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1.
Diagnostics (Basel) ; 14(17)2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39272684

RESUMEN

The recent rise in telemedicine, notably during the COVID-19 pandemic, highlights the potential of integrating artificial intelligence tools in healthcare. This study assessed the effectiveness of ChatGPT versus medical oncologists in the telemedicine-based management of metastatic prostate cancer. In this retrospective study, 102 patients who met inclusion criteria were analyzed to compare the competencies of ChatGPT and oncologists in telemedicine consultations. ChatGPT's role in pre-charting and determining the need for in-person consultations was evaluated. The primary outcome was the concordance between ChatGPT and oncologists in treatment decisions. Results showed a moderate concordance (Cohen's Kappa = 0.43, p < 0.001). The number of diagnoses made by both parties was not significantly different (median number of diagnoses: 5 vs. 5, p = 0.12). In conclusion, ChatGPT exhibited moderate agreement with oncologists in management via telemedicine, indicating the need for further research to explore its healthcare applications.

2.
Kidney Cancer ; 8(1): 135-142, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39263256

RESUMEN

Background: Cabozantinib, a tyrosine kinase inhibitor (TKI), is a prevalent second-line (2 L) therapy and was approved for use after progression on TKIs. However, the 1 L treatment setting has changed since the approval of cabozantinib monotherapy in salvage therapy settings. Objective: To assess the differential effectiveness of cabozantinib after prior progression on 1 L ipilimumab with nivolumab (IPI + NIVO) compared to programmed death receptor-1 (PD-1) or PD-1 ligand (PD-L1) inhibitors (PD1/L1i) with TKIs. Methods: Utilizing a nationwide electronic health record (EHR)-derived de-identified database, we included patients with metastatic clear cell renal cell carcinoma (mccRCC) who received 1 L treatment with an immune checkpoint inhibitor (ICI)-based combination and 2 L treatment with cabozantinib monotherapy. These patients were categorized based on the type of 1 L ICI-based combination received: IPI + NIVO vs. PD1/L1i with TKI. Real-world time to next therapy (rwTTNT) and real-world overall survival (rwOS) were summarized using Kaplan-Meier curves and compared using Cox-proportional hazard models adjusted for International mRCC Database Consortium (IMDC) risk groups. Results: Among 12,285 patients with metastatic renal cell carcinoma, 237 were eligible and included. Median rwTTNT was 8 months for the IPI + NIVO subgroup and 7.5 months for the PD1/L1i + TKI subgroup (HR 1.05, 95% CI: 0.74-1.49, p = 0.8). Median rwOS was 17 months for IPI + NIVO and 16 months for PD1/L1i + TKI subgroup (HR 0.79, 95% CI: 0.52-1.20, p = 0.3). Conclusions: Cabozantinib remains effective as a 2 L therapy for mccRCC independent of the type of prior 1 L ICI-based combination. Further research is needed to validate these findings and explore the ideal sequencing of therapies.

3.
J Kidney Cancer VHL ; 11(3): 13-22, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39100549

RESUMEN

Thromboembolic events (TE) are a common complication in patients with metastatic renal cell carcinoma (mRCC) and are associated with poorer clinical outcomes. However, the incidence of TE and clinical and genomic characteristics of patients with mRCC who develop this complication are poorly understood. Herein, we describe the incidence and clinical features of patients with mRCC with or without TE at our institution, and examine their association with the underlying genomic and transcriptomic characteristics of the tumor. This retrospective study included all consecutive cases of mRCC seen at our institution. A CLIA-certified lab performed tumor genomics and transcriptomics. Patients were classified based on the presence of a TE within the first year of diagnosis. Three hundred and seventy patients with mRCC were included in the study. TE was seen in 11% (42) of the patients. Patients with favorable International mRCC Database Consortium (IMDC) risk were less likely to develop a TE. In contrast, patients receiving combination treatment with a tyrosine kinase inhibitor (TKI) and an immune checkpoint inhibitor were more likely to develop a TE. No difference in overall survival among patients with or without TE was observed (52 vs. 55 months; HR 0.85, 95% CI 0.5574-1.293, p = 0.24). The most upregulated pathways in mRCC with TEs versus those without were the xenobiotic metabolism and mTORC1 signaling pathways. Our findings suggest potential biomarkers that, after external validation, could be used to better select patients who would benefit from prophylactic anticoagulation.

