Functional Outcomes After Localized Prostate Cancer Treatment.

Importance: Adverse outcomes associated with treatments for localized prostate cancer remain unclear. Objective: To compare rates of adverse functional outcomes between specific treatments for localized prostate cancer. Design, Setting, and Participants: An observational cohort study using data from 5 US Surveillance, Epidemiology, and End Results Program registries. Participants were treated for localized prostate cancer between 2011 and 2012. At baseline, 1877 had favorable-prognosis prostate cancer (defined as cT1-cT2bN0M0, prostate-specific antigen level <20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022. Exposures: Radical prostatectomy (n = 1043), external beam radiotherapy (n = 359), brachytherapy (n = 96), or active surveillance (n = 379) for favorable-prognosis disease and radical prostatectomy (n = 362) or external beam radiotherapy with androgen deprivation therapy (n = 206) for unfavorable-prognosis disease. Main Outcomes and Measures: Outcomes were patient-reported sexual, urinary, bowel, and hormone function measured using the 26-item Expanded Prostate Cancer Index Composite (range, 0-100; 100 = best). Associations of specific therapies with each outcome were estimated and compared at 10 years after treatment, adjusting for corresponding baseline scores, and patient and tumor characteristics. Minimum clinically important differences were 10 to 12 for sexual function, 6 to 9 for urinary incontinence, 5 to 7 for urinary irritation, and 4 to 6 for bowel and hormone function. Results: A total of 2445 patients with localized prostate cancer (median age, 64 years; 14% Black, 8% Hispanic) were included and followed up for a median of 9.5 years. Among 1877 patients with favorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, -12.1 [95% CI, -16.2 to -8.0]), but not worse sexual function (adjusted mean difference, -7.2 [95% CI, -12.3 to -2.0]), compared with active surveillance. Among 568 patients with unfavorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, -26.6 [95% CI, -35.0 to -18.2]), but not worse sexual function (adjusted mean difference, -1.4 [95% CI, -11.1 to 8.3), compared with external beam radiotherapy with androgen deprivation therapy. Among patients with unfavorable prognosis, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel (adjusted mean difference, -4.9 [95% CI, -9.2 to -0.7]) and hormone (adjusted mean difference, -4.9 [95% CI, -9.5 to -0.3]) function compared with radical prostatectomy. Conclusions and Relevance: Among patients treated for localized prostate cancer, radical prostatectomy was associated with worse urinary incontinence but not worse sexual function at 10-year follow-up compared with radiotherapy or surveillance among people with more favorable prognosis and compared with radiotherapy for those with unfavorable prognosis. Among men with unfavorable-prognosis disease, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel and hormone function at 10-year follow-up compared with radical prostatectomy.

Definitive local therapy for T4 prostate cancer associated with improved local control and survival.

OBJECTIVES: To evaluate patients with clinical (c)T4 prostate cancer (PCa), which represent both a heterogenous and understudied population, who often present with locally advanced disease and obstructive symptoms causing significant morbidity and mortality. We analysed whether receiving definitive local therapy influenced symptomatic and oncological outcomes. METHODS: Retrospective analysis of 154 patients with cT4 PCa treated at a single institution in 1996-2020. Systemic therapy with or without local treatment (surgery, radiotherapy [RT], or both). Uni- and multivariate analyses of associations between clinicopathological features (including obstructive symptoms) and receipt of local therapy on overall survival (OS) and disease control were done with Cox regression. RESULTS: The median follow-up time was 5.9 years. Most patients had adenocarcinoma (88%), Gleason score 9-10 (77%), and median baseline prostate-specific antigen (PSA) of 20 ng/mL; most (54%) had metastatic cT4N0-1M1 disease; 24% regionally advanced cT4N1M0, and 22% localised cT4N0M0. Local therapies were RT (n = 44), surgery (n = 28), or both (n = nine). Local therapy was associated with improved OS (hazard ratio [HR] 0.3, P < 0.001), longer freedom from local recurrence (HR 0.39, P = 0.002), less local progression (HR 0.41, P = 0.02), fewer obstructive symptoms with progression (HR 0.31, P = 0.01), and less death from local disease (HR 0.25, P = 0.002). On multivariate, local therapy was associated with improved survival (HR 0.58, P = 0.02), and metastatic disease (HR 2.93, P < 0.001) or high-risk pathology (HR 2.05, P = 0.03) was associated with worse survival. CONCLUSION: Definitive local therapy for cT4 PCa was associated with improved symptomatic outcomes and survival even among men with metastatic disease. Pending prospective evaluation, these findings support definitive treatment with local therapy for cT4 disease in select cases.

Prediction of breast cancer-related lymphedema by dermal backflow detected with near-infrared fluorescence lymphatic imaging.

