Understanding Progression

Certain men with non-metastatic CRPC are at risk of developing metastases1

10% to 20%
of men diagnosed with prostate cancer are estimated to develop CRPC within 5 YEARS of follow-up2

Data from 331 subjects in the placebo group of a randomized controlled trial of an investigational agent were analyzed to evaluate the relationship between disease and patient characteristics with time to first bone metastases in men with prostate cancer, rising PSA despite ADT, and no radiographic evidence of metastases.3

After 2 years:

46% had developed at least
1 bone metastasis

In men with non-metastatic CRPC, a faster PSA doubling time (PSADT) has been linked to shorter time to metastasis1

When compared with patients who experienced a PSADT ≥10 months, those with a PSADT <10 months had*4:

12x greater risk of developing
a bone metastasis

*Retrospective study of 347 patients with CRPC from a cohort of 9547 patients who underwent treatment for prostate cancer, using the Center for Prostate Disease Research database.

Androgen receptor (AR) signaling remains relevant in CRPC5

  • The goal of continuous ADT is to maintain castrate levels of serum testosterone (≤50 ng/dL)6
  • However, several resistance mechanisms, including AR overexpression, can lead to CRPC7

ADT = androgen deprivation therapy; CRPC = castration-resistant prostate cancer; PSA = prostate-specific antigen.

References

1. Howard LE, Moreira D, De Hoedt A, et al. Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer. BJU Int. 2017;120(5B):E80-E86.

2. Kirby M, Hirst C, Crawford ED. Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract. 2011;65(11):1180-1192.

3. Smith MR, Cook R, Lee KA, Nelson JB. Disease and host characteristics as predictors of time to first bone metastasis and death in men with progressive castration-resistant nonmetastatic prostate cancer. Cancer. 2011;117(10):2077-2085.

4. Metwalli AR, Rosner IL, Cullen J, et al. Elevated alkaline phosphatase velocity strongly predicts overall survival and the risk of bone metastases in castrate-resistant prostate cancer. Urol Oncol. 2014;32(6):761-768.

5. Mitsiades N. A road map to comprehensive androgen receptor axis targeting for castration-resistant prostate cancer. Cancer Res. 2013;73(15):4599-4605.

6. Scher HI, Morris MJ, Stadler WM, et al. Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016;34(12):1402-1418.

7. Kahn B, Collazo J, Kyprianou N. Androgen receptor as a driver of therapeutic resistance in advanced prostate cancer. Int J Biol Sci. 2014;10(6):588-595.