GTN Therapy on Biomarkers of Immune Escape in Men With Biochemical Recurrence of Prostate Cancer After Primary Therapy

Prostate cancer is the most commonly diagnosed cancer in men in Canada. Over 30% of men over the age of fifty have histological evidence of prostate cancer on biopsy. Despite the stage migration afforded by early detection with serum prostate specific antigen (PSA) testing and an apparent trend toward improved survival over the past several years, prostate cancer remains a significant cause of morbidity and mortality. Biochemical failure after primary therapy (surgery or radiation) remains a significant health care burden and strategies to delay clinical prostate cancer progression and prolong the interval from treatment failure to systemic therapy would be of significant clinical benefit for those men suffering from a finding of PSA recurrence. PSA is widely accepted as the most useful prognostic marker of prostate cancer progression, particularly after primary therapy with radical surgery or radiation. 5 Despite improved cancer control rates with definitive management of early stage prostate cancer, a PSA recurrence is unfortunately a common occurrence (25-50%) in most large case series. Microenvironmental factors have been demonstrated to play a pivotal role in the selection of neoplastic cell subpopulations expressing more malignant phenotypes and contributing to the progression of localized and metastatic disease. Very low levels of O2 (\< 10 mmHg) has been well described in many solid tumours (including prostate cancer) and the extent of hypoxia has been demonstrated to represent an independent marker of a poor prognosis for patients with various types of cancers. Tumour hypoxia contributes to numerous adaptive phenotypes including increased invasion and metastasis, as well as evasion of immune cell surveillance increased resistance to radiotherapy and chemotherapy. Although cellular adaptive responses to hypoxia are likely mediated by various mechanisms, our previous preclinical studies suggest that decreased nitric oxide (NO)-dependent signalling plays a significant role in this progression of a malignant phenotype.

Sex

Male

Minimum age

18 Years

Maximum age

90 Years

Inclusion Criteria:

* Males;
* Legal age of consent (18 years of age);
* Histological evidence of adenocarcinoma of the prostate;
* Patients have chosen watchful waiting or active surveillance as preferred management;
* Patients have biochemical failure (defined below) after primary cancer treatment and prefer deferred cancer management:

  * Patients with an increasing PSA at least 3 months after surgery (at least two values above PSA 0.2 ng/mL);
  * Patients with a PSA 2 ng/ml above their nadir PSA after radiation therapy.

Exclusion Criteria:

* Inability to provide an informed consent;
* Inability to adhere to the study protocol for any reason;
* Receiving any other adjuvant therapies for prostate cancer less than 6 months prior to study entry;
* Any contraindication to GTN (including concomitant use of nitroglycerin formulations or phosphodiesterase inhibitors).