4.
JAMA Netw Open ; 7(7): e2423186, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39023888

RESUMEN

Importance: Targeted therapies based on underlying tumor genomic susceptible alterations have been approved for patients with metastatic prostate cancer (mPC) and advanced urothelial carcinoma (aUC). Objective: To assess trends and disparities in next-generation sequencing (NGS) testing among patients with mPC and aUC. Design, Setting, and Participants: This retrospective cohort study used an electronic health record-derived database to extract deidentified data of patients receiving care from US physician practices, hospital-affiliated clinics, and academic practices. Patients diagnosed with mPC or aUC between March 1, 2015, and December 31, 2022, were included. Exposures: Social determinants of health evaluated by race and ethnicity, socioeconomic status (SES), region, insurance type, and sex (for aUC). Main Outcomes and Measures: The primary outcomes were (1) NGS testing rate by year of mPC and aUC diagnosis using Clopper-Pearson 2-sided 95% CIs and (2) time to NGS testing, which considered death as a competing risk. Cumulative incidence functions were estimated for time to NGS testing. Disparities in subdistributional incidence of NGS testing were assessed by race and ethnicity, SES, region, insurance type, and sex (for aUC) using the Fine-Gray modified Cox proportional hazards model, assuming different subdistribution baseline hazards by year of mPC and aUC diagnosis. Results: A total of 11 927 male patients with mPC (167 Asian [1.6%], 1236 Black [11.6%], 687 Hispanic or Latino [6.4%], 7037 White [66.0%], and 1535 other [14.4%] among 10 662 with known race and ethnicity) and 6490 patients with aUC (4765 male [73.4%]; 80 Asian [1.4%], 283 Black [4.8%], 257 Hispanic or Latino [4.4%], 4376 White [74.9%], and 845 other [14.5%] among 5841 with known race and ethnicity) were eligible and included. Both cohorts had a median age of 73 years (IQR, 66-80 years), and most underwent NGS testing before first-line treatment in the mPC cohort (1502 [43.0%]) and before second-line treatment in the aUC cohort (1067 [51.3%]). In the mPC cohort, the rates of NGS testing increased from 19.0% in 2015 to 27.1% in 2022, but Black patients (hazard ratio [HR], 0.75; 95% CI, 0.67-0.84) and Hispanic or Latino patients (HR, 0.70; 95% CI, 0.60-0.82) were less likely to undergo NGS testing. Patients with mPC who had low SES (quintile 1: HR, 0.74 [95% CI, 0.66-0.83]; quintile 2: HR, 0.89 [95% CI, 0.80-0.99]), had Medicaid (HR, 0.53; 95% CI, 0.38-0.74) or Medicare or other government insurance (HR, 0.89; 95% CI, 0.82-0.98), or lived in the West (HR, 0.81; 95% CI, 0.70-0.94) also were less likely to undergo testing. In the aUC cohort, the NGS rate increased from 14.1% in 2015 to 46.6% in 2022, but Black patients (HR, 0.76; 95% CI, 0.61-0.96) and those with low SES (quintile 1: HR 0.77 [95% CI, 0.66-0.89]; quintile 2: HR, 0.87 [95% CI, 0.76-1.00]) or Medicaid (HR, 0.72; 95% CI, 0.53-0.97) or Medicare or other government insurance (HR, 0.88; 95% CI, 0.78-0.99) were less likely to undergo NGS testing. Patients with aUC living in the South were more likely to undergo testing (HR, 1.29; 95% CI, 1.12-1.49). Conclusions and Relevance: These findings suggest that although NGS tumor testing rates improved over time, the majority of patients still did not undergo testing. These data may help with understanding current disparities associated with NGS testing and improving access to standard-of-care health care services.


