of PSA testing, prostate biopsy, and prostate MRI. We used multivariable mixed effects Poisson regression to determine whether rates of PSA testing and prostate biopsy increased over time. In addition, we identified clinical, sociodemographic, and provider factors associated with the frequency of monitoring tests during observation. RESULTS: We identified 10,639 patients diagnosed at a median age of 73 (IQR 69-77) years. The median follow-up time was 4.3 (IQR 2.7-6.6) years after diagnosis. Among patients managed without treatment for 5 years, 98% received at ≥1 PSA test, 48.0% ≥1 additional prostate biopsy, and 31.0% ≥1 prostate MRI. Among patients managed with observation for ≥12 months, mixed effects Poisson regression revealed that rates of PSA testing and biopsy increased over time (per calendar year: RR 1.02, 95% CI: 1.02-1.03 and RR 1.10, 95% CI: 1.08-1.11, respectively). Clinical and sociodemographic factors including age, clinical risk, race/ethnicity, census tract poverty, and region were associated with rates of biopsy and PSA testing. CONCLUSIONS: Use of recommended monitoring tests including repeat prostate biopsy remains low among Medicare beneficiaries undergoing observation for low- and intermediate-risk prostate cancer.

The effect of integrating knowledge-based planning with multicriteria optimization in treatment planning for prostate SBRT.

Knowledge-based planning (KBP) and multicriteria optimization (MCO) are two powerful tools to assist treatment planners in achieving optimal target coverage and organ-at-risk (OAR) sparing. The purpose of this work is to investigate if integrating MCO with conventional KBP can further improve treatment plan quality for prostate cancer stereotactic body radiation therapy (SBRT). A two-phase study was designed to investigate the impact of MCO and KBP in prostate SBRT treatment planning. The first phase involved the creation of a KBP model based on thirty clinical SBRT plans, generated by manual optimization (KBP_M). A ten-patient validation cohort was used to compare manual, MCO, and KBP_M optimization techniques. The next phase involved replanning the original model cohort with additional tradeoff optimization via MCO to create a second model, KBP_MCO. Plans were then generated using linear integration (KBP_M+MCO), non-linear integration (KBP_MCO), and a combination of integration methods (KBP_MCO+MCO). All plans were analyzed for planning target volume (PTV) coverage, OAR constraints, and plan quality metrics. Comparisons were generated to evaluate plan and model quality. Phase 1 highlighted the necessity of KBP and MCO in treatment planning, as both optimization methods improved plan quality metrics (Conformity and Heterogeneity Indices) and reduced mean rectal dose by 2 Gy, as compared to manual planning. Integrating MCO with KBP did not further improve plan quality, as little significance was seen over KBP or MCO alone. Principal component score (PCS) fitting showed KBP_MCO improved bladder and rectum estimated and modeled dose correlation by 5% and 22%, respectively; however, model improvements did not significantly impact plan quality. KBP and MCO have shown to reduce OAR dose while maintaining desired PTV coverage in this study. Further integration of KBP and MCO did not show marked improvements in treatment plan quality while requiring increased time in model generation and optimization time.

Evaluation of the clinical impact of the differences between planned and delivered dose in prostate cancer radiotherapy based on CT-on-rails IGRT and patient-reported outcome scores.

