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OBJECTIVE: The COVID-19 pandemic resulted in decreased prostate specific antigen (PSA) testing for prostate cancer screening and its impact remains uncharacterized. Our objective was to compare incident PSA testing rates, PSA levels, and prostate cancer treatment rates before and during the pandemic after the state of emergency (SoE) was declared. MATERIALS AND METHODS: This was a population-based, retrospective cohort study among men 50-80 years of age in Ontario, Canada undergoing incident PSA testing from November 23, 2018 to July 9, 2021. Working backwards and forwards from the date of the province-wide SoE (March 17, 2020), 30-day time periods were constructed during which incident PSA testing rates were measured. Our primary outcome was the rate of incident PSA testing. Secondary endpoints included comparison of incident PSA levels and prostate cancer treatment rates. RESULTS: We identified 835,402 men who underwent incident PSA testing. There was a 20% decrease in PSA testing after the SoE (RR = 0.80,95% CI: 0.800.81, P < .001). There was a higher proportion of extreme PSA levels after the SoE with a higher proportion of patients with a PSA >20 ng/mL (rate ratio = 1.63,95% CI: 1.54-1.73, P < .0001) and >100 ng/mL (rate ratio = 1.98,95% CI: 1.77-2.20, P < .0001). This effect was highest for those aged 50-59 years. More patients required active treatment (5,201,59.5% prior to the pandemic vs. 5,072,64.2%, P < .001 after the SoE declaration). CONCLUSIONS: The COVID-19 SoE resulted in patients experiencing a 2-fold increase in the risk of having an extreme PSA level and higher odds of treatment. Future studies are needed to assess the impact on the rates of advanced prostate cancer and cancer-specific mortality.
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INTRODUCTION: Individuals with spina bifida (SB) may experience negative health outcomes because of an informal transition from pediatric to adult care that results in using the emergency room (ER ) for non-acute health problems. METHODS: We conducted a retrospective, population-based cohort study of all people with SB in Ontario, Canada turning 18 years old between 2002 and 2011. These patients were followed for five years before and after age 18. Primary outcome was the annual rate of ER visits. Secondary outcomes included rates of hospitalization, surgery, primary care, and specialist outpatient care. We estimated the association between age and primary and secondary outcomes using negative binomial growth curve models, adjusting for patient-level baseline covariates. RESULTS: Among the 1215 individuals with SB, there was no trend of ER visits seen with increasing age (relative risk [RR ] 0.99, 95% confidence interval [CI] 0.98-1.02); however, there was a significant increase in the rate of ER visits associated with turning 18 years (RR 1.14, 95% CI 1.03-1.27). Turning 18 years old was also associated with a decreased rate of hospital admissions (RR 0.79, 95% CI 0.66-0.95) and no change in surgeries (RR 0.80, 95% CI 0.64-1.02). Visits to primary care physicians remained stable over the same period (RR 0.96, 95% CI 0.90-1.01), while visits to SB-focused specialists decreased after age 18 (RR 0.81, 95% CI 0.75-0.87). CONCLUSIONS: In patients with SB, the rate of ER visits increased significantly at 18 years old, while hospital admissions and specialist physician visits decreased at the same time. Models of transitional care can aim to reduce non-urgent ER visits and facilitate regular specialist care.
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PURPOSE: To determine the prevalence and natural history of nmCRPC prior to the adoption of novel androgen receptor axis-targeting therapies(ARAT). MATERIALS AND METHODS: This was a retrospective population-based cohort study of men with nmCRPC in Ontario, Canada between January 2007-March 2018. Patients with prostate cancer, castrate level of testosterone(<1.7nmol/L) and a PSA>2.0ng/mL with a subsequent rise>25% from the nadir, and without metastasis were included. Annual prevalence of nmCRPC was calculated. Crude time from nmCRPC to metastasis and all-cause death are presented as medians with interquartile range(IQR). Predictors of time from nmCRPC to death were compared using univariable and multivariable cox proportional hazard models. RESULTS: We identified 2045 patients with nmCRPC. Median age was 79(IQR:72-84). 984 patients(48.1%) received upfront hormonal therapy while 583(28.5%) received initial radiotherapy and 478(23.4%) underwent radical prostatectomy. Median time from primary treatment to nmCRPC was 6 years(IQR:3-10). The average annual prevalence of nmCRPC was 8% among men receiving ADT. Crude median time from nmCRPC to death was 37.6 months(IQR:22.1-55.4). Median time from nmCRPC to metastasis and metastasis to death was 20.0 and 8.3 months, respectively. Patients who had primary surgery experienced longer crude survival. Older patients, patients who had a higher PSA at nmCRPC, and patients with grade group 4 to 5 disease had a shorter time from nmCRPC to death. CONCLUSION: This is the largest population-level analysis of the prevalence and natural history of nmCRPC. The current study can be used as a historical cohort to compare how novel imaging modalities and ARAT impact prevalence and disease trajectory over time.
