Hormone naïve prostate cancer: predicting and maximizing response intervals

Abstract

Hormone naïve advanced prostate cancer is subdivided into two disease states: biochemical recurrence and traditional M1 (metastatic) prostate cancer and characterized by no prior hormonal therapy or androgen deprivation therapy (ADT). In biochemical recurrence/prostate-specific antigen (PSA) recurrence, men should be risk-stratified based on their PSA doubling time, the Gleason score and the timing of the recurrence. In general, only men who are at high risk should be considered for early/immediate ADT although this is best done using shared decision with the patient. The type of ADT to be used in biochemical recurrence ranging from oral-only peripheral blockade (peripheral androgen deprivation) to complete hormonal therapy (combined androgen blockade [CAB]) remains in debate owing to lack of randomized controlled trials (RCT). However, there is good RCT support for use of intermittent hormonal therapy (IHT). There is also limited research on biomarker response (PSA and testosterone decline) to predict prognosis. On the other hand, in the setting of M1 hormone naïve prostate cancer, there are many more RCT's to inform our decisions. CAB and gonadotrophin-releasing hormone antagonists perhaps provide a slight efficacy advantage while IHT may be slightly inferior with minimal M1 disease. The PSA nadir at 7 months after starting ADT is a powerful prognostic tool for M1 patients. There is growing recognition that serum testosterone (T) control while on ADT is linked to the development of castrate-resistant prostate cancer. Especially for a M1 patient, maintaining a serum T below 20-30 ng dl-1 prolongs the response to ADT. Novel oral agents (abiraterone and enzalutamide) may soon find use in hormone naïve disease and may alter the treatment landscape. Despite over 75 years of experience with ADT, many questions remain, and the field continues to evolve.

Figure 1

Early hormonal therapy administered at prostate-specific antigen <10 ng ml−1 affects clinical metastasis-free survival. Patients with pathological Gleason Sum > 7 or PSA-DT < 12 months. Used with permission from Moul et al.

Figure 2

Hormone naïve disease-new M1 prostate-specific antigen level as a biomarker of treatment effect. Used with permission from Hussain et al.

Figure 3

Hormone naïve disease-potential importance of lower T levels. A hypothesis-generating analysis from a retrospective study. Used with persmission from Morote et al.

Figure 4

Hormone naïve disease-testosterone suppression with luteinizing hormone-releasing hormone agonists. Used with permission from Pickles.