PURPOSE: To estimate the clinical impact of differences between delivered and planned dose using dose metrics and normal tissue complication probability (NTCP) modeling. METHODS: Forty-six consecutive patients with prostate adenocarcinoma between 2010 and 2015 treated with intensity-modulated radiation therapy (IMRT) and who had undergone computed tomography on rails imaging were included. Delivered doses to bladder and rectum were estimated using a contour-based deformable image registration method. The bladder and rectum NTCP were calculated using dose-response parameters applied to planned and delivered dose distributions. Seven urinary and gastrointestinal symptoms were prospectively collected using the validated prostate cancer symptom indices patient reported outcome (PRO) at pre-treatment, weekly treatment, and post-treatment follow-up visits. Correlations between planned and delivered doses against PRO were evaluated in this study. RESULTS: Planned mean doses to bladder and rectum were 44.9 ± 13.6 Gy and 42.8 ± 7.3 Gy, while delivered doses were 46.1 ± 13.4 Gy and 41.3 ± 8.7 Gy, respectively. D10cc for rectum was 64.1 ± 7.6 Gy for planned and 60.1 ± 9.3 Gy for delivered doses. NTCP values of treatment plan were 22.3% ± 8.4% and 12.6% ± 5.9%, while those for delivered doses were 23.2% ± 8.4% and 9.9% ± 8.3% for bladder and rectum, respectively. Seven of 25 patients with follow-up data showed urinary complications (28%) and three had rectal complications (12%). Correlations of NTCP values of planned and delivered doses with PRO follow-up data were random for bladder and moderate for rectum (0.68 and 0.67, respectively). CONCLUSION: Sensitivity of bladder to clinical variations of dose accumulation indicates that an automated solution based on a DIR that considers inter-fractional organ deformation could recommend intervention. This is intended to achieve additional rectum sparing in cases that indicate higher than expected dose accumulation early during patient treatment in order to prevent acute severity of bowel symptoms.

TrueNTH Sexual Recovery Intervention for couples coping with prostate cancer: Randomized controlled trial results.

BACKGROUND: Despite significant sexual dysfunction and distress after localized prostate cancer treatment, patients typically receive only physiologic erectile dysfunction management. The authors performed a randomized controlled trial of an online intervention supporting couples' posttreatment recovery of sexual intimacy. METHODS: Patients treated with surgery, radiation, or combined radiation and androgen deprivation therapy who had partners were recruited and randomized to an online intervention or a control group. The intervention, tailored to treatment type and sexual orientation, comprised 6 modules addressing expectations for sexual and emotional sequelae of treatment, rehabilitation, and guidance toward sexual intimacy recovery. Couples, recruited from 6 sites nationally, completed validated measures at the baseline and 3 and 6 months after treatment. Primary outcome group differences were assessed with t tests for individual outcomes. RESULTS: Among 142 randomized couples, 105 patients (mostly surgery) and 87 partners completed the 6-month survey; this reflected challenges with recruitment and attrition. There were no differences between the intervention and control arms in Patient-Reported Outcomes Measurement Information System Global Satisfaction With Sex Life scores 6 months after treatment (the primary outcome). Three months after treatment, intervention patients and partners reported more engagement in penetrative and nonpenetrative sexual activities than controls. More than 73% of the intervention participants reported high or moderate satisfaction with module content; more than 85% would recommend the intervention to other couples. CONCLUSIONS: Online psychosexual support for couples can help couples to connect and experience sexual pleasure early after treatment despite patients' sexual dysfunction. Participants' high endorsement of the intervention reflects the importance of sexual health support to couples after prostate cancer treatment. LAY SUMMARY: This study tested a web-based program supporting couples' sexual recovery of sexual intimacy after prostate cancer treatment. One hundred forty-two couples were recruited and randomly assigned to the program (n = 60) or to a control group (n = 82). The program did not result in improvements in participants' satisfaction with their sex life 6 months after treatment, but couples in the intervention group engaged in sexual activity sooner after treatment than couples in the control group. Couples evaluated the program positively and would recommend it to others facing prostate cancer treatment.

Do reminder emails and past due notifications improve patient completion and institutional data submission for patient-reported outcome measures?

PURPOSE: NRG Oncology, part of the National Cancer Institute's National Clinical Trials Network, took efforts to increase patient-reported outcome measures (PROMs) completion and institutional data submission rates within clinical trials. Lack of completion diminishes power to draw conclusions and can be a waste of resources. It is hypothesized that trials with automatic email reminders and past due notifications will have PROM forms submitted more timely with higher patient completion. METHODS: Automatic emails sent to the research associate were added to selected NRG Oncology trials. Comparisons between trials with and without automatic emails were analyzed using Chi-square tests with respect to patient completion and timeliness of form submission rates. Multivariable analyses were conducted using repeated measures generalized estimating equations. If PROMs were not completed, a form providing the reason why was submitted and counted towards form submission. RESULTS: For both disease sites, form submission was significantly higher within 1 month of the form's due date for the studies with automatic emails vs. those without (prostate: 79.7% vs. 75.7%, p < 0.001; breast: 59.2% vs. 31.3%, p < 0.001). No significant differences in patient completion were observed between the breast trials. The prostate trial with automatic emails had significantly higher patient completion but this result was not confirmed in the multivariable analysis. CONCLUSIONS: Although patient completion rates were higher on trials with automatic emails, there may be confounding factors requiring future study. The automatic emails appeared to have increased the timeliness of form submission, thus supporting their continued use on NRG Oncology trials.

