PSA Stratification for Predicting Advanced Prostate Cancer Events in Men Approaching Age-Limits for Recommended Screening.

PURPOSE: To quantify the ability of various PSA values in predicting the likelihood of developing metastatic or fatal prostate cancer in older men. MATERIALS/METHODS: We used a random sample of patients in the United States Veterans Health Administration to identify 80,706 men who had received PSA testing between ages 70 to 75. Our primary endpoint was time to development of either metastatic prostate cancer or death from prostate cancer. We used cumulative/dynamic modeling to account for competing events (death from non-prostate cancer causes) in studying both the discriminative ability of PSA as well as for positive predictive value and negative predictive value at three time points. RESULTS: PSA demonstrated time-dependent predictive discrimination, with receiver operating characteristic area under the curve at 5, 10, and 14 years decreasing from 0.83 to 0.77 to 0.73, respectively, but without statistically significant difference when stratified by race. At PSA thresholds between 1 and 8 ng/mL, the positive predictive value of developing advanced prostate cancer was significantly greater in Black than White patients. For instance, at a PSA > 3, at 5, 10, and 14 years, White patients had 2.4%, 2.9%, and 3.7% risk of an event, whereas Black patients had 4.3%, 6.5%, and 8.3% risk. CONCLUSIONS: In men aged 70 to 75 deciding whether to cease PSA testing with borderline-elevated PSA values, the risk of developing metastatic or fatal prostate cancer is quantifiable and relatively low. Risk assessment in this setting must account for the higher incidence of prostate cancer in Black men.

Patient perspectives of prostate cancer screening vary by race following 2018 guideline changes.

BACKGROUND: The 2018 US Preventive Services Task Force guidelines recommend individualizing prostate cancer screening in 55- to 69-year-old men. Given the higher incidence of prostate cancer in African American (AA) compared to non-Hispanic White (NHW) men, this study compared reported rates of prostate-specific antigen (PSA) screening hypothesizing that it would not be commensurate with the relative risk between these two groups. METHODS: Using the 2020 Behavioral Risk Factor Surveillance System, we identified 43,685 men (40,301 NHW and 3384 AA) interviewed about PSA screening. RESULTS: AA men had an odds ratio (OR) of 0.80 (95% confidence interval [CI], 0.69-0.93; p = .004) of reporting PSA screening; sequentially correcting for access to care, smoking, and age had minimal effect on this finding, but when correcting for income significantly attenuated this difference (OR, 0.95; 95% CI, 0.81-1.12). Further adding education level eliminated the effect size of AA race entirely with OR, 0.99 (95% CI, 0.84-1.17; p = .91). Further analysis found significant interaction between education and race, with college-educated AA men having 1.42 OR of receiving screening compared to college-educated NHW men. CONCLUSIONS: Despite prostate cancer being more common and having higher population-level mortality in AA than NHW men, PSA screening and education patterns do not reflect this increased risk even when adjusting for health access disparities. The authors' findings of significant effect from both income and education suggest that systemic racism is an important factor in the observed difference in PSA screening between AA men and NHW men. LAY SUMMARY: In the United States, prostate cancer is more common in African American men New guidelines from 2018 encourage physicians to consider risk factors in deciding whether or not to recommend screening, but overall African American men continue to be screened at a lower rate than non-Hispanic White men This effect disappears when correcting for income and education level, suggesting that several factors including systemic racism, medical mistrust, and self-advocacy may impact this observed difference.

The Unfolded Protein Response Triggers Site-Specific Regulatory Ubiquitylation of 40S Ribosomal Proteins.

