Frailty and cancer: Implications for oncology surgery, medical oncology, and radiation oncology.

Answer questions and earn CME/CNE The concept of frailty has become increasingly recognized as one of the most important issues in health care and health outcomes and is of particular importance in patients with cancer who are receiving treatment with surgery, chemotherapy, and radiotherapy. Because both cancer itself, as well as the therapies offered, can be significant additional stressors that challenge a patient's physiologic reserve, the incidence of frailty in older patients with cancer is especially high-it is estimated that over one-half of older patients with cancer have frailty or prefrailty. Defining frailty can be challenging, however. Put simply, frailty is a state of extreme vulnerability to stressors that leads to adverse health outcomes. In reality, frailty is a complex, multidimensional, and cyclical state of diminished physiologic reserve that results in decreased resiliency and adaptive capacity and increased vulnerability to stressors. In addition, over 70 different measures of frailty have been proposed. Still, it has been demonstrated that frail patients are at increased risk of postoperative complications, chemotherapy intolerance, disease progression, and death. Although international standardization of frailty cutoff points are needed, continued efforts by oncology physicians and surgeons to identify frailty and promote multidisciplinary decision making will help to develop more individualized management strategies and optimize care for patients with cancer. CA Cancer J Clin 2017;67:362-377. © 2017 American Cancer Society.

Diagnostic Performance and Safety of 18F-rhPSMA-7.3 Positron Emission Tomography in Men With Suspected Prostate Cancer Recurrence: Results From a Phase 3, Prospective, Multicenter Study (SPOTLIGHT).

PURPOSE: SPOTLIGHT (NCT04186845) evaluated diagnostic performance and safety of radiohybrid 18F-rhPSMA-7.3, a novel high-affinity positron emission tomography radiopharmaceutical. MATERIALS AND METHODS: Men with prostate cancer recurrence underwent positron emission tomography/CT 50-70 minutes after intravenous administration of 296±20% MBq 18F-rhPSMA-7.3. To assess the coprimary end points (verified detection rate and combined region-level positive predictive value), 3 blinded, independent central readers evaluated the scans. Verified detection rate is equivalent to the overall detection rate × positive predictive value. Standard of truth was established for each patient using histopathology or confirmatory imaging. Statistical thresholds (lower bounds of the confidence intervals) of 36.5% and 62.5% were prespecified for verified detection rate and combined region-level positive predictive value, respectively. Additional end points included detection rate, verified detection rate, and combined region-level positive predictive value in patients with histopathology standard of truth, and safety. RESULTS: The overall 18F-rhPSMA-7.3 detection rate among all 389 patients with an evaluable scan was 83% (majority read). Among the 366 patients (median prostate-specific antigen 1.27 ng/mL) for whom a standard of truth (histopathology [n=69]/confirmatory imaging only [n=297]) was available, verified detection rate ranged from 51% (95% CI 46.1-56.6) to 54% (95% CI 48.8-59.3), exceeding the prespecified statistical threshold. Combined region-level positive predictive value ranged from 46% (95% CI 42.0-50.3) to 60% (95% CI 55.1-65.5) across the readers, not meeting the threshold. In the subset of patients with histopathology standard of truth, the verified detection rate and combined region-level positive predictive value were both above the prespecified thresholds (majority read, 81% [95% CI 69.9-89.6] and 72% [95% CI 62.5-80.7], respectively). No significant safety concerns were identified. CONCLUSIONS: 18F-rhPSMA-7.3 offers a clinically meaningful verified detection rate for localization of recurrent prostate cancer. Despite missing the coprimary end point of combined region-level positive predictive value, the totality of the data support the potential clinical utility of 18F-rhPSMA-7.3.

Rapid unpaired CBCT-based synthetic CT for CBCT-guided adaptive radiotherapy.

In this work, we demonstrate a method for rapid synthesis of high-quality CT images from unpaired, low-quality CBCT images, permitting CBCT-based adaptive radiotherapy. We adapt contrastive unpaired translation (CUT) to be used with medical images and evaluate the results on an institutional pelvic CT dataset. We compare the method against cycleGAN using mean absolute error, structural similarity index, root mean squared error, and Frèchet Inception Distance and show that CUT significantly outperforms cycleGAN while requiring less time and fewer resources. The investigated method improves the feasibility of online adaptive radiotherapy over the present state-of-the-art.

