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BACKGROUND: The objective of this study was to quantify disparities in cancer treatment delivery between minority-serving hospitals (MSHs) and non-MSHs for breast, prostate, nonsmall cell lung, and colon cancers from 2010 to 2019 and to estimate the impact of improving care at MSHs on national disparities. METHODS: Data from the National Cancer Database (2010-2019) identified patients who were eligible for definitive treatments for the specified cancers. Hospitals in the top decile by minority patient proportion were classified as MSHs. Multivariable logistic regression adjusted for patient and hospital characteristics compared the odds of receiving definitive treatment at MSHs versus non-MSHs. A simulation was used to estimate the increase in patients receiving definitive treatment if MSH care matched the levels of non-MSH care. RESULTS: Of 2,927,191 patients from 1330 hospitals, 9.3% were treated at MSHs. MSHs had significant lower odds of delivering definitive therapy across all cancer types (adjusted odds ratio: breast cancer, 0.83; prostate cancer, 0.69; nonsmall cell lung cancer, 0.73; colon cancer, 0.81). No site of care-race interaction was significant for any of the cancers (p > .05). Equalizing treatment rates at MSHs could result in 5719 additional patients receiving definitive treatment over 10 years. CONCLUSIONS: The current findings underscore systemic disparities in definitive cancer treatment delivery between MSHs and non-MSHs for breast, prostate, nonsmall cell lung, and colon cancers. Although targeted improvements at MSHs represent a critical step toward equity, this study highlights the need for integrated, system-wide efforts to address the multifaceted nature of racial and ethnic health disparities. Enhancing care at MSHs could serve as a pivotal strategy in a broader initiative to achieve health care equity for all.
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Neoplasias da Mama , Neoplasias do Colo , Disparidades em Assistência à Saúde , Hospitais , Neoplasias Pulmonares , Neoplasias da Próstata , Humanos , Masculino , Disparidades em Assistência à Saúde/etnologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Feminino , Neoplasias da Próstata/terapia , Neoplasias da Próstata/etnologia , Neoplasias do Colo/terapia , Neoplasias do Colo/etnologia , Neoplasias da Mama/terapia , Neoplasias da Mama/etnologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/etnologia , Hospitais/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso , Estados Unidos , Grupos Minoritários/estatística & dados numéricosRESUMO
BACKGROUND: Patients with localized, unfavorable intermediate-risk and high-risk prostate cancer have an increased risk of relapse after radical prostatectomy (RP). The authors previously reported on part 1 of this phase 2 trial testing neoadjuvant apalutamide, abiraterone, prednisone, plus leuprolide (AAPL) or abiraterone, prednisone, and leuprolide (APL) for 6 months followed by RP. The results demonstrated favorable pathologic responses (tumor <5 mm) in 20.3% of patients (n = 24 of 118). Herein, the authors report the results of part 2. METHODS: For part 2, patients were randomized 1:1 to receive either AAPL for 12 months (arm 2A) or observation (arm 2B), stratified by neoadjuvant therapy and pathologic tumor classification. The primary end point was 3-year biochemical progression-free survival. Secondary end points included safety and testosterone recovery (>200 ng/dL). RESULTS: Overall, 82 of 118 patients (69%) enrolled in part 1 were randomized to part 2. A higher proportion of patients who were not randomized to adjuvant therapy had a favorable prostatectomy pathologic response (32.3% in nonrandomized patients compared with 17.1% in randomized patients). In the intent-to-treat analysis, the 3-year biochemical progression-free survival rate was 81% for arm 2A and 72% for arm 2B (hazard ratio, 0.81; 90% confidence interval, 0.43-1.49). Of the randomized patients, 81% had testosterone recovery in the AAPL group compared with 95% in the observation group, with a median time to recovery of <12 months in both arms. CONCLUSIONS: In this study, because 30% of patients declined adjuvant treatment, part B was underpowered to detect differences between arms. Future perioperative studies should be biomarker-directed and include strategies for investigator and patient engagement to ensure compliance with protocol procedures.
