Mortality reduction and cumulative excess incidence (CEI) in the prostate-specific antigen (PSA) screening era.

The extent to which PSA screening is related to prostate cancer mortality reduction in the United States (US) is controversial. US Surveillance, Epidemiology, and End Results Program (SEER) data from 1980 to 2016 were examined to assess the relationship between prostate cancer mortality and cumulative excess incidence (CEI) in the PSA screening era and to clarify the impact of race on this relationship. CEI was considered as a surrogate for the intensity of prostate cancer screening with PSA testing and subsequent biopsy as appropriate. Data from 163,982,733 person-years diagnosed with 544,058 prostate cancers (9 registries, 9% of US population) were examined. Strong inverse linear relationships were noted between CEI and prostate cancer mortality, and 317,356 prostate cancer deaths were avoided. Eight regions of the US demonstrated prostate cancer mortality reduction of 46.0-63.7%. On a per population basis, the lives of more black men than white men were saved in three of four registries with sufficient black populations for comparison. Factor(s) independent of CEI (potential effects of treatment advances) explained 14.6% of the mortality benefit (p-value = 0.3357) while there was a significant main effect of CEI (effect = -0.0064; CI: [-0.0088, -0.0040]; p-value < 0.0001). Therefore, there is a strong relationship between CEI and prostate cancer mortality reduction that was not related to factors independent of screening utilization. Minority populations have experienced large mortality reductions in the context of PSA mass utilization.

Use of combined hormonal contraception and stroke: A case-control study of the impact of migraine type and estrogen dose on ischemic stroke risk.

OBJECTIVE: To clarify how factors such as estrogen dose and migraine history (including migraine subtype) impact ischemic stroke risks associated with combined hormonal contraceptive (CHC) use. BACKGROUND: CHC use in those with migraine with aura has been restricted due to concerns about stroke risk. METHODS: We conducted a case-control analysis of stroke risk associated with estrogen dose and migraine history among CHC users in a large tertiary care center. All women aged 18-55 who used a CHC between January 1, 2010, and December 31, 2019, were identified. Those with a stroke diagnosis were identified using ICD codes and confirmed via chart and imaging review. Details of personal and family medical history, stroke evaluation, ethinyl estradiol dosing (EE; ≥30 vs. <30 µg), and demographics were collected. From a random sample of 20,000 CHC users without stroke, a control cohort (n = 635) was identified and matched based on patient characteristics, medical and family histories, as well as stroke risk factors, to assess association between migraine diagnosis, migraine subtype, estrogen dose, and stroke. RESULTS: Of the 203,853 CHC users in our cohort, 127 had confirmed stroke (0.06%; CI 0.05%, 0.07%). In unadjusted analyses, a higher number of patients in the case cohort had a diagnosis of migraine (34/127, 26.8%) compared to controls (109/635, 17.2%; p = 0.011). Stroke risk was higher with ≥30-µg EE doses compared to those using a <30-µg dose (OR, 1.52; CI 1.02, 2.26; p = 0.040). Compared to no migraine, personal history of migraine increased the odds of stroke (OR, 2.00; CI 1.27, 3.17; p = 0.003). Compared to no migraine, stroke risk was not significantly increased in those with migraine with aura, but migraine without aura increased the risk (OR, 2.35; CI 1.32, 4.2; p = 0.004). CONCLUSIONS: Overall stroke risk in our cohort of CHC users was low. When CHCs are used in those with migraine, formulations containing ≤30 µg EE are preferred. Shared decision-making should include discussions about ischemic stroke risks in patients with migraine, even those without aura.

Outcomes following radical prostatectomy or external beam radiation for veterans with Gleason 9 and 10 prostate cancer.