Insults to ER homeostasis activate the unfolded protein response (UPR), which elevates protein folding and degradation capacity and attenuates protein synthesis. While a role for ubiquitin in regulating the degradation of misfolded ER-resident proteins is well described, ubiquitin-dependent regulation of translational reprogramming during the UPR remains uncharacterized. Using global quantitative ubiquitin proteomics, we identify evolutionarily conserved, site-specific regulatory ubiquitylation of 40S ribosomal proteins. We demonstrate that these events occur on assembled cytoplasmic ribosomes and are stimulated by both UPR activation and translation inhibition. We further show that ER stress-stimulated regulatory 40S ribosomal ubiquitylation occurs on a timescale similar to eIF2α phosphorylation, is dependent upon PERK signaling, and is required for optimal cell survival during chronic UPR activation. In total, these results reveal regulatory 40S ribosomal ubiquitylation as an important facet of eukaryotic translational control.

Validation of an oncology-specific opioid risk calculator in cancer survivors.

BACKGROUND: Clinical guidelines recommend that providers risk-stratify patients with cancer before prescribing opioids. Prior research has demonstrated that a simple cancer opioid risk score might help identify to patients with cancer at the time of diagnosis with a high likelihood of long-term posttreatment opioid use. This current project validates this cancer opioid risk score in a generalizable, population-based cohort of elderly cancer survivors. METHODS: This study identified 44,932 Medicare beneficiaries with cancer who had received local therapy. Longitudinal opioid use was ascertained from Medicare Part D data. A risk score was calculated for each patient, and patients were categorized into low-, moderate-, and high-risk groups on the basis of the predicted probability of persistent opioid use. Model discrimination was assessed with receiver operating characteristic curves. RESULTS: In the study cohort, 5.2% of the patients were chronic opioid users 1 to 2 years after the initiation of cancer treatment. The majority of the patients (64%) were at low risk and had a 1.2% probability of long-term opioid use. Moderate-risk patients (33% of the cohort) had a 5.6% probability of long-term opioid use. High-risk patients (3.5% of the cohort) had a 75% probability of long-term opioid use. The opioid risk score had an area under the receiver operating characteristic curve of 0.869. CONCLUSIONS: This study found that a cancer opioid risk score could accurately identify individuals with a high likelihood of long-term opioid use in a large, generalizable cohort of cancer survivors. Future research should focus on the implementation of these scores into clinical practice and how this could affect prescriber behavior and patient outcomes. LAY SUMMARY: A novel 5-question clinical decision tool allows physicians treating patients with cancer to accurately predict which patients will persistently be using opioid medications after completing therapy.

Prognostic implications of RAS alterations in diverse malignancies and impact of targeted therapies.

RAS alterations are often found in difficult-to-treat malignancies and are considered "undruggable." To better understand the clinical correlates and coaltered genes of RAS alterations, we used targeted next-generation sequencing (NGS) to analyze 1,937 patients with diverse cancers. Overall, 20.9% of cancers (405/1,937) harbored RAS alterations. Most RAS-altered cases had genomic coalterations (95.3%, median: 3, range: 0-51), often involving genes implicated in oncogenic signals: PI3K pathway (31.4% of 405 cases), cell cycle (31.1%), tyrosine kinase families (21.5%) and MAPK signaling (18.3%). Patients with RAS-altered versus wild-type RAS malignancies had significantly worse overall survival (OS; p = 0.02 [multivariate]), with KRAS alterations, in particular, showing shorter survival. Moreover, coalterations in both RAS and PI3K signaling or cell-cycle-associated genes correlated with worse OS (p = 0.004 and p < 0.0001, respectively [multivariate]). Among RAS-altered patients, MEK inhibitors alone did not impact progression-free survival (PFS), while matched targeted therapy against non-MAPK pathway coalterations alone showed a trend toward longer PFS (vs. patients who received unmatched therapy) (HR: 0.79, 95% CI: 0.61-1.03, p = 0.07). Three of nine patients (33%) given tailored combination therapies targeting both MAPK and non-MAPK pathways achieved objective responses. In conclusion, RAS alterations correlated with poor survival across cancers. The majority of RAS alterations were accompanied by coalterations impacting other oncogenic pathways. MEK inhibitors alone were ineffective against RAS-altered cancers while matched targeted therapy against coalterations alone correlated with a trend toward improved PFS. A subset of the small number of patients given MEK inhibitors plus tailored non-MAPK-targeting agents showed responses, suggesting that customized combinations warrant further investigation.