18F-fluciclovine-PET/CT imaging versus conventional imaging alone to guide postprostatectomy salvage radiotherapy for prostate cancer (EMPIRE-1): a single centre, open-label, phase 2/3 randomised controlled trial.

BACKGROUND: Molecular imaging is increasingly used to guide treatment decisions and planning in prostate cancer. We aimed to evaluate the role of 18F-fluciclovine-PET/CT in improving cancer control compared with conventional imaging (bone scan and either CT or MRI) alone for salvage postprostatectomy radiotherapy. METHODS: In EMPIRE-1, a single-centre, open-label, phase 2/3 randomised controlled trial, patients with prostate cancer with detectable PSA after prostatectomy and negative conventional imaging (no extrapelvic or bone findings) were randomly assigned in a 1:1 ratio to radiotherapy directed by conventional imaging alone or to conventional imaging plus 18F-fluciclovine-PET/CT. Computer-generated randomisation was stratified by PSA concentration, adverse pathology indicators, and androgen deprivation therapy intent. In the 18F-fluciclovine-PET/CT group, radiotherapy decisions were rigidly determined by PET findings, which were also used for target delineation. The primary endpoint was 3 year event-free survival, with events defined as biochemical or clinical recurrence or progression, or initiation of systemic therapy, using univariate and multivariable analyses in patients who received radiotherapy. This trial is registered with ClinicalTrials.gov, NCT01666808 and is closed to new participants. FINDINGS: From Sept 18, 2012, to March 4, 2019, 165 patients were randomly assigned, with median follow-up of 3·52 years (95% CI 2·98-3·95). PET findings resulted in four patients in the 18F-fluciclovine-PET/CT group having radiotherapy aborted; these patients were excluded from survival analyses. Median survival was not reached (95% CI 35·2-not reached; 33% of 81 patients had events) in the conventional imaging group compared with not reached (95% CI not reached-not reached; 20% of 76 patients) in the 18F-fluciclovine-PET/CT group, and 3 year event-free survival was 63·0% (95% CI 49·2-74·0) in the conventional imaging group versus 75·5% (95% CI 62·5-84·6) for 18F-fluciclovine-PET/CT (difference 12·5; 95% CI 4·3-20·8; p=0·0028). In adjusted analyses, study group (hazard ratio 2·04 [95% CI 1·06-3·93], p=0·0327) was significantly associated with event-free survival. Toxicity was similar in both study groups, with the most common adverse events being late urinary frequency or urgency (37 [46%] of 81 patients in the conventional imaging group and 31 [41%] of 76 in the PET group), and acute diarrhoea (11 [14%] in the conventional imaging group and 16 [21%] in the PET group). INTERPRETATION: Inclusion of 18F-fluciclovine-PET into postprostatectomy radiotherapy decision making and planning significantly improved survival free from biochemical recurrence or persistence. Integration of novel PET radiotracers into radiotherapy decisions and planning for prostate cancer patients warrants further study. FUNDING: National Institutes of Health/National Cancer Institute, Blue Earth Diagnostics, and Winship Cancer Institute of Emory University.

Videos improve patient understanding of misunderstood chemotherapy terminology.

BACKGROUND: Chemotherapy is the backbone of many cancer therapies; however, the terminology used to describe chemotherapy may be difficult for patients to understand, particularly in underserved populations. Studies have shown that educational videos can improve patient understanding of cancer-related terms. The goal of this study was to identify chemotherapy terms that were difficult for an underserved population to understand and then develop and test educational videos describing these terms. METHODS: A word bank of 50 difficult-to-understand chemotherapy terms was developed by querying 15 providers and 50 patients at an underserved hospital. Twenty of these terms were then tested with 50 additional patients to determine rates of misunderstanding. Six pilot educational videos describing 6 important terms were created using VideoScribe and then assessed with 50 patients to see if they improved understanding. RESULTS: Fifteen of the 20 terms tested to establish rates of misunderstanding were misunderstood by more than one third of patients, with 98% unable to define maintenance, 74% unable to define cancer, and 58% unable to define chemotherapy. Patient understanding of all 6 terms improved by at least 20% after watching the videos. Notable improvement was reported for palliative chemotherapy, where before-and-after video understanding increased from 0% to 72%. CONCLUSION: Chemotherapy, a backbone of cancer treatment, is described with terms that are difficult to understand. Short, animated educational videos can significantly increase patient understanding of chemotherapy terminology.

