Nonlinear joint models for individual dynamic prediction of risk of death using Hamiltonian Monte Carlo: application to metastatic prostate cancer

223 Background: Skeletal related events (SREs), defined as pathological fracture, spinal cord compression, surgery or radiotherapy to the bone, occur in nearly half of men diagnosed with metastatic prostate cancer. Accurate assessment of the risk of death associated with SREs is important to making decisions about the use of recently approved treatments, which have been shown to decrease the frequency of skeletal events, yet estimating the impact of SREs on survival presents several methodological challenges given the recurrent time-dependent nature of exposure. Methods: A cohort of men >65years of age, diagnosed with prostate cancer and bone metastasis between January 1, 2004 and December 31, 2009 was identified from the Surveillance Epidemiology and End Results (SEER) registries were linked to Medicare Parts A and B claims. The outcome of interest, death from any cause, was ascertained from SEER and survival time was calculated from the date of metastatic prostate cancer diagnosis. Multivariable Cox proportional hazards models treating the occurrence of an SRE as a time-dependent exposure were used to estimate the hazard ratios (HR) and corresponding 95% confidence intervals (CI) for the association between SRE occurrence, number, and type, and death. Results: Among 3,297 men with metastatic prostate cancer, 40% experienced ≥1 SRE during the observational follow-up period (median 19 months). Compared to men who remained SRE-free, cohort members who had ≥1 SREs had a two-fold higher risk of death (HR 2.2, 95% CI 2.0-2.4). Those whose first SRE was a pathological fracture had a 2.7-fold higher risk of death (HR 2.7, 95% CI 2.3-3.1), followed by spinal cord compression (HR 2.1, 95% CI 1.8-2.5), surgery (HR 1.8, 95% CI 1.5-2.2) and radiotherapy (HR 2.2, 95% CI 1.9-2.4). Compared to those experiencing only one SRE, men who experienced a second SRE of any type had double the risk of death (HR 2.2, 95% CI 1.9-2.6). Conclusions: SREs were associated with ≥50% reduction in overall survival. This finding is consistent across different types of SREs and supports using therapies to prevent or treat SREs in patients with prostate cancer metastatic to the bones.

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Bone Scan Index: A Quantitative Treatment Response Biomarker for Castration-Resistant Metastatic Prostate Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2011.36.5791 ◽

2012 ◽

Vol 30 (5) ◽

pp. 519-524 ◽

Cited By ~ 113

Author(s):

Elizabeth R. Dennis ◽

Xiaoyu Jia ◽

Irina S. Mezheritskiy ◽

Ryan D. Stephenson ◽

Heiko Schoder ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Scintigraphy ◽

Bone Scan ◽

Metastatic Prostate Cancer ◽

Univariate Analysis ◽

Imaging Biomarker ◽

Bone Scan Index ◽

Risk Of Death ◽

Percent Change ◽

Castration Resistant

Purpose There is currently no imaging biomarker for metastatic prostate cancer. The bone scan index (BSI) is a promising candidate, being a reproducible, quantitative expression of tumor burden seen on bone scintigraphy. Prior studies have shown the prognostic value of a baseline BSI. This study tested whether treatment-related changes in BSI are prognostic for survival and compared BSI to prostate-specific antigen (PSA) as an outcome measure. Patients and Methods We retrospectively examined serial bone scans from patients with castration-resistant metastatic prostate cancer (CRMPC) enrolled in four clinical trials. We calculated BSI at baseline and at 3 and 6 months on treatment and performed univariate and bivariate analyses of PSA, BSI, and survival. Results Eighty-eight patients were scanned, 81 of whom have died. In the univariate analysis, the log percent change in BSI from baseline to 3 and 6 months on treatment prognosticated for survival (hazard ratio [HR], 2.44; P = .0089 and HR, 2.54; P < .001, respectively). A doubling in BSI resulted in a 1.9-fold increase in risk of death. Log percent change in PSA at 6 months on treatment was also associated with survival (HR, 1.298; P = .013). In the bivariate analysis, change in BSI while adjusting for PSA was prognostic at 3 and 6 months on treatment (HR, 2.368; P = .012 and HR, 2.226; P = .002, respectively), but while adjusting for BSI, PSA was not prognostic. Conclusion These data furnish early evidence that on-treatment changes in BSI are a response indicator and support further exploration of bone scintigraphy as an imaging biomarker in CRMPC.

