BERKELEY, CA (UroToday.com) - Only recently, men with metastatic prostate cancer were often cared for with palliative care principles, i.e., improved short term quality of life. However, the longevity of men with metastatic prostate cancer and castrate resistant prostate cancer (CRPC) in a recent cohort as demonstrated by Omlin et al. emphasizes the importance of changing the dogmatic point of view.[1] Rather, metastatic prostate cancer should be viewed as a chronic illness, where the adverse effects of androgen deprivation therapy (ADT) are actively anticipated, screened for, and treated. With such change in the paradigm, it may become appropriate to approach these patients with a multi-disciplinary team consisting of endocrinologist, cardiologist, geriatrician, dietician, exercise physiologist, and psychologist. A recent clinical trial by Cormie et al. is an example of successful exercise intervention in men starting ADT.[2] In appropriately selected men who are able to tolerate a moderate intensity exercise programme, the authors demonstrated improvements in lean body weight, cardiovascular fitness, muscle strength, cholesterol profile, sexual function, fatigue, and psychological status.
Apart from the potential cardiovascular and bone health benefits of active management of iatrogenic adverse effects of ADT, there are growing epidemiological and clinical trials data to associate metabolic syndrome with adverse prostate cancer outcome. The presence of elevated C-peptide (a surrogate marker of hyperinsulinaemia) prior to treatment with ADT was associated with significantly shorter time to development of CRPC (16 vs 36 months).[3] Further, men with the highest Insulin-like growth factor -1 (IGF-1)/insulin-like growth factor binding protein-1 (IGFBP-1) ratio compared to those in the lowest tertile after 3 months of ADT had a significant reduction in time to progression to CRPC in a recent retrospective study (12.4 months vs 21.9 months).[4] It is highly ironic that whilst ADT remains an essential strategy in managing both localized and metastatic prostate cancer, ADT is also a potent trigger for the development and exacerbation of metabolic syndrome. In turn, such adverse effects can be the cause of cardiovascular death and potentially the early development of CRPC.[5]
Abiraterone, enzalutamide, tasquinimod, and ipilimumab are likely to be only a tip of the iceberg in treating men with metastatic prostate cancer. As patients live longer with the help of these novel agents, proactively caring for men with the disease has become more important than ever.
References:
- Omlin, A., et al., Improved survival in a cohort of trial participants with metastatic castration-resistant prostate cancer demonstrates the need for updated prognostic nomograms. Eur Urol, 2013. 64(2): p. 300-6.
- Cormie, P., et al., Can Supervised Exercise Prevent Treatment Toxicity in Prostate Cancer Patients Initiating Androgen Deprivation Therapy: A Randomised Controlled Trial. BJU Int, 2014.
- Flanagan, J., et al., Presence of the metabolic syndrome is associated with shorter time to castration-resistant prostate cancer. Ann Oncol, 2011. 22(4): p. 801-7.
- Sharma, J., et al., Elevated insulin-like growth factor binding protein-1 (IGFBP-1) in men with metastatic prostate cancer starting androgen deprivation therapy (ADT) is associated with shorter time to castration resistance and overall survival. Prostate, 2014. 74(3): p. 225-34.
- Levine, G.N., et al., Androgen-deprivation therapy in prostate cancer and cardiovascular risk: a science advisory from the American Heart Association, American Cancer Society, and American Urological Association: endorsed by the American Society for Radiation Oncology. Circulation, 2010. 121(6): p. 833-40.
Written by:
Handoo Rhee and Ian Vela as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Australian Prostate Cancer Research Centre – Queensland
Adverse effects of androgen deprivation therapy in prostate cancer and their management - Abstract