The role of adjuvant radiotherapy in pathologically lymph node-positive prostate cancer.

BACKGROUND: Postoperative management of prostate cancer with lymph node involvement (LNI) is controversial. Retrospective evidence supports the selective use of radiotherapy (RT) after extended pelvic lymph node dissection. It is unclear whether this is generalizable to practice in the United States, where extended dissection is uncommon. The authors identified patients with LNI who potentially could derive a survival benefit with adjuvant RT plus androgen-deprivation therapy (ADT). METHODS: Patients with N1M0 prostate adenocarcinoma who underwent radical prostatectomy (RP) and subsequently received ADT from 2003 through 2011 were identified from the National Cancer Database. Kaplan-Meier analyses, log-rank tests, and multivariable Cox proportional hazards regression were performed using overall survival (OS) as the primary outcome. RESULTS: In total, 906 of 2569 eligible patients (35.3%) received RT, and RT was more frequently received by patients who were diagnosed in later years, had fewer positive lymph nodes, had involved surgical margins, and were aged <65 years (all P < .05). The 5-year OS rate was 87% versus 82% in those who received RT versus those who did not (P = .007). After propensity score matching, 826 patients remained in each cohort. RT retained an association with OS (5-year OS: 88% vs 81%; P = .009; hazard ratio, 1.43; 95% confidence interval, 1.10-1.86; P = .008). No interaction was identified between the effect of RT on OS across tested strata of total lymph nodes examined, lymph node ratio, total number of positive lymph nodes, margin status, Gleason score, and prostate-specific antigen. CONCLUSIONS: RT plus ADT was associated with improved OS after RP in patients with LNI. These results may help guide therapy in the absence of randomized evidence. Cancer 2017;123:512-520. © 2016 American Cancer Society.

Improved prostate delineation in prostate HDR brachytherapy with TRUS-CT deformable registration technology: A pilot study with MRI validation.

Accurate prostate delineation is essential to ensure proper target coverage and normal-tissue sparing in prostate HDR brachytherapy. We have developed a prostate HDR brachytherapy technology that integrates intraoperative TRUS-based prostate contour into HDR treatment planning through TRUS-CT deformable registration (TCDR) to improve prostate contour accuracy. In a perspective study of 16 patients, we investigated the clinical feasibility as well as the performance of this TCDR-based HDR approach. We compared the performance of the TCDR-based approach with the conventional CT-based HDR in terms of prostate contour accuracy using MRI as the gold standard. For all patients, the average Dice prostate volume overlap was 91.1 ± 2.3% between the TCDR-based and the MRI-defined prostate volumes. In a subset of eight patients, inter and intro-observer reliability study was conducted among three experienced physicians (two radiation oncologists and one radiologist) for the TCDR-based HDR approach. Overall, a 10 to 40% improvement in prostate volume accuracy can be achieved with the TCDR-based approach as compared with the conventional CT-based prostate volumes. The TCDR-based prostate volumes match closely to the MRI-defined prostate volumes for all 3 observers (mean volume difference: 0.5 ± 7.2%, 1.8 ± 7.2%, and 3.5 ± 5.1%); while CT-based contours overestimated prostate volumes by 10.9 ± 28.7%, 13.7 ± 20.1%, and 44.7 ± 32.1%. This study has shown that the TCDR-based HDR brachytherapy is clinically feasible and can significantly improve prostate contour accuracy over the conventional CT-based prostate contour. We also demonstrated the reliability of the TCDR-based prostate delineation. This TCDR-based HDR approach has the potential to enable accurate dose planning and delivery, and potentially enhance prostate HDR treatment outcome.

Recurrent prostate cancer detection with anti-3-[(18)F]FACBC PET/CT: comparison with CT.

