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

Mayo Clinic

Status

Active, not recruiting

Conditions

Prostate Cancer

Study type

Observational

Funder types

Other

Identifiers

NCT03017794

16-008637

Details and patient eligibility

About

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.

Full description

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.

Enrollment

118 patients

Sex

Male

Ages

18+ years old

Volunteers

No Healthy Volunteers

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