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Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Leuprolida/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/diagnóstico , Antagonistas de Androgênios/efeitos adversos , Androgênios , Prednisona , Resultado do Tratamento , Recidiva Local de Neoplasia/cirurgia , Prostatectomia/métodos , TestosteronaRESUMO
BACKGROUND: This study aims to assess the impact of healthy lifestyle on prostate cancer (PCa) risk in a diverse population. METHODS: Data for 281,923 men from the Million Veteran Program (MVP), a nationwide, health system-based cohort study, were analyzed. Self-reported information at enrollment included smoking status, exercise, diet, family history of PCa, and race/ethnicity. Body mass index (BMI) was obtained from clinical records. Genetic risk was assessed via a validated polygenic score. Cox proportional hazards models were used to assess associations with PCa outcomes. RESULTS: After accounting for ancestry, family history, and genetic risk, smoking was associated with an increased risk of metastatic PCa (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.64-2.02; p < 10-16) and fatal PCa (HR, 2.73; 95% CI, 2.36-3.25; p < 10-16). Exercise was associated with a reduced risk of fatal PCa (HR, 0.86; 95% CI, 0.76-0.98; p = .03). Higher BMI was associated with a slightly reduced risk of fatal PCa, and diet score was not independently associated with any end point. Association with exercise was strongest among those who had nonmetastatic PCa at MVP enrollment. Absolute reductions in the risk of fatal PCa via lifestyle factors were greatest among men of African ancestry (1.7% for nonsmokers vs. 6.1% for smokers) or high genetic risk (1.4% for nonsmokers vs. 4.3% for smokers). CONCLUSIONS: Healthy lifestyle is minimally related to the overall risk of developing PCa but is associated with a substantially reduced risk of dying from PCa. In multivariable analyses, both exercise and not smoking remain independently associated with reduced metastatic and fatal PCa.
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BACKGROUND: Androgen deprivation therapy (ADT) in prostate cancer (PCa) has been associated with development of insulin resistance. However, the predominant site of insulin resistance remains unclear. METHODS: The ADT & Metabolism Study was a single-center, 24-week, prospective observational study that enrolled ADT-naive men without diabetes who were starting ADT for at least 24 weeks (ADT group, n = 42). The control group comprised men without diabetes with prior history of PCa who were in remission after prostatectomy (non-ADT group, n = 23). Prevalent diabetes mellitus was excluded in both groups using all three laboratory criteria defined in the American Diabetes Association guidelines. All participants were eugonadal at enrollment. The primary outcome was to elucidate the predominant site of insulin resistance (liver or skeletal muscle). Secondary outcomes included assessments of body composition, and hepatic and intramyocellular fat. Outcomes were assessed at baseline, 12, and 24 weeks. RESULTS: At 24 weeks, there was no change in hepatic (1.2; 95% confidence interval [CI], -2.10 to 4.43; p = .47) or skeletal muscle (-3.2; 95% CI, -7.07 to 0.66; p = .10) insulin resistance in the ADT group. No increase in hepatic or intramyocellular fat deposition or worsening of glucose was seen. These changes were mirrored by those observed in the non-ADT group. Men undergoing ADT gained 3.7 kg of fat mass. CONCLUSIONS: In men with PCa and no diabetes, 24 weeks of ADT did not change insulin resistance despite adverse body composition changes. These findings should be reassuring for treating physicians and for patients who are being considered for short-term ADT.
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PURPOSE: Family history and germline genetic risk single nucleotide polymorphisms (SNPs) have been separately shown to stratify lifetime risk of prostate cancer. Here, we evaluate the combined prognostic value of family history of prostate and other related cancers and germline risk SNPs among patients with favorable-risk prostate cancer. MATERIALS AND METHODS: A total of 1367 participants from the prospective Health Professionals Follow-up Study diagnosed with low- or favorable intermediate-risk prostate cancer from 1986 to 2017 underwent genome-wide SNP genotyping. Multivariable Cox regression was used to estimate the association between family history, specific germline risk variants, and a 269 SNP polygenic risk score with prostate cancerâspecific death. RESULTS: Family history of prostate, breast, and/or pancreatic cancer was observed in 489 (36%) participants. With median follow-up from diagnosis of 14.9 years, participants with favorable-risk prostate cancer with a positive family history had a significantly higher risk of prostate cancerâspecific death (HR 1.95, 95% CI 1.15-3.32, P = .014) compared to those without any family history. The rs2735839 (19q13) risk allele was associated with prostate cancerâspecific death (HR 1.81 per risk allele, 95% CI 1.04-3.17, P = .037), whereas the polygenic risk score was not. Combined family history and rs2735839 risk allele were each associated with an additive risk of prostate cancerâspecific death (HR 1.78 per risk factor, 95% CI 1.25-2.53, P = .001). CONCLUSIONS: Family history of prostate, breast, or pancreatic cancer and/or a 19q13 germline risk allele are associated with an elevated risk of prostate cancerâspecific death among favorable-risk patients. These findings have implications for how family history and germline genetic risk SNPs should be factored into clinical decision-making around favorable-risk prostate cancer.