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Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Idoso , Neoplasias de Próstata Resistentes à Castração/epidemiologia , Neoplasias de Próstata Resistentes à Castração/terapia , Estudos Retrospectivos , Estudos de Coortes , Prevalência , Antagonistas de Androgênios/uso terapêuticoRESUMO
OBJECTIVES: To compare the risk of bladder cancer and bladder cancer mortality among patients with chronic bladder catheterisation (indwelling or intermittent) to patients from the general population. DESIGN: Retrospective cohort study. SETTING: Population-based study in Ontario, Canada between 2003 and 2018. PARTICIPANTS: Adult patients 18-90 years of age with chronic bladder catheterisation were hard matched to patients from the general population without a history of bladder catheterisation. INTERVENTIONS: The presence of a chronic catheter was defined as a minimum of two physician encounters for bladder catheterisation, suprapubic tube insertion or home care for catheter care separated by at least 28 days. Urinary tract infection (UTI) rates were collected. MAIN OUTCOME MEASURES: Bladder cancer and bladder cancer-specific mortality after a 1-year lag period were compared between groups. RESULTS: We identified 36 903 patients with chronic catheterisation matched to 110 709 patients without a history of catheterisation. Patients were followed for a median of 8.8 years (IQR: 5.2-11.9 years). The median age was 62 years (IQR: 50-71) and 52% were female. More patients in the catheter group developed bladder cancer (393 (1.1%) vs 304 (0.3%),p<0.001). There were 106 (0.3%) bladder cancer deaths in the catheter group and 59 (0.1%) in the comparison group (p<0.001). Chronic catheterisation (adjusted subdistribution HR (sdHR)=4.80, 95% CI: 4.26 to 5.42,p<0.001) and the number of UTIs (adjusted sdHR=1.04 per UTI, 95% CI: 1.04 to 1.05,p<0.001) were independent predictors of bladder cancer. The relative rate of bladder cancer-specific death was more than eightfold higher among patients with chronic catheterisation (adjusted sdHR=8.68, 95% CI: 6.97 to 10.81,p<0.001). Subgroup analysis among patients with neurogenic bladder and bladder calculi similarly revealed an increased risk of bladder cancer diagnosis and mortality. Bladder cancer risk was highest among patients in the two longest catheter duration quintiles (2.9-5.9 and 5.9-15.5 years). CONCLUSIONS: This is the first study to quantify the increase in bladder cancer incidence and mortality in a large, diverse cohort of patients with chronic indwelling or intermittent bladder catheterisation. The risk was highest among patients with a chronic catheter beyond 2.9 years.
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Neoplasias da Bexiga Urinária , Infecções Urinárias , Adulto , Cateteres de Demora , Estudos de Coortes , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Ontário/epidemiologia , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/epidemiologia , Cateterismo Urinário/efeitos adversosRESUMO
BACKGROUND: We previously identified a panel of five miRNAs associated with prostate cancer recurrence and metastasis. Expression of one of the down-regulated miRNAs, miR-139-5p, was significantly associated with a lower incidence of biochemical recurrence and metastasis. Transcriptome profiling of miR-139-expressing prostate cancer cells revealed up-regulation of genes involved in interferon (IFN) stimulation. The association between miR-139 and IFN-ß was further explored in this study. MATERIALS AND METHODS: We examined miR-139 transfected PC3, Du145 and LNCaP cells and the associated IFN response by transcriptome sequencing, immunoblotting and pulldown assays. RESULTS: Treatment of prostate cancer cells by miR-139 resulted in the up-regulation of IFN-related genes. Specifically, miR-139 induced expression of the IFN-ß protein. The ability of miR-139 to induce IFN-ß was due to its binding to RIG-1 and the induction of IFN-related genes was found to be dependent on RIG-1 expression. CONCLUSION: miR-139 acts as an immune agonist of RIG-1 to enhance IFN-ß response in prostate cancer cells.