PURPOSE: Mild breast cancer-related lymphedema (BCRL) is clinically diagnosed as a 5%-10% increase in arm volume, typically measured no earlier than 3-6 months after locoregional treatment. Early BCRL treatment is associated with better outcomes, yet amid increasing evidence that lymphedema exists in a latent form, treatment is typically delayed until arm swelling is obvious. In this study, we investigated whether near-infrared fluorescence lymphatic imaging (NIRF-LI) surveillance could characterize early onset of peripheral lymphatic dysfunction as a predictor of BCRL. METHODS: In a prospective, longitudinal cohort/observational study (NCT02949726), subjects with locally advanced breast cancer who received axillary lymph node dissection and regional nodal radiotherapy (RT) were followed serially, between 2016 and 2021, before surgery, 4-8 weeks after surgery, and 6, 12, and 18 months after RT. Arm volume was measured by perometry, and lymphatic (dys) function was assessed by NIRF-LI. RESULTS: By 18 months after RT, 30 of 42 study subjects (71%) developed mild-moderate BCRL (i.e., ≥ 5% arm swelling relative to baseline), all manifested by "dermal backflow" of lymph into lymphatic capillaries or interstitial spaces. Dermal backflow had an 83% positive predictive value and 86% negative predictive value for BCRL, with a sensitivity of 97%, specificity of 50%, accuracy of 83%, positive likelihood ratio of 1.93, negative likelihood ratio of 0.07, and odds ratio of 29.00. Dermal backflow appeared on average 8.3 months, but up to 23 months, before the onset of mild BCRL. CONCLUSION: BCRL can be predicted by dermal backflow, which often appears months before arm swelling, enabling early treatment before the onset of edema and irreversible tissue changes.

Patient-reported Outcomes After External Beam Radiotherapy With Low Dose Rate Brachytherapy Boost vs Radical Prostatectomy for Localized Prostate Cancer: Five-year Results From a Prospective Comparative Effectiveness Study.

PURPOSE: Data comparing radical prostatectomy and external beam radiation therapy with low dose rate brachytherapy boost are lacking. To better guide shared decision making regarding treatment, we compared patient reported outcomes through 5 years following radical prostatectomy or external beam radiation therapy with low dose rate brachytherapy boost for localized prostate cancer. MATERIALS AND METHODS: From 2011-2012, men aged <80 years with localized prostate adenocarcinoma were enrolled and followed longitudinally. Patient reported outcomes included the Expanded Prostate Index Composite. Regression models adjusted for baseline scores and covariates were constructed. RESULTS: The study population included 112 men treated with external beam radiation therapy with low dose rate brachytherapy boost and 1,553 treated with radical prostatectomy. Compared to radical prostatectomy, external beam radiation therapy with low dose rate brachytherapy boost was associated with clinically meaningful worse urinary irritative/obstructive (adjusted mean score difference [95% confidence interval]: 5.0 [-8.7, -1.3]; P = .008 at 5 years) and better urinary incontinence function (13.3 [7.7, 18.9]; P < .001 at 5 years) through 5 years. Urinary function bother was similar between groups (P > .4 at all timepoints). Treatment with external beam radiation therapy with low dose rate brachytherapy boost was associated with worse bowel function (-4.0 [-6.9, -1.1]; P = .006 at 5 years) through 5 years compared to radical prostatectomy. Treatment with external beam radiation therapy with low dose rate brachytherapy boost was associated with better sexual function at 1 year (12.0 [6.5, 17.5]; P < .001 at 1 year) compared to radical prostatectomy, but there was insufficient evidence to reject the supposition that no difference was seen at 3 or 5 years. CONCLUSIONS: Compared to radical prostatectomy, external beam radiation therapy with low dose rate brachytherapy boost was associated with clinically meaningful worse urinary irritative/obstructive and bowel functions but better urinary incontinence function through 5 years after treatment. These patient-reported functional outcomes may clarify treatment expectations and help inform treatment choices for localized prostate cancer.

Association between Treatment for Localized Prostate Cancer and Mental Health Outcomes.

PURPOSE: We aimed to compare patient-reported mental health outcomes for men undergoing treatment for localized prostate cancer longitudinally over 5 years. MATERIALS AND METHODS: We conducted a prospective population-based analysis using the Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study. Patient-reported depressive symptoms (Centers for Epidemiologic Studies Depression [CES-D]) and domains of the Medical Outcomes Study 36-item Short Form survey evaluating emotional well-being and energy/fatigue were assessed through 5 years after treatment with surgery, radiotherapy (with or without androgen deprivation therapy) and active surveillance. Regression models were adjusted for outcome-specific baseline function, demographic and clinicopathological characteristics, and treatment approach. RESULTS: A total of 2,742 men (median [quartiles] age 64 [59-70]) met inclusion criteria. Baseline depressive symptoms, as measured by the CES-D, were low (median 4, quartiles 1-8) without differences between groups. We found no effect of treatment modality on depressive symptoms (p=0.78), though older age, poorer health, being unmarried and baseline CES-D score were associated with declines in mental health. There was no clinically meaningful association between treatment modality and scores for either emotional well-being (p=0.81) or energy/fatigue (p=0.054). CONCLUSIONS: This prospective, population-based cohort study of men with localized prostate cancer showed no clinically important differences in mental health outcomes including depressive symptoms, emotional well-being, and energy/fatigue according to the treatment received (surgery, radiotherapy, or surveillance). However, we identified a number of characteristics associated with worse mental health outcomes including: older age, poorer health, being unmarried, and baseline CES-D score which may allow for early identification of patients most at risk of these outcomes following treatment.