BACKGROUND: The optimal upfront treatment modality for patients with nonmetastatic Gleason Score 9 and 10 prostate cancer (GS 9-10 PCa) is unknown. METHODS: We conducted a retrospective cohort study of patients in the Veterans Health Administration (VHA) with GS 9-10 PCa treated with radical prostatectomy (RP) or external beam radiation therapy with androgen deprivation therapy (EBRT+ADT) from 1/2000 to 12/2010. Outcomes included overall survival (OS), distant metastasis-free survival (DMFS), and salvage/adjuvant therapy-free survival (SAFS), as assessed by Kaplan-Meier analysis. RESULTS: We identified 1220 veterans with GS 9-10 PCa; 335 were treated with RP, and 885 were treated with EBRT+ADT. With a median follow-up of 9.9 years, propensity score-matched analyses demonstrated that RP had superior 10-year OS (70.8% [RP] vs. 61.2% [EBRT+ADT], p < 0.001), 10-year DMFS rates were similar between RP (76.7%) and EBRT+ADT (81.0%), and 10-year SAFS rates were lower for RP vs EBRT + ADT (35.2% [RP] vs. 75.2% [EBRT+ADT], p < 0.001). The receipt of salvage ADT was higher with upfront RP (51.9% vs. 26.1%, p < 0.001), despite receipt of adjuvant/salvage EBRT in 41.8% of RP patients. Among patients treated with RP, there were no differences in outcomes by race. However, higher survival rates were noted among Black patients treated with EBRT+ADT compared with White patients. CONCLUSIONS: This analysis demonstrated higher 10-year OS rates among men treated with upfront RP versus EBRT+ADT, though missing confounders and similar DMFS rates suggest the long-term cause-specific OS rates may be similar. We also highlight real-world outcomes of a diverse patient population in the VHA and improved outcomes for Black patients receiving EBRT+ADT.

Machine-Learning Models for Multicenter Prostate Cancer Treatment Plans.

Clinical factors, including T-stage, Gleason score, and baseline prostate-specific antigen, are used to stratify patients with prostate cancer (PCa) into risk groups. This provides prognostic information for a heterogeneous disease such as PCa and guides treatment selection. In this article, we hypothesize that nonclinical factors may also impact treatment selection and their adherence to treatment guidelines. A total of 552 patients with intermediate- and high-risk PCa treated with definitive radiation with or without androgen deprivation therapy (ADT) between 2010 and 2017 were identified from 34 medical centers within the Veterans Health Administration. Medical charts were manually reviewed, and details regarding each patient's clinical history and treatment were extracted. Support Vector Machine and Random forest-based classification was used to identify clinical and nonclinical predictors of adherence to the treatment guidelines from the National Comprehensive Cancer Network (NCCN). We created models for predicting both initial treatment intent and treatment alterations. Our results demonstrate that besides clinical factors, the center in which the patient was treated (nonclinical factor) played a significant role in adherence to NCCN guidelines. Furthermore, the treatment center served as an important predictor to decide on whether or not to prescribe ADT; however, it was not associated with ADT duration and weakly associated with treatment alterations. Such center-bias motivates further investigation on details of center-specific barriers to both NCCN guideline adherence and on oncological outcomes. In addition, we demonstrate that publicly available data sets, for example, that from Surveillance, Epidemiology, and End Results (SEERs), may not be well equipped to build such predictive models on treatment plans.

Outcomes of microvascular decompression for trigeminal neuralgia with purely venous compression: A systematic review and meta-analysis.

OBJECTIVE: Microvascular decompression (MVD) is a commonly-used treatment option for medically-refractory trigeminal neuralgia (TN) with arterial neurovascular compression. Pain control and recurrence rates after MVD in patients with purely venous compression are not well understood. In this systematic review and meta-analysis, we studied outcomes after MVD in patients with purely venous compression and reviewed the operative management in these patients. METHODS: We performed a systematic review and meta-analysis following the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. We searched PubMed, Google Scholar, and Scopus databases for studies reporting surgical outcomes after MVD for purely venous compression. Pain control and recurrence rates were extracted and summarized. Studies that reported outcomes after mobilization/decompression compared with coagulation/transection of compressive veins were reviewed. RESULTS: We identified and included 24 studies with a total of 330 patients in this study. 75.6 % of patients achieved a Barrow Neurological Institute (BNI) I pain score with a mean follow-up of 38.0 months. Pain recurred in 23.1 % of patients at a mean follow-up of 51.4 months. There was no significant difference in pain control outcomes between patients with mobilization/decompression and patients with coagulation/transection of compressive veins. CONCLUSION: After MVD in patients with venous compression alone, pain control rates were similar to those reported for arterial compression, though recurrence rates were higher. There was no difference between vein coagulation/transection compared to mobilization/decompression. Further studies are needed to determine the optimal treatment paradigm for patients with purely venous compression.