Asunto(s)
Disparidades en Atención de Salud , Secuenciación de Nucleótidos de Alto Rendimiento , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Anciano , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Persona de Mediana Edad , Disparidades en Atención de Salud/estadística & datos numéricos , Femenino , Estados Unidos/epidemiología , Neoplasias Urológicas/genética , Neoplasias Urológicas/patología , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Carcinoma de Células Transicionales/genética , Anciano de 80 o más Años
5.
Cancers (Basel) ; 16(11)2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38893262

RESUMEN

Metastatic urinary tract cancer (mUTC) is challenging to treat in older adults due to comorbidities. We compared the clinical courses of younger and older (≥70 years) adults with mUTC receiving first-line (1L) systemic therapy in a tertiary cancer center. Baseline clinical characteristics, treatments received, tolerability, and survival outcomes were analyzed. Among 212 patients (103 older vs. 109 younger), the older patients had lower hemoglobin at baseline (84% vs. 71%, p = 0.03), the majority were cisplatin-ineligible (74% vs. 45%, p < 0.001), received more immunotherapy-based treatments in the 1L (52% vs. 36%, p = 0.01), received fewer subsequent lines of treatment (median 0 vs. 1, p = 0.003), and had lower clinical trial participation (30% vs. 18%, p = 0.05) compared to the younger patients. When treated with 1L chemotherapy, older patients required more dose adjustments (53.4% vs. 23%, p = 0.001) and received fewer cycles of chemotherapy (median 4 vs. 5, p= 0.01). Older patients had similar OS (11.2 months vs. 14 months, p = 0.06) and similar rates of treatment-related severe toxicity and healthcare visits, independent of the type of systemic treatment received, compared to younger patients. We conclude that select older adults with mUTC can be safely treated with immunotherapy and risk-adjusted regimens of chemotherapy with tangible survival benefits.

6.
JCO Precis Oncol ; 8: e2300574, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38781543

RESUMEN

PURPOSE: An increased BMI is linked to increased prostate adenocarcinoma incidence and mortality. Baseline tumor gene expression profiling (GEP) can provide a comprehensive picture of the biological processes related to treatment response and disease progression. We interrogate and validate the underlying differences in tumor GEP on the basis of BMI in patients with prostate adenocarcinoma. METHODS: The inclusion criteria consisted of histologically confirmed prostate adenocarcinoma and the availability of RNA sequencing data obtained from treatment-naïve primary prostate tissue. RNA sequencing was performed by a Clinical Laboratory Improvement Amendments-certified laboratory (Tempus or Caris Life Sciences). The Tempus cohort was used for interrogation and the Caris cohort for validation. Patients were stratified on the basis of BMI at the time of prostate cancer diagnosis: BMI-high (BMIH; BMI ≥30) and BMI-low (BMIL; BMI <30). Differential gene expression analysis between the two cohorts was conducted using the DEseq2 pipeline. The resulting GEPs were further analyzed using Gene Set Enrichment software to identify pathways that exhibited enrichment in each cohort. RESULTS: Overall, 102 patients were eligible, with 60 patients in the Tempus cohort (BMIL = 38, BMIH = 22) and 42 patients in the Caris cohort (BMIL = 24, BMIH = 18). Tumor tissues obtained from patients in the BMIL group exhibited higher expression of genes associated with inflammation pathways. BMIH displayed increased expression of genes involved in pathways such as heme metabolism and androgen response. CONCLUSION: Our study shows the upregulation of distinct genomic pathways in BMIL compared with BMIH patients with prostate cancer. These hypothesis-generating data could explain different survival outcomes in both groups and guide personalized therapy for men with prostate cancer.


Asunto(s)
Adenocarcinoma , Índice de Masa Corporal , Perfilación de la Expresión Génica , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/genética , Adenocarcinoma/genética , Anciano , Persona de Mediana Edad , Estudios de Cohortes
7.
Eur Urol Oncol ; 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38735779