Knowledge-based planning for the radiation therapy treatment plan quality assurance for patients with head and neck cancer.

This study aimed to investigate the feasibility of using a knowledge-based planning technique to detect poor quality VMAT plans for patients with head and neck cancer. We created two dose-volume histogram (DVH) prediction models using a commercial knowledge-based planning system (RapidPlan, Varian Medical Systems, Palo Alto, CA) from plans generated by manual planning (MP) and automated planning (AP) approaches. DVHs were predicted for evaluation cohort 1 (EC1) of 25 patients and compared with achieved DVHs of MP and AP plans to evaluate prediction accuracy. Additionally, we predicted DVHs for evaluation cohort 2 (EC2) of 25 patients for which we intentionally generated plans with suboptimal normal tissue sparing while satisfying dose-volume limits of standard practice. Three radiation oncologists reviewed these plans without seeing the DVH predictions. We found that predicted DVH ranges (upper-lower predictions) were consistently wider for the MP model than for the AP model for all normal structures. The average ranges of mean dose predictions among all structures was 9.7 Gy (MP model) and 3.4 Gy (AP model) for EC1 patients. RapidPlan models identified 7 MP plans as outliers according to mean dose or D1% for at least one structure, while none of AP plans were flagged. For EC2 patients, 22 suboptimal plans were identified by prediction. While re-generated AP plans validated that these suboptimal plans could be improved, 40 out of 45 structures with predicted poor sparing were also identified by oncologist reviews as requiring additional planning to improve sparing in the clinical setting. Our study shows that knowledge-based DVH prediction models can be sufficiently accurate for plan quality assurance purposes. A prediction model built by a small cohort automatically-generated plans was effective in detecting suboptimal plans. Such tools have potential to assist the plan quality assurance workflow for individual patients in the clinic.

Five-year outcomes from a prospective comparative effectiveness study evaluating external-beam radiotherapy with or without low-dose-rate brachytherapy boost for localized prostate cancer.

BACKGROUND: To inform patients who are in the process of selecting prostate cancer treatment, the authors compared disease-specific function after external-beam radiotherapy (EBRT) alone versus EBRT plus a low-dose-rate (LDR) brachytherapy boost (EBRT-LDR). METHODS: For this prospective study, men who had localized prostate cancer in 2011 and 2012 were enrolled. Assessments at baseline, 0.5, 1, 3, and 5 years included the patient-reported Expanded Prostate Index Composite, the 36-item Medical Outcomes Study Short-Form Health Survey, and treatment-related regret. Regression models were adjusted for baseline function and for patient and treatment characteristics. The minimum clinically important difference in scores on the Expanded Prostate Index Composite 26-item instrument was from 5 to 7 for urinary irritation and from 4 to 6 for bowel function. RESULTS: Six-hundred ninety-five men met inclusion criteria and received either EBRT (n = 583) or EBRT-LDR (n = 112). Patients in the EBRT-LDR group were younger (median age, 66 years [interquartile range [IQR], 60-71 years] vs 69 years [IQR, 64-74 years]; P < .001), were less likely to receive pelvic radiotherapy (10% vs 18%; P = .040), and had higher baseline 36-item Medical Outcomes Study Short-Form Health Survey physical function scores (median score, 95 [IQR, 86-100] vs 90 [IQR, 70-100]; P < .001). Over a 3-year period, compared with EBRT, EBRT-LDR was associated with worse urinary irritative scores (adjusted mean difference at 3 years, -5.4; 95% CI, -9.3, -1.6) and bowel function scores (-4.1; 95% CI, -7.6, -0.5). The differences were no longer clinically meaningful at 5 years (difference in urinary irritative scores: -4.5; 95% CI, -8.4, -0.5; difference in bowel function scores: -2.1; 95% CI, -5.7, -1.4). However, men who received EBRT-LDR were more likely to report moderate or big problems with urinary function bother (adjusted odds ratio, 3.5; 95% CI, 1.5-8.2) and frequent urination (adjusted odds ratio, 2.6; 95% CI, 1.2-5.6) through 5 years. There were no differences in survival or treatment-related regret between treatment groups. CONCLUSIONS: Compared with EBRT alone, EBRT-LDR was associated with clinically meaningful worse urinary irritative and bowel function over 3 years after treatment and more urinary bother at 5 years. LAY SUMMARY: In men with prostate cancer who received external-beam radiation therapy (EBRT) with or without a brachytherapy boost (EBRT-LDR), EBRT-LDR was associated with clinically worse urinary irritation and bowel function through 3 years but resolved after 5 years. Men who received EBRT-LDR continued to report moderate-to-big problems with urinary function bother and frequent urination through 5 years. There was no difference in treatment-related regret or survival between patients who received EBRT and those who received EBRT-LDR. These intermediate-term estimates of function may facilitate counseling for men who are selecting treatment.

