Artificial Intelligence-Based PTEN Loss Assessment as an Early Predictor of Prostate Cancer Metastasis After Surgery: A Multicenter Retrospective Study.

Phosphatase and tensin homolog (PTEN) loss is associated with adverse outcomes in prostate cancer and can be measured via immunohistochemistry. The purpose of the study was to establish the clinical application of an in-house developed artificial intelligence (AI) image analysis workflow for automated detection of PTEN loss on digital images for identifying patients at risk of early recurrence and metastasis. Postsurgical tissue microarray sections from the Canary Foundation (n = 1264) stained with anti-PTEN antibody were evaluated independently by pathologist conventional visual scoring (cPTEN) and an automated AI-based image analysis pipeline (AI-PTEN). The relationship of PTEN evaluation methods with cancer recurrence and metastasis was analyzed using multivariable Cox proportional hazard and decision curve models. Both cPTEN scoring by the pathologist and quantification of PTEN loss by AI (high-risk AI-qPTEN) were significantly associated with shorter metastasis-free survival (MFS) in univariable analysis (cPTEN hazard ratio [HR], 1.54; CI, 1.07-2.21; P = .019; AI-qPTEN HR, 2.55; CI, 1.83-3.56; P < .001). In multivariable analyses, AI-qPTEN showed a statistically significant association with shorter MFS (HR, 2.17; CI, 1.49-3.17; P < .001) and recurrence-free survival (HR, 1.36; CI, 1.06-1.75; P = .016) when adjusting for relevant postsurgical clinical nomogram (Cancer of the Prostate Risk Assessment [CAPRA] postsurgical score [CAPRA-S]), whereas cPTEN does not show a statistically significant association (HR, 1.33; CI, 0.89-2; P = .2 and HR, 1.26; CI, 0.99-1.62; P = .063, respectively) when adjusting for CAPRA-S risk stratification. More importantly, AI-qPTEN was associated with shorter MFS in patients with favorable pathological stage and negative surgical margins (HR, 2.72; CI, 1.46-5.06; P = .002). Workflow also demonstrated enhanced clinical utility in decision curve analysis, more accurately identifying men who might benefit from adjuvant therapy postsurgery. This study demonstrates the clinical value of an affordable and fully automated AI-powered PTEN assessment for evaluating the risk of developing metastasis or disease recurrence after radical prostatectomy. Adding the AI-qPTEN assessment workflow to clinical variables may affect postoperative surveillance or management options, particularly in low-risk patients.

Bystander-initiated cardiopulmonary resuscitation and automated external defibrillator use after out-of-hospital cardiac arrest: Uncovering disparities in care and survival across the urban-rural spectrum.

AIM: To evaluate the association between bystander cardiopulmonary resuscitation (CPR), automated external defibrillator (AED) use, and survival after out-of-hospital cardiac arrest (OHCA) across the urban-rural spectrum. METHODS: This was a retrospective cohort study of 325,477 adult OHCAs within the Cardiac Arrest Registry to Enhance Survival from 2013 to 2019. Bystander interventions were categorized into no bystander intervention, bystander CPR alone, and bystander AED use (with or without CPR). The primary outcome was survival to hospital discharge with good neurological outcome. Multivariable logistic regression was used to evaluate the association between bystander interventions and survival by geographical status (urban, suburban, large rural, small town, or rural). RESULTS: Bystander CPR alone occurred most often in rural areas (50.8%), and least often in urban areas (35.4%). Bystander AED use in public settings was similar across the urban-rural spectrum (10.5-13.1%). Survival with good neurological outcome varied for urban (8.1%), suburban (7.7%), large rural (9.1%), small town (7.1%), and rural areas (6.1%). In comparison to no bystander intervention, the adjusted odds ratios (95% confidence intervals) for bystander AED use and survival were 2.57 (2.37-2.79) in urban areas, 2.58 (1.81-3.67) in suburban areas, 1.99 (1.44-2.76) in large rural areas, 1.90 (1.27-2.86) in small towns, and 3.05 (1.99-4.68) in rural areas. Bystander CPR alone was also associated with survival in all areas (adjusted odds ratio range: 1.29-1.45). There was no strong evidence of interaction between bystander interventions and geographical status on the primary outcome (p = 0.63). CONCLUSION: Bystander CPR and AED use are associated with positive clinical outcomes after OHCA in all areas along the urban-rural spectrum.

Risk Stratification of Prostate Cancer Through Quantitative Assessment of PTEN Loss (qPTEN).

BACKGROUND: Phosphatase and tensin homolog (PTEN) loss has long been associated with adverse findings in early prostate cancer. Studies to date have yet to employ quantitative methods (qPTEN) for measuring of prognostically relevant amounts of PTEN loss in postsurgical settings and demonstrate its clinical application. METHODS: PTEN protein levels were measured by immunohistochemistry in radical prostatectomy samples from training (n = 410) and validation (n = 272) cohorts. PTEN loss was quantified per cancer cell and per tissue microarray core. Thresholds for identifying clinically relevant PTEN loss were determined using log-rank statistics in the training cohort. Univariate (Kaplan-Meier) and multivariate (Cox proportional hazards) analyses on various subpopulations were performed to assess biochemical recurrence-free survival (BRFS) and were independently validated. All statistical tests were two-sided. RESULTS: PTEN loss in more than 65% cancer cells was most clinically relevant and had statistically significant association with reduced BRFS in training (hazard ratio [HR] = 2.48, 95% confidence interval [CI] = 1.59 to 3.87; P < .001) and validation cohorts (HR = 4.22, 95% CI = 2.01 to 8.83; P < .001). The qPTEN scoring method identified patients who recurred within 5.4 years after surgery (P < .001). In men with favorable risk of biochemical recurrence (Cancer of the Prostate Risk Assessment - Postsurgical scores <5 and no adverse pathological features), qPTEN identified a subset of patients with shorter BRFS (HR = 5.52, 95% CI = 2.36 to 12.90; P < .001) who may be considered for intensified monitoring and/or adjuvant therapy. CONCLUSIONS: Compared with previous qualitative approaches, qPTEN improves risk stratification of postradical prostatectomy patients and may be considered as a complementary tool to guide disease management after surgery.