Mapping the Memorial Anxiety Scale for Prostate Cancer to the SF-6D.

PURPOSE: To create a crosswalk that predicts Short Form 6D (SF-6D) utilities from Memorial Anxiety Scale for Prostate Cancer (MAX-PC) scores. METHODS: The data come from prostate cancer patients enrolled in the North Carolina Prostate Cancer Comparative Effectiveness & Survivorship Study (NC ProCESS, N = 1016). Cross-sectional data from 12- to 24-month follow-up were used as estimation and validation datasets, respectively. Participants' SF-12 scores were used to generate SF-6D utilities in both datasets. Beta regression mixture models were used to evaluate SF-6D utilities as a function of MAX-PC scores, race, education, marital status, income, employment status, having health insurance, year of cancer diagnosis and clinically significant prostate cancer-related anxiety (PCRA) status in the estimation dataset. Models' predictive accuracies (using mean absolute error [MAE], root mean squared error [RMSE], Akaike information criterion [AIC] and Bayesian information criterion [BIC]) were examined in both datasets. The model with the highest prediction accuracy and the lowest prediction errors was selected as the crosswalk. RESULTS: The crosswalk had modest prediction accuracy (MAE = 0.092, RMSE = 0.114, AIC = - 2708 and BIC = - 2595.6), which are comparable to prediction accuracies of other SF-6D crosswalks in the literature. About 24% and 52% of predictions fell within ± 5% and ± 10% of observed SF-6D, respectively. The observed mean disutility associated with acquiring clinically significant PCRA is 0.168 (standard deviation = 0.179). CONCLUSION: This study provides a crosswalk that converts MAX-PC scores to SF-6D utilities for economic evaluation of clinically significant PCRA treatment options for prostate cancer survivors.

Racial differences in user experiences and perceived value of electronic symptom monitoring in a cohort of black and white bladder and prostate cancer patients.

PURPOSE: Electronic patient-reported outcomes (ePROs) are increasingly being used for symptom monitoring during routine cancer care, but have rarely been evaluated in diverse patient populations. We assessed ePRO user experiences and perceived value among Black and White cancer patients. METHODS: We recruited 30 Black and 49 White bladder and prostate cancer patients from a single institution. Participants reported symptoms using either a web-based or automated telephone interface over 3 months and completed satisfaction surveys and qualitative interviews focused on user experiences and value. Using a narrative mixed methods approach, we evaluated overall and race-specific differences in ePRO user experiences and perceived value. RESULTS: Most participants selected the web-based system, but Blacks were more likely to use the automated telephone-based system than Whites. In satisfaction surveys, Whites more commonly reported ease in understanding and reporting symptoms compared with Blacks. Blacks more often reported that the ePRO system was helpful in facilitating symptom-related discussions with clinicians. During interviews, Blacks described how the ePRO helped them recognize symptoms, while Whites found value in better understanding and tracking symptoms longitudinally. Blacks also expressed preferences for paper-based ePRO options due to perceived ease in better understanding of symptom items. CONCLUSION: Electronic patient-reported outcomes are perceived as valuable for variable reasons by Black and White cancer populations, with greater perceived value for communicating with clinicians reported among Blacks. To optimize equitable uptake of ePROs, oncology practices should offer several ePRO options (e.g., web-based, phone-based), as well as paper-based options, and consider the e-health literacy needs of patients during implementation.

Quality-adjusted survival with first-line cabozantinib or sunitinib for advanced renal cell carcinoma in the CABOSUN randomized clinical trial (Alliance).