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Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/mortalidade , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Medição de Risco , Seguimentos , PrognósticoRESUMO
PURPOSE: To evaluate how limited English proficiency (LEP) impacts the prevalence of prostate-specific antigen (PSA) screening in a contemporary, nationally representative cohort of men in the USA. METHODS: The Medical Expenditure Panel Survey was utilized to identify the prevalence of PSA screening between 2013 and 2016 among men ≥ 55. Men who speak a language other than English at home were stratified by self-reported levels of English proficiency (men who speak English very well, well, not well, or not at all). Survey weights were applied, and groups were compared using the adjusted Wald test. A multivariable logistic regression model was used to identify predictors of PSA screening adjusting for patient-level covariates. RESULTS: The cohort included 2,889 men, corresponding to a weighted estimate of 4,765,682 men. 79.6% of men who speak English very well reported receiving at least one lifetime PSA test versus 58.4% of men who do not speak English at all (p < 0.001). Men who reported not speaking English at all had significantly lower prevalence of PSA screening (aOR 0.56; 95% CI 0.35-0.91; p = 0.019). Other significant predictors of PSA screening included older age, income > 400% of the federal poverty level, insurance coverage, and healthcare utilization. CONCLUSIONS: Limited English proficiency is associated with significantly lower prevalence of PSA screening among men in the USA. Interventions to mitigate disparities in prostate cancer outcomes should account for limited English proficiency among the barriers to guideline-concordant care.
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Proficiência Limitada em Inglês , Neoplasias da Próstata , Masculino , Humanos , Estados Unidos , Antígeno Prostático Específico , Idioma , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/prevenção & controle , RendaRESUMO
BACKGROUND: The US government considers veterans to have been exposed to Agent Orange if they served in Vietnam while the carcinogen was in use, and these veterans are often deemed at high risk of prostate cancer (PCa). Here, we assess whether presumed Agent Orange exposure is independently associated with increased risk of any metastatic or fatal PCa in a diverse Veteran cohort still alive in the modern era (at least 2011), when accounting for race/ethnicity, family history, and genetic risk. PATIENTS AND METHODS: Participants in the Million Veteran Program (MVP; enrollment began in 2011) who were on active duty during the Vietnam War era (August 1964-April 1975) were included (n = 301,470). Agent Orange exposure was determined using the US government definition. Genetic risk was assessed via a validated polygenic hazard score. Associations with age at diagnosis of any PCa, metastatic PCa, and death from PCa were assessed via Cox proportional hazards models. RESULTS AND INTERPRETATION: On univariable analysis, exposure to Agent Orange was not associated with increased PCa (hazard ratio [HR]: 1.02, 95% confidence interval [CI]: 1.00-1.04, p = 0.06), metastatic PCa (HR: 0.98, 95% CI: 0.91-1.05, p = 0.55), or fatal PCa (HR: 0.94, 95% CI: 0.79-1.09, p = 0.41). When accounting for race/ethnicity and family history, Agent Orange exposure was independently associated with slightly increased risk of PCa (HR: 1.06, 95% CI: 1.04-1.09, <10-6) but not with metastatic PCa (HR: 1.07, 95% CI: 0.98-1.15, p = 0.10) or PCa death (HR: 1.02, 95% CI: 0.83-1.23, p = 0.09). Similar results were found when accounting for genetic risk. Agent Orange exposure history may not improve modern PCa risk stratification.
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Agente Laranja , Neoplasias da Próstata , Veteranos , Guerra do Vietnã , Humanos , Masculino , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/mortalidade , Veteranos/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso , Estados Unidos/epidemiologia , Desfolhantes Químicos/efeitos adversos , Fatores de Risco , Ácido 2,4,5-Triclorofenoxiacético/efeitos adversos , Ácido 2,4-Diclorofenoxiacético/efeitos adversos , Ácido 2,4-Diclorofenoxiacético/toxicidade , Dibenzodioxinas Policloradas/efeitos adversosRESUMO
INTRODUCTION: Robot-assisted laparoscopic prostatectomy (RALP) and transurethral resection of bladder tumor (TURBT) are two common surgeries for prostate and bladder cancer. We aim to assess the trends in the site of care for RALP and TURBT before and after the COVID outbreak. MATERIALS AND METHODS: We identified adults who underwent RALP and TURBT within the California Healthcare Cost and Utilization Project State Inpatient Database and the State Ambulatory Surgery Database between 2018 and 2020. Multivariable analysis and spline analysis with a knot at COVID outbreak were performed to investigate the time trend and factors associated with ambulatory RALP and TURBT. RESULTS: Among 17,386 RALPs, 6,774 (39.0%) were ambulatory. Among 25,070 TURBTs, 21,573 (86.0%) were ambulatory. Pre-COVID, 33.5% of RALP and 85.3% and TURBT were ambulatory, which increased to 53.8% and 88.0% post-COVID (both p < 0.001). In multivariable model, RALP and TURBT performed after outbreak in March 2020 were more likely ambulatory (OR 2.31, p < 0.0001; OR 1.25, p < 0.0001). There was an overall increasing trend in use of ambulatory RALP both pre- and post-COVID, with no significant change of trend at the time of outbreak (p = 0.642). TURBT exhibited an increased shift towards ambulatory sites post-COVID (p < 0.0001). CONCLUSIONS: We found a shift towards ambulatory RALP and TURBT following COVID outbreak. There was a large increase in ambulatory RALP post-COVID, but the trend of change was not significantly different pre- and post-COVID - possibly due to a pre-existing trend towards ambulatory RALP which predated the pandemic.