RESUMEN

BACKGROUND AND OBJECTIVE: It has been reported that patients with de novo metastatic castration-sensitive prostate cancer (dn-mCSPC) have worse prognosis and outcomes than those whose cancer relapses after prior local therapy (PLT-mCSPC). Our aim was to interrogate and validate underlying differences in tumor gene expression profiles between dn-mCSPC and PLT-mCSPC. METHODS: The inclusion criteria were histologically confirmed prostate adenocarcinoma and the availability of RNA sequencing data for treatment-naïve primary prostate tissue. RNA sequencing was performed by Tempus or Caris Life Sciences, both of which have Clinical Laboratory Improvement Amendments certification. The Tempus cohort was used for interrogation, while the Caris cohort was used for validation. Differential gene expression analysis between the cohorts was conducted using the DEseq2 pipeline. The resulting gene expression profiles were further analyzed using Gene Set Enrichment software to identify pathways with enrichment in each cohort. KEY FINDINGS AND LIMITATIONS: Overall, 128 patients were eligible, of whom 78 were in the Tempus cohort (dn-mCSPC 37, PLT-mCSPC 41) and 50 were in the Caris cohort (dn-mCSPC 30, PLT-mCSPC 20). Tumor tissues from patients with dn-mCSPC had higher expression of genes associated with inflammation pathways, while tissues from patients with PLT-mCSPC had higher expression of genes involved in oxidative phosphorylation, fatty acid metabolism, and androgen response pathways. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study revealed upregulation of distinct genomic pathways in dn-mCSPC in comparison to PLT-mCSPC. These hypothesis-generating data could guide personalized therapy for men with prostate cancer and explain different survival outcomes for dn-mCSPC and PLT-mCSPC. PATIENT SUMMARY: We measured gene expression levels in tumors from patients with metastatic castration-sensitive prostate cancer. In patients with metastatic disease at first diagnosis, inflammatory pathways were upregulated. In patients whose metastasis occurred on relapse after treatment, androgen response pathways were upregulated. These findings could help in personalizing therapy for prostate cancer and explaining differences in survival.

8.
JAMA Netw Open ; 7(5): e249417, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38696168

RESUMEN

Importance: The treatment paradigm for advanced urothelial carcinoma (aUC) has undergone substantial transformation due to the introduction of effective, novel therapeutic agents. However, outcomes remain poor, and little is known about current treatment approaches and attrition rates for patients with aUC. Objectives: To delineate evolving treatment patterns and attrition rates in patients with aUC using a US-based patient-level sample. Design, Setting, and Participants: This retrospective cohort study used patient-level data from the nationwide deidentified electronic health record database Flatiron Health, originating from approximately 280 oncology clinics across the US. Patients included in the analysis received treatment for metastatic or local aUC at a participating site from January 1, 2011, to January 31, 2023. Patients receiving treatment for 2 or more different types of cancer or participating in clinical trials were excluded from the analysis. Main Outcomes and Measures: Frequencies and percentages were used to summarize the (1) treatment received in each line (cisplatin-based regimens, carboplatin-based regimens, programmed cell death 1 and/or programmed cell death ligand 1 [PD-1/PD-L1] inhibitors, single-agent nonplatinum chemotherapy, enfortumab vedotin, erdafitinib, sacituzumab govitecan, or others) and (2) attrition of patients with each line of therapy, defined as the percentage of patients not progressing to the next line. Results: Of the 12 157 patients within the dataset, 7260 met the eligibility criteria and were included in the analysis (5364 [73.9%] men; median age at the start of first-line treatment, 73 [IQR, 66-80] years). All patients commenced first-line treatment; of these, only 2714 (37.4%) progressed to receive second-line treatment, and 857 (11.8%) advanced to third-line treatment. The primary regimens used as first-line treatment contained carboplatin (2241 [30.9%]), followed by PD-1/PD-L1 inhibitors (2174 [29.9%]). The PD-1/PD-L1 inhibitors emerged as the predominant choice in the second- and third-line (1412 of 2714 [52.0%] and 258 of 857 [30.1%], respectively) treatments. From 2019 onward, novel therapeutic agents were increasingly used in second- and third-line treatments, including enfortumab vedotin (219 of 2714 [8.1%] and 159 of 857 [18.6%], respectively), erdafitinib (39 of 2714 [1.4%] and 28 of 857 [3.3%], respectively), and sacituzumab govitecan (14 of 2714 [0.5%] and 34 of 857 [4.0%], respectively). Conclusions and Relevance: The findings of this cohort study suggest that approximately two-thirds of patients with aUC did not receive second-line treatment. Most first-line treatments do not include cisplatin-based regimens and instead incorporate carboplatin- or PD-1/PD-L1 inhibitor-based therapies. These data warrant the provision of more effective and tolerable first-line treatments for patients with aUC.


