A practical guide for assessing and managing cardiovascular risk during androgen-deprivation therapy in patients with prostate cancer.

Prostate cancer is the most common malignancy among men worldwide, and androgen-deprivation therapy (ADT) is a mainstay of treatment. There are observational data demonstrating an increased risk of cardiovascular events in patients who receive ADT, particularly those who have an elevated baseline cardiovascular risk. Because, for most patients with prostate cancer, death is predominantly from noncancer-related causes, cardiovascular disease and its risk factors should be optimized during cancer treatment. This review provides an overview of the landscape of ADT treatment and serves as a guide for appropriate cardiovascular screening and risk-mitigation strategies. The authors emphasize the importance of shared communication between the multidisciplinary cancer team and primary care to improve baseline cardiovascular screening and treatment of modifiable risk factors within this higher risk population.

Radical cystectomy versus trimodality therapy for muscle-invasive bladder cancer: a multi-institutional propensity score matched and weighted analysis.

BACKGROUND: Previous randomised controlled trials comparing bladder preservation with radical cystectomy for muscle-invasive bladder cancer closed due to insufficient accrual. Given that no further trials are foreseen, we aimed to use propensity scores to compare trimodality therapy (maximal transurethral resection of bladder tumour followed by concurrent chemoradiation) with radical cystectomy. METHODS: This retrospective analysis included 722 patients with clinical stage T2-T4N0M0 muscle-invasive urothelial carcinoma of the bladder (440 underwent radical cystectomy, 282 received trimodality therapy) who would have been eligible for both approaches, treated at three university centres in the USA and Canada between Jan 1, 2005, and Dec 31, 2017. All patients had solitary tumours less than 7 cm, no or unilateral hydronephrosis, and no extensive or multifocal carcinoma in situ. The 440 cases of radical cystectomy represent 29% of all radical cystectomies performed during the study period at the contributing institutions. The primary endpoint was metastasis-free survival. Secondary endpoints included overall survival, cancer-specific survival, and disease-free survival. Differences in survival outcomes by treatment were analysed using propensity scores incorporated in propensity score matching (PSM) using logistic regression and 3:1 matching with replacement and inverse probability treatment weighting (IPTW). FINDINGS: In the PSM analysis, the 3:1 matched cohort comprised 1119 patients (837 radical cystectomy, 282 trimodality therapy). After matching, age (71·4 years [IQR 66·0-77·1] for radical cystectomy vs 71·6 years [64·0-78·9] for trimodality therapy), sex (213 [25%] vs 68 [24%] female; 624 [75%] vs 214 [76%] male), cT2 stage (755 [90%] vs 255 [90%]), presence of hydronephrosis (97 [12%] vs 27 [10%]), and receipt of neoadjuvant or adjuvant chemotherapy (492 [59%] vs 159 [56%]) were similar between groups. Median follow-up was 4·38 years (IQR 1·6-6·7) versus 4·88 years (2·8-7·7), respectively. 5-year metastasis-free survival was 74% (95% CI 70-78) for radical cystectomy and 75% (70-80) for trimodality therapy with IPTW and 74% (70-77) and 74% (68-79) with PSM. There was no difference in metastasis-free survival either with IPTW (subdistribution hazard ratio [SHR] 0·89 [95% CI 0·67-1·20]; p=0·40) or PSM (SHR 0·93 [0·71-1·24]; p=0·64). 5-year cancer-specific survival for radical cystectomy versus trimodality therapy was 81% (95% CI 77-85) versus 84% (79-89) with IPTW and 83% (80-86) versus 85% (80-89) with PSM. 5-year disease-free survival was 73% (95% CI 69-77) versus 74% (69-79) with IPTW and 76% (72-80) versus 76% (71-81) with PSM. There were no differences in cancer-specific survival (IPTW: SHR 0·72 [95% CI 0·50-1·04]; p=0·071; PSM: SHR 0·73 [0·52-1·02]; p=0·057) and disease-free survival (IPTW: SHR 0·87 [0·65-1·16]; p=0·35; PSM: SHR 0·88 [0·67-1·16]; p=0·37) between radical cystectomy and trimodality therapy. Overall survival favoured trimodality therapy (IPTW: 66% [95% CI 61-71] vs 73% [68-78]; hazard ratio [HR] 0·70 [95% CI 0·53-0·92]; p=0·010; PSM: 72% [69-75] vs 77% [72-81]; HR 0·75 [0·58-0·97]; p=0·0078). Outcomes for radical cystectomy and trimodality therapy were not statistically different among centres for cancer-specific survival and metastasis-free survival (p=0·22-0·90). Salvage cystectomy was done in 38 (13%) trimodality therapy patients. Pathological stage in the 440 radical cystectomy patients was pT2 in 124 (28%), pT3-4 in 194 (44%), and 114 (26%) node positive. The median number of nodes removed was 39, the soft tissue positive margin rate was 1% (n=5), and the perioperative mortality rate was 2·5% (n=11). INTERPRETATION: This multi-institutional study provides the best evidence to date showing similar oncological outcomes between radical cystectomy and trimodality therapy for select patients with muscle-invasive bladder cancer. These results support that trimodality therapy, in the setting of multidisciplinary shared decision making, should be offered to all suitable candidates with muscle-invasive bladder cancer and not only to patients with significant comorbidities for whom surgery is not an option. FUNDING: Sinai Health Foundation, Princess Margaret Cancer Foundation, Massachusetts General Hospital.