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COVID-19 , Laparoscopia , Neoplasias da Próstata , Neoplasias da Bexiga Urinária , Masculino , Adulto , Humanos , Pandemias , Prostatectomia , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Procedimentos Cirúrgicos Ambulatórios , COVID-19/epidemiologia , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
PURPOSE: The aim of this study was to develop and validate a predictive model for clinically significant prostate cancer (csPCa) using prostate MRI and patient risk factors. METHODS: In total, 960 men who underwent MRI from 2015 to 2019 and biopsy either 6 months before or 6 months after MRI were identified. Men diagnosed with csPCa were identified, and csPCa risk was modeled using known patient factors (age, race, and prostate-specific antigen [PSA] level) and prostate MRI findings (location, Prostate Imaging Reporting and Data System score, extraprostatic extension, dominant lesion size, and PSA density). csPCa was defined as Gleason score sum ≥ 7. Using a derivation cohort, a multivariable logistic regression model and a point-based scoring system were developed to predict csPCa. Discrimination and calibration were assessed in a separate independent validation cohort. RESULTS: Among 960 MRI reports, 552 (57.5%) were from men diagnosed with csPCa. Using the derivation cohort (n = 632), variables that predicted csPCa were Prostate Imaging Reporting and Data System scores of 4 and 5, the presence of extraprostatic extension, and elevated PSA density. Evaluation using the validation cohort (n = 328) resulted in an area under the curve of 0.77, with adequate calibration (Hosmer-Lemeshow P = .58). At a risk threshold of >2 points, the model identified csPCa with sensitivity of 98.4% and negative predictive value of 78.6% but prevented only 4.3% potential biopsies (0-2 points; 14 of 328). At a higher threshold of >5 points, the model identified csPCa with sensitivity of 89.5% and negative predictive value of 70.1% and avoided 20.4% of biopsies (0-5 points; 67 of 328). CONCLUSIONS: The point-based model reported here can potentially identify a vast majority of men at risk for csPCa, while avoiding biopsy in about 1 in 5 men with elevated PSA levels.
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OBJECTIVES: We conducted a focus group to assess the attitudes of primary care physicians (PCPs) toward prostate-specific antigen (PSA)-screening algorithms, perceptions of using decision support tools, and features that would make such tools feasible to implement. METHODS: A multidisciplinary team (primary care, urology, behavioral sciences, bioinformatics) developed the decision support tool that was presented to a focus group of 10 PCPs who also filled out a survey. Notes and audio-recorded transcripts were analyzed using Thematic Content Analysis. RESULTS: The survey showed that PCPs followed different guidelines. In total, 7/10 PCPs agreed that engaging in shared decision-making about PSA screening was burdensome. The majority (9/10) had never used a decision aid for PSA screening. Although 70% of PCPs felt confident about their ability to discuss PSA screening, 90% still felt a need for a provider-facing platform to assist in these discussions. Three major themes emerged: (1) confirmatory reactions regarding the importance, innovation, and unmet need for a decision support tool embedded in the electronic health record; (2) issues around implementation and application of the tool in clinic workflow and PCPs' own clinical bias; and (3) attitudes/reflections regarding discrepant recommendations from various guideline groups that cause confusion. CONCLUSION: There was overwhelmingly positive support for the need for a provider-facing decision support tool to assist with PSA-screening decisions in the primary care setting. PCPs appreciated that the tool would allow flexibility for clinical judgment and documentation of shared decision-making. Incorporation of suggestions from this focus group into a second version of the tool will be used in subsequent pilot testing.