Asunto(s)
Carboplatino , Humanos , Masculino , Femenino , Estudios Retrospectivos , Anciano , Estados Unidos , Carboplatino/uso terapéutico , Persona de Mediana Edad , Carcinoma de Células Transicionales/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/patología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Cisplatino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico
9.
Prostate ; 84(9): 888-892, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38561317

RESUMEN

BACKGROUND: Androgen deprivation therapy (ADT) intensification (ADTi) (i.e., ADT with androgen receptor pathway inhibitor or docetaxel, or both) has significantly improved survival outcomes of patients with metastatic hormone-sensitive prostate cancer (mHSPC). However, the impact of prior ADTi in the mHSPC setting on the disease presentation and survival outcomes in metastatic castration-resistant prostate cancer (mCRPC) is not well characterized. In this study, our objective was to compare the disease characteristics and survival outcomes of patients with new mCRPC with respect to receipt of intensified or nonintensified ADT in the mHSPC setting. METHODS: In this institutional review board-approved retrospective study, eligibility criteria were as follows: patients diagnosed with mCRPC, treated with an approved first-line mCRPC therapy, and who received either intensified or nonintensified ADT in the mHSPC setting. Progression-free survival (PFS) was defined from the start of first-line therapy for mCRPC to progression per Prostate Cancer Working Group 2 criteria or death, and overall survival (OS) was defined from the start of first-line therapy for mCRPC to death or censored at the last follow-up. A multivariable analysis using the Cox proportional hazards model was used, adjusting for potential confounders. RESULTS: Patients (n = 387) treated between March 20, 2008, and August 18, 2022, were eligible and included: 283 received nonintensified ADT, whereas 104 were treated with ADTi. At mCRPC diagnosis, patients in the ADTi group were significantly younger, had more visceral metastasis, lower baseline prostate-specific antigen (all p < 0.01), and lower hemoglobin (p = 0.027). Furthermore, they had significantly shorter PFS (median 4.8 vs. 8.4 months, adjusted hazard ratio [HR]: 1.46, 95% confidence interval [95% CI]: 1.07-2, p = 0.017) and OS (median 21.3 vs. 33.1 months, adjusted HR: 1.53, 95% CI: 1.06-2.21, p = 0.022) compared to patients in the nonintensified ADT group. CONCLUSION: Patients treated with ADTi in the mHSPC setting and experiencing disease progression to mCRPC had more aggressive disease features of mCRPC (characterized by a higher number of poor prognostic factors at mCRPC presentation). They also had shorter PFS on first-line mCRPC treatment and shorter OS after the onset of mCRPC compared to those not receiving ADTi in the mHSPC setting. Upon external validation, these findings may impact patient counseling, prognostication, treatment selection, and design of future clinical trials in the mCRPC setting. There remains an unmet need to develop novel life-prolonging therapies with new mechanisms of action to improve mCRPC prognosis in the current era.


Asunto(s)
Antagonistas de Andrógenos , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Estudios Retrospectivos , Anciano , Antagonistas de Andrógenos/uso terapéutico , Antagonistas de Andrógenos/administración & dosificación , Persona de Mediana Edad , Docetaxel/uso terapéutico , Docetaxel/administración & dosificación , Metástasis de la Neoplasia , Anciano de 80 o más Años , Supervivencia sin Progresión , Progresión de la Enfermedad
10.
Urol Pract ; 11(1): 32-35, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37903742

RESUMEN

INTRODUCTION: Patients with synchronous (de novo) metastatic castration-sensitive prostate cancer appear to have worse survival outcomes and shorter time to develop castration resistance than patients with metachronous disease. However, the impact of synchronous metastasis on outcomes in metastatic castration-resistant prostate cancer (mCRPC) setting is unknown in patients without prior exposure to androgen receptor pathway inhibitors (ARPIs). In this study, we assessed the impact of initial timing of metastasis (synchronous vs metachronous) on survival outcomes of patients with new-onset mCRPC in a real-world population treated with first-line abiraterone or enzalutamide. METHODS: Data were collected retrospectively from 323 patients with a confirmed diagnosis of mCRPC who received ARPIs as first-line therapy and had no prior exposure to ARPIs. The study endpoints were progression-free survival and overall survival. RESULTS: The results showed that median overall survival was significantly shorter in patients with synchronous disease than those with metachronous disease (26 vs 38.7 months, HR 1.42, 95% CI 1.09-1.86, P = .011). However, there was no difference in median progression-free survival. CONCLUSIONS: The initial presentation with synchronous metastasis remained an independent factor associated with shorter OS in the multivariable analysis. These hypothesis-generating data, after external validation, may have implications in patient counseling, prognostication, and design of future clinical trials in the new-onset mCRPC setting.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Humanos , Masculino , Antagonistas de Receptores Androgénicos/uso terapéutico , Supervivencia sin Progresión , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Receptores Androgénicos/metabolismo , Estudios Retrospectivos , Resultado del Tratamiento
11.
Cancers (Basel) ; 15(21)2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-37958345