Racial/ethnic disparities in patient experiences with care and Gleason score at diagnosis of prostate cancer: a SEER-CAHPS study.

PURPOSE: To determine whether racial/ethnic differences in patient experiences with care, potentially leading to underutilization of necessary care, are associated with disparities in Gleason score at diagnosis. METHODS: We used the SEER-CAHPS linked dataset to identify Medicare beneficiaries who completed a Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey prior to diagnosis of prostate cancer. Independent variables included aspects of patient experiences with care captured by CAHPS surveys. We conducted survey weighted multivariable multinomial logistic regression analyses, stratified by patient race/ethnicity, to estimate associations of CAHPS measures with Gleason score at diagnosis. RESULTS: Of the 4,245 patients with prostate cancer, most were non-Hispanic white (NHW) (77.6%), followed by non-Hispanic black (NHB) (8.4%), Hispanic (8.4%), and Asian (5.6%). Excellent experience with getting needed prescription drugs was associated with lower odds of Gleason scores of 7 and 8-10 in NHBs (7: OR = 0.19, 95% CI = 0.05-0.67; 8-10: OR = 0.04, 95% CI = 0.01-0.2) and lower odds of 8-10 in NHWs (OR = 0.61, 95% CI = 0.40-0.93). For NHBs, excellent primary physician ratings were associated with greater odds of a Gleason score of 8-10 (OR = 13.28, 95% CI = 1.53-115.21). CONCLUSION: Patient experiences with access to care and physician relationships may influence Gleason score in different ways for patients of different racial/ethnic groups. More research, including large observational studies with greater proportions of racial/ethnic minority patients, is necessary to understand these relationships and target interventions to overcome disparities and improve patient outcomes.

Challenges in Reporting the Effect of Radiotherapy on Erectile Function.

BACKGROUND: Erectile dysfunction (ED) is the most common side effect of prostate radiotherapy (RT), but reported rates over time and across modalities have varied widely. AIM: To evaluate the published literature between 2002 and 2018 for high quality data utilizing prospectively gathered patient-reported ED, and to summarize the challenges in reporting of RT-induced ED (RIED). METHODS: A PubMed search and literature review was performed to identify articles describing rates of ED before and after definitive external beam RT or brachytherapy without androgen deprivation. OUTCOMES: Patient-reported ED, patient and treatment variables, and study follow-up constituted the main outcomes of this study. RESULTS: 24 articles were identified, reporting RIED rates between 17% and 90%. Variables contributing to this range included patient, treatment, and study characteristics known to impact ED reporting. CLINICAL IMPLICATIONS: For future studies, we recommend the use of validated patient-reported questionnaires and reporting of baseline function and comorbidities, RT type and dose, and use of androgen deprivation therapy and erectile aids at the time of ED measurement. With sufficient follow-up to understand the late nature of RIED, these recommendations will improve comparison of results between studies and the applicability of results to patients undergoing pretreatment counseling regarding the risks of RIED. STRENGTHS & LIMITATIONS: The literature search and formulation of results were based on a broad understanding of the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and the literature, but because of the focus on data reporting, a comprehensive systematic review of all RIED literature was not performed. CONCLUSION: Reported rates of ED after RT vary widely due to differences in patients' baseline reported erectile function, age, comorbidities, and characteristics of the treatment delivered. The methodology of ED measurement has significant impact on the applicability and comparability of results to other studies and clinical practice. Nukala V, Incrocci L, Hunt AA, et al. Challenges in Reporting the Effect of Radiotherapy on Erectile Function. J Sex Med 2020;17:1053-1059.