Quality of care at safety-net hospitals and the impact on pay-for-performance reimbursement.

BACKGROUND: Pay-for-performance reimbursement ties hospital payments to standardized quality-of-care metrics. To the authors' knowledge, the impact of pay-for-performance reimbursement models on hospitals caring primarily for uninsured or underinsured patients remains poorly defined. The objective of the current study was to evaluate how standardized quality-of-care metrics vary by a hospital's propensity to care for uninsured or underinsured patients and demonstrate the potential impact that pay-for-performance reimbursement could have on hospitals caring for the underserved. METHODS: The authors identified 1,703,865 patients with cancer who were diagnosed between 2004 and 2015 and treated at 1344 hospitals. Hospital safety-net burden was defined as the percentage of uninsured or Medicaid patients cared for by that hospital, categorizing hospitals into low-burden, medium-burden, and high-burden hospitals. The authors evaluated the impact of safety-net burden on concordance with 20 standardized quality-of-care measures, adjusting for differences in patient age, sex, stage of disease at diagnosis, and comorbidity. RESULTS: Patients who were treated at high-burden hospitals were more likely to be young, male, Black and/or Hispanic, and to reside in a low-income and low-educated region. High-burden hospitals had lower adherence to 13 of 20 quality measures compared with low-burden hospitals (all P < .05). Among the 350 high-burden hospitals, concordance with quality measures was found to be lowest for those caring for the highest percentage of uninsured or Medicaid patients, minority patients, and less educated patients (all P < .001). CONCLUSIONS: Hospitals caring for uninsured or underinsured individuals have decreased quality-of-care measures. Under pay-for-performance reimbursement models, these lower quality-of-care scores could decrease hospital payments, potentially increasing health disparities for at-risk patients with cancer.

Survival of African American and non-Hispanic white men with prostate cancer in an equal-access health care system.

BACKGROUND: African American (AA) men in the general US population are more than twice as likely to die of prostate cancer (PC) compared with non-Hispanic white (NHW) men. The authors hypothesized that receiving care through the Veterans Affairs (VA) health system, an equal-access medical system, would attenuate this disparity. METHODS: A longitudinal, centralized database of >20 million veterans was used to assemble a cohort of 60,035 men (18,201 AA men [30.3%] and 41,834 NHW men [69.7%]) who were diagnosed with PC between 2000 and 2015. RESULTS: AA men were more likely to live in regions with a lower median income ($40,871 for AA men vs $48,125 for NHW men; P < .001) and lower high school graduation rates (83% for AA men vs 88% for NHW men; P < .001). At the time of diagnosis, AA men were younger (median age, 63.0 years vs 66.0 years; P < .001) and had a higher prostate-specific antigen level (median, 6.7 ng/mL vs 6.2 ng/mL; P < .001), but were less likely to have Gleason score 8 to 10 disease (18.8% among AA men vs 19.7% among NHW men; P < .001), a clinical T classification ≥3 (2.2% vs 2.9%; P < .001), or distant metastatic disease (2.7% vs 3.1%; P = 0.01). The 10-year PC-specific mortality rate was slightly lower for AA men (4.4% vs 5.1%; P = .005), which was confirmed in multivariable competing-risk analysis (subdistribution hazard ratio, 0.85; 95% CI, 0.78-0.93; P < .001). CONCLUSIONS: AA men diagnosed with PC in the VA health system do not appear to present with more advanced disease or experience worse outcomes compared with NHW men, in contrast to national trends, suggesting that access to care is an important determinant of racial equity.

Prognostic Utility of Pre- and Postoperative Circulating Tumor DNA Liquid Biopsies in Patients with Peritoneal Metastases.