RESUMEN

Compared to the urban population, patients in rural areas face healthcare disparities and experience inferior healthcare-related outcomes. To compare the healthcare quality metrics and outcomes between patients with advanced genitourinary cancers from rural versus urban areas treated at a tertiary cancer hospital, in this retrospective study, eligible patients with advanced genitourinary cancers were treated at Huntsman Cancer Institute, an NCI-Designated Comprehensive Cancer Center in Utah. Rural-urban commuting area codes were used to classify the patients' residences as being in urban (1-3) or rural (4-10) areas. The straight line distances of the patients' residences from the cancer center were also calculated and included in the analysis. The median household income data were obtained and calculated from "The Michigan Population Studies Center", based on individual zip codes. In this study, 2312 patients were screened, and 1025 eligible patients were included for further analysis (metastatic prostate cancer (n = 679), metastatic bladder cancer (n = 184), and metastatic renal cell carcinoma (n = 162). Most patients (83.9%) came from urban areas, while the remainder were from rural areas. Both groups had comparable demographic profiles and tumor characteristics at baseline. The annual median household income of urban patients was $8604 higher than that of rural patients (p < 0.001). There were fewer urban patients with Medicare (44.9% vs. 50.9%) and more urban patients with private insurance (40.4% vs. 35.1%). There was no difference between the urban and rural patients regarding receiving systemic therapies, enrollment in clinical trials, or tumor genomic profiling. The overall survival rate was not significantly different between the two populations in metastatic prostate, bladder, and kidney cancer, respectively. As available in a tertiary cancer hospital, access to care can mitigate the difference in the quality of healthcare and clinical outcomes in urban versus rural patients.

13.
Prostate ; 83(16): 1602-1609, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37644774

RESUMEN

BACKGROUND: Androgen receptor (AR) gene alterations, as detected by circulating tumor cell-free DNA (cfDNA) genomic profiling, have been shown to emerge after a variable duration of androgen signaling inhibition. AR alterations were associated with inferior outcomes on treatment with androgen receptor pathway inhibitors (ARPI) in the first line metastatic castration-resistant prostate cancer (mCRPC) setting in a phase 2 trial. Here in, we assessed the impact of these AR alterations on survival outcomes in a real-world patient population of mCRPC experiencing disease progression on an ARPI. METHODS: In this IRB-approved retrospective study, consecutively seen patients with a confirmed diagnosis of mCRPC, with disease progression on a treatment with ARPIs in the first line mCRPC setting, with no prior exposure to an ARPI in the castration sensitive setting, and with available cfDNA profiling from a CLIA certified laboratory were included. Patients were categorized based on AR status: wild-type (ARwt ) or alteration-positive (AR+ ). The objective was to correlate overall survival (OS) after disease progression on the first-line ARPI with the presence or absence of AR alterations. Kaplan-Meier and Cox Regression Tests were used as implemented in R-Studio (v.4.2). RESULTS: A total of 137 mCRPC patients were eligible: 69 with ARwt versus 68 with AR+ . The median OS posttreatment with the first ARPI was significantly higher for ARwt than AR+ patients (30.1 vs. 15.2 mos; p < 0.001). Of 108 patients who received a subsequent line of therapy, 63 received an alternate ARPI (AR+ 39 vs. 24 ARwt ), while 20 received a taxane-based therapy (11 AR+ vs. 9 ARwt ). Among patients receiving an alternate ARPI, AR+ had numerically shorter OS (16.8 vs. 30.4 mos, p = 0.1). Among patients receiving taxane-based regimens, the OS was not significantly different between AR+ and ARwt (14.5 vs. 10.1 mos, p = 0.18). CONCLUSION: In this real-world study, mCRPC patients with AR alterations on cfDNA had inferior OS after disease progression on the first ARPI, compared to those who did not, and may impact outcomes on a subsequent ARPI but not on subsequent taxane-based therapy received. By providing survival estimates for patients with or without AR alterations, our data may aid in patient counseling, prognostication, treatment decision, and for designing future clinical trials in this setting.