Addition of Androgen-Deprivation Therapy or Brachytherapy Boost to External Beam Radiotherapy for Localized Prostate Cancer: A Network Meta-Analysis of Randomized Trials.

PURPOSE: In men with localized prostate cancer, the addition of androgen-deprivation therapy (ADT) or a brachytherapy boost (BT) to external beam radiotherapy (EBRT) have been shown to improve various oncologic end points. Practice patterns indicate that those who receive BT are significantly less likely to receive ADT, and thus we sought to perform a network meta-analysis to compare the predicted outcomes of a randomized trial of EBRT plus ADT versus EBRT plus BT. MATERIALS AND METHODS: A systematic review identified published randomized trials comparing EBRT with or without ADT, or EBRT (with or without ADT) with or without BT, that reported on overall survival (OS). Standard fixed-effects meta-analyses were performed for each comparison, and a meta-regression was conducted to adjust for use and duration of ADT. Network meta-analyses were performed to compare EBRT plus ADT versus EBRT plus BT. Bayesian analyses were also performed, and a rank was assigned to each treatment after Markov Chain Monte Carlo analyses to create a surface under the cumulative ranking curve. RESULTS: Six trials compared EBRT with or without ADT (n = 4,663), and 3 compared EBRT with or without BT (n = 718). The addition of ADT to EBRT improved OS (hazard ratio [HR], 0.71 [95% CI, 0.62 to 0.81]), whereas the addition of BT did not significantly improve OS (HR, 1.03 [95% CI, 0.78 to 1.36]). In a network meta-analysis, EBRT plus ADT had improved OS compared with EBRT plus BT (HR, 0.68 [95% CI, 0.52 to 0.89]). Bayesian modeling demonstrated an 88% probability that EBRT plus ADT resulted in superior OS compared with EBRT plus BT. CONCLUSION: Our findings suggest that current practice patterns of omitting ADT with EBRT plus BT may result in inferior OS compared with EBRT plus ADT in men with intermediate- and high-risk prostate cancer. ADT for these men should remain a critical component of treatment regardless of radiotherapy delivery method until randomized evidence demonstrates otherwise.

Population-Based Observational Studies in Oncology: Proceed With Caution.

A principle goal of research in Oncology is to determine the optimal treatment for our patients. This often takes the form of comparing 2 existing therapies to one another to determine which is superior, or to introduce a new therapy and determine if it is superior or noninferior to the existing standard of care. This type of research is termed comparative effectiveness research (CER), and the gold-standard is through the conduct of randomized trials. This is the preferred approach, and the only true methodologic approach that can assign a cause-and-effect relationship between a treatment effect and the observed outcome. An alternative approach that is gaining popularity is the use of population-based registry analysis given that it is quicker, cheaper, and easier to perform. However, there are unavoidable forms of bias and confounding that exist when using observational research to perform CER, and recent evidence suggests that population-based CER often results in erroneous results, and that statistical methods to minimize bias are ineffective to overcome the numerous limitations of these databases. In this article, the strengths and weaknesses of both randomized and observational research will be discussed.

The current state of randomized clinical trial evidence for prostate brachytherapy.