PURPOSE: To compare the diagnostic performance of the synthetic amino acid analogue PET radiotracer anti-3-[(18)F]FACBC (fluciclovine) with that of CT in the detection of recurrent prostate carcinoma. METHODS: This was a retrospective analysis of 53 bone scan-negative patients with suspected recurrent prostate carcinoma who underwent fluciclovine PET/CT and routine clinical CT within 90 days of each other. The correlation between imaging findings and histology and clinical follow-up was evaluated. Positivity rates and diagnostic performance were calculated for fluciclovine PET/CT and CT. RESULTS: Of 53 fluciclovine PET/CT and 53 CT examinations, 41 (77.4 %) and 10 (18.9 %), respectively, had positive findings for recurrent disease. Positivity rates were higher with fluciclovine PET/CT than with CT at all prostate-specific antigen (PSA) levels, PSA doubling times and original Gleason scores. In the prostate/bed, fluciclovine PET/CT was true-positive in 31 and CT was true-positive in 4 of 51 patients who met the reference standard. In extraprostatic regions, fluciclovine PET/CT was true-positive in 12 and CT was true-positive in 3 of 41 patients who met the reference standard. Of the 43 index lesions used to prove positivity, 42 (97.7 %) had histological proof. In 51 patients with sufficient follow-up to calculate diagnostic performance in the prostate/bed, fluciclovine PET/CT demonstrated a sensitivity of 88.6 %, a specificity of 56.3 %, an accuracy of 78.4 %, a positive predictive value (PPV) of 81.6 %, and a negative predictive value (NPV) of 69.2 %; the respective values for CT were 11.4 %, 87.5 %, 35.3 %, 66.7 % and 31.1 %. In 41 patients with sufficient follow-up to calculate diagnostic performance in extraprostatic regions, fluciclovine PET/CT demonstrated a sensitivity of 46.2 %, a specificity of 100 %, an accuracy of 65.9 %, a PPV of 100 %, and an NPV of 51.7 %; the respective values for CT were 11.5 %, 100 %, 43.9 %, 100 % and 39.5 %. CONCLUSION: The diagnostic performance of fluciclovine PET/CT in recurrent prostate cancer is superior to that of CT and fluciclovine PET/CT provides better delineation of prostatic from extraprostatic recurrence.

Video-based educational tool improves patient comprehension of common prostate health terminology.

BACKGROUND: Health care providers often counsel prostate cancer patients about treatment options with medical terminology. However, studies have demonstrated a severe lack of comprehension of these terms, particularly in underserved populations. It was hypothesized that a video-based educational tool would significantly improve the understanding of key terms related to prostate health in a predominantly lower literacy population. METHODS: A software application was developed by various experts, including urologists and human-computer interaction specialists, to serve as a video-based educational tool emphasizing narrated animations to promote understanding of terms related to urinary, bowel, and sexual function. This application was viewed by patients recruited from 2 low-income safety net clinics, where a previously developed survey was administered to assess pre- and postintervention levels of comprehension. RESULTS: Fifty-six patients with a mean literacy level of 7th to 8th grade completed the study. Patients achieved statistically significant improvements in comprehension for the majority of the terms after the video intervention, with notable improvements including the terms incontinence (from 14% to 50%), bowels (from 14% to 46%), and impotence (from 58% to 84%). Patients demonstrated significant gains in their understanding of the function of the prostate (from 11% to 30%) and in their ability to locate the prostate on anatomic drawings (from 50% to 82%). CONCLUSIONS: This video-based educational tool is an effective method for overcoming the severe lack of comprehension of prostate health terminology among patients. The improvements achieved have the potential to enhance patient participation in shared and informed decision making and to support combined visual-audio multimedia as a promising tool for prostate cancer education.

Anti-3-[(18)F]FACBC positron emission tomography-computerized tomography and (111)In-capromab pendetide single photon emission computerized tomography-computerized tomography for recurrent prostate carcinoma: results of a prospective clinical trial.

PURPOSE: We prospectively evaluated the amino acid analogue positron emission tomography radiotracer anti-3-[(18)F]FACBC compared to ProstaScint® ((111)In-capromab pendetide) single photon emission computerized tomography-computerized tomography to detect recurrent prostate carcinoma. MATERIALS AND METHODS: A total of 93 patients met study inclusion criteria who underwent anti-3-[(18)F]FACBC positron emission tomography-computerized tomography plus (111)In-capromab pendetide single photon emission computerized tomography-computerized tomography for suspected recurrent prostate carcinoma within 90 days. Reference standards were applied by a multidisciplinary board. We calculated diagnostic performance for detecting disease. RESULTS: In the 91 of 93 patients with sufficient data for a consensus on the presence or absence of prostate/bed disease anti-3-[(18)F]FACBC had 90.2% sensitivity, 40.0% specificity, 73.6% accuracy, 75.3% positive predictive value and 66.7% negative predictive value compared to (111)In-capromab pendetide with 67.2%, 56.7%, 63.7%, 75.9% and 45.9%, respectively. In the 70 of 93 patients with a consensus on the presence or absence of extraprostatic disease anti-3-[(18)F]FACBC had 55.0% sensitivity, 96.7% specificity, 72.9% accuracy, 95.7% positive predictive value and 61.7% negative predictive value compared to (111)In-capromab pendetide with 10.0%, 86.7%, 42.9%, 50.0% and 41.9%, respectively. Of 77 index lesions used to prove positivity histological proof was obtained in 74 (96.1%). Anti-3-[(18)F]FACBC identified 14 more positive prostate bed recurrences (55 vs 41) and 18 more patients with extraprostatic involvement (22 vs 4). Anti-3-[(18)F]FACBC positron emission tomography-computerized tomography correctly up-staged 18 of 70 cases (25.7%) in which there was a consensus on the presence or absence of extraprostatic involvement. CONCLUSIONS: Better diagnostic performance was noted for anti-3-[(18)F]FACBC positron emission tomography-computerized tomography than for (111)In-capromab pendetide single photon emission computerized tomography-computerized tomography for prostate carcinoma recurrence. The former method detected significantly more prostatic and extraprostatic disease.

