Evaluation of Neuroendocrine Differentiation as a Potential Mechanism of Tumor Recurrence Following Radiotherapy

Study Overview
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Brief Summary
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This is a pilot study to test a hypothesis that a greater increase in serum chromogranin A (CgA) after a definitive radiotherapy (RT) with or without androgen deprivation therapy (ADT) is associated with a higher risk of prostate cancer recurrence after RT. Serum CgA level is measured before the start of RT and/or the start of neoadjuvant ADT for patients undergoing a definitive RT with or without ADT. CgA is also measured at various pre-defined post-RT time points. The study will analyze the followings: 1. Change in CgA level at various pre-defined post-RT time points from the baseline, 2. Correlation between the extent of post-therapy CgA change and Gleason score of malignancy, 3. Correlation between the extent of post-therapy CgA change and treatment outcome.

Detailed Description
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Neuroendocrine differentiation (NED) in prostate cancer is a well-recognized phenotypic change by which prostate cancer cells transdifferentiate into neuroendocrine-like (NE-like) cells. Accumulated evidences have suggested that the prevalence of NE-like cells is associated with disease progression and poor prognosis. NED can be induced by a therapeutic agent. Such therapeutic agents include RT and ADT. RT-induced NED represents a novel pathway by which prostate cancer cells survive radiotherapy and contribute to treatment failure and tumor recurrence. Chromogranin A is the serum biomarker for NED and correlates well with CgA-positive staining in biopsy specimens. It has been reported that elevated serum CgA is associated with poor therapeutic response, androgen-independent growth, and biochemical recurrence. The study tests whether the extent of serum CgA increase by RT +/- ADT, which reflects radiation-induced NED, is correlated with the risk of prostate cancer recurrence following RT and a Gleason score of prostate carcinoma.

Official Title
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Evaluation of Neuroendocrine Differentiation as a Potential Mechanism of Tumor Recurrence Following Radiotherapy

Conditions
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Prostate Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically localized prostate carcinoma, T1-T4 N0M0, any Gleason Score, any prostate-specific antigen (PSA), or Biochemical relapse with clinically suspicious (based on MRI or clinical examination) or biopsy-proven local recurrence in the prostatic fossa after a radical prostatectomy ≥18 years old Histologic diagnosis of prostate adenocarcinoma Signed informed consent Exclusion Criteria: Biochemical relapse alone without clinically suspicious (i.e. no suspicious lesion on MRI of the prostatic bed) or biopsy-proven local recurrence in the prostatic fossa Regional pelvic node metastasis (N1) Distant metastasis (M1) Concurrent or previous cytotoxic medications Medical or psychological conditions that in the opinion of the investigator would not allow follow-up

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Gleason score 6 or less<br>Prostate adenocarcinoma with Gleason score 6 or less | |
| Gleason score 7<br>Prostate adenocarcinoma with Gleason score 7 | |
| Gleason score 8 -10<br>Prostate adenocarcinoma with Gleason score 8 -10 | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlate the extent of post-RT CgA change with Gleason score of malignancy |  | 18 months | 
| Correlate the extent of post-RT CgA change with treatment outcome, using biochemical recurrence as an endpoint |  | 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Examine the extent of CgA change at various post-RT time points |  | 18 months | 
| Examine the effect of ADT on CgA level for patients receiving RT + ADT, and Compare the extent of post-therapy CgA change between patients receiving RT alone and those undergoing RT + ADT |  | 18 months | 
| Compare the extent of post-therapy CgA change between patients receiving photon-based RT and those undergoing proton-based RT |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiotherapy, Chromogranin A, Neuroendocrine differentiation