Trimodality therapy for bladder cancer: modern management and future directions.

PURPOSE OF REVIEW: This review examines both trimodality therapy (TMT) in the definitive management of bladder cancer as well as the use of adjuvant radiotherapy for bladder cancer with a specific focus on publications from the last 2 years. RECENT FINDINGS: TMT is an effective management strategy for muscle invasive bladder cancer with outcomes similar to radical cystectomy. Effectiveness of this strategy exists in variant histologies and can be personalized with use of biomarkers. There is a role for adjuvant radiotherapy in locally advanced bladder cancer, especially in the age of improved imaging and modern radiotherapy techniques. SUMMARY: This review should provide the reader data necessary to support use of TMT and adjuvant radiation therapy in their clinic.

Using hospital medical record data to assess the accuracy of the SEER Los Angeles Cancer Surveillance Program for initial treatment of prostate cancer: a small pilot study.

PURPOSE: Treatment information from the Surveillance, Epidemiology, and End Result Program (SEER) cancer registries is increasingly being used for population-based cancer research; however, it may be incomplete for outpatient procedures and is not quality controlled. We sought to validate SEER information on initial treatment of prostate cancer by comparison to electronic medical record (EMR) review. METHODS: Patients diagnosed with prostate cancer between 1 January 2010 and 31 December 2014 in Los Angeles County who received treatment at our institution within 6 months of diagnosis were identified from the SEER registry. We reviewed the hospital EMR for these patients and identified initial treatment received within 6 months of diagnosis. We compared data reported to SEER data to our re-abstracted hospital EMR data (defined as the gold standard) to identify the completeness of SEER treatment data (sensitivity) and the accuracy of the SEER information (positive predictive value). RESULTS: Based on 266 eligible patients, SEER's sensitivity in capturing initial treatment was 95.9% (118/123) for prostatectomy, 95.8% (69/72) for no treatment, 87.5% (21/24) for radiation therapy, 68.3% (28/41) for active surveillance or watchful waiting, and 50.0% (2/4) for cryosurgery. The SEER positive predictive value was 100% for radiation therapy and cryosurgery, 97.5% (118/121) for radical prostatectomy, 82.3% (28/34) for active surveillance or watchful waiting, and 78.4% (69/88) for no treatment. CONCLUSION: The SEER data were highly sensitive and has a high positive predictive value for surgery and radiation therapy but underreported use of active surveillance. These results may assist researchers in understanding the strengths and weaknesses of using SEER prostate cancer treatment data.

Current Management Strategy for Penile Cancer and Future Directions.

PURPOSE OF REVIEW: The aim of this review is to evaluate the trends in multidisciplinary management of localized penile cancer and systemic therapy for advanced disease in the evolving era of targeted and immune checkpoint therapy. RECENT FINDINGS: Organ preservation (surgical or incorporating radiation) and reconstructive techniques are important considerations for quality of life in penile cancer survivors. Although local recurrence may be higher with organ preservation, salvage therapy appears successful. Inguinal and pelvic node management requires multidisciplinary care, including chemotherapy; optimal use of radiation has not been fully defined. Advanced in understanding the biology of penile cancer, particularly with regard to epidermal growth factor receptor (EGFR) and HPV status, have led to clinical trials of targeted and immune therapy for patients with refractory disease. Refinements in the management of penile cancer are occurring, though level 1 evidence remains scarce. Referral to specialized centers will facilitate successful completion of clinical trials to advance standard care in this disease.

Immunotherapy in urothelial cancer, part 1: T-cell checkpoint inhibition in advanced or metastatic disease.

