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

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

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.

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.

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