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising technology for treatment selection, prognostication, and surveillance after definitive therapy. Its use in the perioperative setting for patients with metastatic disease has not been well studied. We characterize perioperative plasma ctDNA and its association with progression-free survival (PFS) in patients undergoing surgery for peritoneal metastases. PATIENTS AND METHODS: We recruited 71 patients undergoing surgery for peritoneal metastases and evaluated their plasma with a targeted 73-gene ctDNA next-generation sequencing test before and after surgery. The association between perioperative ctDNA, as well as other patient factors, and PFS was evaluated by Cox regression. RESULTS: ctDNA was detectable in 28 patients (39.4%) preoperatively and in 37 patients (52.1%) postoperatively. Patients with high ctDNA [maximum somatic variant allele fraction (MSVAF) > 0.25%] had worse PFS than those with low MSVAF (< 0.25%) in both the pre- and postoperative settings (median 4.8 vs. 19.3 months, p < 0.001, and 9.2 vs.15.0 months, p = 0.049, respectively; log-rank test). On multivariate analysis, high-grade histology [hazard ratio (HR) 3.42, p = 0.001], incomplete resection (HR 2.35, p = 0.010), and high preoperative MSVAF (HR 3.04, p = 0.001) were associated with worse PFS. Patients with new postoperative alterations in the context of preoperative alteration(s) also had a significantly shorter PFS compared with other groups (HR 4.28, p < 0.001). CONCLUSIONS: High levels of perioperative ctDNA and new postoperative ctDNA alterations in the context of preoperative alterations predict worse outcomes in patients undergoing resection for peritoneal metastases. This may highlight a role for longitudinal ctDNA surveillance in this population.

Advancements in Urothelial Cancer Care: Optimizing Treatment for Your Patient.

The standard treatment paradigm for muscle invasive bladder cancer has been neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy. However, efforts are ongoing to personalize treatment by incorporating biomarkers to better guide treatment selection. In addition, bladder preservation strategies are aimed at avoiding cystectomy in well-selected patients. Similarly, in the metastatic urothelial cancer space, the standard frontline treatment option of platinum-based chemotherapy has changed with the availability of data from EV-302 trial, making the combination of enfortumab vedotin (EV) and pembrolizumab the preferred first-line treatment option. Here, we examine the optimization of treatment intensity and sequencing, focusing on the challenges and opportunities associated with EV/pembrolizumab therapy, including managing toxicities and exploring alternative dosing approaches. Together, these articles provide a comprehensive overview of contemporary strategies in bladder cancer management, highlighting the importance of individualized treatment approaches, ongoing research, and multidisciplinary collaboration to improve patient outcomes in this complex disease landscape.

Prostate Cancer Screening Uptake in Transgender Women.

Importance: There is no consensus in prostate-specific antigen (PSA) screening guidelines regarding transgender women despite their known prostate cancer risk. Objective: To identify factors associated with recent (within the last 2 years) PSA screening in transgender women compared with cisgender men. Design, Setting, and Participants: This case-control study used data from the 2018 and 2020 Behavioral Risk Factor Surveillance System (BRFSS) surveys to characterize rates of PSA screening for prostate cancer within the past 2 years and multivariable logistic regressions to characterize factors associated with recent screening among transgender women. The BRFSS program of the Centers for Disease Control and Prevention annually surveys over 400 000 US adults on behavioral risk factors, chronic illnesses, and use of preventive services. Respondents to the BRFSS who were cisgender men or transgender women 40 years or older and who had complete PSA testing responses and no prostate cancer history were included; 313 transgender women and 138 937 cisgender men met inclusion criteria. Matching was performed by age, race and ethnicity, educational level, employment, annual income, survey year, and cost barriers to care. Data were collected on November 2, 2022, and analyzed from November 2, 2022, to December 3, 2023. Main Outcomes and Measures: Rates of and factors associated with recent PSA screening in transgender women. Results: Among the 1275 participants included in the matched cohort (255 transgender women and 1020 cisgender men; 570 [44.7%] aged 55-69 years), recent PSA screening rates among transgender women and cisgender men aged 55 to 69 were 22.2% (n = 26) and 36.3% (n = 165), respectively; among those 70 years and older, these rates were 41.8% (n = 26) and 40.2% (n = 98), respectively. In the matched cohort, transgender women had lower univariable odds of recent screening than cisgender men (odds ratio [OR], 0.65 [95% CI, 0.46-0.92]; P = .02). In a hierarchical regression analysis adding time since the last primary care visit, effect size and significance were unchanged (OR, 0.61 [95% CI, 0.42-0.87]; P = .007). After adding whether a clinician recommended a PSA test, there was no statistically significant difference in odds of screening between transgender women and cisgender men (OR, 0.83 [95% CI, 0.45-1.27]; P = .21). The results were further attenuated when clinician-led discussions of PSA screening advantages and disadvantages were added (OR, 0.87 [95% CI, 0.47-1.31]; P = .32). In a multivariable logistic regression among transgender women, having a recommendation for PSA testing was the factor with the strongest association with recent screening (OR, 12.40 [95% CI, 4.47-37.80]; P < .001). Conclusions and Relevance: In this case-control study of one of the largest cohorts of transgender women studied regarding PSA screening, the findings suggest that access to care or sociodemographic factors were not principal drivers of the screening differences between transgender women and cisgender men; rather, these data underscore the clinician's role in influencing PSA screening among transgender women.