Cancer of the urothelium is the sixth most common cancer in the United States and is seen predominantly in men. Most cases of this disease present as non-muscle-invasive bladder cancer (NMIBC), with cancer recurrence or progression to muscle-invasive cancer in more than 50% of patients after initial therapy. NMIBC is an immune-responsive disease, as indicated by the use of intravesical bacillus Calmette-Guérin as treatment for more than 3 decades. More recently, immunotherapy has seen much progress in a variety of cancers, including advanced and metastatic bladder cancer, in which historical 5-year survival rates are approximately 15%. The advent of T-cell checkpoint inhibitors, especially those directed at programmed death 1 (PD-1) and its ligand (PD-L1), has had a significant effect on the therapy of advanced urothelial cancer. This had led to accelerated approval by the US Food and Drug Administration for atezolizumab and nivolumab in advanced urothelial cancer previously treated with platinum-based chemotherapy. In addition, level 1 evidence supports the use of pembrolizumab over single-agent tubulin-directed chemotherapy in the same setting. Several other treatments with immune-mediating mechanisms of action are in development and hold great promise, including monoclonal antibodies directed at other checkpoint molecules, oncolytic virus therapy, adoptive T-cell therapy, combination immunotherapy, and antibody-drug conjugates. This review focuses on the recent development of T-cell checkpoint inhibitors in advanced and metastatic urothelial cancer and addresses their potential use in combination. It also discusses a spectrum of novel immunotherapies with potential use in urothelial cancer.

Immunotherapy in urothelial cancer, part 2: adjuvant, neoadjuvant, and adjunctive treatment.

Urothelial cancer, which is predominantly seen in men, is common throughout the world. Most disease presents as non-muscle invasive bladder cancer (NMIBC), with cancer recurring or progressing to muscle invasive disease in more than 50% of patients after initial therapy. NMIBC is an immune responsive disease, as indicated by the use of intravesical bacillus Calmette-Guérin as treatment for more than 3 decades. The advent of T-cell checkpoint inhibitors, especially those directed at programmed death 1 (PD-1) and its ligand (PD-L1), has had a significant impact on the therapy of advanced urothelial cancer. This had led to a revisitation of immunotherapy in urothelial cancer, as well as the genesis of trials using novel immunotherapeutic agents. This review focuses on immunotherapy in NMIBC, both on its own and as a potential treatment in combination with RT. It also discusses the development of immunotherapies in early bladder cancer disease states, and in neoadjuvant and adjuvant perioperative settings for localized muscle invasive cancers.

ACR Appropriateness Criteria® Recurrent Hodgkin Lymphoma.

This topic addresses the management of recurrent Hodgkin lymphoma. While autologous stem cell transplantation may be appropriate for select cases of recurrent disease following comprehensive combined-modality therapy, other options exist for patients treated with lower-dose therapy for early-stage disease. Additionally, innovative targeted therapies provide newer salvage options to consider. The American College of Radiology Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation, or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. By combining the most recent medical literature and expert opinion, this revised guideline can aid clinicians in the complex decision-making associated with the management of recurrent Hodgkin lymphoma.

Radical Prostatectomy or External Beam Radiation Therapy vs No Local Therapy for Survival Benefit in Metastatic Prostate Cancer: A SEER-Medicare Analysis.

PURPOSE: We assessed survival after radical prostatectomy, intensity modulated radiation therapy or conformal radiation therapy vs no local therapy for metastatic prostate cancer adjusting for patient comorbidity, androgen deprivation therapy and other factors. MATERIALS AND METHODS: We identified men 66 years old or older with metastatic prostate cancer treated with radical prostatectomy, intensity modulated radiation therapy, conformal radiation therapy or no local therapy in the SEER-Medicare linked database from 2004 to 2009. Multivariable Cox proportional hazards models before and after inverse propensity score weighting were used to assess all cause and prostate cancer specific mortality. Competing risk regression analysis was done to assess prostate cancer specific mortality. RESULTS: Of 4,069 men with metastatic prostate cancer radical prostatectomy in 47, intensity modulated radiation therapy in 88 and conformal radiation therapy in 107 were selected as local therapy vs no local therapy in 3,827. Radical prostatectomy was associated with a 52% decrease (HR 0.48, 95% CI 0.27-0.85) in the risk of prostate cancer specific mortality after adjusting for sociodemographics, primary tumor characteristics, comorbidity, androgen deprivation therapy and bone radiation within 6 months of diagnosis. Intensity modulated radiation therapy was associated with a 62% decrease (HR 0.38, 95% CI 0.24-0.61) in the risk of prostate specific cancer specific mortality. Conformal radiation therapy was not associated with improved survival compared to no local therapy. Propensity score weighting yielded comparable results. Competing risk analysis revealed a 42% and 57% decrease (SHR 0.58, 95% CI 0.35-0.95 and SHR 0.43, 95% CI 0.27-0.68, respectively) in the risk of prostate cancer specific mortality for radical prostatectomy and intensity modulated radiation therapy. CONCLUSIONS: Local therapy with radical prostatectomy and intensity modulated radiation therapy but not with conformal radiation therapy was associated with a survival benefit in men with metastatic prostate cancer. This finding warrants prospective evaluation in clinical trials.

