Modeling Clinical Failure in Prostate Cancer Patients Based on a Two-stage Statistical Model

Prostate Cancer Clinical Trial

— PREDYC  

Official title:

Modeling Clinical Failure in Prostate Cancer Patients Based on a Two-stage Statistical Model

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03979079
• Other study ID #: IB2010-PREDYC
• Status: Completed
• Start date: January 2010
• Est. completion date: January 1, 2017

Study information

• Verified date: December 2020
• Source: Institut Bergonié
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Biomarker series can indicate disease progression and predict clinical endpoints. When a treatment is prescribed depending on the biomarker, confounding by indication might be introduced if the treatment modifies the marker profile and risk of failure.

The two-stage model fitted within a Bayesian Markov Chain Monte Carlo framework is particularly flexible to account for such data. Prostate-specific antigens in prostate cancer patients treated with external beam radiation therapy can be monitored. In the presence of rising prostate-specific antigens after external beam radiation therapy, salvage hormone therapy can be prescribed to reduce both the prostate-specific antigens concentration and the risk of clinical failure, an illustration of confounding by indication. The prognostic value of hormone therapy and prostate-specific antigens trajectory on the risk of failure based on a two-stage model within a Bayesian framework to assess the role of the prostate-specific antigens profile on clinical failure while accounting for a secondary treatment prescribed by indication. the aim of this research is to model prostate specific antigens using a hierarchical piecewise linear trajectory with a random changepoint. Residual prostate-specific antigens variability can be expressed as a function of prostate-specific antigens concentration. Covariates in the survival model can include : hormone therapy, baseline characteristics, and individual predictions of the prostate-specific antigens nadir and timing and prostate-specific antigens slopes before and after the nadir as provided by the longitudinal process.

Description:

The two-stage modeling approach allows estimation of the regression coefficients in a time-dependent Cox model, while addressing the limitations with the knowledge of the true marker trajectory. In the first stage, the longitudinal process is modeled using a repeated measures component model, such as a random effects model. In the second stage, estimated characteristics of the longitudinal marker trajectory, such as slopes, are included as covariates in a survival model to assess their prognostic value.

Our aim was to highlight the flexibility of a two-stage model fitted within a Bayesian Markov Chain Monte Carlo (MCMC) framework. We applied this model to assess the prognostic value of the prostate-specific antigens (PSA) profile (level and timing of the nadir; pre- and post-nadir slopes) as well as salvage hormonal treatment (HT) on the risk of clinical failure following external beam radiation therapy (EBRT) in the presence of confounding by indication. We first present the longitudinal hierarchical PSA model that we developed earlier. This model was particularly flexible since it allowed us to account for the presence of a random changepoint as well as the modeling of the residual variability as a function of the PSA concentration. We next extend the longitudinal model to a two-stage model by using estimated parameters of the longitudinal process as covariates in a Cox proportional hazards model to assess prognostic factors of clinical failure including baseline characteristics, PSA trajectory, and HT.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2384
• Est. completion date: January 1, 2017
• Est. primary completion date: January 1, 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• clinically localized prostate cancer

• Clinical stage T1 to T4

• Node and metastasis negative

• Treated with external beam radiation therapy (RT).

Exclusion Criteria:

• Patients with baseline or planned hormonotherapy

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Radiation:
• external beam radiation therapy

Locations

Country	Name	City	State
France	INSERM	Bordeaux

Sponsors (2)

Lead Sponsor	Collaborator
Institut Bergonié	Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

References & Publications (1)

Bellera C, Proust-Lima C, Joseph L, Richaud P, Taylor J, Sandler H, Hanley J, Mathoulin-Pélissier S. A two-stage model in a Bayesian framework to estimate a survival endpoint in the presence of confounding by indication. Stat Methods Med Res. 2018 Apr;27( — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Clinical Failure After Initiation of Radiotherapy	Clinical failure is defined as any of the following events following initiation of radiotherapy: distant metastases, nodal recurrence, or any palpable or biopsy-detected local recurrence three years after radiation; any local recurrence within three years of RT if the most previous PSA was>2 ng/ml; and death from prostate cancer.	within 10 years following initiation of radiotherapy
Secondary	Number of Participants With Initiation of Salvage Therapy After Radiotherapy		within 10 years following initiation of radiotherapy