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Proteína DEAD-box 58/metabolismo , Interferon beta/biossíntese , MicroRNAs/metabolismo , Neoplasias da Próstata/metabolismo , Receptores Imunológicos/metabolismo , Linhagem Celular Tumoral , Proteína DEAD-box 58/imunologia , Células HEK293 , Humanos , Interferon beta/genética , Interferon beta/imunologia , Masculino , MicroRNAs/administração & dosagem , MicroRNAs/genética , Células PC-3 , Neoplasias da Próstata/genética , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/terapia , Receptores Imunológicos/imunologia , Transdução de Sinais , Transfecção , Regulação para CimaRESUMO
INTRODUCTION: The aim of this study was to assess the effect of an enhanced care pathway on length of stay (LOS) for open radical prostatectomy (RP) given that robotic-assisted laparoscopic prostatectomy (RALP) is not available to all patients in Canada. METHODS: A retrospective review was conducted of all RPs performed. An enhanced care pathway was established for RPs in 2011. Patients were compared in the period before (2005-2010) and after (2011-2019) the introduction of the pathway. RESULTS: During the study period, 581 RPs were performed by a single surgeon with a median followup of 66.9 months (range 3-176). A total of 211 (36.3%) RPs were performed from 2005-2010, while 370 (63.9%) were performed from 2011-2019. The median age at RP was 65 years (range 44-81). Following the introduction of an enhanced care pathway, there were significant decreases in intraoperative blood loss (350 ml vs. 200 ml; p=0.0001) and the use of surgical drains (90% vs. 9.5%; p=0.0001). The median LOS over the whole study period was one day (range 1-7), which significantly decreased with the enhanced care pathway (3 vs. 1 day; p=0.0001). Since introducing the enhanced care pathway in 2011, 344 (93%) patients were discharged day 1 following surgery. There were no differences in post-discharge presentations to the emergency department (5.7% vs. 9%; p=0.15) or 30-day readmission rates (3.8% vs. 3.8%; p=1.00). CONCLUSIONS: A single-night stay for open RP is safe and achievable for most patients. A dedicated, multifaceted pathway is required to attain targets for a safe and timely discharge.
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INTRODUCTION: We sought to assess seven-day and 30-day complications following renal mass biopsy (RMB), including mortality, hospitalizations, emergency department (ED) visits, and operative and non-operative complications and compare these to rates in population-matched controls. METHODS: We performed a population-based, matched, retrospective cohort study of patients undergoing RMB following consultation with a urologist and axial imaging from 2003-2015 in Ontario, Canada. Data on seven-day and 30-day rates of mortality, as well as operative and non operative complications after RMB were reported. The seven-day and 30-day rates of mortality, operative and non-operative interventions, hospitalizations, and ED visits were compared to matched controls using multivariable logistic regression. RESULTS: Among 6840 patients who underwent RMB in the study period, 24 (0.4%) and 159 (2.3%) died within seven and 30 days of their biopsy, respectively. Seven- and 30-day operative intervention rates were 79 (1.2%) and 236 (3.4%), respectively. Seven- and 30-day non-operative intervention rates were 227 (3.3%) and 529 (7.7%), respectively. Thirty-day mortality (odds ratio [OR] 8.1, 95% confidence interval [CI] 5.1-13.0), hospitalizations (OR 12.6, 95% CI 10.6-15.2), and ED visits (OR 3.8, 95% CI 3.4-4.3) were more common among patients who underwent RMB than the matched controls (p<0.001 for each). CONCLUSIONS: Patients undergoing RMB may have a small but non-negligible increased risk of mortality, hospital readmission, and ED visits compared to matched controls. However, limitations in the granularity of the dataset limits the strength of these conclusions. Further studies are needed to confirm our results. These risks should be discussed with patients for shared decision-making and considered in the risk/benefit tradeoff for the management of small renal masses.