Impact of Rectal Spacer on Toxicity Reduction in Men Treated With Proton Versus Photon Therapy.

Purpose: Rectal toxicity after prostate cancer (PCa) radiation therapy (RT) may be greater with protons compared with photon intensity-modulated RT, perhaps due to lateral penumbra and end-of-range uncertainty. Rectal spacers (RSs) have been shown to mitigate RT-associated acute/late rectal toxicity in men treated with photons. The relative benefit of RS in men treated with protons versus photons is unknown. We hypothesize that RS will confer greater bowel toxicity benefits in PCa treated with protons versus photons. Materials and Methods: We conducted a single institution, retrospective review of men receiving photon intensity-modulated RT or pencil-beam scanning proton RT for localized PCa. Four cohorts were compared: photon with or without RS, and proton with or without RS. Acute (<3 months), late (≥3 months), and most recent toxicity were compared among the 4 cohorts. The cumulative incidence of physician-reported grade 1 to 2 gastrointestinal (GI) toxicity (common terminology criteria for adverse events V5.0) was compared using χ2 or Fisher exact test. Patient-reported toxicity was evaluated using the International Prostate Expanded Prostate Composite Index-Clinical Practice and compared using linear mixed modeling. Results: In total, 164 patients were eligible for analysis: 38 photons without RS, 50 photons with RS, 26 protons without RS, and 50 protons with RS. The median follow-up was 17.6 months. In proton patients, acute (6.12% vs 30.77%, P = .009) and most recent (4.26% vs 26.09%, P = .01) G1-2 GI toxicity was lower with versus without RS. In photon patients, there were no significant differences in toxicity with versus without RS. No significant differences in patient-reported outcomes were observed with versus without RS in photon or proton groups. Conclusion: The rectal spacer was associated with lower G1-2 acute and most recent GI toxicity in men treated with protons; this difference was not observed in men treated with photons. While this study is limited by sample size, a relatively greater benefit of RS with proton versus photon therapy was observed.

Impact of Clinical Factors on 18F-Flotufolastat Detection Rates in Men With Recurrent Prostate Cancer: Exploratory Analysis of the Phase 3 SPOTLIGHT Study.

Purpose: 18F-Flotufolastat (18F-rhPSMA-7.3) is a newly approved prostate-specific membrane antigen targeting radiopharmaceutical for diagnostic imaging of prostate cancer (PCa). SPOTLIGHT (National Clinical Trials 04186845) evaluated 18F-flotufolastat in men with suspected PCa recurrence. Here, we present results of predefined exploratory endpoints from SPOTLIGHT to evaluate the impact of clinical factors on 18F-flotufolastat detection rates (DR). Methods and Materials: The impact of baseline prostate-specific antigen (PSA), PSA doubling time (PSAdt), and International Society of Urologic Pathology Grade Group (GG) on 18F-flotufolastat DR was evaluated among all SPOTLIGHT patients with an evaluable scan, with DR stratified according to the patients' prior treatment (radical prostatectomy ± radiation therapy [RP] or radiation therapy only [RT]). The patients underwent positron emission tomography 50 to 70 minutes after receiving 18F-flotufolastat (296 MBq IV), and scans were read by 3 blinded central readers, with the majority read representing agreement between ≥2 readers. Results: In total, 389 men (median PSA: 1.10 ng/mL) were evaluable. By majority read, 18F-flotufolastat identified distant lesions in 39% and 43% of patients treated with prior RP or RT, respectively. The overall DR broadly increased with increasing PSA (<0.2 ng/mL: 33%; ≥10 ng/mL: 100%). Among patients with PSA <1 ng/mL, 68% had positive scans, and 27% had extrapelvic findings. PSAdt was available for 145/389 (37%) patients. PSAdt did not appear to influence 18F-flotufolastat DR (77%-90% across all PSAdt categories). Among patients with prior RP, DR ranged from 70% to 83% across PSAdt categories, and 100% DR was reported for all post-RT patients. In total, 362/389 (93%) patients had baseline GG data. Overall DRs were uniformly high (75%‒95%) across all GG. When stratified by prior treatment, DRs across all GG were 69% to 89% in patients with prior RP and ≥96% in patients with prior RT. Conclusions: 18F-Flotufolastat-positron emission tomography enabled the accurate detection of recurrent PCa lesions across a wide range of PSA, PSAdt, and International Society of Urologic Pathology GG, thus supporting its clinical utility for a broad range of patients with recurrent PCa.