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Prostate-Specific Antigen Response Duration and Risk of Death for Patients With Hormone-Refractory Metastatic Prostate Cancer

Yearbook of Urology ◽

10.1016/s0084-4071(08)70377-4 ◽

2006 ◽

Vol 2006 ◽

pp. 212-213

Author(s):

G.L. Andriole

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Metastatic Prostate Cancer ◽

Specific Antigen ◽

Response Duration ◽

Risk Of Death ◽

Hormone Refractory

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Epidemiological Characteristics and Survival in Patients with de novo Metastatic Prostate Cancer.

10.20944/preprints202008.0117.v1 ◽

2020 ◽

Author(s):

Carlo Cattrini ◽

Davide Soldato ◽

Alessandra Rubagotti ◽

Linda Zinoli ◽

Elisa Zanardi ◽

...

Keyword(s):

Prostate Cancer ◽

Metastatic Prostate Cancer ◽

Cox Regression ◽

De Novo ◽

Cancer Specific Survival ◽

Risk Of Death ◽

The Usa ◽

Epidemiological Characteristics ◽

Risk Of Cancer ◽

Reduced Risk

The real-world outcomes of patients with metastatic prostate cancer (mPCa) are largely unexplored. We investigated the improvements in overall survival (OS) and cancer-specific survival (CSS) in patients with de novo mPCa in latest years. The USA SEER Research Data (2000-2017) were analyzed using the SEER*Stat software. The Kaplan-Meier method and Cox regression were used. Patients with de novo mPCa were allocated to 3 cohorts based on year of diagnosis: A (2000-2003), B (2004-2010), C (2011-2014). Maximum follow-up was fixed to 5 years. Overall, 26434 patients were included. Age, race and metastatic stage significantly affected OS and CSS. After adjustment for age and race, patients in cohort C showed 9% reduced risk of death (HR:0.91 [95% CI, 0.87-0.95], p&lt;0.001) and 8% reduced risk of cancer-specific death (HR:0.91 [95% CI, 0.87-0.95], p&lt;0.001) compared to those in cohort A. After adjustment for age, race and metastatic stage, patients in cohort C showed an improvement in OS and CSS compared to cohort B (HR:0.94 [95% CI, 0.91-0.97], p=0.001 and HR:0.89 [95% CI, 0.85-0.92], p&lt;0.001). Patients with M1c disease had a more pronounced improvement in OS and CSS compared with the other stages. No differences were found between cohort B and C. In conclusion, the prognosis of de novo mPCa remains poor with a median OS of 30 months and a median CSS of 35 months. Limited OS and CSS improvements were observed in latest years.

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Epidemiological Characteristics and Survival in Patients with De Novo Metastatic Prostate Cancer

Cancers ◽

10.3390/cancers12102855 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2855 ◽

Cited By ~ 1

Author(s):

Carlo Cattrini ◽

Davide Soldato ◽

Alessandra Rubagotti ◽

Linda Zinoli ◽

Elisa Zanardi ◽

...

Keyword(s):

Prostate Cancer ◽

Real World ◽

Metastatic Prostate Cancer ◽

Cox Regression ◽

De Novo ◽

The Real ◽

Risk Of Death ◽

Epidemiological Characteristics ◽

Risk Of Cancer ◽

Reduced Risk

The real-world outcomes of patients with metastatic prostate cancer (mPCa) are largely unexplored. We investigated the trends in overall survival (OS) and cancer-specific survival (CSS) in patients with de novo mPCa according to distinct time periods. The U.S. Surveillance, Epidemiology, and End Results (SEER) Research Data (2000–2017) were analyzed using the SEER*Stat software. The Kaplan–Meier method and Cox regression were used. Patients with de novo mPCa were allocated to three cohorts based on the year of diagnosis: A (2000–2003), B (2004–2010), and C (2011–2014). The maximum follow-up was fixed to 5 years. Overall, 26,434 patients were included. Age, race, and metastatic stage (M1) significantly affected OS and CSS. After adjustment for age and race, patients in Cohort C showed a 9% reduced risk of death (hazard ratio (HR): 0.91 (95% confidence interval [CI] 0.87–0.95), p < 0.001) and an 8% reduced risk of cancer-specific death (HR: 0.92 (95% CI 0.88–0.96), p < 0.001) compared with those in Cohort A. After adjustment for age, race, and metastatic stage, patients in Cohort C showed an improvement in OS and CSS compared with Cohort B (HR: 0.94 (95% CI 0.91–0.97), p = 0.001; HR: 0.89 (95% CI 0.85–0.92), p < 0.001). Patients with M1c disease had a more pronounced improvement in OS and CSS compared with the other stages. No differences were found between Cohorts B and C. In conclusion, the real-world survival of de novo mPCa remains poor, with a median OS and CSS improvement of only 4 months in the latest years.