Modern radiotherapeutic strategies in the management of lymphoma.

The history of radiation therapy in the treatment of malignancies is closely linked to its use in Hodgkin lymphoma. It was less than a decade after the first publication on x-rays that radiotherapy was used in the treatment of a Hodgkin lymphoma. Over time, radiotherapy has evolved with newer technology and better understanding of radiobiology. During this same time frame, the treatment of Hodgkin and non-Hodgkin lymphomas has also seen great progress. This review will provide detail on modern radiotherapy techniques, indications for utilization, and modern radiation field sizes and doses.

Brachytherapy based microboosting to the dominant intraprostatic lesion in prostate cancer: A systematic review on treatment outcomes and toxicities.

PURPOSE: Whether brachytherapy based microboosting of the dominant intraprostatic lesion (DIL) improves outcomes over standard approaches is not known. The purpose of this study is to perform a systematic review on brachytherapy microboosting of the DIL to evaluate clinical outcomes and toxicities with this treatment approach. MATERIALS AND METHODS: This review was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Databases including Pubmed, Embase, and Google Scholar were queried. About 16 studies met our inclusion criteria. These studies reported PSA control and/or toxicities based on standardized scales. RESULTS: There were 10 studies (two monotherapy, eight combination) that used HDR microboosting on a total of 516 patients. HDR dose (EQD2 assuming alpha/beta of 1.5) to the DIL ranged from 90 to 180 Gy. Most patients were low/intermediate risk. PSA control rates at 5-8 years ranged from 69% to 100%. Acute/late G3-G4 GU/GI toxicities ranged from 0% to 12%. There were six studies (five monotherapy, one combination) that used LDR microboosting on a total of 1041 patients. Studies performed a microboost of 130-150% of the whole gland prescription to the DIL. Most patients were low/intermediate risk. PSA control rates at 5 years ranged from 69% to 98%. Acute/late G3-4 GU/GI toxicities ranged from 0% to 4%. CONCLUSIONS: Over 1000 patients have been treated with a brachytherapy based microboost in published series. Severe acute/late toxicities appear limited. PSA control rates with more than 5 years of follow-up are limited. Longer-term follow-up is needed to determine ideal utilization of this approach.

Intra-fractional geometric and dose/volume metric variations of magnetic resonance imaging-guided stereotactic radiotherapy of prostate bed after radical prostatectomy.

Background and purpose: Magnetic Resonance Imaging (MRI)-guided Stereotactic body radiotherapy (SBRT) treatment to prostate bed after radical prostatectomy has garnered growing interests. The aim of this study is to evaluate intra-fractional anatomic and dose/volume metric variations for patients receiving this treatment. Materials and methods: Nineteen patients who received 30-34 Gy in 5 fractions on a 0.35T MR-Linac were included. Pre- and post-treatment MRIs were acquired for each fraction (total of 75 fractions). The Clinical Target Volume (CTV), bladder, rectum, and rectal wall were contoured on all images. Volumetric changes, Hausdorff distance, Mean Distance to Agreement (MDA), and Dice similarity coefficient (DSC) for each structure were calculated. Median value and Interquartile range (IQR) were recorded. Changes in target coverage and Organ at Risk (OAR) constraints were compared and evaluated using Wilcoxon rank sum tests at a significant level of 0.05. Results: Bladder had the largest volumetric changes, with a median volume increase of 48.9 % (IQR 28.9-76.8 %) and a median MDA of 5.1 mm (IQR 3.4-7.1 mm). Intra-fractional CTV volume remained stable with a median volume change of 1.2 % (0.0-4.8 %). DSC was 0.97 (IQR 0.94-0.99). For the dose/volume metrics, there were no statistically significant changes observed except for an increase in bladder hotspot and a decrease of bladder V32.5 Gy and mean dose. The CTV V95% changed from 99.9 % (IQR 98.8-100 %) to 99.6 % (IQR 93.9-100 %). Conclusion: Despite intra-fractional variations of OARs, CTV coverage remained stable during MRI-guided SBRT treatments for the prostate bed.

