{"doi":"10.1093/jnci/djad140","title":"The growing implications of obesity for prostate cancer risk and mortality: where do we go from here?","abstract":"Obesity tends to fan the flames of cancer in multiple organs by way of increasing incidence, promoting progression, and decreasing survival (1). With respect to prostate cancer, obesity is often tied to an increased risk of mortality and advanced disease, though the last notion is still debated. Questions remain about what causes the association between obesity and advanced prostate cancer; whether obesity propagates a molecular mechanism that drives aggressive prostate cancer; or whether obesity leads to delayed diagnoses that are left unchecked, resulting in patients ultimately presenting with more advanced disease. Prostate-specific antigen (PSA)–based prostate cancer screening has certainly saved many lives, but it remains controversial and possibly underutilized because of concerns about overdiagnosis and overtreatment (ie, the “harms” from widespread screening). Although some research suggests that obese patients are more likely to undergo PSA screening, we also know that PSA levels from people with a higher body mass index (BMI) are diluted, giving them a false sense of security (2). All this begs the question: if annual prostate cancer screening were universal, would prostate cancer still be associated with a higher risk of advanced prostate cancer and related mortality? In this issue of the Journal, Hurwitz and colleagues (3) seek to answer this question using a unique study population. In an analysis of 36 756 men enrolled between 1993 and 2001 in the intervention (ie, screening) arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, Hurwitz et al. evaluated associations between BMI, advanced prostate cancer, and prostate cancer-specific mortality in an almost universally screened population (3). Middle-aged and older men with no history of prostate, colorectal, or lung cancer were randomly assigned to receive the same prostate screening protocol. Specifically, men underwent annual PSA testing for 5 years, for the first 3 years of which they also received an annual digital rectal examination. PSA screening was considered positive if values were greater than 4 ng/mL and digital rectal examination considered positive if the clinician encountered any asymmetry, loss of anatomic landmarks, nodularity, or induration. Some noteworthy characteristics observed at higher BMI included younger age, less chance of being a current smoker, and higher likelihood of comorbid diabetes. Regarding prostate cancer screening and obesity, men with a higher BMI were more likely to have an inadequate test result (mainly digital rectal examinations because of participant discomfort, refusal, or difficult palpation). Moreover, men with high BMI in this study were less likely to have had more than 1 PSA screening in the past 3 years before PLCO enrollment. Surprisingly, when assessing the relationship between high BMI and prostate cancer incidence and mortality, men at higher BMI levels had a lower risk of either early prostate cancer or advanced prostate cancer incidence, although higher BMI was still associated with a higher risk of dying from prostate cancer. A unique strength of this study was the large population of men receiving a uniform cancer screening protocol from the intervention arm of the PLCO trial. Another strength included the rigorously designed and well-thought-out analyses to account for multiple potentially confounding variables, such as diabetes, smoking status, race, PSA screening history, family history of prostate cancer, and education. The population of men enrolled in the PCLO trial were primarily non-Hispanic White men (88%); thus, the study did not capture the higher incidence, higher mortality, and more aggressive prostate cancer seen in Black men. Moreover, some data show that Black race and obesity interact to create a particularly high risk of aggressive prostate cancer (4), again something that could not easily be tested in this cohort. In addition, obesity was measured using a singl","journal":"JNCI Journal of the National Cancer Institute","year":2023,"id":364370,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9575,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":260294,"name":"Stephen J. Freedland","orcid":"0000-0002-8104-6419","position":1,"is_corresponding":false},{"id":465520,"name":"Gillian Gresham","orcid":"0000-0001-7142-1230","position":2,"is_corresponding":false},{"id":1100659,"name":"James P. Daniels","orcid":"0000-0002-2401-2474","position":0,"is_corresponding":true}],"reference_count":8,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:14:36.728255Z","pmid":"37587090","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}