Highlights d Autophagy promotes primary tumor growth, yet suppresses metastatic outgrowth d Autophagy deficiency elicits a pro-metastatic basal tumor cell subpopulation d NBR1 accumulation mediates the effects of autophagy inhibition on metastasis d Enforced autophagy induction prevents the outgrowth of disseminated tumor cells

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ImportanceThe 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.ObjectiveTo characterize the factors associated with low-value PSA screening in males 70 years or older.Design, Setting, and ParticipantsThis 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 MeasuresThe 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.ResultsThe 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 RelevanceResults 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.

Squamous cell carcinoma (SCC) from an unknown primary tumor (SCCUP) accounts for 2.0%–5.0% of all head and neck cancers. SCCUP presents as enlarged cervical lymph nodes without evidence of a primary tumor upon physical examination. Primary site detection is important to target treatment and avoid treatment-related morbidity. In this review, we discuss updates in SCCUP management. Diagnostic workup should focus on localization of the primary tumor in SCCUP. Initial workup centers on neck biopsy to confirm the presence of SCC. Given the increasing incidence of HPV-related SCC in the oropharynx, HPV testing is crucial. An HPV-positive status can localize the tumor to the oropharynx, a common site for occult tumors. Imaging includes neck CT and/or MRI, and PET/CT. After imaging, panendoscopy, palatine tonsillectomy or diagnostic transoral robotic surgery can facilitate high rates of primary tumor localization. Primary tumor localization influences treatments administered. SCCUP has traditionally been treated aggressively with large treatment fields to all potential disease sites, which can induce weight loss and swallowing dysfunction. As a result, primary localization can reduce radiation fields and provide possible de-escalation to primary surgical management. Advances in intensity-modulated radiation therapy and dose management also have the potential to improve functional outcomes in SCCUP patients. Given the improved prognosis associated with HPV-positive SCCs, HPV tumor status may also inform future treatment de-intensification to reduce treatment-related toxicity.

ImportancePrimary care physicians (PCPs) are significant contributors of early cancer detection, yet few studies have investigated whether consistent primary care translates to improved downstream outcomes.ObjectiveTo evaluate the association of prediagnostic primary care use with metastatic disease at diagnosis and cancer-specific mortality (CSM).Design, Setting, and ParticipantsThis cohort study used databases with primary care and referral linkage from multiple Veterans’ Affairs centers from 2004 to 2017 and had a 68-month median follow-up. Analysis was completed between July 2021 and September 2022. Participants included veterans older than 39 years who had been diagnosed with 1 of 12 cancers. Inclusion criteria included known clinical staging, survival follow-up, cause of death, and receiving care at the Veterans Affairs health system (VA).ExposuresPrediagnostic PCP use, measured in the 5 years prior to diagnosis. PCP visits were binned into none (0 visits), some (1-4 visits), and annual (5 visits).Main Outcomes and MeasuresMetastatic disease at diagnosis, cancer-specific mortality (CSM) for entire cohort and stratified by tumor subtype.ResultsAmong 245 425 patients representing 12 tumor subtypes, mean age was 65.8 (9.3) years, and the cohort skewed male (97.6%), and White (76.1%), with higher levels of comorbidity (58.6% with Charlson Comorbidity Index scores ≥2). Compared with no prior visit, some PCP use was associated with 26% decreased odds of metastatic disease at diagnosis (odds ratio [OR], 0.74; 95% CI, 0.71-0.76; P < .001) and 12% reduced risk of CSM (subdistribution hazard ratio [SHR], 0.88; 95% CI, 0.86-0.89; P < .001). Annual PCP use was associated with 39% decreased odds of metastatic disease (OR, 0.61; 95% CI, 0.59-0.63; P < .001) and 21% reduced risk of CSM (SHR, 0.79; 95% CI, 0.77-0.81; P < .001). Among tumor subtypes, prostate cancer had the largest effect size for prior PCP use on metastatic disease at diagnosis (OR for annual use, 0.32; 95% CI, 0.30-0.35; P < .001) and CSM (SHRfor annual use, 0.51; 95% CI, 0.48-0.55; P < .001).Conclusions and RelevanceIn this cohort study, increased primary care use before cancer diagnosis was associated with significant decreases in metastatic disease at diagnosis and cancer-related death, with potentially the greatest difference from annual use. PCPs play a vital role in cancer prevention, and additional resources should be allocated to assist these physicians.

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 prostatespecific 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 selfadvocacy may impact this observed difference 82 -Cancer.

Subclavian artery occlusion (SAO) is a rare form of peripheral artery disease, sometimes associated with arterial thoracic outlet syndrome (ATOS). Subclavian arterial and venous occlusions are often misdiagnosed initially, and their clinical presentation can be confusing in bodybuilding athletes with increased vascularity in combination with anabolic steroid use. We present a 63-year-old male weightlifter with a history of hypertensive cardiomyopathy, renal transplant with left upper extremity arteriovenous fistula and subsequent takedown, cervical spinal stenosis, left rotator cuff surgery, and decades of testosterone injections who presented with years of left shoulder and neck pain. After having seen multiple providers and being diagnosed with various common disorders, CT angiography and conventional angiography were eventually performed and confirmed the presence of chronic SAO. The chronic occlusion was not deemed amenable to surgery or endovascular intervention and was treated medically with anticoagulation. Although anabolic steroid use is associated with arterial thrombosis, to our knowledge, this is the first reported case of SAO in a weightlifter. Initial misdiagnosis resulted in a long and costly workup. Although the patient's symptoms were consistent with occlusion (and his increased vascularity could potentially suggest chronic thrombosis of any kind), these key signs were masked given his weightlifting history, anabolic steroid use, and concurrent degenerative musculoskeletal conditions common to the weightlifting population. A thorough history, comprehensive physical examination, appropriate imaging studies, and a high index of suspicion for vascular occlusion in athletes who use steroids are critical for the timely diagnosis and treatment of SAO.