Patient-Reported Financial Toxicity Associated with Contemporary Treatment for Localized Prostate Cancer.

PURPOSE: Contemporary treatment modalities for localized prostate cancer provide comparable overall and cancer-specific survival. However, the degree of financial burden imposed by treatment, the factors contributing to that burden, and how different treatments compare with regard to financial toxicity remain poorly understood. MATERIALS AND METHODS: The Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study enrolled men with localized prostate cancer from 2011 to 2012. Questionnaires were collected at 6, 12, 36, and 60 months after enrollment. Differences in patient-reported financial burden were compared between active surveillance, radical prostatectomy, and external beam radiotherapy using multivariable logistic regression. RESULTS: Among 2,121 patients meeting inclusion criteria, 15% reported large or very large burden of treatment costs within 6 months, declining to 3% by year 5. When controlling for age, education, income and other covariates, external beam radiotherapy was associated with greater financial burden than active surveillance and radical prostatectomy at 1 year (OR 2.2, 95% CI 1.2-4.1 and OR 1.5, 95% CI 1.0-2.3, respectively) and 3 years (OR 3.1 95% CI 1.1-8.8 and OR 2.1, 95% CI 1.2-3.7, respectively). Radical prostatectomy and active surveillance had similar rates of financial burden at all time points. Age, race, education, and D'Amico risk group were associated with financial burden. CONCLUSIONS: External beam radiotherapy was associated with the highest financial burden, even when controlling for age, education and income. Prospective studies that directly measure out-of-pocket and indirect costs and account more thoroughly for baseline socioeconomic differences are warranted in order to identify those most at risk.

Contemporary prostate cancer treatment choices in multidisciplinary clinics referenced to national trends.

BACKGROUND: The purpose of this study was to assess treatment choices among men with prostate cancer who presented at The University of Texas MD Anderson Cancer Center multidisciplinary (MultiD) clinic compared with nationwide trends. METHODS: In total, 4451 men with prostate cancer who presented at the MultiD clinic from 2004 to 2016 were analyzed. To assess nationwide trends, the authors analyzed 392,710 men with prostate cancer who were diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. The primary endpoint was treatment choice as a function of pretreatment demographics. RESULTS: Univariate analyses revealed similar treatment trends in the MultiD and SEER cohorts. The use of procedural forms of definitive therapy decreased with age, including brachytherapy and prostatectomy (all P < .05). Later year of diagnosis/clinic visit was associated with decreased use of definitive treatments, whereas higher risk grouping was associated with increased use (all P < .001). Patients with low-risk disease treated at the MultiD clinic were more likely to receive nondefinitive therapy than patients in SEER, whereas the opposite trend was observed for patients with high-risk disease, with a substantial portion of high-risk patients in SEER not receiving definitive therapy. In the MultiD clinic, African American men with intermediate-risk and high-risk disease were more likely to receive definitive therapy than white men, but for SEER the opposite was true. CONCLUSIONS: Presentation at a MultiD clinic facilitates the appropriate disposition of patients with low-risk disease to nondefinitive strategies of patients with high-risk disease to definitive treatment, and it may obviate the influence of race.

Assessing the Quality of Surgical Care for Clinically Localized Prostate Cancer: Results from the CEASAR Study.

PURPOSE: Prior studies suggest that nationally endorsed quality measures for prostate cancer care are not linked closely with outcomes. Using a prospective, population based cohort we measured clinically relevant variation in structure, process and outcome measures in men undergoing radical prostatectomy. MATERIALS AND METHODS: The Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) Study enrolled men with clinically localized prostate cancer diagnosed from 2011 to 2012 with 1,069 meeting the final inclusion criteria. Quality of life was assessed using the Expanded Prostate Index Composite (EPIC-26) and clinical data by chart review. Six quality measures were assessed, including pelvic lymphadenectomy with risk of lymph node involvement 2% or greater, appropriate nerve sparing, negative surgical margins, urinary and sexual function, treatment by high volume surgeon, and 30-day and 1-year complications. Receipt of high quality care was compared across categories of race, age, surgeon volume and surgical approach via multivariable analysis. RESULTS: There were no significant differences in quality across race, age or surgeon volume strata, except for worse urinary incontinence in Black men. However, robotic surgery patients experienced fewer complications (3% vs 9.3% short-term and 11% vs 16% long-term), were more likely to be treated by a high volume surgeon (47% vs 25%) and demonstrated better sexual function. CONCLUSIONS: In this cohort we did not identify meaningful variation in quality of care across racial groups, age groups and surgeon volume strata, suggesting that men are receiving comparable quality of care across these strata. However, we did find variation between open and robotic surgery with fewer complications, improved sexual function and increased use of high volume surgeons in the robotic group, possibly reflecting differences in quality between approaches, differences in practice patterns and/or biases in patient selection.