Asunto(s)
Ácidos Nucleicos Libres de Células , Neoplasias de la Próstata Resistentes a la Castración , Humanos , Masculino , Antagonistas de Receptores Androgénicos/farmacología , Antagonistas de Receptores Androgénicos/uso terapéutico , Biomarcadores de Tumor/genética , Progresión de la Enfermedad , Genómica , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Estudios Retrospectivos , Taxoides/farmacología
15.
Artículo en Inglés | MEDLINE | ID: mdl-37460732

RESUMEN

INTRODUCTION: In patients with metastatic hormone-sensitive prostate cancer (mHSPC) undergoing intensified androgen deprivation therapy (ADT), not achieving an optimal PSA response, defined as PSA nadir >0.2 ng/ml (PSAsubOR) has been associated with worse survival outcomes in clinical trials (1)(10)(11). Here, we externally evaluate, the impact of optimal PSA response on survival outcomes in these patients and provide absolute PFS and OS measures in those with PSAsubOR in the context of ADT intensification in real world setting. METHODS: In this retrospective study, all consecutive patients with mHSPC who underwent intensified ADT treated at our institution, and whose outcomes data were available, were included. We classified patients based on their PSA nadir on treatment: those with a on treatment PSAOR (PSA nadir ≤0.2 ng/ml) versus PSAsubOR. RESULTS: A total of 205 patients were eligible: 136 (66.3%) patients achieved PSAOR versus 69 (33.7%) patients had PSAsubOR. Patients who experienced a PSAOR had significantly improved PFS and OS from the start of intensified ADT versus who did not: PFS was not reached (NR) versus 11 months (hazard ratio (HR) 0.20, P < 0.001) and OS was NR versus 38.9 months (HR 0.21, P < 0.001). Survival outcomes were poor with PSAsubOR regardless of intensification with docetaxel or an ARPI (absolute PFS and OS measures for each group are provided in the text). CONCLUSION: Our study is the first to explore the negative impact of PSAsubOR in patients with mHSPC undergoing intensified ADT in the real-world setting, and is the first to provide absolute PFS and OS in patients with PSAsubOR receiving ADT intensification with ARPIs or docetaxel outside of clinical trial setting. These data will aid with prognostication, patient counseling, and for designing future clinical trials for patients with PSAsubOR.

16.
Cancers (Basel) ; 15(14)2023 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-37509379

RESUMEN

BACKGROUND: Accurate and efficient triage is crucial for prioritizing care and managing resources in emergency rooms. This study investigates the effectiveness of ChatGPT, an advanced artificial intelligence system, in assisting health providers with decision-making for patients presenting with metastatic prostate cancer, focusing on the potential to improve both patient outcomes and resource allocation. METHODS: Clinical data from patients with metastatic prostate cancer who presented to the emergency room between 1 May 2022 and 30 April 2023 were retrospectively collected. The primary outcome was the sensitivity and specificity of ChatGPT in determining whether a patient required admission or discharge. The secondary outcomes included the agreement between ChatGPT and emergency medicine physicians, the comprehensiveness of diagnoses, the accuracy of treatment plans proposed by both parties, and the length of medical decision making. RESULTS: Of the 147 patients screened, 56 met the inclusion criteria. ChatGPT had a sensitivity of 95.7% in determining admission and a specificity of 18.2% in discharging patients. In 87.5% of cases, ChatGPT made the same primary diagnoses as physicians, with more accurate terminology use (42.9% vs. 21.4%, p = 0.02) and more comprehensive diagnostic lists (median number of diagnoses: 3 vs. 2, p < 0.001). Emergency Severity Index scores calculated by ChatGPT were not associated with admission (p = 0.12), hospital stay length (p = 0.91) or ICU admission (p = 0.54). Despite shorter mean word count (169 ± 66 vs. 272 ± 105, p < 0.001), ChatGPT was more likely to give additional treatment recommendations than physicians (94.3% vs. 73.5%, p < 0.001). CONCLUSIONS: Our hypothesis-generating data demonstrated that ChatGPT is associated with a high sensitivity in determining the admission of patients with metastatic prostate cancer in the emergency room. It also provides accurate and comprehensive diagnoses. These findings suggest that ChatGPT has the potential to assist health providers in improving patient triage in emergency settings, and may enhance both efficiency and quality of care provided by the physicians.

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