Biochemical Relapse-Free Survival in Postprostatectomy Patients Receiving 18F-Fluciclovine-Guided Prostate Bed-Only Radiation: Post Hoc Analysis of a Prospective Randomized Trial.

PURPOSE: Whole-pelvis (WP) radiation therapy (radiation) improved biochemical relapse-free survival (bRFS) compared with prostate bed (PB)-only radiation in the Radiation Therapy Oncology Group 0534, but was performed in an era prior to positron emission tomography (PET) staging. Separately, 18F-fluciclovine PET/CT-guided postprostatectomy radiation improved 3-year bRFS versus radiation guided by conventional imaging alone. We hypothesized that patients who were changed from WP to PB-only radiation after PET would have bRFS that was: (a) no higher than patients initially planned for PB-only radiation; and (b) lower than patients planned for WP radiation without PET guidance. METHODS AND MATERIALS: We conducted a post hoc analysis of a prospective, randomized trial comparing conventional (arm 1) versus PET-guided (arm 2) postprostatectomy radiation. In arm 2, pre-PET treatment field decisions were recorded and post-PET fields were defined per protocol; pathologic node negative (pN0) without pelvic or extrapelvic PET uptake received PB-only radiation. Three-year bRFS was compared in patients planned for WP with change to PB-only radiation (arm 2 [WP:PB]) vs arm 2 patients planned for PB-only with final radiation to PB-only (arm 2 [PB:PB]) and arm 1 pN0 patients treated with WP radiation (arm 1 [WP]) using the Z test and log-rank test. Demographics were compared using the chi-square test, Fisher exact test, or analysis of variance, as appropriate. RESULTS: We identified 10 arm 2 (WP:PB), 31 arm 2 (PB:PB) and 11 arm 1 (WP) patients. Androgen deprivation was used in 50.0% of arm 2 (WP:PB) and 3.2% of arm 2 (PB:PB) patients, P < .01. Median preradiation prostate-specific antigen was higher in arm 2 (WP:PB) vs arm 2 (PB:PB) patients (0.4 vs 0.2 ng/mL, P = .03); however, there were no significant differences in T stage, Gleason score, or margin positivity. Three-year bRFS was 80% in arm 2 (WP:PB) vs 87.4% in arm 2 (PB:PB), P = .47, respectively. Arm 1(WP) patients had significantly worse 3-year (23%) bRFS vs arm 2 (WP:PB), P < .01. CONCLUSIONS: Patients initially planned for WP radiation with field decision change to PB-only radiation after PET showed (1) no significant difference in 3-year bRFS compared with patients initially planned for PB-only radiation; and (2) improved bRFS compared with patients receiving WP radiation without PET guidance. PET-guided volume de-escalation in selected patients may be 1 approach to mitigating toxicity without compromising outcomes.

Long-Term Results of Bladder Preservation with Twice-Daily Radiation plus 5-Flourouracil/Cisplatin or Daily Radiation plus Gemcitabine for MIBC - Updated Report of NRG/RTOG 0712: A Randomized Phase 2 Trial.

