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.