Opioid tapering in older cancer survivors does not increase psychiatric or drug hospitalization rates.

BACKGROUND: Opioid tapering in the general population is linked to increases in hospitalizations or emergency department visits related to psychiatric or drug-related diagnoses. Cancer survivors represent a unique population with different opioid indications, prescription patterns, and more frequent follow-up care. This study sought to describe patterns of opioid tapering among older cancer survivors and to test the hypothesis of whether older cancer survivors face increased risks of adverse events with opioid tapering. METHODS: Using the Surveillance, Epidemiology and End Results Medicare-linked database, we identified 15 002 Medicare-beneficiary cancer survivors diagnosed between 2010 and 2017 prescribed opioids consistently for at least 6 months after their cancer diagnosis. Tapering was defined as a binary time-varying event occurring with any monthly oral morphine equivalent reduction of 15% or more from the previous month. Primary diagnostic billing codes associated with emergency room or hospital admissions were used for the composite endpoint of psychiatric- or drug-related event(s). RESULTS: There were 3.86 events per 100 patient-months, with 97.8% events being mental health emergencies, 1.91% events being overdose emergencies, and 0.25% involving both. Using a generalized estimating equation for repeated measure time-based analysis, opioid tapering was not statistically associated with acute events in the 3-month posttaper period (odds ratio [OR] = 1.02; P = .62) or at any point in the future (OR = 0.96; P = .46). CONCLUSIONS: Opioid tapering in older cancer survivors does not appear to be linked to a higher risk of acute psychiatric- or drug-related events, in contrast to prior research in the general population.

Androgen Deprivation Therapy and Outcomes After Radiation Therapy in Black Patients With Prostate Cancer.