PURPOSE: 5-FU/cisplatin and twice-daily radiation (FCT) or gemcitabine and once daily radiation (GD) are effective chemoradiation (CRT) regimens for bladder sparing treatment of muscle-invasive bladder cancer (MIBC). This trial evaluated these regimens and demonstrated efficacy with either regimen at 3 years. With further follow-up, longer term results are reported here. METHODS AND MATERIALS: Patients with cT2-4a MIBC were randomized to FCT or GD. Patients had a transurethral resection and induction CRT to 40 Gy. Patients with a complete response (CR) received consolidation CRT to 64 Gy. Others had cystectomy. Adjuvant gemcitabine/cisplatin chemotherapy was administered. The primary endpoint was freedom from distant metastasis (FDM). This updated analysis reports 7-year data. Toxicity and efficacy endpoints, including bladder intact distant metastasis free survival (BI-DMFS) were also assessed. RESULTS: From 12/2008 to 4/2014, 70 patients were enrolled; 66 eligible for analysis, 33 per arm. Median follow-up was 9.1 years for eligible living patients. At 7 years, FDM was 65% and 73% for FCT and GD, respectively. BI-DMFS was 58% (95% CI: 41 - 76) and 68% (95% CI: 51-84), respectively. The post-hoc hazard ratio of 0.75 (95% CI: 0.37-1.55) showed no difference between treatments (p=0.44). Overall survival at 7 years was 48% and 59%. There were 4 and 5 cystectomies performed for FCT and GD, respectively. In the FCT arm, there were 5 (16%), 1 (3%) and 0 grade 3, 4 and 5 late toxicities reported. In the GD arm, there were 7 (23%), 0 and 0. CONCLUSIONS: Both regimens maintained high FDM rates at 7 years. Cystectomy rates were low and overall survival rates high on both arms. Late toxicity rates were low. Either gemcitabine and daily radiation or a cisplatin-based regimen are effective bladder sparing therapies.

Prognostic Significance of Immune Cell Infiltration in Muscle-invasive Bladder Cancer Treated with Definitive Chemoradiation: A Secondary Analysis of RTOG 0524 and RTOG 0712.

Chemoradiation therapy (CRT) is a treatment for muscle-invasive bladder cancer (MIBC). Using a novel transcriptomic profiling panel, we validated prognostic immune biomarkers to CRT using 70 pretreatment tumor samples from prospective trials of MIBC (NRG/RTOG 0524 and 0712). Disease-free survival (DFS) and overall survival (OS) were estimated via the Kaplan-Meier method and stratified by genes correlated with immune cell activation. Cox proportional-hazards models were used to assess group differences. Clustering of gene expression profiles revealed that the cluster with high immune cell content was associated with longer DFS (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.26-1.10; p = 0.071) and OS (HR 0.48, 95% CI 0.24-0.97; p = 0.040) than the cluster with low immune cell content. Higher expression of T-cell infiltration genes (CD8A and ICOS) was associated with longer DFS (HR 0.40, 95% CI 0.21-0.75; p = 0.005) and OS (HR 0.49, 95% CI 0.25-0.94; p = 0.033). Higher IDO1 expression (IFNγ signature) was also associated with longer DFS (HR 0.44, 95% CI 0.24-0.88; p = 0.021) and OS (HR 0.49, 95% CI 0.24-0.99; p = 0.048). These findings should be validated in prospective CRT trials that include biomarkers, particularly for trials incorporating immunotherapy for MIBC. PATIENT SUMMARY: We analyzed patient samples from two clinical trials (NRG/RTOG 0524 and 0712) of chemoradiation for muscle-invasive bladder cancer using a novel method to assess immune cells in the tumor microenvironment. Higher expression of genes associated with immune activation and high overall immune-cell content were associated with better disease-free survival and overall survival for patients treated with chemoradiation.

The association between C-reactive protein (CRP) level and biochemical failure-free survival in patients after radiation therapy for nonmetastatic adenocarcinoma of the prostate.