Patient-Reported Outcomes Through 5 Years for Active Surveillance, Surgery, Brachytherapy, or External Beam Radiation With or Without Androgen Deprivation Therapy for Localized Prostate Cancer.

Importance: Understanding adverse effects of contemporary treatment approaches for men with favorable-risk and unfavorable-risk localized prostate cancer could inform treatment selection. Objective: To compare functional outcomes associated with prostate cancer treatments over 5 years after treatment. Design, Setting, and Participants: Prospective, population-based cohort study of 1386 men with favorable-risk (clinical stage cT1 to cT2bN0M0, prostate-specific antigen [PSA] ≤20 ng/mL, and Grade Group 1-2) prostate cancer and 619 men with unfavorable-risk (clinical stage cT2cN0M0, PSA of 20-50 ng/mL, or Grade Group 3-5) prostate cancer diagnosed in 2011 through 2012, accrued from 5 Surveillance, Epidemiology and End Results Program sites and a US prostate cancer registry, with surveys through September 2017. Exposures: Treatment with active surveillance (n = 363), nerve-sparing prostatectomy (n = 675), external beam radiation therapy (EBRT; n = 261), or low-dose-rate brachytherapy (n = 87) for men with favorable-risk disease and treatment with prostatectomy (n = 402) or EBRT with androgen deprivation therapy (n = 217) for men with unfavorable-risk disease. Main Outcomes and Measures: Patient-reported function, based on the 26-item Expanded Prostate Index Composite (range, 0-100), 5 years after treatment. Regression models were adjusted for baseline function and patient and tumor characteristics. Minimum clinically important difference was 10 to 12 for sexual function, 6 to 9 for urinary incontinence, 5 to 7 for urinary irritative symptoms, and 4 to 6 for bowel and hormonal function. Results: A total of 2005 men met inclusion criteria and completed the baseline and at least 1 postbaseline survey (median [interquartile range] age, 64 [59-70] years; 1529 of 1993 participants [77%] were non-Hispanic white). For men with favorable-risk prostate cancer, nerve-sparing prostatectomy was associated with worse urinary incontinence at 5 years (adjusted mean difference, -10.9 [95% CI, -14.2 to -7.6]) and sexual function at 3 years (adjusted mean difference, -15.2 [95% CI, -18.8 to -11.5]) compared with active surveillance. Low-dose-rate brachytherapy was associated with worse urinary irritative (adjusted mean difference, -7.0 [95% CI, -10.1 to -3.9]), sexual (adjusted mean difference, -10.1 [95% CI, -14.6 to -5.7]), and bowel (adjusted mean difference, -5.0 [95% CI, -7.6 to -2.4]) function at 1 year compared with active surveillance. EBRT was associated with urinary, sexual, and bowel function changes not clinically different from active surveillance at any time point through 5 years. For men with unfavorable-risk disease, EBRT with ADT was associated with lower hormonal function at 6 months (adjusted mean difference, -5.3 [95% CI, -8.2 to -2.4]) and bowel function at 1 year (adjusted mean difference, -4.1 [95% CI, -6.3 to -1.9]), but better sexual function at 5 years (adjusted mean difference, 12.5 [95% CI, 6.2-18.7]) and incontinence at each time point through 5 years (adjusted mean difference, 23.2 [95% CI, 17.7-28.7]), than prostatectomy. Conclusions and Relevance: In this cohort of men with localized prostate cancer, most functional differences associated with contemporary management options attenuated by 5 years. However, men undergoing prostatectomy reported clinically meaningful worse incontinence through 5 years compared with all other options, and men undergoing prostatectomy for unfavorable-risk disease reported worse sexual function at 5 years compared with men who underwent EBRT with ADT.

Hypofractionated Radiation Therapy for Localized Prostate Cancer: Executive Summary of an ASTRO, ASCO and AUA Evidence-Based Guideline.