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Médicos de Atenção Primária , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico , Antígeno Prostático Específico , Detecção Precoce de Câncer , Registros Eletrônicos de Saúde , Padrões de Prática Médica , Programas de RastreamentoRESUMO
Multi-parametric magnetic resonance imaging (mpMRI) has emerged as an important tool for identifying clinically significant prostate cancer. We examined if the addition of a 400-variant multi-ancestry polygenic risk score (PRS) to mpMRI has the potential to improve identification. Based on data from 24 617 men from the Mass General Brigham Biobank, we identified 1243 men who underwent mpMRI. Men in the top PRS quartile were more likely to have clinically significant prostate cancer (47.1% vs 28.6% in the bottom PRS quartile, adjusted relative proportion 1.72 [95% CI = 1.35 to 2.19]). Both among men with a positive and a negative mpMRI, men in the top PRS quartile had the highest frequency of clinically significant cancer. In a constructed scenario for selecting men to undergo biopsy, use of the PRS lowered the frequency of missed clinically significant cancers from 9.1% to 5.9%. Our study provides initial support for using the PRS to improve identification of potentially lethal prostate cancer.
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Estratificação de Risco Genético , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/genética , Imageamento por Ressonância Magnética/métodos , BiópsiaRESUMO
Importance: Multiple strategies integrating magnetic resonance imaging (MRI) and clinical data have been proposed to determine the need for a prostate biopsy in men with suspected clinically significant prostate cancer (csPCa) (Gleason score ≥3 + 4). However, inconsistencies across different strategies create challenges for drawing a definitive conclusion. Objective: To determine the optimal prostate biopsy decision-making strategy for avoiding unnecessary biopsies and minimizing the risk of missing csPCa by combining MRI Prostate Imaging Reporting & Data System (PI-RADS) and clinical data. Data Sources: PubMed, Ovid MEDLINE, Embase, Web of Science, and Cochrane Library from inception to July 1, 2022. Study Selection: English-language studies that evaluated men with suspected but not confirmed csPCa who underwent MRI PI-RADS followed by prostate biopsy were included. Each study had proposed a biopsy plan by combining PI-RADS and clinical data. Data Extraction and Synthesis: Studies were independently assessed for eligibility for inclusion. Quality of studies was appraised using the Quality Assessment of Diagnostic Accuracy Studies 2 tool and the Newcastle-Ottawa Scale. Mixed-effects meta-analyses and meta-regression models with multimodel inference were performed. Reporting of this study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Main Outcomes and Measures: Independent risk factors of csPCa were determined by performing meta-regression between the rate of csPCa and PI-RADS and clinical parameters. Yields of different biopsy strategies were assessed by performing diagnostic meta-analysis. Results: The analyses included 72 studies comprising 36â¯366 patients. Univariable meta-regression showed that PI-RADS 4 (ß-coefficient [SE], 7.82 [3.85]; P = .045) and PI-RADS 5 (ß-coefficient [SE], 23.18 [4.46]; P < .001) lesions, but not PI-RADS 3 lesions (ß-coefficient [SE], -4.08 [3.06]; P = .19), were significantly associated with a higher risk of csPCa. When considered jointly in a multivariable model, prostate-specific antigen density (PSAD) was the only clinical variable significantly associated with csPCa (ß-coefficient [SE], 15.50 [5.14]; P < .001) besides PI-RADS 5 (ß-coefficient [SE], 9.19 [3.33]; P < .001). Avoiding biopsy in patients with lesions with PI-RADS category of 3 or less and PSAD less than 0.10 (vs <0.15) ng/mL2 resulted in reducing 30% (vs 48%) of unnecessary biopsies (compared with performing biopsy in all suspected patients), with an estimated sensitivity of 97% (vs 95%) and number needed to harm of 17 (vs 15). Conclusions and Relevance: These findings suggest that in patients with suspected csPCa, patient-tailored prostate biopsy decisions based on PI-RADS and PSAD could prevent unnecessary procedures while maintaining high sensitivity.