Interstitial brachytherapy is one of several curative therapeutic options for the treatment of localized prostate cancer. In this review, we summarize all available randomized data to support the optimal use of prostate brachytherapy. Evidence from completed randomized controlled trials is the focus of this review with a presentation also of important ongoing trials. Gaps in knowledge are identified where future investigation may be fruitful with intent to inspire well-designed prospective studies with standardized treatment that focuses on improving oncological outcomes, reducing morbidity, or maintaining quality of life.

Association of Black Race With Prostate Cancer-Specific and Other-Cause Mortality.

Importance: Black men are more likely to die of prostate cancer than white men. In men with similar stages of disease, the contribution of biological vs nonbiological differences to this observed disparity is unclear. Objective: To quantify the association of black race with long-term survival outcomes after controlling for known prognostic variables and access to care among men with prostate cancer. Design, Setting, and Participants: This multiple-cohort study included updated individual patient-level data of men with clinical T1-4N0-1M0 prostate cancer from the following 3 cohorts: Surveillance, Epidemiology, and End Results (SEER [n = 296 273]); 5 equal-access regional medical centers within the Veterans Affairs health system (VA [n = 3972]); and 4 pooled National Cancer Institute-sponsored Radiation Therapy Oncology Group phase 3 randomized clinical trials (RCTs [n = 5854]). Data were collected in the 3 cohorts from January 1, 1992, through December 31, 2013, and analyzed from April 27, 2017, through April 13, 2019. Exposures: In the VA and RCT cohorts, all patients received surgery and radiotherapy, respectively, with curative intent. In SEER, radical treatment, hormone therapy, or conservative management were received. Main Outcomes and Measures: Prostate cancer-specific mortality (PCSM). Secondary measures included other-cause mortality (OCM). To adjust for demographic-, cancer-, and treatment-related baseline differences, inverse probability weighting (IPW) was performed. Results: Among the 306 100 participants included in the analysis (mean [SD] age, 64.9 [8.9] years), black men constituted 52 840 patients (17.8%) in the SEER cohort, 1513 (38.1%) in the VA cohort, and 1129 (19.3%) in the RCT cohort. Black race was associated with an increased age-adjusted PCSM hazard (subdistribution hazard ratio [sHR], 1.30; 95% CI, 1.23-1.37; P < .001) within the SEER cohort. After IPW adjustment, black race was associated with a 0.5% (95% CI, 0.2%-0.9%) increase in PCSM at 10 years after diagnosis (sHR, 1.09; 95% CI, 1.04-1.15; P < .001), with no significant difference for high-risk men (sHR, 1.04; 95% CI, 0.97-1.12; P = .29). No significant differences in PCSM were found in the VA IPW cohort (sHR, 0.85; 95% CI, 0.56-1.30; P = .46), and black men had a significantly lower hazard in the RCT IPW cohort (sHR, 0.81; 95% CI, 0.66-0.99; P = .04). Black men had a significantly increased hazard of OCM in the SEER (sHR, 1.30; 95% CI, 1.27-1.34; P < .001) and RCT (sHR, 1.17; 95% CI, 1.06-1.29; P = .002) IPW cohorts. Conclusions and Relevance: In this study, after adjustment for nonbiological differences, notably access to care and standardized treatment, black race did not appear to be associated with inferior stage-for-stage PCSM. A large disparity remained in OCM for black men with nonmetastatic prostate cancer.

Stereotactic Body Radiation Therapy for Localized Prostate Cancer: A Systematic Review and Meta-Analysis of Over 6,000 Patients Treated On Prospective Studies.