PURPOSE: The aim of this guideline is to present recommendations regarding moderately hypofractionated (240-340 cGy per fraction) and ultrahypofractionated (500 cGy or more per fraction) radiation therapy for localized prostate cancer. METHODS AND MATERIALS: The American Society for Radiation Oncology convened a task force to address 8 key questions on appropriate indications and dose-fractionation for moderately and ultrahypofractionated radiation therapy, as well as technical issues, including normal tissue dose constraints, treatment volumes, and use of image guided and intensity modulated radiation therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and Society-approved tools for grading evidence quality and recommendation strength. RESULTS: Based on high-quality evidence, strong consensus was reached for offering moderate hypofractionation across risk groups to patients choosing external beam radiation therapy. The task force conditionally recommends ultrahypofractionated radiation may be offered for low- and intermediate-risk prostate cancer but strongly encourages treatment of intermediate-risk patients on a clinical trial or multi-institutional registry. For high-risk patients, the task force conditionally recommends against routine use of ultrahypofractionated external beam radiation therapy. With any hypofractionated approach, the task force strongly recommends image guided radiation therapy and avoidance of nonmodulated 3-dimensional conformal techniques. CONCLUSIONS: Hypofractionated radiation therapy provides important potential advantages in cost and convenience for patients, and these recommendations are intended to provide guidance on moderate hypofractionation and ultrahypofractionation for localized prostate cancer. The limits in the current evidentiary base-especially for ultrahypofractionation-highlight the imperative to support large-scale randomized clinical trials and underscore the importance of shared decision making between clinicians and patients.

Interpretation of Domain Scores on the EPIC-How Does the Domain Score Translate into Functional Outcomes?

PURPOSE: The EPIC-26 (Expanded Prostate Cancer Index Composite-Short Form) is a validated questionnaire for measuring health related quality of life. However, the relationship between domain scores and functional outcomes remains unclear, leading to potential confusion about expectations after treatment. For instance, does a sexual function domain score of 80 mean that a patient can achieve erection sufficient for intercourse? Consequently we sought to determine the relationship between the domain score and the response to obtaining the best possible outcome for each question. MATERIALS AND METHODS: Using data from the CEASAR (Comparative Effectiveness Analysis of Surgery and Radiation) study, a multicenter, prospective study of men diagnosed with localized prostate cancer, we analyzed 11,464 EPIC-26 questionnaires from a total of 2,563 men at baseline through 60 months of followup who were treated with robotic prostatectomy, radiotherapy or active surveillance. We dichotomized every item into its best possible outcome and assessed the percent of men at each domain score who achieved the best result. RESULTS: For every EPIC-26 item the frequency of the best possible outcome was reported by domain score category. For example, a score of 80 to 100 on sexual function corresponded to 97% of men reporting erections sufficient for intercourse while at a score of 40 to 60 only 28% reported adequate erections. Also, at a score of 80 to 100 on the urinary incontinence domain 93% of men reported rarely or never leaking vs 6% at a score of 61 to 80. CONCLUSIONS: Our findings indicate a novel way to interpret EPIC-26 domain scores, demonstrating large variations in the percent of respondents reporting the best possible outcomes over narrow domain score differences. This information may be valuable when counseling men on treatment options.

Neoadjuvant Radiotherapy to Facilitate Immediate Breast Reconstruction: A Systematic Review and Current Clinical Trials.

BACKGROUND: Postmastectomy radiotherapy currently is used for locally advanced breast cancers that carry a high risk of locoregional failure. However, radiotherapy can have deleterious effects on immediate breast reconstruction (IBR). Neoadjuvant radiotherapy (NART) to facilitate postmastectomy IBR is an emerging new therapeutic sequence. A systematic review was undertaken to evaluate the current evidence on the feasibility and safety of this sequence. METHODS: A comprehensive search of MEDLINE, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov from inception to 2018 was conducted, resulting in 592 records. The review included 18 retrospective and prospective studies of NART and IBR. RESULTS: The majority of the studies used whole-breast radiotherapy with 50 Gy, conventionally fractionated, and waited 6-8 weeks before surgery. The IBR methods were varied, with both implant and autologous reconstructions. No intraoperative complications occurred, and the postoperative complication rates ranged from 3 to 36%. The partial and total flap loss rates were very low. Studies reporting cosmetic outcomes rated the majority of cases as good or excellent. The pathologic complete response rates ranged from 17 to 55%, and the locoregional recurrence rates were low (≤ 10%), with a short follow-up period. The current MD Anderson Cancer Center prospective clinical trial is described. CONCLUSIONS: The initial results of NART and IBR demonstrate the safety of this treatment both technically and oncologically. Longer follow-up evaluation of these studies and larger prospective controlled clinical trials are needed to establish this new therapeutic sequence as a standard of care.

Radical prostatectomy or radiotherapy for high- and very high-risk prostate cancer: a multidisciplinary prostate cancer clinic experience of patients eligible for either treatment.