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Imageamento por Ressonância Magnética , Neoplasias da Próstata , Masculino , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Antígeno Prostático Específico , Próstata/diagnóstico por imagem , Próstata/patologia , BiópsiaRESUMO
OBJECTIVES: Our objective was to pilot test an electronic health record-embedded decision support tool to facilitate prostate-specific antigen (PSA) screening discussions in the primary care setting. METHODS: We pilot-tested a novel decision support tool that was used by 10 primary care physicians (PCPs) for 6 months, followed by a survey. The tool comprised (1) a risk-stratified algorithm, (2) a tool for facilitating shared decision-making (Simple Schema), (3) three best practice advisories (BPAs: <45, 45-75, and >75 years), and (4) a health maintenance module for scheduling automated reminders about PSA rescreening. RESULTS: All PCPs found the tool feasible, acceptable, and clear to use. Eight out of ten PCPs reported that the tool made PSA screening conversations somewhat or much easier. Before using the tool, 70% of PCPs felt confident in their ability to discuss PSA screening with their patient, and this improved to 100% after the tool was used by PCPs for 6 months. PCPs found the BPAs for eligible (45-75 years) and older men (>75 years) more useful than the BPA for younger men (<45 years). Among the 10 PCPs, 60% found the Simple Schema to be very useful, and 50% found the health maintenance module to be extremely or very useful. Most PCPs reported the components of the tool to be at least somewhat useful, with 10% finding them to be very burdensome. CONCLUSION: We demonstrated the feasibility and acceptability of the tool, which is notable given the marked low acceptance of existing tools. All PCPs reported that they would consider continuing to use the tool in their clinic and were likely or very likely to recommend the tool to a colleague.
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Médicos de Atenção Primária , Neoplasias da Próstata , Masculino , Humanos , Idoso , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/prevenção & controle , Antígeno Prostático Específico , Projetos Piloto , Detecção Precoce de Câncer , Tomada de Decisões , Atenção Primária à Saúde , Programas de RastreamentoRESUMO
OBJECTIVE: To demonstrate the added benefit of multiparametric (mp)MRI risk stratification during active surveillance. METHODS: This prospective, single-arm, nonrandomized study included 82 men with low-risk prostate cancer (PCa). We compared two biopsy strategies in parallel. The first biopsy strategy was an in-bore and transrectal ultrasound (TRUS) biopsy in men with suspicious mpMRI findings. The second was a TRUS biopsy in all 82 men, blinded to the results of the previously performed mpMRI. RESULTS: We identified 27/82 men with suspicious mpMRI. Of those 27 men, we detected 8/27 with csPCa on biopsy, and we identified two men with in-bore biopsy exclusively, three men with TRUS biopsy exclusively, and three men with both biopsy strategies. Of the 55/82 men with nonsuspicious mpMRI (who only received TRUS biopsies), two men had csPCa. TRUS biopsy of the entire cohort of 82 men would have led to the correct diagnosis of 80% men with csPCa, requiring all 82 men to receive biopsies (csPCa in 10% of the 82 biopsies). Conducting in-bore biopsies plus TRUS biopsies in men with suspicious mpMRI would have also led to the detection of 80% of men with csPCa, requiring only 27 men to receive biopsies (csPCa in 30% of the 27 biopsies). CONCLUSION: The combination of TRUS and in-bore biopsies, limited to men with suspicious mpMRI, resulted in a similar detection rate of csPCa compared to TRUS biopsies of all men but required only one-third of men to undergo biopsy. Our results indicate that in-bore and TRUS biopsies continue to complement each other.
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Neoplasias da Próstata , Conduta Expectante , Masculino , Humanos , Estudos Prospectivos , Ultrassonografia de Intervenção/métodos , Neoplasias da Próstata/patologia , Biópsia , Imageamento por Ressonância Magnética/métodos , Biópsia Guiada por Imagem/métodosRESUMO
BACKGROUND: The rise in advanced prostate cancer has coincided with increased use of Magnetic Resonance Imaging (MRI), leading to the hypothesis that this increase in surveillance registries is an artifact of more sensitive imaging tools. We assessed the association between regional variation in prostate MRI and advanced prostate cancer diagnoses. METHODS: We utilized SEER-Medicare data (2004-2015), including men > 65 diagnosed with localized prostate cancer. The predictor variable was the utilization of prostate MRI in each hospital referral region (HRR, representing regional healthcare markets). We compared the proportion of disease recorded as locally advanced or of regional risk group (cT3, cT4, and cN1) which would plausibly have been detected by prostate MRI. We conducted adjusted multivariable analysis and performed correlation analysis with Spearman rank coefficient at the level of the HRR. Sensitivity analysis for years 2011 to 2015 was conducted. RESULTS: Of 98,921 men diagnosed, 4.01% had locally advanced or regional disease. The median prostate MRI utilization rate was 4.58% (IQR [3.03%, 8.12%]). Adjusted multivariable analysis revealed no statistically significant correlation between MRI utilization and proportion of advanced prostate cancer (aORâ¯=â¯1.01, 95% CI, [0.99,1.03]) in each region. The correlation between MRI usage and advanced diagnosis was not significant (Spearman Ρâ¯=â¯0.09, Pâ¯=â¯0.4). Sensitivity analysis conducted between 2011 and 2015 showed similar results (aORâ¯=â¯1.008, 95% CI, [0.989, 1.027]; Spearman Ρâ¯=â¯0.16, Pâ¯=â¯0.1). CONCLUSIONS: During our study period, HRR-level utilization of MRI was not associated with higher incidences of advanced prostate cancer. This suggests the rising advanced prostate cancer diagnoses observed in this period are unlikely an artifact of greater sensitivity of modern imaging tests, but potentially due to other factors such as changes in screening or risk factors. With increased utilization and evolving techniques in recent years, the association between MRI and advanced prostate cancer detection warrants continued monitoring.