PURPOSE: Utilization of stereotactic body radiation therapy (SBRT) for treatment of localized prostate cancer is increasing. Guidelines and payers variably support the use of prostate SBRT. We therefore sought to systematically analyze biochemical recurrence-free survival (bRFS), physician-reported toxicity, and patient-reported outcomes after prostate SBRT. METHODS AND MATERIALS: A systematic search leveraging Medline via PubMed and EMBASE for original articles published between January 1990 and January 2018 was performed. This was supplemented by abstracts with sufficient extractable data from January 2013 to March 2018. All prospective series assessing curative-intent prostate SBRT for localized prostate cancer reporting bRFS, physician-reported toxicity, and patient-reported quality of life with a minimum of 1-year follow-up were included. The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Meta-analyses were performed with random-effect modeling. Extent of heterogeneity between studies was determined by the I2 and Cochran's Q tests. Meta-regression was performed using Hartung-Knapp methods. RESULTS: Thirty-eight unique prospective series were identified comprising 6116 patients. Median follow-up was 39 months across all patients (range, 12-115 months). Ninety-two percent, 78%, and 38% of studies included low, intermediate, and high-risk patients. Overall, 5- and 7-year bRFS rates were 95.3% (95% confidence interval [CI], 91.3%-97.5%) and 93.7% (95% CI, 91.4%-95.5%), respectively. Estimated late grade ≥3 genitourinary and gastrointestinal toxicity rates were 2.0% (95% CI, 1.4%-2.8%) and 1.1% (95% CI, 0.6%-2.0%), respectively. By 2 years post-SBRT, Expanded Prostate Cancer Index Composite urinary and bowel domain scores returned to baseline. Increasing dose of SBRT was associated with improved biochemical control (P = .018) but worse late grade ≥3 GU toxicity (P = .014). CONCLUSIONS: Prostate SBRT has substantial prospective evidence supporting its use, with favorable tumor control, patient-reported quality of life, and levels of toxicity demonstrated. SBRT has sufficient evidence to be supported as a standard treatment option for localized prostate cancer while ongoing trials assess its potential superiority.

Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Current State and Future Opportunities.

Hepatocellular carcinoma is a rising cause of morbidity and mortality in the USA and around the world. Surgical resection and liver transplantation are the preferred management strategies; however, less than 30% of patients are eligible for surgery. Stereotactic body radiation therapy is a promising local treatment option for non-surgical candidates. Local control rates between 95 and 100% have been reported at 1-2 years post-treatment, and classical radiation-induced liver disease described with conventional radiation is an unlikely complication from stereotactic radiotherapy. Enrollment in randomized trials will be essential in establishing the role of stereotactic radiation in treatment paradigms for hepatocellular carcinoma.

Comparison of Population-Based Observational Studies With Randomized Trials in Oncology.

PURPOSE: Comparative efficacy research performed using population registries can be subject to significant bias. There is an absence of objective data demonstrating factors that can sufficiently reduce bias and provide accurate results. METHODS: MEDLINE was searched from January 2000 to October 2016 for observational studies comparing two treatment regimens for any diagnosis of cancer, using SEER, SEER-Medicare, or the National Cancer Database. Reporting quality and statistical methods were assessed using components of the STROBE criteria. Randomized trials comparing the same treatment regimens were identified. Primary outcome was correlation between survival hazard ratio (HR) estimates provided by the observational studies and randomized trials. Secondary outcomes included agreement between matched pairs and predictors of agreement. RESULTS: Of 3,657 studies reviewed, 350 treatment comparisons met eligibility criteria and were matched to 121 randomized trials. There was no significant correlation between the HR estimates reported by observational studies and randomized trials (concordance correlation coefficient, 0.083; 95% CI, -0.068 to 0.230). Forty percent of matched studies were in agreement regarding treatment effects (κ, 0.037; 95% CI, -0.027 to 0.1), and 62% of the observational study HRs fell within the 95% CIs of the randomized trials. Cancer type, data source, reporting quality, adjustment for age, stage, or comorbidities, use of propensity weighting, instrumental variable or sensitivity analysis, and well-matched study population did not predict agreement. CONCLUSION: We were unable to identify any modifiable factor present in population-based observational studies that improved agreement with randomized trials. There was no agreement beyond what is expected by chance, regardless of reporting quality or statistical rigor of the observational study. Future work is needed to identify reliable methods for conducting population-based comparative efficacy research.