OBJECTIVE: To compare radical prostatectomy (RP) vs radiotherapy (RT) with androgen-deprivation therapy (ADT) in the setting of patients with high-risk and very high-risk (VHR) prostate cancer who were deemed eligible for either therapy and made a treatment choice after consultation in a multidisciplinary prostate cancer clinic (MDPCC), and to compare the MDPCC patients' outcomes to a matched Surveillance, Epidemiology and End Results (SEER) cohort. PATIENTS AND METHODS: Prospectively collected, retrospective study comparing patients who underwent RP (231 patients) vs RT+ADT (73) from 2004 to 2013. Biochemical recurrence (BCR), local recurrence, distant metastasis failure, and overall survival (OS) were calculated for each treatment group overall and according to National Comprehensive Cancer Network risk strata. A propensity score matched comparison with a SEER cohort was performed for OS. RESULTS: There was no difference in local recurrence (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.0-7.9; P = 0.06), distant metastasis failure (HR 2.5, 95% CI 0.8-7.8; P = 0.1) and OS (HR 1.35, 95% CI 0.4-4.8; P = 0.6) between patients undergoing RP vs RT+ADT. Patients treated via the MDPCC survived on average 16.9 months (95% CI 13.1-20.8) longer than those in the matched SEER cohort. CONCLUSIONS: Long-term outcomes appear similar amongst patients with high-risk and VHR prostate cancer deemed eligible for either RP or RT, and treated after consultation in a MDPCC. Outcomes of the MDPCC patients were superior to those of the matched SEER cohort.

Travel distance and stereotactic body radiotherapy for localized prostate cancer.

BACKGROUND: Definitive stereotactic body radiotherapy (SBRT) represents an emerging and debated treatment option for patients with prostate cancer, with potential economic savings and reports of short-term efficacy since 2006. The current study sought to define national trends in definitive prostate SBRT use and determine whether patterns vary by travel distance for treatment. METHODS: The National Cancer Data Base identified 181,544 men with localized prostate cancer who were treated with definitive external beam radiotherapy from 2004 through 2012. Joinpoint regression analyzed definitive prostate SBRT trends over time, whereas multivariable logistic regression defined the odds for its receipt by travel distance for treatment. RESULTS: Definitive prostate SBRT use increased from 1.8% in 2004 to 5.9% in 2012 (P for trend <.0001), with a joinpoint for increased use noted in 2006 (P<.0001). Higher SBRT use was found to be associated with longer travel distance for treatment, younger age, white race, more affluent zip code of residence, academic treatment center, favorable disease characteristics, and fewer comorbidities (all P<.0001). Compared with travel distances <25 miles for treatment, travel distances of 25 to 50 miles and >50 miles were associated with increasing adjusted odds of receipt of definitive prostate SBRT (1.63 [95% confidence interval, 1.51-1.76] and 2.35 [95% confidence interval, 2.14-2.57], respectively; both P < .0001). CONCLUSIONS: Definitive prostate SBRT use increased more than 3-fold since 2004, with a significant increase in use coinciding with early reports of short-term efficacy. Long-distance travel for treatment was associated with greater than twice the odds of receipt of definitive prostate SBRT compared with short-distance travel, suggesting that treatment decisions with unknown long-term clinical implications may be strongly driven by sociodemographic factors. Cancer 2018;124:1141-9. © 2017 American Cancer Society.

Racial variation in receipt of quality radiation therapy for prostate cancer.

PURPOSE: Racial disparities are apparent in the management and outcomes for prostate cancer; however, disparities in compliance to quality measures for radiation therapy for prostate cancer have not been previously studied. Therefore, the goal of the study was to characterize disparities in the compliance rates with quality measures. METHODS: The comparative effectiveness analysis of radiation therapy and surgery study is a population-based, prospective cohort study that enrolled 3708 men with clinically localized prostate cancer from 2011 to 2012. Compliance with 5 radiation-specific quality measures endorsed by national consortia as of 2011 was assessed, and compliance was compared by race using logistic regression. RESULTS: Overall, 604 men received definitive external beam radiation therapy (EBRT) of which 20% were self-reported black, 74% non-Hispanic white, and 6% Hispanic. Less than two-thirds of black and Hispanic men received EBRT that was compliant with all available quality measures (p = 0.012). Compared to white men, black men were less likely to receive dose-escalated EBRT (95% vs. 87%, p = 0.011) and less likely to avoid unnecessary pelvic radiation for low-risk disease (99% vs. 20%, p < 0.001). Compared to white men, Hispanic men were less likely to undergo image guidance (87% vs. 71%, p = 0.04). Black and Hispanic men were more likely to receive EBRT from low-quality providers than white men. CONCLUSIONS: Addressing disparities in access to providers that meet quality guidelines, and improving adherence to evidence-based processes of care may decrease racial/ethnic disparities in prostate cancer outcomes.

The Effect of Nerve Sparing Status on Sexual and Urinary Function: 3-Year Results from the CEASAR Study.