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BACKGROUND: Upper tract urothelial carcinoma (UTUC) is clinically understudied, and there are no definitive recommendations regarding timing of perioperative chemotherapy. The objective of this study was to compare 3 treatment pathways in UTUC: nephroureterectomy (NU) alone, neoadjuvant chemotherapy (NAC), and adjuvant chemotherapy (AC) using a microsimulation model. PATIENTS AND METHODS: An individual-level state transition model was constructed using TreeAgePro software to compare treatment strategies for patients with newly diagnosed UTUC. The base case was that of a 70-year-old patient with a radiographically localized upper tract tumor. Primary outcome was quality-adjusted life expectancy. Secondary outcomes included crude overall survival, rates of adverse events, and bladder cancer diagnoses. RESULTS: A total of 100,000 patients were simulated. NAC was preferred, with an estimated quality-adjusted life expectancy of 7.50 years versus 6.79 years with NU alone and 7.23 years with AC. Median crude overall survival was 123 months with NAC, 96 months with NU only, and 111 months with AC. Overall, 40.0% of patients in the AC group with invasive pathology completed chemotherapy. In the NAC group, 83.3% of patients completed chemotherapy. In the NAC group, 37.5% of patients experienced an adverse chemotherapy event compared to 15.1% of patients in the AC group. Bladder cancer recurrence rates were 64.9%, 65.9%, and 67.4% over the patient's lifetime for the NU, NAC, and AC strategies, respectively. CONCLUSION: This study supports the increased use of NAC in UTUC until robust randomized trials are completed. The ultimate choice should be based on patient and tumor factors.
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Carcinoma de Células de Transição , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Idoso , Carcinoma de Células de Transição/tratamento farmacológico , Quimioterapia Adjuvante , Humanos , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Estudos Retrospectivos , Neoplasias Ureterais/tratamento farmacológicoRESUMO
INTRODUCTION: Patients with renal cell carcinoma (RCC) with level 3 or 4 caval thrombus have a poor prognosis, with reported five-year survival rates of 30-40%. The aim of this study was to assess the perioperative morbidity and long-term oncological outcomes for radical nephrectomy with resection of vena cava thrombus using a combined surgical approach, including extracorporeal circulation and deep hypothermic circulatory arrest. METHODS: A retrospective review was performed of the institutional case log to identify all radical nephrectomies with caval thrombus performed from January 2006 to May 2020. RESULTS: Twenty-five patients were identified with level 2 thrombus in one (4%), level 3 thrombus in eight (32%), and level 4 in 16 (64%). The median followup was 20.6 months (range 0.2-133.3). The median age at surgery was 68.4 years (range 44.2-85.5). Twenty-one (84%) patients were symptomatic at presentation. Six (24%) patients had distant metastases at diagnosis. The median circulatory arrest time was 15 minutes (range 6-35). The 30-day grade ≥3 complication rate was 8%. The 30-day mortality rate was 8%. The one-year, two-year, three-year, and five-year recurrence-free survival (RFS) rates were 53%, 18%, 10%, and 10%, respectively. The median time to systemic treatment was 7.7 months (range 1.2-25.7). The one-year, two-year, three-year, and five-year overall survival (OS) rates were 70%, 43%, 36%, and 31%, respectively. CONCLUSIONS: Radical nephrectomy with resection of vena cava thrombus using extracorporeal circulation and deep hypothermic circulatory arrest is associated with some morbidity and mortality but remains a safe and effective strategy for advanced RCC patients who would otherwise be managed palliatively.
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AIM: Cystoscopic placement of ureteric stents during colorectal surgery (CRS) may aid in the intraoperative identification of the ureters and thus prevent ureteric injury, but may also be associated with prolonged operating time, increased cost and adverse events. No formal recommendations exist regarding the use of ureteric stents prior to CRS. Our aim was to determine the effect of prophylactic ureteric stent insertion on the risk of ureteric injury among adult patients undergoing CRS. METHOD: A systematic search using the Ovid platform was completed. The primary outcome was risk of ureteric injury. Secondary outcomes included the risk of acute kidney injury (AKI), urinary tract infection (UTI), sepsis, length of stay (LOS) and mortality. The Paule-Mandel pooling and a random effects model was used to produce odds ratios (ORs) with 95% confidence intervals (CIs) for binary outcomes. Standardized mean differences (MD) were reported for continuous variables. Analyses were completed using R3.5. RESULTS: Nine retrospective cohort studies evaluating 98 507 patients were included. The incidence of ureteric injury was 0.6%. Overall, 5.1% of patients underwent ureteric stenting. There was no change in the odds of ureteric injury among stented patients compared with controls (OR 1.30, 95% CI 0.39-4.29, I2 = 25%). Operating time was significantly longer (MD 49.3 min, 95% CI 35.3-63.4, I2 = 96%) in the intervention group. There was no difference in rates of AKI, UTI, sepsis, LOS or mortality between groups. CONCLUSION: Given the retrospective nature of the identified studies, the benefit of prophylactic ureteric stenting remains uncertain. Prophylactic ureteric stenting was not associated with increased patient morbidity but did significantly increase operating time.