PD-L1 Expression in Circulating Tumor Cells Increases during Radio(chemo)therapy and Indicates Poor Prognosis in Non-small Cell Lung Cancer.

Preclinical studies demonstrated that radiation up-regulates PD-L1 expression in tumor cells, providing a rationale for combining PD-1/PD-L1 inhibitors with radiation. However this has not been validated in patients with non-small cell lung cancer due to the difficulty to obtain serial biopsies. Measuring PD-L1 expression in circulating tumor cells (CTCs), may allow real-time monitoring of immune activation in tumor. In this study, whole blood from non-metastatic NSCLC patients was collected before, during, and after radiation or chemoradiation using a microfluidic chip. PD-L1 expression in CTCs was assessed by immunofluorescence and qPCR and monitored through the course of treatment. Overall, PD-L1(+) CTCs were detected in 25 out of 38 samples (69.4%) with an average of 4.5 cells/ml. After initiation of radiation therapy, the proportion of PD-L1(+) CTCs increased significantly (median 0.7% vs. 24.7%, P < 0.01), indicating up-regulation of PD-L1 in tumor cells in response to radiation. In addition, patients positive for PD-L1 (≥5% of CTCs positive for PD-L1) at baseline had shorter PFS. Gene expression analysis revealed that higher levels of PD-L1 were associated with poor prognosis. Therefore, CTCs can be used to monitor dynamic changes of PD-L1 during radiation therapy which is potentially prognostic of response to treatment.

Patient-Reported Sexual Aid Utilization and Efficacy After Radiation Therapy for Localized Prostate Cancer.

PURPOSE: To report sexual health-related quality of life outcomes and utilization and efficacy of sexual aids in a contemporary cohort of patients treated for localized prostate cancer. PATIENTS AND METHODS: Between 2008 and 2013, 471 consecutive men with localized prostate cancer were treated on 2 institutional protocols (NCT01766492, NCT01618851) or on a prospective institutional registry with patient-reported health-related quality of life. All patients were treated with ultra-hypofractionated radiation therapy. Erectile function (EF) was defined as "firm enough for intercourse" with or without aids per Expanded Prostate Cancer Index Composite-26 (n = 222 at baseline); results apply to this cohort unless specifically noted. Sexual aid utilization and efficacy were patient reported. Multivariable analysis of EF was performed. RESULTS: Median follow-up was 60 months, median age was 67 years, and 70% had intermediate- or high-risk disease per National Comprehensive Cancer Network guidelines. At 24 and 60 months, questionnaire response rates were 86% and 67%, and EF was retained in 53% and 41%, respectively. Baseline sexual aid utilization was 37% (n = 82) and was associated with lower 24-month EF preservation on multivariable analysis (adjusted odds ratio 0.49, 95% confidence interval 0.26-0.92). By 60 months, 70% of men had tried aids. Of those who found aids helpful at baseline, 84% to 89% reported continued benefit at 24 to 60 months. Among aid-naïve patients, efficacy was 80% with first-time use within 12 months and 70% more than 12 months after radiation therapy (P = .02). Among men who developed erectile dysfunction but found sexual aids helpful, 25% were not current users at 60 months. CONCLUSIONS: One-third of men used sexual aids at baseline, which doubled by 5 years after radiation therapy. Self-reported efficacy was high and sustained. Despite significant declines in EF, a number of men reported helpfulness of aids but were not active users. Future study is required to understand drivers of aid utilization to optimize posttreatment sexual function.

Impact of Biochemical Failure After Salvage Radiation Therapy on Prostate Cancer-specific Mortality: Competition Between Age and Time to Biochemical Failure.