Importance: Prostate cancer in Black men compared with White men may be more sensitive to radiation therapy resulting in better outcomes in equal-access settings. The outcomes of androgen-deprivation therapy (ADT) vs radiation therapy itself remains uncharacterized. Objectives: To quantify any outcome modification by receipt of ADT on the association between Black race and prostate cancer outcomes following radiation therapy. Design, Setting, and Participants: This was a retrospective, nationwide cohort study of Black and White patients treated in the US Veterans Healthcare system between 2000 and 2020 receiving definitive radiation for localized prostate cancer. Data were analyzed from January 2000 to December 2020. Exposure: Patient self-identified race and use of ADT defined as any gonadotrophin-releasing hormone agonist or antagonist prescription within 6 months of radiation. Main Outcomes and Measures: Biochemical recurrence (BCR) from time of completion of radiation therapy (prostate-specific antigen nadir plus 2 ng/mL) and development of metastatic disease or prostate cancer mortality (PCSM) from time of recurrence. Results: A total of 26 542 patients (8716 Black men with median [IQR] age of 64 [59-69] years and 17 826 White men with median [IQR] age of 67 [62-72] years) received definitive radiation therapy for nonmetastatic prostate cancer and had complete staging and follow-up data. A total of 5144 patients experienced BCR (3384 White and 1760 Black patients). The cumulative incidence of BCR at 10 years was not significantly different between Black and White men (1602 [22.14%] vs 3099 [20.13%], respectively) with multivariable hazard ratio (HR) of 1.03 (95% CI, 0.97-1.09; P = .33). In men receiving ADT, Black men had an HR for BCR of 0.90 (95% CI, 0.82-0.99; P = .03) compared with White men, and in men not receiving ADT, Black men had an HR of 1.13 (95% CI, 1.05-1.22; P = .002). Black race was associated with a decreased risk of developing metastatic disease (HR, 0.90; 95% CI, 0.82-0.98; P = .02) or PCSM (subdistribution HR, 0.72; 95% CI, 0.63-0.82; P < .001) from time of biochemical recurrence. Conclusions and Relevance: Black patients treated with radiation appear to specifically benefit from the addition of ADT with regard to biochemical control. Additionally, BCR in Black men results in a lower rate of metastatic disease and death from prostate cancer. Future analyses of radiosensitivity in Black men should evaluate for the possibility of outcome modification by ADT.

Racial disparities in colorectal cancer outcomes and access to care: a multi-cohort analysis.

Introduction: Non-Hispanic Black (NHB) Americans have a higher incidence of colorectal cancer (CRC) and worse survival than non-Hispanic white (NHW) Americans, but the relative contributions of biological versus access to care remain poorly characterized. This study used two nationwide cohorts in different healthcare contexts to study health system effects on this disparity. Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER) registry as well as the United States Veterans Health Administration (VA) to identify adults diagnosed with colorectal cancer between 2010 and 2020 who identified as non-Hispanic Black (NHB) or non-Hispanic white (NHW). Stratified survival analyses were performed using a primary endpoint of overall survival, and sensitivity analyses were performed using cancer-specific survival. Results: We identified 263,893 CRC patients in the SEER registry (36,662 (14%) NHB; 226,271 (86%) NHW) and 24,375 VA patients (4,860 (20%) NHB; 19,515 (80%) NHW). In the SEER registry, NHB patients had worse OS than NHW patients: median OS of 57 months (95% confidence interval (CI) 55-58) versus 72 months (95% CI 71-73) (hazard ratio (HR) 1.14, 95% CI 1.12-1.15, p = 0.001). In contrast, VA NHB median OS was 65 months (95% CI 62-69) versus NHW 69 months (95% CI 97-71) (HR 1.02, 95% CI 0.98-1.07, p = 0.375). There was significant interaction in the SEER registry between race and Medicare age eligibility (p < 0.001); NHB race had more effect in patients <65 years old (HR 1.44, 95% CI 1.39-1.49, p < 0.001) than in those ≥65 (HR 1.13, 95% CI 1.11-1.15, p < 0.001). In the VA, age stratification was not significant (p = 0.21). Discussion: Racial disparities in CRC survival in the general US population are significantly attenuated in Medicare-aged patients. This pattern is not present in the VA, suggesting that access to care may be an important component of racial disparities in this disease.

The impact of a corrective tether on a scoliosis porcine model: a detailed 3D analysis with a 20 weeks follow-up.