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Cirurgia Colorretal , Ureter , Infecções Urinárias , Adulto , Humanos , Estudos Retrospectivos , Stents/efeitos adversos , Ureter/cirurgia , Infecções Urinárias/epidemiologia , Infecções Urinárias/etiologia , Infecções Urinárias/prevenção & controleRESUMO
BACKGROUND/AIM: We previously identified a panel of five miRNAs (including miR-139) associated with biochemical recurrence and metastasis in prostate cancer patients. MATERIALS AND METHODS: We examined miR-139 transfected PC3, DU145 and LNCaP cells by morphology as well as by cell-based assays, confocal microscopy and immunoblotting. RESULTS: We found that treatment of prostate cancer cells with miR-139 resulted in phenotypic changes characteristic of autophagic cells. MiR-139 increased the autophagy-related conversion of the microtubule-associated protein light chain 3 (LC3-I to LC3-II) that was specifically inhibited by the miR-139 antagomir. The upregulation of LC3 II was further confirmed by confocal microscopy. miR-139 regulated activation of both mTOR and Beclin1 the two important autophagy-related molecules. We found that upon miR-139 treatment, the cargo adaptor protein p62 which is degraded during autophagy, accumulates. CONCLUSION: These results suggest that miR-139 is inducing autophagic flux blockade leading to apoptosis in prostate cancer cells through the mTOR and Beclin-1 proteins.
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Autofagia/genética , Proteína Beclina-1/metabolismo , MicroRNAs/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Apoptose/genética , Linhagem Celular Tumoral , Forma Celular/genética , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Regulação para Cima/genéticaRESUMO
Importance: The association of radiation and chemotherapy with the development of secondary sarcoma is known, but the contemporary risk has not been well characterized for patients with cancers of the abdomen and pelvis. Objective: To compare the risk of secondary sarcoma among patients treated with combinations of surgery, radiation, or chemotherapy with patients treated with surgery alone and the general population. Design, Setting, and Participants: This population-based cohort study included 173â¯580 patients in Ontario, Canada, with nonmetastatic cancer of the prostate, bladder, colon, rectum or anus, cervix, uterus, or testis. Patients were enrolled from January 1, 2002, to January 31, 2017. Data analysis was conducted from March 1, 2019, to January 31, 2020. Exposures: Treatment combinations of radiation, chemotherapy, and surgery. Main Outcome and Measures: Diagnosis of sarcoma based on histologic codes from the Ontario Cancer Registry. Time to sarcoma was compared using a cause-specific proportional hazard model. Results: Of 173â¯580 patients, most were men (125â¯080 [72.1%]), and the largest group was aged between 60 and 69 years (58â¯346 [33.6%]). Most patients had genitourinary cancer (86â¯235 [51.4%]) or colorectal cancer (69â¯241 [39.9%]). Overall, 64â¯301 (37.1%) received surgery alone, 51â¯220 (29.5%) received radiation alone, 15â¯624 (9.0%) were treated with radiation and chemotherapy, 15â¯252 (8.8%) received radiation with surgery, and 11â¯822 (6.8%) received all 3 treatments. A total of 332 patients (0.2%) had sarcomas develop during a median (interquartile range) follow-up of 5.7 (2.2-8.9) years. The incidence of sarcoma was 0.3% among those who underwent radiation alone (138 of 51â¯220) and radiation with chemotherapy (40 of 15â¯624), 0.2% among those who received radiation and surgery (36 of 15â¯252) and all 3 modalities (25 of 11â¯822), and 0.1% among those who received surgery with chemotherapy (13 of 14â¯861) and surgery alone (80 of 64â¯801). Compared with a reference group of patients who had surgery alone, the greatest risk of sarcoma was found among patients who underwent a combination of radiation and chemotherapy (cause-specific relative hazard [csRH], 4.07; 95% CI, 2.75-6.01; P < .001), followed by patients who had radiation alone (csRH, 2.35; 95% CI, 1.77-3.12; P < .001), radiation with surgery (csRH, 2.33; 95% CI, 1.57-3.46; P < .001), and all 3 modalities (csRH, 2.27; 95% CI, 1.44-3.58; P < .001). In the general population, 7987 events occurred during 46â¯554â¯803 person-years (17.2 events per 100â¯000 person-years). The standardized incidence ratio for sarcoma among patients treated with radiation compared with the general population was 2.41 (95% CI, 1.57-3.69; 41.3 events per 100â¯000 person-years). The annual number of cases of sarcoma increased from 2009 (15 per 100â¯000 persons) to 2016 (32 per 100â¯000 persons), but the annual rate did not change during the study period. Conclusions and Relevance: In this cohort study, patients treated with radiation or chemotherapy for abdominopelvic cancers had an increased rate of sarcoma. Although the absolute rate is low, patients and physicians should be aware of this increased risk of developing sarcoma.