BACKGROUND: C-reactive protein (CRP) has been associated with outcomes in patients with metastatic adenocarcinoma of the prostate. Associations between prostate adenocarcinoma-specific endpoints and CRP in patients who are treated for localized disease remain unknown. METHODS: In total, 206 patients who received radiation therapy for adenocarcinoma of the prostate had at least 1 CRP measured in follow-up and were analyzed. The primary outcome was biochemical failure-free survival. In addition, associations were examined between CRP and prostate-specific antigen (PSA). RESULTS: On univariate analysis, higher CRP levels were associated significantly with shorter biochemical failure-free survival for patients who received radiation therapy after undergoing radical prostatectomy. For patients who were managed with definitive radiation therapy alone, higher CRP levels also were associated significantly with shorter biochemical failure-free survival on univariate and multivariable analyses (hazard ratio, 2.03; 95% confidence interval, 1.19-3.47; P = .009). In addition, CRP levels were associated significantly with PSA after radical prostatectomy for patients who had Gleason scores ≥ 8 (P = .037), for high-risk patients (P = .008), and for those with pretreatment PSA levels > 20 ng/mL (P = .05). In patients who received definitive radiation therapy, CRP levels also were associated with PSA both for those with pretreatment PSA levels > 20 ng/mL (P < .001), and for the intermediate-risk (P = .029) and high-risk (P = .009) subgroups. CONCLUSIONS: A higher CRP level was associated with shorter biochemical failure-free survival on univariate and multivariable analyses in patients who received definitive radiation therapy. CRP was also associated with PSA in exploratory subgroups. These findings warrant further exploration in a prospectively enrolled patient cohort.

Severe lack of comprehension of common prostate health terms among low-income inner-city men.

BACKGROUND: Patients diagnosed with prostate cancer are often counseled about treatment options with the use of terms that are part of the "core vocabulary" of prostate cancer. It is hypothesized that predominantly lower literacy patients would demonstrate a severe lack of comprehension of prostate cancer terms, thus validating the findings of a previous single-institution study. METHODS: A previously developed survey was used to evaluate understanding of terms related to urinary, bowel, and sexual function. The survey was administered by trained evaluators at 2 safety net clinics that provide care for low-income, predominantly African American patients. Comprehension was assessed using semiqualitative methods coded by 2 independent investigators. Literacy and numeracy were also evaluated. RESULTS: Among 109 patients who completed the study, only 5% understood the function of the prostate, and 15%, 29%, and 32% understood the terms "incontinence," "urinary function," and "bowel habits," respectively. Lower levels of comprehension were observed for compound words, such as "vaginal intercourse" (58%), versus single words such as "intercourse" (95%), validating previous work. Median school level was 13 years, yet median literacy level was only ninth grade, and reading level was significantly correlated with comprehension. Only 30% of patients correctly calculated both a fraction and a percent. CONCLUSIONS: Lack of comprehension of prostate health terminology is pronounced in this patient population and may be widespread. This lack of comprehension potentially limits the ability of patients to participate in informed decision-making. These results validate the findings of previous studies and supports a continued need for refined methods of prostate cancer education.

Influence of vascular comorbidities and race on erectile dysfunction after prostate cancer radiotherapy.

INTRODUCTION: Vascular comorbidities (VC) (hypertension, diabetes, and hyperlipidemia) are known factors related to erectile dysfunction (ED) in men. However, no data are yet available for the effects of VC on ED incidence after prostate cancer radiotherapy (XRT). AIM: To investigate the influence of VC on post-XRT ED incidence and to further characterize ED incidence by racial groups. MAIN OUTCOME MEASURES: ED incidence. METHODS: We reviewed 732 charts of patients (267 Caucasian and 465 African American [AA]) who received prostate XRT (external beam radiotherapy and/or brachytherapy) with or without hormone therapy between 1999 and 2010. The number of pre-XRT VC (0, 1, 2, or 3) was determined by medical history and medication list. ED (defined by use of erectile aids or by documentation of moderate or high sexual dysfunction on patient history) was determined pre-XRT as well as 1, 2, and 4 years post-XRT. RESULTS: ED incidence progressively increased from 22% pre-XRT to 58% 4 years post-XRT (P < 0.01). Additionally, ED incidence significantly increased with number of VC-4-year incidence between patients with 1 vs. 0 (P = 0.02), 2 vs. 0 (P < 0.01), 3 vs. 0 (P < 0.01), 3 vs. 1 (P < 0.01), and 3 vs. 2 (P = 0.04) VC (2 vs. 1 VC was nonsignificant). Compared with the Caucasian patients, ED incidences were slightly higher for the AA group with 0, 1, 2, and 3 comorbidities at 4 years follow-up (but statistically nonsignificant). CONCLUSIONS: The number of VCs have a significant effect on development of post-XRT ED. Pre- and post-XRT ED appear to be independent of race when number of VCs are considered. Our results can be used to guide physicians in counseling patients on the incidence of ED by number of VC and as preliminary data for prospective efforts aimed at reducing post-XRT ED.