BACKGROUND: Cabozantinib Versus Sunitinib as Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial (CABOSUN) was a randomized, open-label, phase 2 trial evaluating first-line cabozantinib versus sunitinib in patients with advanced renal cell carcinoma (aRCC). This post hoc analysis evaluated quality-adjusted survival using Quality-adjusted Time Without Symptoms of disease or Toxicity of treatment (Q-TWiST). METHODS: Survival plots for cabozantinib and sunitinib (650-day follow-up) were partitioned into 3 health states: time spent before disease progression without toxicity (TWiST; toxicity based on National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0] grade 3/4 adverse events), time spent before disease progression with toxicity (TOX; durations of adverse events based on published literature), and time after disease recurrence (relapse) or progression to death (REL). Q-TWiST was the sum of the mean time spent in each state, with each state weighted to reflect patient preferences (from 0 [worst] to 1 [best]) using utility scores. TWiST was always weighted as 1. Overall survival and time to disease progression were based on all randomized patients (157 patients); TOX was based on all randomized and treated patients (150 patients). RESULTS: Across all utility combinations tested, Q-TWiST was found to be longer with cabozantinib versus sunitinib (range of differences, +24 days to +137 days). Q-TWiST differences that were found to be statistically significant (+92 days [95% confidence interval, 5-178 days] to +137 days [95% confidence interval, 60-214 days]) were of a clinically meaningful effect size (≥80 days), and were based on utility values that included those considered relevant for patients with aRCC (REL utility weight of 0.355, TOX utility weight of 0-1, and TWiST utility weight of 1). CONCLUSIONS: In patients with aRCC, first-line cabozantinib was found to provide longer quality-adjusted survival compared with sunitinib. These findings may help to inform clinical decision making. LAY SUMMARY: Cabozantinib and sunitinib are drugs that are used to treat patients with advanced kidney cancer. Clinical trials have shown that cabozantinib offers benefits over sunitinib, giving patients more time before their cancer progresses. It is important that this additional time before disease progression does not come at the expense of patients' quality of life, which can be affected by treatment side effects and/or ongoing cancer symptoms. Both quantity and quality of life are central to optimal treatment. In the current analysis of patients with advanced kidney cancer who were initiating treatment for the first time, cabozantinib provided more quality time before cancer progression compared with sunitinib.

Evaluation of a commercial DIR platform for contour propagation in prostate cancer patients treated with IMRT/VMAT.

PURPOSE: To assess the performance and limitations of contour propagation with three commercial deformable image registration (DIR) algorithms using fractional scans of CT-on-rails (CTOR) and Cone Beam CT (CBCT) in image guided prostate therapy patients treated with IMRT/VMAT. METHODS: Twenty prostate cancer patients treated with IMRT/VMAT were selected for analysis. A total of 453 fractions across those patients were analyzed. Image data were imported into MIM (MIM Software, Inc., Cleveland, OH) and three DIR algorithms (DIR Profile, normalized intensity-based (NIB) and shadowed NIB DIR algorithms) were applied to deformably register each fraction with the planning CT. Manually drawn contours of bladder and rectum were utilized for comparison against the DIR propagated contours in each fraction. Four metrics were utilized in the evaluation of contour similarity, the Hausdorff Distance (HD), Mean Distance to Agreement (MDA), Dice Similarity Coefficient (DSC), and Jaccard indices. A subfactor analysis was performed per modality (CTOR vs. CBCT) and time (fraction). Point estimates and 95% confidence intervals were assessed via a Linear Mixed Effect model for the contour similarity metrics. RESULTS: No statistically significant differences were observed between the DIR Profile and NIB algorithms. However, statistically significant differences were observed between the shadowed NIB and NIB algorithms for some of the DIR evaluation metrics. The Hausdorff Distance calculation showed the NIB propagated contours vs. shadowed NIB propagated contours against the manual contours were 14.82 mm vs. 8.34 mm for bladder and 15.87 mm vs. 11 mm for rectum, respectively. Similarly, the Mean Distance to Agreement calculation comparing the NIB propagated contours vs. shadowed NIB propagated contours against the manual contours were 2.43 mm vs. 0.98 mm for bladder and 2.57 mm vs. 1.00 mm for rectum, respectively. The Dice Similarity Coefficients comparing the NIB propagated contours and shadowed NIB propagated contours against the manual contours were 0.844 against 0.936 for bladder and 0.772 against 0.907 for rectum, respectively. The Jaccard indices comparing the NIB propagated contours and shadowed NIB propagated contours against the manual contours were 0.749 against 0.884 for bladder and 0.637 against 0.831 for rectum, respectively. The shadowed NIB DIR, which showed the closest agreement with the manual contours performed significantly better than the DIR Profile in all the comparisons. The OAR with the greatest agreement varied substantially across patients and image guided radiation therapy (IGRT) modality. Intra-patient variability of contour metric evaluation was insignificant across all the DIR algorithms. Statistical significance at α = 0.05 was observed for manual vs. deformably propagated contours for bladder for all the metrics except Hausdorff Distance (P = 0.01 for MDA, P = 0.02 for DSC, P = 0.01 for Jaccard), whereas the corresponding values for rectum were: P = 0.03 for HD, P = 0.01 for MDA, P < 0.01 for DSC, P < 0.01 for Jaccard. The performance of the different metrics varied slightly across the fractions of each patient, which indicates that weekly contour propagation models provide a reasonable approximation of the daily contour propagation models. CONCLUSION: The high variance of Hausdorff Distance across all automated methods for bladder indicates widely variable agreement across fractions for all patients. Lower variance across all modalities, methods, and metrics were observed for rectum. The shadowed NIB propagated contours were substantially more similar to the manual contours than the DIR Profile or NIB contours for both the CTOR and CBCT imaging modalities. The relationship of each algorithm to similarity with manual contours is consistent across all observed metrics and organs. Screening of image guidance for substantial differences in bladder and rectal filling compared with the planning CT reference could aid in identifying fractions for which automated DIR would prove insufficient.