BACKGROUND: Disease progression following salvage radiotherapy (SRT) for prostate cancer (PC) is common, and the time to biochemical recurrence (BCR) is heterogeneous. OBJECTIVE: To describe the temporal distribution and clinical impact of BCR following SRT and model outcomes using patient age and time to BCR from SRT. DESIGN, SETTING, AND PARTICIPANTS: A retrospective multi-institutional study included 547 consecutive men with lymph node-negative PC receiving SRT from 1985 to 2013. The median follow-up after SRT was 8.4 yr. Intervention All men received SRT with three-dimensional or intensity-modulated RT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: BCR was defined as a rise in prostate-specific antigen (PSA) ≥0.2ng/ml above the PSA nadir followed by a sequentially equal or higher value. Additional outcomes included distant metastasis (DM), PC-specific mortality (PCSM), and overall mortality (OM). Cox proportional hazards models, a landmark analysis, and comparison of c-indices were used. Cumulative incidence curves were estimated from a Fine and Gray regression model. RESULTS AND LIMITATIONS: The estimated 10-yr cumulative incidence of BCR was 60%. Of the 274 men experiencing BCR, 149 (54%) had BCR within 18 mo of SRT. BCR ≤18 mo after SRT was associated with a higher risk of DM (hazard ratio [HR] 7.44, 95% confidence interval [CI] 4.91-11.3; p<0.001), PCSM (HR 12.3, 95% CI 5.95-25.2; p<0.001), and OM (HR 2.85, 95% CI 1.94-4.17; p<0.001). We provide a model to estimate the cumulative incidence of DM and PCSM using age and time to BCR. The retrospective nature of our analysis limits our findings. CONCLUSIONS: A strikingly large proportion of men experience early BCR following SRT and are at higher risk of DM and PCSM. Novel predictive biomarkers are needed to identify men harboring micrometastatic disease to avoid potentially futile local therapies or allow for intensification of systemic therapies. PATIENT SUMMARY: Many men will develop biochemical recurrence of prostate cancer after salvage radiotherapy. Men with biochemical recurrence within 18 mo of salvage radiotherapy constitute a cohort at higher risk of distant metastasis and prostate cancer-specific mortality.

Erectile function after stereotactic body radiotherapy for localized prostate cancer.

OBJECTIVE: To elucidate the functional erection rate after prostate stereotactic body radiotherapy (SBRT) and to develop a comprehensive prognostic model of outcomes after treatment. PATIENTS AND METHODS: Between 2008 and 2013, 373 consecutive men with localized prostate cancer were treated with SBRT at a single academic institution as part of a prospective clinical trial or prospective registry. Prospective longitudinal patient-reported health-related quality of life (HRQoL) data was collected using the Expanded Prostate Cancer Index Composite (EPIC)-26 instrument. Functional erections were strictly defined as 'firm enough for intercourse' according to EPIC-26. Detailed comorbidity data were also collected. Logistic regression models were used to predict 24- and 60-month functional erection rates. Observed erection rates after SBRT were compared with those after other radiation therapies (external beam radiation therapy [EBRT] and brachytherapy) using prospectively validated models. RESULTS: The median (interquartile range) follow-up was 56 (37-73) months and the response rate at 2 years was 84%. For those with functional erections at baseline, 57% and 45% retained function at 24 and 60 months, respectively. On multivariable analysis for 24-month erectile function, significant variables included higher baseline sexual HRQoL (adjusted odds ratio [aOR] 1.55 per 10 points, 95% confidence interval [CI] 1.37-1.74; P < 0.001) and older age (aOR 0.66 per 10 years, 95% CI 0.43-1.00; P = 0.05). At 60 months, baseline HRQoL and age remained associated with erectile function, along with body mass index (aOR 0.45, 95% CI 0.26-0.78; P < 0.001). The 24- and 60-month models had excellent discrimination (c-index 0.81 and 0.84, respectively). Erection rates after SBRT were not statistically different from model-predicted rates after EBRT or brachytherapy for the whole cohort and the cohort with baseline erectile function. CONCLUSIONS: Intermediate- to long-term post-SBRT erectile function results are promising and not significantly different from other radiotherapy techniques. Clinicians can use our prognostic model to counsel patients regarding expected erectile function after SBRT.

External beam radiation therapy with or without low-dose-rate brachytherapy: Analysis of favorable and unfavorable intermediate-risk prostate cancer patients.