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Neoplasias Abdominais/tratamento farmacológico , Neoplasias Abdominais/radioterapia , Neoplasias Abdominais/cirurgia , Segunda Neoplasia Primária/etiologia , Neoplasias Pélvicas/tratamento farmacológico , Neoplasias Pélvicas/radioterapia , Neoplasias Pélvicas/cirurgia , Sarcoma/etiologia , Neoplasias Abdominais/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Neoplasias Pélvicas/complicações , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: The rate of primary and secondary treatment while on active surveillance (AS) for localized prostate cancer at the general population level is unknown. Our objective was to determine the patterns of secondary treatments after primary surgery or radiation for patients who undergo AS. METHODS: This was a population-based retrospective cohort study of men aged 50-80 years old in Ontario, Canada, between 2008 and 2016. We identified 26 742 patients with prostate cancer, a Gleason grade score ≤7, and an index prostate-specific antigen ≤10 ng/mL. Patients were categorized as undergoing AS with or without delayed primary treatment (DT; treatment >6 months after diagnosis) versus immediate treatment (IT; treatment ≤6 months). Patients receiving DT and IT were propensity score matched and the rate of secondary treatment (surgery or radiation ± androgen deprivation treatment) was compared using Cox proportional hazards models. RESULTS: We identified 10 214 patients who underwent AS and 11 884 patients who underwent IT. Among patients undergoing AS, 3724 (36.5%) eventually underwent DT and among them, 406 (10.9%) underwent secondary treatment. The median time to DT was 1.2 years (IQR 0.5-8.1 years). The relative rate of undergoing secondary treatment was similar in the DT vs IT group (HR 0.92; 95% CI: 0.79-1.08). The risk of death in the DT group was higher compared to patients who did not undergo treatment (HR 1.23, 95% CI: 1.01-1.49). CONCLUSIONS: Among patients with localized prostate cancer on AS, one third undergo DT. The rate of secondary treatment was similar between the DT and IT groups. Patients in the DT group may experience a higher risk of mortality compared to those who remained on AS.
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Antagonistas de Androgênios/uso terapêutico , Padrões de Prática Médica/tendências , Prostatectomia/tendências , Neoplasias da Próstata/terapia , Conduta Expectante/tendências , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Ontário/epidemiologia , Prostatectomia/efeitos adversos , Prostatectomia/mortalidade , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Radioterapia/tendências , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Terapia de Salvação/tendências , Fatores de Tempo , Resultado do TratamentoRESUMO
INTRODUCTION: Our aim was to determine whether androgen deprivation therapy (ADT) with abiraterone acetate (AA) or ADT with docetaxel chemotherapy (DC) resulted in improved quality-adjusted life years (QALYs) among men with de novo metastatic castration-sensitive prostate cancer (mCSPC) and the cost effectiveness of the preferred strategy using decision analytic techniques. METHODS: A microsimulation model with a lifetime time horizon was constructed. Our primary outcome was QALYs. Secondary outcomes included cost, incremental cost effectiveness ratio (ICER), unadjusted overall survival (OS), rates of second- and third-line therapy, and adverse events. A systematic literature review was used to generate probabilities and utilities to populate the model. The base case was a 65-year-old patient with de novo mCSPC. RESULTS: A total of 100 000 microsimulations were generated. Initial AA resulted in a gain of 0.45 QALYs compared to DC (3.36 vs. 2.91 QALYs) with an ICER of $276 251.82 per QALY gained with initial AA therapy. Median crude OS was 51 months with AA and 48 months with DC. Overall, 46.6% and 42.6% of patients received second-line therapy and 8.7% and 7.9% patients received third-line therapy in the AA and DC groups, respectively. Grade 3/4 adverse events were experienced in 17.6% of patients receiving initial AA and 22.3% of patients receiving initial DC. CONCLUSIONS: Although ADT with AA results in a gain in QALYs and crude OS compared to DC, AA therapy is not a cost-effective treatment strategy to apply uniformly to all patients. The availability of AA as a generic medication may help to close this gap. The ultimate choice should be based on patient and tumor factors.