Patient-reported sexual quality of life after different types of radical prostatectomy and radiotherapy: Analysis of a population-based prospective cohort.

BACKGROUND: Although patients with prostate cancer face many treatment options, to the authors' knowledge the comparative effects of different surgical and radiotherapy (RT) options on sexual function are unclear. METHODS: In the current study, a population-based cohort of 835 men with newly diagnosed prostate cancer from 2011 through 2013 was recruited throughout North Carolina in collaboration with the Rapid Case Ascertainment system of the North Carolina Central Cancer Registry. All men were enrolled prior to treatment and followed prospectively using the validated Prostate Cancer Symptom Indices (PCSI) instrument. This analysis compares the sexual dysfunction scores of the PCSI among patients who received external-beam RT (EBRT), EBRT with androgen deprivation therapy (ADT), brachytherapy, nerve-sparing radical prostatectomy (RP), and non-nerve-sparing RP. Propensity scores were used to balance patient characteristics across groups, and multiple imputation was used for missing data. RESULTS: EBRT and brachytherapy resulted in similar PCSI scores through 24 months. Compared with those receiving EBRT, patients treated with EBRT with ADT and RP with or without nerve sparing were found to have worse PCSI scores at all posttreatment time points. Preservation of useful sexual function at 24 months was associated with treatment type, baseline score, and age. Predicted preservation rates were 14.1% to 70.7% for EBRT, 8.4% to 52.3% for EBRT with ADT, 4.7% to 45.3% for nerve-sparing RP, and 4.8% to 34.5% for non-nerve-sparing RP. CONCLUSIONS: The findings of the current study indicate that RT alone results in the best preservation of sexual function, and brachytherapy provides similar outcomes. RT with ADT and nerve-sparing RP yielded similar outcomes, whereas patients treated with non-nerve-sparing RP experienced the worst sexual function. These results help patients to make decisions among the specific types of surgery and RT they face based on each individual's diagnosis.

Factors influencing prostate cancer treatment decisions for African American and white men.