Variation in content discussed by specialty in consultations for clinically localized prostate cancer.

INTRODUCTION: Multidisciplinary consultations improve decisional conflict and guideline-concordant treatment for men with prostate cancer (PC), but differences in the content discussed by specialty during consultations are unknown. METHODS: We audiorecorded and transcribed 50 treatment consultations for localized PC across a multidisciplinary sample of urologists, radiation oncologists, and medical oncologists. Conversation was coded for narrative content using an open coding approach, grouping similar topics into major content areas. The number of words devoted to each content area per consult was used as a proxy for time spent. Multivariable Poisson regression calculated incidence rate ratios (IRR) for content-specific word count across specialties after adjustment for tumor risk and patient demographics. RESULTS: Coders identified 8 narrative content areas: overview of PC; medical history; baseline risk; cancer prognosis; competing risks; treatment options; physician recommendations; and shared decision making (SDM). In multivariable models, specialties significantly differed in proportion of time spent on treatment options, SDM, competing risks, and cancer prognosis. Urologists spent 1.8-fold more time discussing cancer prognosis than medical oncologists (IRR1.80, 95%CI:1.14-2.83) and radiation oncologists (IRR1.84, 95%CI:1.10-3.07). Urologists (IRR11.38, 95%CI:6.62-19.56) and medical oncologists (IRR10.60, 95%CI:6.01-18.72) spent over 10-fold more time discussing competing risks than radiation oncologists. Medical oncologists (IRR2.60, 95%CI:1.65-4.10) and radiation oncologists (IRR1.77, 95%CI:1.06-2.95) spent 2.6- and 1.8-fold more time on SDM than urologists, respectively. CONCLUSIONS: Specialists focus on different content in PC consultations. Our results suggest that urologists should spend more time on SDM and radiation oncologists on competing risks. Our results also highlight the importance of medical oncologists in facilitating SDM.

Irradiated Bone Marrow Volume is Associated with Hematologic Toxicity in Patients with Multiple Myeloma.

PURPOSE/OBJECTIVE(S): Palliative radiotherapy (RT) is effective for multiple myeloma (MM) but may cause cytopenia. Bone marrow volume receiving 10Gy (BMV10Gy) has been associated with hematologic toxicity (HT) in cervical cancer, but no studies have investigated this in MM. We hypothesized that absolute BMV10Gy is associated with acute HT in MM patients receiving palliative RT. MATERIALS/METHODS: This single-institution retrospective analysis evaluated 125 MM patients who received palliative RT between 2007-2023 and had ≥ 2 weeks of follow up laboratory data. Lab values were recorded pre-RT, post-RT, and at nadir within 90 days of completing RT. Clinical HT was defined as new transfusion/growth factor, admission for hematologic toxicity, and/or systemic therapy pause/discontinuation. BM was defined as bone volume within RT field. BMV5-40Gy (cc) was recorded for each treatment. Logistic regressions were performed with clinical HT as the primary endpoint. RESULTS: 105 (84%) patients received concurrent systemic therapy. Median BMV10Gy was 266cc (IQR 157-501cc). Median RT EqD2 was 26Gy (IQR 23-33Gy). On univariable analysis, BMV5Gy, BMV10Gy, and BMV15Gy were significantly associated with clinical HT (p=0.014, p=0.018, p=0.050, respectively) while RT EqD2 dose was not (p=0.997). On multivariable analysis, BMV10Gy was significantly associated with clinical HT (p=0.049) after adjusting for dose, number of lesions treated, lesion location (spine, pelvis, limb, soft tissue), and systemic therapy class. Disease course (number of prior systemic therapies) was significantly associated with clinical HT on univariable and multivariable analysis, with late relapsed/refractory patients (≥3 prior systemic therapies) having 9.6 higher odds of clinical HT compared to newly diagnosed patients (p<0.001). CONCLUSION: To our knowledge, this is the first study to associate volume of irradiated BM with acute HT in MM. In addition to BM V5-15Gy, number of prior relapses and systemic therapy lines were significantly associated with HT. Disease history should be evaluated, and RT field volumes minimized for patients with poor bone marrow reserve (e.g., late relapsed/refractory disease).