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Importance: Prostate cancer, a leading cause of cancer death among men, urgently requires new prevention strategies, which may involve targeting men with an underlying genetic susceptibility. Objective: To explore differences in risk of early prostate cancer death among men with higher vs lower genetic risk to inform prevention efforts. Design, Setting, and Participants: This cohort study used a combined analysis of genotyped men without prostate cancer at inclusion and with lifestyle data in 2 prospective cohort studies in Sweden and the US, the Malmö Diet and Cancer Study (MDCS) and the Health Professionals Follow-Up Study (HPFS), followed up from 1991 to 2019. Data were analyzed between April 2023 and April 2024. Exposures: Men were categorized according to modifiable lifestyle behaviors and genetic risk. A polygenic risk score above the median or a family history of cancer defined men at higher genetic risk (67% of the study population); the remaining men were categorized as being at lower genetic risk. Main Outcomes and Measures: Prostate cancer death analyzed using time-to-event analysis estimating hazard ratios (HR), absolute risks, and preventable deaths by age. Results: Among the 19â¯607 men included for analysis, the median (IQR) age at inclusion was 59.0 (53.0-64.7) years (MDCS) and 65.1 (58.0-71.8) years (HPFS). During follow-up, 107 early (by age 75 years) and 337 late (after age 75 years) prostate cancer deaths were observed. Compared with men at lower genetic risk, men at higher genetic risk had increased rates of both early (HR, 3.26; 95% CI, 1.82-5.84) and late (HR, 2.26; 95% CI, 1.70-3.01) prostate cancer death, and higher lifetime risks of prostate cancer death (3.1% vs 1.3% [MDCS] and 2.3% vs 0.6% [HPFS]). Men at higher genetic risk accounted for 94 of 107 early prostate cancer deaths (88%), of which 36% (95% CI, 12%-60%) were estimated to be preventable through adherence to behaviors associated with a healthy lifestyle (not smoking, healthy weight, high physical activity, and a healthy diet). Conclusions and Relevance: In this 20-year follow-up study, men with a genetic predisposition accounted for the vast majority of early prostate cancer deaths, of which one-third were estimated to be preventable. This suggests that men at increased genetic risk should be targeted in prostate cancer prevention strategies.
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Predisposição Genética para Doença , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/mortalidade , Pessoa de Meia-Idade , Idoso , Suécia/epidemiologia , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Estilo de Vida , Estudos de CoortesRESUMO
BACKGROUND AND OBJECTIVE: There exists ongoing debate about the benefits and harms of prostate-specific antigen (PSA) screening for prostate cancer. This study sought to evaluate the association of county-level PSA screening rates with county-level incidence of metastatic prostate cancer and prostate cancer mortality in the USA. METHODS: This ecological study used data from the 2004-2012 Behavioral Risk Factor Surveillance System (BRFSS) to build a multilevel mixed-effect model with poststratification using US Census data to estimate county-level PSA screening rates for all 3143 US counties adjusted for age, race, ethnicity, and county-level poverty rates. The exposure of interest was average county-level PSA screening rate from 2004 to 2012, defined as the proportion of men aged 40-79 yr who underwent PSA screening within the prior 2 yr. The primary outcomes were county-level age-adjusted incidence of regional/distant prostate cancer during 2015-2019 and age-adjusted prostate cancer mortality during 2016-2020. KEY FINDINGS AND LIMITATIONS: A total of 416â¯221 male BRFSS respondents aged 40-79 yr met the inclusion criteria and were used in the multilevel mixed-effect model. The model was poststratified using 63.4 million men aged 40-79 yr from all 3143 counties in the 2010 Decennial Census. County-level estimated PSA screening rates exhibited geographic variability and were pooled at the state level for internal validation with direct BRFSS state-level estimates, showing a strong correlation with Pearson correlation coefficients 0.77-0.90. A 10% higher county-level probability of PSA screening in 2004-2012 was associated with a 14% lower county-level incidence of regional/distant prostate cancer in 2015-2019 (rate ratio 0.86, 95% confidence interval [CI] 0.85-0.87, pâ¯<â¯0.001) and 10% lower county-level prostate cancer mortality in 2016-2020 (rate ratio 0.90, 95% CI 0.89-0.91, pâ¯<â¯0.001). CONCLUSIONS AND CLINICAL IMPLICATIONS: In this population-based ecological study of all US counties, higher PSA screening rates were associated with a lower incidence of regional/distant prostate cancer and lower prostate cancer mortality at extended follow-up. PATIENT SUMMARY: US counties with higher rates of prostate-specific antigen (PSA) screening had significantly lower rates of metastatic prostate cancer and prostate cancer mortality in subsequent years. These data may inform shared decision-making regarding PSA screening for prostate cancer.