BACKGROUND: Prostate cancer racial disparities in mortality outcomes are the largest in all of oncology, and less aggressive treatment received by African American (AA) patients versus white patients is likely a contributing factor. However, the reasons underlying the differences in treatment are unclear. METHODS: This study examined a prospective, population-based cohort of 1170 men with newly diagnosed nonmetastatic prostate cancer enrolled from 2011 to 2013 before treatment throughout North Carolina. By phone survey, each participant was asked to rate the aggressiveness of his cancer, and his response was compared to the actual diagnosis based on a medical record review. Participants were also asked to rate the importance of 10 factors for their treatment decision-making process. RESULTS: Among AA and white patients with low-risk cancer (according to National Comprehensive Cancer Network guidelines), 78% to 80% perceived their cancers to be "not very aggressive." However, among high-risk patients, 54% of AA patients considered their cancers to be "not very aggressive," whereas 24% of white patients did (P < .001). Although both AA and white patients indicated that a cure was a very important decision-making factor, AAs were significantly more likely to consider cost, treatment time, and recovery time as very important. In a multivariable analysis, perceived cancer aggressiveness and cure as the most important factor were significantly associated with receiving any aggressive treatment and were associated with surgery (vs radiation). After adjustments for these factors and sociodemographic factors, race was not significantly associated with the treatment received. CONCLUSIONS: Racial differences in perceived cancer aggressiveness and factors important in treatment decision making provide novel insights into reasons for the known racial disparities in prostate cancer as well as potential targets for interventions to reduce these disparities.

Prevalence and predictors of probable depression in prostate cancer survivors.

BACKGROUND: The early diagnosis and treatment of depression are cancer care priorities. These priorities are critical for prostate cancer survivors because men rarely seek mental health care. However, little is known about the epidemiology of depression in this patient population. The goal of this study was to describe the prevalence and predictors of probable depression in prostate cancer survivors. METHODS: The data were from a population-based cohort of North Carolinian prostate cancer survivors who were enrolled from 2004 to 2007 in the North Carolina-Louisiana Prostate Cancer Project (n = 1031) and were prospectively followed annually from 2008 to 2011 in the Health Care Access and Prostate Cancer Treatment in North Carolina study (n = 805). Generalized estimating equations were used to evaluate an indicator of probable depression (Short Form 12 mental composite score ≤48.9; measured at enrollment and during the annual follow-up) as a function of individual-level characteristics within the longitudinal data set. RESULTS: The prevalence of probable depression fell from 38% in the year of the cancer diagnosis to 20% 6 to 7 years later. Risk factors for probable depression throughout the study were African American race, unemployment, low annual income, younger age, recency of cancer diagnosis, past depression, comorbidities, treatment decisional regret, and nonadherence to exercise recommendations. CONCLUSIONS: Depression is a major challenge for prostate cancer survivors, particularly in the first 5 years after the cancer diagnosis. To the authors' knowledge, this is the first study to demonstrate an association between treatment decisional regret and probable depression.

Symptom and function profiles of men with localized prostate cancer.

BACKGROUND: Men diagnosed with localized prostate cancer seek information on how treatment options may impact their health-related quality of life (HRQOL). The authors used latent profile analysis (LPA) to group men according to their symptom burden and functional status and to identify patient characteristics associated with each HRQOL profile. METHODS: Patients completed the Patient-Reported Outcomes Measurement Information System and the Expanded Prostate Index Composite measures 3 months after treatment initiation. Anxiety, depression, fatigue, sleep disturbance, pain, diarrhea, urinary obstruction, urinary incontinence, erectile function, and sex satisfaction were modeled jointly using LPA, and the analysis was adjusted for covariates to examine associations between patient characteristics and profiles. RESULTS: One-third of the 373 men were not non-Hispanic white (26% were black). Four LPA profiles were identified. Men who experienced the "best HRQOL" were less likely to receive treatment, to be older, and to smoke. Men in the second best profile experienced symptoms similar to men in the best HRQOL group but reported poor sexual and urinary function, because they were more likely to receive therapy. The third profile included men with increased symptom burden and poor functioning who were likely to undergo prostatectomy and to have increased comorbidity. The "worst HRQOL" group experienced the worst symptoms and the poorest functioning, and these men were more likely to be younger, to have more comorbidities, and to smoke. CONCLUSIONS: LPA revealed that men who receive the same treatment can experience very different HRQOL impact. Understanding the factors most associated with poorer HRQOL allows clinicians to focus their care on individuals most in need of symptom management and support. Cancer 2018;124:2832-2840. © 2018 American Cancer Society.