Eligibility and Endpoints for Clinical Trials in Trimodality Therapy for Bladder Cancer.

BACKGROUND: Trimodality therapy (TMT) is a viable option for muscle-invasive localized bladder cancer, providing an alternative to radical cystectomy in properly selected patients. The approval of novel therapeutics in different stages of bladder cancer treatment has sparked interest in exploring concurrent systemic therapies with radiation in clinical trials to enhance long-term outcomes. Achieving uniformity in trial eligibility criteria and endpoint definitions is imperative in describing clinical significance, comparing trials, and changing standard of care guidelines. OBJECTIVE: To delineate eligibility criteria and appropriate endpoints for TMT clinical trials in an attempt to achieve uniformity in trial eligibility criteria and endpoint definitions which will then help move the field of bladder preservation forward and improve the current standard of care. METHODS: An expert panel, comprising individuals with extensive experience in bladder cancer clinical trials, clinical practice focused on bladder cancer treatment, and patient advocacy, was assembled. The panel systematically reviewed phase II/III clinical trials previously published and assessing the role of radiation in definitive therapy with the specific goal of preserving native bladder function during bladder cancer treatment. Recommendations were summarized based on review of these trials and past experiences of the investigators. To ensure a holistic perspective, the summary was further subjected to rigorous reevaluation by a patient advocate, who added valuable insights from a patient's standpoint. The resulting consensus statements were summarized in this publication to contribute to the evolving landscape of bladder cancer research and treatment. RESULTS: The eligibility criteria for TMT should be pragmatic to encompass patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, bladder cancer stage T2-T4a N0±N1M0, unilateral tumor-associated hydronephrosis, attempted maximal transurethral resection of bladder tumor (TURBT), both pure urothelial carcinoma and/or mixed histologic subtypes (excluding rare and aggressive small cell variants) and patients who are non- cystectomy candidates. Bladder intact event-free survival (BIEFS) is proposed as a suitable endpoint for registration trials designed to compare two different treatment interventions, defined as the time from randomization to muscle-invasive or locoregional recurrence, systemic recurrence, radical cystectomy from any cause, or death from any cause. Overall survival is deemed an appropriate secondary endpoint or a co-primary end point as recent improvements in systemic therapy can produce significant improvement in long-term outcomes. Primary and secondary endpoints should be supported with patient-reported quality of life assessments, when available. CONCLUSIONS: The standardization of clinical trial design, eligibility criteria, and endpoints is essential for expediting progress in the field. Inclusivity, patient-centricity, and clinically meaningful endpoints will facilitate the analysis, comparison, and meta-analysis of different trials, fostering advancements in bladder cancer treatment.

Prostate Cancer Disparities in Clinical Characteristics and Survival among Black and Latino Patients Considering Nativity: Findings from the California Cancer Registry.