PURPOSE: To compare the tumor control and toxicity in men with intermediate-risk prostate cancer treated with either external beam radiation therapy (EBRT) or EBRT plus low-dose-rate brachytherapy (combo-RT). METHODS AND MATERIALS: Between 1995 and 2012, 579 men with intermediate-risk prostate cancer were treated with either EBRT (n = 388) or combo-RT (n = 191). Outcomes assessed included biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and cumulative incidence of genitourinary (GU) and gastrointestinal toxicity. Favorable and unfavorable intermediate-risk subgroups were analyzed. RESULTS: Median followup was 7.5 years. Combo-RT group had improved 10-year bRFS compared with EBRT (91.7% vs. 75.4%, p = 0.014). On multivariable analysis, combo-RT (hazard ratio, 0.48; 95% confidence interval: 0.25, 0.92; p = 0.03) was associated with improved bRFS. Combo-RT had significantly improved bRFS compared with EBRT in the unfavorable subgroup (p = 0.02) but not in the favorable subgroup (p = 0.37). DMFS was similar within the entire cohort and by risk group. Combo-RT was associated with an increased rate in the 6-year cumulative incidence of Grade 3 GU toxicity (hazard ratio, 3.48; 95% confidence interval: 1.1, 11.1; p = 0.026); however, 57% of Grade 3 GU toxicity was resolved, 29% had partial improvement, and only 1 patient had persistent Grade 3 GU toxicity. CONCLUSIONS: In intermediate-risk prostate cancer, combo-RT improved bRFS but not DMFS and increased Grade 3 GU toxicity. The bRFS benefit was limited to unfavorable intermediate-risk patients.

Cardiac Events After Radiation Therapy: Combined Analysis of Prospective Multicenter Trials for Locally Advanced Non-Small-Cell Lung Cancer.

Purpose Radiation therapy is a critical component in the care of patients with non-small-cell lung cancer (NSCLC), yet cardiac injury after treatment is a significant concern. Therefore, we wished to elucidate the incidence of cardiac events and their relationship to radiation dose to the heart. Patients and Materials Study eligibility criteria included patients with stage II to III NSCLC treated on one of four prospective radiation therapy trials at two centers from 2004 to 2013. All cardiac events were reviewed and graded per Common Terminology Criteria for Adverse Events (v4.03). The primary end point was the development of a grade ≥ 3 cardiac event. Results In all, 125 patients met eligibility criteria; median follow-up was 51 months for surviving patients. Median prescription dose was 70 Gy, 84% received concurrent chemotherapy, and 27% had pre-existing cardiac disease. Nineteen patients had a grade ≥ 3 cardiac event at a median of 11 months (interquartile range, 6 to 24 months), and 24-month cumulative incidence was 11% (95% CI, 5% to 16%). On multivariable analysis (MVA), pre-existing cardiac disease (hazard ratio [HR], 2.96; 95% CI, 1.07 to 8.21; P = .04) and mean heart dose (HR, 1.07/Gy; 95% CI, 1.02 to 1.13/Gy; P = .01) were significantly associated with grade ≥ 3 cardiac events. Analyzed as time-dependent variables on MVA analysis, both disease progression (HR, 2.15; 95% CI, 1.54 to 3.00) and grade ≥ 3 cardiac events (HR, 1.76; 95% CI, 1.04 to 2.99) were associated with decreased overall survival. However, disease progression (n = 71) was more common than grade ≥ 3 cardiac events (n = 19). Conclusion The 24-month cumulative incidence of grade ≥ 3 cardiac events exceeded 10% among patients with locally advanced NSCLC treated with definitive radiation. Pre-existing cardiac disease and higher mean heart dose were significantly associated with higher cardiac event rates. Caution should be used with cardiac dose to minimize risk of radiation-associated injury. However, cardiac risks should be balanced against tumor control, given the unfavorable prognosis associated with disease progression.