PURPOSE: Non-fusion treatment for adolescent idiopathic scoliosis generates interest due to the potential for growth preservation and mobility. Using an established porcine scoliotic model, this study aims to evaluate the global alignment and the morphology of the spine with and without application of a non-fusion corrective tether. METHODS: At 12 weeks of age, 21 immature Yorkshire pigs had an induction of scoliosis. Once a 50° Cobb angle was obtained; animals were placed into one of the following groups: a scoliosis model group (SM, n = 11) where animals were euthanized, tether release group (TR, n = 5) where the inducing tether was removed, and an anterior correction group (AC, n = 5) where the inducing tether was removed and non-fusion corrective tether was applied. TR and AC were observed for a further 20 weeks and then euthanized. Post-mortem CT scans were used to create 3D spinal reconstructions to obtain global and morphologic parameters. RESULTS: Maximal Cobb angle of the scoliotic deformity was significantly lower for AC (27.9° ± 12.0°) than for the two other groups (TR 52.7° ± 10.0°, SM 48.3° ± 7.6°). AC experienced an increase in kyphosis (24.2° ± 15.9°) compared to TR (7.1° ± 6.4°). Correction in the axial plane was also observed in AC versus TR. Correction of vertebral wedging was found for AC compared to SM and TR in the three apical vertebrae. CONCLUSIONS: 3D realignment of scoliotic curves was observed with application of the corrective tether. The correction was the product of both mechanical action and growth modulation. These findings are encouraging for future development of a non-fusion device for the treatment of immature scoliotic curves.

Retrospective Review of Follow-up Strategies for Patients Receiving Palliative Radiotherapy.

CONTEXT: There is no current standard-of-care follow-up strategy for patients who receive palliative radiotherapy (PRT) for bone metastases. Within our institution there is currently a heterogenous practice in which some providers schedule routine follow up 1-3 months after initial PRT while others do follow up only as needed (PRN). OBJECTIVES: Our study aims to compare rates of retreatment based on follow-up strategies (planned vs. PRN), explore factors that potentially affect retreatment, and evaluate whether provider follow-up strategy correlates with measurable differences in quality of care. METHODS: In a retrospective chart review, PRT courses for bone metastases at our single institution were divided by follow-up strategies (planned vs. PRN). Demographic, clinical, and PRT data were collected and analyzed via descriptive statistics. The relationship between planned follow-up appointment and subsequent retreatment was studied. RESULTS: More patients received retreatment within one year of initial PRT in the planned follow-up group than in the PRN follow-up group (40.4% vs. 14.4%, p<0.001). Retreatment was achieved sooner in the planned follow-up group than in the PRN follow-up group (137 days vs. 156 days). When accounting for other variables, having a planned follow-up appointment remains the most important factor in establishing retreatment (OR = 3.32, 2.11-5.29, p<0.001). CONCLUSION: Having a planned follow-up appointment after the initial course of PRT improves identification of patients who would benefit from additional treatment, thus improving patient experience and quality of care.

Adjuvant Radiation in Resectable Node-Positive Merkel Cell Carcinoma in the Immunotherapy Era: Implications for Future and Ongoing Trials.

Merkel cell carcinoma (MCC) is a cutaneous malignancy often treated with surgical resection followed by adjuvant radiation therapy (RT). In the node-positive setting, adjuvant RT reduces the risk of locoregional recurrence, but historical data suggest that distant failure is a persistent issue and often fatal. This has prompted new efforts to intensify treatment in these patients with the addition of neoadjuvant or adjuvant immune checkpoint inhibitor therapy. However, newer diagnostic techniques have led to stage migration in patients with previously subclinical metastatic disease; consequently, preventing locoregional recurrence may be a higher priority in node-positive MCC patients than was previously believed. Recent trials in node-positive MCC, such as ADMEC-O, have had lower rates of adjuvant RT utilization in treatment versus control arms, which may have attenuated the observed effect of adjuvant immunotherapy. The low utilization of adjuvant RT may have also resulted in a higher recurrence rate in patients who did not have a complete response to neoadjuvant immunotherapy in the CHECKMATE 358 trial. Altogether, these are important considerations for ongoing and future immunotherapy trials in MCC and may affect the interpretation of their results. Ongoing clinical trials may determine which patients are at low risk of recurrence when treated with immunotherapy and whether adjuvant RT could be omitted in select patients.

Low-Value Prostate-Specific Antigen Screening in Older Males.