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Bayesian inference using Hamiltonian Monte‐Carlo algorithm for nonlinear joint modeling in the context of cancer immunotherapy

Statistics in Medicine ◽

10.1002/sim.8756 ◽

2020 ◽

Vol 39 (30) ◽

pp. 4853-4868

Author(s):

Marion Kerioui ◽

Francois Mercier ◽

Julie Bertrand ◽

Coralie Tardivon ◽

René Bruno ◽

...

Keyword(s):

Monte Carlo ◽

Bayesian Inference ◽

Cancer Immunotherapy ◽

Joint Modeling ◽

Monte Carlo Algorithm ◽

Hamiltonian Monte Carlo ◽

Nonlinear Joint

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Real-world survival improvements in patients with newly diagnosed metastatic prostate cancer treated in the United States.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.48 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 48-48

Author(s):

Carlo Cattrini ◽

Elisa Zanardi ◽

Alessandra Rubagotti ◽

Linda Zinoli ◽

Matteo Capaia ◽

...

Keyword(s):

Prostate Cancer ◽

Metastatic Prostate Cancer ◽

Cox Regression ◽

De Novo ◽

The United States ◽

New Drugs ◽

Rank Test ◽

Cancer Specific Survival ◽

Risk Of Death ◽

T1 And T2

48 Background: New drugs have become available for the treatment of metastatic prostate cancer (mPCa) during the last two decades. Here, we explored the clinical outcomes of de novo mPCa in 3 large cohorts of patients diagnosed in 3 treatment eras: pre-docetaxel 2000-2003 (T1), docetaxel 2004-2010 (T2) and new androgen-receptor signalling inhibitors (ARSi) + cabazitaxel 2011-2016 (T3). Methods: The USA Surveillance Epidemiology and End Results (SEER) Incidence Data were investigated using the SEER*Stat software. We used the Kaplan – Meier method, log-rank test, Cox regression, hazard ratio (HR) and confidence intervals (CI) to analyse overall survival (OS) and cancer-specific survival (CSS). The maximum follow-up time point was 5 years. Results: A total 34.034 patients with de novo mPCa were analysed for OS, of these 6.621 T1, 12.711 T2 and 14.702 T3. Median OS was 29 months (mo) [95% CI: 28.5-29.5], 28 mo [27.0-28.9], 28 mo [27.3-28.7] and 31 mo [30.2-31.8] in whole, T1, T2 and T3 cohorts, respectively. In the multivariable model, adjusted for age and race, T3 patients showed better OS compared to T1 and T2 patients (HR: 0,92 [95% CI: 0,88-0,95] and 0,92 [0,89 to 0,95], respectively, p<0.001). A total of 33.641 patients were analysed for CSS, of these 6.514 T1, 12.540 T2 and 14.587 T3. Median CSS was 36 mo [35.3-36.7], 34 mo [32.6-35.3], 34 mo [33.0-35.0] and 38 mo [36.9-39.1] in whole, T1, T2, T3 cohorts, respectively. T3 patients had better CSS compared to T1 and T2 patients (HR: 0,93 [0,89-0,97] and 0,92 [0,89 to 0,96], respectively, p<0.001). No difference in OS or CSS was found between T1 and T2 cohorts. Conclusions: The prognosis of patients with de novo mPCa remains poor, with a median CSS of 3 years and a 5-year CSS of 35%. Approximately 8% decrease in the risk of death was found in the era of ARSi and cabazitaxel. The recent intensification of therapy in metastatic hormone-sensitive setting might lead to better outcomes in the next years.[Table: see text]

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