BACKGROUND: We investigated clinical characteristics and prostate cancer survival patterns among Latino patients considering nativity compared with non-Latino Black (NLB) and non-Latino White (NLW) patients. METHODS: We used data from the California Cancer Registry (1995-2021), which included 347,540 NLW, 50,032 NLB, and 75,238 Latino patients with prostate cancer. Frequencies of sociodemographic and clinical variables were assessed using χ2 tests. Multivariable regression models were fitted to evaluate determinants of treatment reception, Gleason upgrade, and survival differences. Exploratory analyses were conducted grouping Latino cases into US born and non-US born by country of origin. RESULTS: Compared with NLW, NLB cases had the greatest proportion of younger patients, whereas non-US-born Latino patients had the greatest proportion of low socioeconomic status and uninsured patients. Non-US-born Latinos showed a greater proportion of diagnoses completed with <6 core biopsies, Gleason >8, stage IV tumors, and metastasis. Multivariable analyses showed that compared with NLW, Latino patients were as likely to receive treatment, whereas NLB cases were less likely (OR = 0.81; 95% confidence interval, 0.67-0.98; P = 0.029). Compared with NLW, non-US-born Latino cases were less likely to die of prostate cancer (HR = 0.78; 95% confidence interval, 0.64-0.94; P = 0.011), with no difference reported for NLB cases. CONCLUSIONS: Considering sociodemographic and clinical characteristics, non-US-born Latino patients with prostate cancer had better survival than NLW. This highlights the need to identify key determinants of these survival differences and the importance of sociodemographic and clinical determinants in survival disparities. IMPACT: Our study emphasizes the importance of considering nativity among Latino patients to understand prostate cancer disparities and outcomes in this population.

Real-World Utilization of Radiation Therapy in Multiple Myeloma: An Analysis of the Connect MM Registry.

PURPOSE: Radiation therapy (RT) is an important treatment modality for patients with multiple myeloma (MM). Although patients are living longer with MM, they are more likely to have comorbidities related to treatment, such as bone pain; however, RT can provide symptom relief. To date, the characterization of patients who have received RT in the real-world setting has been limited. METHODS AND MATERIALS: The Connect® MM Registry is a large, US multicenter, prospective observational cohort study of adult patients with newly diagnosed MM from mostly community sites. RT utilization and outcomes were analyzed quarterly throughout treatment. Factors associated with RT use were identified via multivariable analysis. RESULTS: A total of 3011 patients were enrolled in the Connect MM Registry with 903 patients (30%) having received RT at any time. There was a significant difference (P < .05) in overall RT use among patients with an Eastern Cooperative Oncology Group performance status of 0 to 1 versus ≥2, International Staging System disease stage I/II versus III, a history of plasmacytoma or a novel agent in their first regimen, and any number of bone lesions or severe osteoporosis/fracture. RT use was associated with having bone lesions or severe osteoporosis (vs not having bone lesions). Additionally, RT use was associated with ethnicity (Hispanic vs not) and Connect MM Registry cohort (cohort 1 [enrolled 2009-2011] vs 2 [enrolled 2012-2016]). In the 6 months before death, increased RT use was associated with increasing number of treatment lines (P < .0001) and high- versus standard-risk disease (per International Myeloma Working Group criteria; P = .0028). CONCLUSIONS: Real-world results from the Connect MM Registry show RT is frequently used and is associated with clinical factors, including performance status and disease stage. Earlier in MM diagnosis, RT may be used as an adjunct to palliate symptoms or delay systemic therapy. Toward the end of life, RT is more frequently used for palliation when treatment options are often limited.

Radiation target nomenclature for lymphoma trials: consensus recommendations from the National Clinical Trials Network groups.

Contemporary lymphoma radiation target volumes that rely on post-systemic therapy imaging do not have standardised nomenclature. A forum of radiation oncology lymphoma leaders from the National Clinical Trials Network groups (NRG Oncology, Children's Oncology Group, SWOG Cancer Research Network, Alliance for Clinical Trials in Oncology, Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group, and the Canadian Cancer Trials Group) was convened and established standardised nomenclature for these volumes in the autumn of 2024. Involved-site radiotherapy includes the full cranial-caudal extent of prechemotherapy disease and takes into account axial anatomical changes only. Residual site radiotherapy targets only the postchemotherapy CT-anatomical mass. PET-directed radiotherapy exclusively targets PET-positive disease and includes three types: PET-directed involved site radiotherapy using the superior-inferior aspect of prechemotherapy involved disease sites that remain PET-avid on post-treatment imaging; PET-directed residual site radiotherapy using only the postchemotherapy CT-anatomical residual mass that contains the PET-avid lesion on post-treatment imaging, without excluding sites that had complete metabolic response; and PET-directed residual PET radiotherapy using only the PET-avid focus, irrespective of the corresponding adjacent non-PET-avid CT-anatomical disease surrounding it.