PURPOSE: Nerve sparing contributes to the recovery of sexual and urinary function after radical prostatectomy but it may be ineffective in some patients or carry the risk of a positive surgical margin. We evaluated sexual and urinary function outcomes according to the degree of nerve sparing in patients with prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: The CEASAR (Comparative Effectiveness Analysis of Surgery and Radiation) study is a prospective, population based, observational study of men diagnosed with localized prostate cancer in 2011 to 2012. Patient reported sexual and urinary functions were measured using the 26-item Expanded Prostate Index Composite at baseline within 6 months after diagnosis, and 6, 12 and 36 months after enrollment. Study inclusion criteria included radical prostatectomy as primary treatment, documentation of nerve sparing status and absent androgen deprivation therapy. Nerve sparing status was defined as none, unilateral or bilateral according to the operative report. RESULTS: The final analytical cohort included 991 men. The 11 men treated with unilateral nerve sparing and the 75 treated with a nonnerve sparing procedure were grouped together. In the multivariable model there was a significant difference in the sexual function score 3 years after radical prostatectomy in the bilateral nerve sparing group compared with the unilateral and nonnerve sparing group (6.1 points, 95% CI 2.0-10.3, p = 0.004). This was more pronounced in men with high baseline sexual function (8.23 points, 95% CI 1.6-14.8, p = 0.014) but not in those with low baseline function (4.0 points, 95% CI -0.6-8.7, p = 0.090). Similar effects were demonstrated on urinary incontinence scores. CONCLUSIONS: Bilateral nerve sparing resulted in better sexual and urinary function outcomes than unilateral or nonnerve sparing but the difference was not significant in men with low baseline sexual function.

Quality of life after brachytherapy or bilateral nerve-sparing robot-assisted radical prostatectomy for prostate cancer: a prospective cohort.

OBJECTIVE: To provide comparative data on quality of life (QoL) after prostate cancer treatment to help patients make an informed decision regarding their choice of treatment. METHODS: Patients with pathologically proven, non-metastatic, T1-T3bN0 prostate cancer were included in this prospective non-randomized study if they were to receive treatment with curative intent. Sample size was at least 181 patients per cohort/treatment type. QoL was recorded at baseline and at each follow-up using the Expanded Prostate Cancer Index Composite (EPIC) instrument. The minimal clinically important difference was defined as half of the standard deviation of the baseline score for each domain. A mixed effects model was used to compare the different treatments. Data are presented on the brachytherapy and the bilateral nerve-sparing robot-assisted radical prostatectomy (RARP) cohorts. Hormonotherapy was not allowed. RESULTS: Between November 2007 and January 2013, 181 patients who received brachytherapy and 210 patients who underwent RARP were included. Of the patients who underwent RARP, 178 had bilateral nerve-sparing and were included in the present analysis. Response rate to EPIC questionnaires were higher in the brachytherapy than in the RARP arm: 82% vs 57% at 2 years after treatment and 55% vs 45% at 4 years after treatment. In the mixed effects model, patients in the RARP arm had better QoL with regard to urinary irritation/obstruction or bother and bowel function, and lower QoL regarding sexual function and urinary incontinence. Results were confirmed in a propensity score-matched model. Patient satisfaction was significantly higher in the brachytherapy group at 1, 2 and 3 years after treatment. CONCLUSION: This prospective non-randomized study shows long-term differences in QoL domains after bilateral nerve-sparing RARP and brachytherapy. Differences in patient satisfaction should be further explored. These results could be used to counsel patients in the decision-making process.

Discerning the survival advantage among patients with prostate cancer who undergo radical prostatectomy or radiotherapy: The limitations of cancer registry data.

BACKGROUND: The objective of this study was to compare the overall survival of patients who undergo radical prostatectomy or radiotherapy versus noncancer controls to discern whether there is a survival advantage according to prostate cancer treatment and the impact of selection bias on these results. METHODS: A matched cohort study was performed using the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database. In total, 34,473 patients ages 66 to 75 years were identified who were without significant comorbidity, were diagnosed with localized prostate cancer, and received treatment treated with surgery or radiotherapy between 2004 and 2011. These patients were matched to a noncancer control cohort. The rates of all-cause mortality that occurred within the study period were compared. Cox proportional hazards regression analysis was used to identify determinants associated with overall survival. RESULTS: Of 34,473 patients who were included in the analysis, 21,740 (63%) received radiation therapy, and 12,733 (37%) underwent surgery. There was improved survival in patients who underwent surgery (hazard ratio, 0.35; 95% confidence interval, 0.32-0.38) and in those who received radiotherapy (hazard ratio, 0.72; 95% confidence interval, 0.68-0.75) compared with noncancer controls. Overall survival improved significantly in both treatment groups, with the greatest benefit observed among patients who underwent surgery (log rank P < .001). CONCLUSIONS: Population-based data indicated that patients with prostate cancer who received treatment with either surgery or radiotherapy had improved overall survival compared with a cohort of matched noncancer controls. Surgery produce longer survival compared with radiation therapy. These results suggest an inherent selection-bias because of unmeasured confounding variables. Cancer 2017;123:1617-1624. © 2017 American Cancer Society.