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BACKGROUND: We previously identified a panel of five microRNAs (miRNAs) associated with biochemical recurrence and metastasis following prostatectomy from prostate cancer patients using next-generation sequencing-based whole miRNome sequencing and quantitative polymerase chain reaction-based validation analysis. In this study, we examined the mechanism of action of miR-139-5p, one of the downregulated miRNAs identified in the panel. METHODS: Using a cohort of 585 patients treated with radical prostatectomy, we examined the prognostic significance of miR-139 (dichotomized around the median) using the Kaplan-Meier method and Cox proportional hazard models. We validated these results using The Cancer Genome Atlas (TCGA) data. We created cell lines that overexpressed miR-139 to confirm its targets as well as examine pathways through which miR-139 may function using cell-based assays. RESULTS: Low miR-139 expression was significantly associated with a variety of prognostic factors in prostate cancer, including Gleason score, pathologic stage, margin positivity, and lymph node status. MiR-139 expression was associated with prognosis: the cumulative incidence of biochemical recurrence and metastasis were significantly lower among patients with high miR-139 expression (P = .0004 and .038, respectively). Validation in the TCGA data set showed a significant association between dichotomized miR-139 expression and biochemical recurrence (odds ratio, 0.52; 95% confidence interval, 0.33-0.82). Overexpression of miR-139 in prostate cancer cells led to a significant reduction in cell proliferation and migration compared with control cells, with cells arrested in G2 of cell cycle. IGF1R and AXL were identified as potential targets of miR-139 based on multiple miRNA-binding sites in 3'-untranslated regions of both the genes and their association with prostate cancer growth pathways. Luciferase assays verified AXL and IGF1R as direct targets of miR-139. Furthermore, immunoblotting of prostate cancer cells demonstrated IGF1R and AXL protein expression were inhibited by miR-139 treatment, which was reversed by the addition of miR-139 antagomir. Examination of the molecular mechanism of growth inhibition by miR-139 revealed the downregulation of activated AKT and cyclin D1, with upregulation of the CDK inhibitor p21. CONCLUSIONS: miR-139 is associated with improved prognosis in patients with localized prostate cancer, which may be mediated through downregulation of IGF1R and/or AXL and associated signaling pathway components.
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Pontos de Checagem do Ciclo Celular/fisiologia , MicroRNAs/biossíntese , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas/biossíntese , Receptores Proteína Tirosina Quinases/biossíntese , Receptor IGF Tipo 1/metabolismo , Idoso , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Próstata/patologia , Neoplasias da Próstata/patologia , Transdução de Sinais , Receptor Tirosina Quinase AxlRESUMO
BACKGROUND: Previous studies have demonstrated an association between a diagnosis of cancer and the risk of suicide; however, they failed to account for psychiatric care before a cancer diagnosis, which may confound this relationship. The objective of this study was to assess the effect of a cancer diagnosis on the risk of suicide, accounting for prediagnosis psychiatric care utilization. METHODS: All adult residents of Ontario, Canada who were diagnosed with cancer (1 of prostate, breast, colorectal, melanoma, lung, bladder, endometrial, thyroid, kidney, or oral cancer) between 1997 and 2014 were identified. Noncancer controls were matched 4:1 based on sociodemographics, including a psychiatric utilization gradient (PUG) score (with 0 indicating none; 1, outpatient; 2, emergency department; and 3, hospital admission). A marginal, cause-specific hazard model was used to assess the effect of cancer on the risk of suicidal death. RESULTS: Among 676,470 patients with cancer and 2,152,682 matched noncancer controls, there were 8.2 and 11.4 suicides per 1000 person-years of follow-up, respectively. Patients with cancer had an overall higher risk of suicidal death compared with matched patients without cancer (hazard ratio, 1.34; 95% CI, 1.22-1.48). This effect was pronounced in the first 50 months after cancer diagnosis (hazard ratio, 1.60; 95% CI, 1.42-1.81); patients with cancer did not demonstrate an increased risk thereafter. Among individuals with a PUG score 0 or 1, those with cancer were significantly more likely to die of suicide compared with controls. There was no difference in suicide risk between patients with cancer and controls for those who had a PUG score of 2 or 3. CONCLUSIONS: A cancer diagnosis is associated with increased risk of death from suicide compared with the general population even after accounting for precancer diagnosis psychiatric care utilization. The specific factors underlying the observed associations remain to be elucidated.