Importance: The US Preventive Services Task Force guidelines advise against prostate-specific antigen (PSA) screening for prostate cancer in males older than 69 years due to the risk of false-positive results and overdiagnosis of indolent disease. However, this low-value PSA screening in males aged 70 years or older remains common. Objective: To characterize the factors associated with low-value PSA screening in males 70 years or older. Design, Setting, and Participants: This survey study used data from the 2020 Behavioral Risk Factor Surveillance System (BRFSS), a nationwide annual survey conducted by the Centers for Disease Control and Prevention that collects information via telephone from more than 400 000 US adults on behavioral risk factors, chronic illnesses, and use of preventive services. The final cohort comprised male respondents to the 2020 BRFSS survey who were categorized into the following age groups: 70 to 74 years, 75 to 79 years, or 80 years or older. Males with a former or current prostate cancer diagnosis were excluded. Main Outcomes and Measures: The outcomes were recent PSA screening rates and factors associated with low-value PSA screening. Recent screening was defined as PSA testing within the past 2 years. Weighted multivariable logistic regressions and 2-sided significance tests were used to characterize factors associated with recent screening. Results: The cohort included 32 306 males. Most of these males (87.6%) were White individuals, whereas 1.1% were American Indian, 1.2% were Asian, 4.3% were Black, and 3.4% were Hispanic individuals. Within this cohort, 42.8% of respondents were aged 70 to 74 years, 28.4% were aged 75 to 79 years, and 28.9% were 80 years or older. The recent PSA screening rates were 55.3% for males in the 70-to-74-year age group, 52.1% in the 75-to-79-year age group, and 39.4% in the 80-year-or-older group. Among all racial groups, non-Hispanic White males had the highest screening rate (50.7%), and non-Hispanic American Indian males had the lowest screening rate (32.0%). Screening increased with higher educational level and annual income. Married respondents were screened more than unmarried males. In a multivariable regression model, discussing PSA testing advantages with a clinician (odds ratio [OR], 9.09; 95% CI, 7.60-11.40; P < .001) was associated with increased recent screening, whereas discussing PSA testing disadvantages had no association with screening (OR, 0.95; 95% CI, 0.77-1.17; P = .60). Other factors associated with a higher screening rate included having a primary care physician, a post-high school educational level, and income of more than $25 000 per year. Conclusions and Relevance: Results of this survey study suggest that older male respondents to the 2020 BRFSS survey were overscreened for prostate cancer despite the age cutoff for PSA screening recommended in national guidelines. Discussing the benefits of PSA testing with a clinician was associated with increased screening, underscoring the potential of clinician-level interventions to reduce overscreening in older males.

Temporal Trends and Predictors of Opioid Use Among Older Patients With Cancer.

OBJECTIVES: While opioids represent a cornerstone of cancer pain management, the timing and patterns of opioid use in the cancer population have not been well studied. This study sought to explore longitudinal trends in opioid use among Medicare beneficiaries with nonmetastatic cancer. MATERIALS AND METHODS: Within a cohort of 16,072 Medicare beneficiaries ≥66 years old diagnosed with nonmetastatic cancer between 2007 and 2013, we determined the likelihood of receiving a short-term (0 to 6 mo postdiagnosis), intermediate-term (6 to 12 mo postdiagnosis), long-term (1 to 2 y postdiagnosis), and high-risk (morphine equivalent dose ≥90 mg/day) opioid prescription after cancer diagnosis. Multivariable logistic regression models were used to identify patient and cancer risk factors associated with these opioid use endpoints. RESULTS: During the study period, 74.6% of patients received an opioid prescription, while only 2.66% of patients received a high-risk prescription. Factors associated with use varied somewhat between short-term, intermediate-term, and long-term use, though in general, patients at higher risk of receiving an opioid prescription after their cancer diagnosis were younger, had higher stage disease, lived in regions of higher poverty, and had a history of prior opioid use. Prescriptions for high-risk opioids were associated with individuals living in regions with lower poverty. CONCLUSIONS: Temporal trends in opioid use in cancer patients depend on patient, demographic, and tumor characteristics. Overall, understanding these correlations may help physicians better identify patient-specific risks of opioid use and could help better inform future evidence-based, cancer-specific opioid prescription guidelines.