Assuntos
Detecção Precoce de Câncer , Antígeno Prostático Específico , Neoplasias da Próstata , Humanos , Masculino , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Pessoa de Meia-Idade , Idoso , Adulto , Detecção Precoce de Câncer/estatística & dados numéricos , Estados Unidos/epidemiologia , Metástase Neoplásica , IncidênciaRESUMO
Current treatments for advanced prostate cancer (PCa) primarily target androgen receptor (AR)-pathways. However, the emergence of castration-resistant prostate cancer (CRPC) and resistance to AR signaling inhibitors (ARSI) remains a significant clinical challenge. This study introduces BSJ-5-63, a novel triple degrader targeting cyclin-dependent kinases (CDKs) CDK12, CDK7, and CDK9, with potential to transform CRPC therapy. BSJ-5-63 effectively downregulates homologous recombination repair (HRR) genes, including BRCA1 and BRCA2, through CDK12 degradation, and attenuates AR signaling through CDK7 and CDK9 degradation, further enhancing its therapeutic impact. Importantly, BSJ-5-63 induces a "BRCAness" state that persists for a significant duration, enabling sequential combination therapy with PARP inhibitors (PARPis) while potentially minimizing drug-related toxicity and resistance. In both in vitro and in vivo studies, BSJ-5-63 exhibited potent antiproliferative effects in both AR-positive and AR-negative CRPC models. This study presents a promising multi-pronged approach for CRPC treatment, addressing both DNA repair mechanisms and AR signaling, with the potential to benefit a wide range of patients regardless of their BRCA1/2 mutational status. SIGNIFICANCE: This study introduces BSJ-5-63, a triple degrader designed to target CDK12, CDK7, and CDK9, making a significant advancement in CRPC therapy. The distinctive mechanism of BSJ-5-63 involves downregulating HRR genes and inhibiting AR signaling, thereby inducing a BRCAness state. This enhances sensitivity to PARP inhibition, effectively addressing ARSI resistance and improving the overall efficacy of treatment. The development of BSJ-5-63 represents a promising therapeutic approach, with the potential to benefit a broad spectrum of CRPC patients.
RESUMO
BACKGROUND: In the United States, Black men are at highest risk for being diagnosed with and dying from prostate cancer. Given this disparity, we examined relevant data to establish clinical prostate-specific antigen (PSA) screening guidelines for Black men in the United States. METHODS: A comprehensive literature search identified 1848 unique publications for screening. Of those screened, 287 studies were selected for full-text review, and 264 were considered relevant and form the basis for these guidelines. The numbers were reported according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. RESULTS: Three randomized controlled trials provided Level 1 evidence that regular PSA screening of men 50 to 74 years of age of average risk reduced metastasis and prostate cancer death at 16 to 22 years of follow-up. The best available evidence specifically for Black men comes from observational and modeling studies that consider age to obtain a baseline PSA, frequency of testing, and age when screening should end. Cohort studies suggest that discussions about baseline PSA testing between Black men and their clinicians should begin in the early 40s, and data from modeling studies indicate prostate cancer develops 3 to 9 years earlier in Black men compared with non-Black men. Lowering the age for baseline PSA testing to 40 to 45 years of age from 50 to 55 years of age, followed by regular screening until 70 years of age (informed by PSA values and health factors), could reduce prostate cancer mortality in Black men (approximately 30% relative risk reduction) without substantially increasing overdiagnosis. CONCLUSIONS: These guidelines recommend that Black men should obtain information about PSA screening for prostate cancer. Among Black men who elect screening, baseline PSA testing should occur between ages 40 and 45. Depending on PSA value and health status, annual screening should be strongly considered. (Supported by the Prostate Cancer Foundation.).