Assuntos
Neoplasias/diagnóstico , Neoplasias/psicologia , Suicídio/psicologia , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Psicoterapia , Fatores de Risco , Suicídio/estatística & dados numéricosRESUMO
BACKGROUND: Among patients with cancer, prior research suggests that patients with mental illness may have reduced survival. The objective was to assess the impact of psychiatric utilisation (PU) prior to cancer diagnosis on survival outcomes. METHODS: All residents of Ontario diagnosed with one of the top 10 malignancies (1997-2014) were included. The primary exposure was psychiatric utilisation gradient (PUG) score in 5 years prior to cancer: 0: none, 1: outpatient, 2: emergency department, 3: hospital admission. A multivariable, cause-specific hazard model was used to assess the effect of PUG score on cancer-specific mortality (CSM), and a Cox proportional hazard model for effect on all-cause mortality (ACM). RESULTS: A toal of 676,125 patients were included: 359,465 (53.2%) with PUG 0, 304,559 (45.0%) PUG 1, 7901 (1.2%) PUG 2, and 4200 (0.6%) PUG 3. Increasing PUG score was independently associated with worse CSM, with an effect gradient across the intensity of pre-diagnosis PU (vs PUG 0): PUG 1 h 1.05 (95% CI 1.04-1.06), PUG 2 h 1.36 (95% CI 1.30-1.42), and PUG 3 h 1.73 (95% CI 1.63-1.84). Increasing PUG score was also associated with worse ACM. CONCLUSIONS: Pre-cancer diagnosis PU is independently associated with worse CSM and ACM following diagnosis among patients with solid organ malignancies.
Assuntos
Transtornos Mentais/psicologia , Neoplasias/psicologia , Idoso , Canadá/epidemiologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Transtornos Mentais/complicações , Transtornos Mentais/mortalidade , Transtornos Mentais/patologia , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/mortalidade , Neoplasias/patologia , Modelos de Riscos ProporcionaisRESUMO
OBJECTIVES: To examine the complication rates after benign prostatic enlargement (BPE) surgery and the effects of age, comorbidity and preoperative medical therapy. DESIGN: A retrospective, population-based cohort study using linked administrative data. SETTING: Ontario, Canada. PARTICIPANTS: 52 162 men≥66 years undergoing first BPE surgery between 1 January 2003 to 31 December 2014. INTERVENTION: Medical therapy preoperatively and surgery for BPE. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was overall 30-day postoperative complication rates. Secondary outcomes included BPE-specific event rates (bleeding, infection, obstruction, trauma) and non-BPE specific event rates (cardiovascular, pulmonary, thromboembolic and renal). Multivariable analysis examined the association between preoperative medical therapy and postoperative complication rates. RESULTS: The 30-day overall complication rate after BPE surgery was 2828 events/10 000 procedures and increased annually over the study period. Receipt of preoperative α-blocker monotherapy (relative rate (RR) 1.05; 95% CI 1.00 to 1.09; p=0.033) and antithrombotic medications (RR 1.27; 95% CI 1.22 to 1.31; p<0.0001) was associated with increased complication rates. Among the ≥80-year-old group, the rate of complications increased by 39% from 2003 to 2014 (RR 1.39; 95% CI 1.21 to 1.61; p<0.0001). The mean duration of medical and conservative management increased by a mean of 2.1 years between 2007 and 2014 (p<0.0001 for trend). CONCLUSIONS: Thirty-day complication rates after BPE surgery have increased annually between 2003 and 2014. Preoperative medical therapy with alpha blockers or antithrombotics was independently associated with higher rates of complications. Over this time, the duration of conservative therapy also increased.