EAU 2017: State-of-the-art Lecture: EAU Guidelines on mCRPC – An Update

London, England (UroToday.com) Dr. Philip Cornford delivered the highly anticipated update of the EAU Guidelines for metastatic castration-resistant prostate cancer (mCPRC) [1].  Dr. Cornford reviewed the definition of CRPC, including a castrate level of serum testosterone <50 ng/mL plus either (i) biochemical progression – three consecutive rises of PSA, resulting in two 50% increases above the nadir value, with PSA >2 ng/mL, or (ii) radiological progression – the appearance of two or more bone lesions on bone scan or enlargement of a soft tissue lesion based on RECIST criteria.

Patients with biochemical CRPC are at high risk for progression, as 1/3 will develop metastasis within 2 years, although there is no current evidence for early intervention. The RADAR group consensus statement regarding this high risk cohort is that bone scan and CT scan should be performed when the PSA reaches 2 ng/mL and if negative, these studies should be repeated when the PSA reaches 5 ng/nL and after every PSA doubling. Indeed, this area is an important area of research and clinical trials.

Dr. Cornford elegantly reviewed the ‘Castrate Resistant Prostate Cancer Care-Pathway’ in an attempt to answer questions to important issues regarding mCRPC: (i) When should you start treatment? (ii) Which treatment to start with? (iii) How should you monitor the patient? (iv) When should you move on to a different treatment? Dr. Cornford stated emphatically that in the non-metastatic setting, patients should undergo ‘watchful waiting’ with surveillance imaging scheduled as delineated above. Which treatment to start with is highly dependent on patient performance status and symptoms – asymptomatic or mildly symptomatic patients should be offered either Sipuleucel-T immunotherapy (IMPACT), abiraterone + prednisone (COU-AA-302), enzalutamide (Prevail) or docetaxel (TAX 327). Symptomatic patients without visceral metastasis should be offered radium-223 (ALSYMPCA) or docetaxel; patients with visceral metastasis should also receive docetaxel. Based on consensus statements form the 2015 Advanced Prostate Cancer Consensus Conference, patients should be assessed every 2-3 months with a history and physical examination, PSA, CBC, and metabolic panel, including LFTs and alkaline phosphatase. Imaging should be every six months and include a bone scan and CT chest, abdomen and pelvis. Finally, treatment should be changed when two of the three following are met: PSA progression, radiological progression, or clinical deterioration. These second line treatment options include use of abiraterone (COU-AA-301), enzalutamide (AFFIRM), cabazitaxel (TROPIC), docetaxel, or radium-223. Notably, patients starting second line therapy are at risk of treatment resistance (AR-V7).

Patients with poor performance status that are asymptomatic should be considered for watchful waiting. For those with progressive disease, palliative care should be discussed with the patient and family. In the final year of life, patients with mCRPC are prone to complications and side effects, most commonly anemia, lower urinary tract symptoms, and bone pain; up to 1/3 will require palliative procedures including ureteral stents, nephrostomy tubes, and channel TURP.

In summary, patients with CRPC should not receive treatment outside of a clinical trial until they are metastatic. Treatment decision making is largely based on patient performance status. Judicious follow-up and scheduled imaging surveillance are of primary importance.

1. Cornford P, Bellmunt J, Bolla M, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part II: Treatment of Relapsing, Metastatic, and Castration-Resistant Prostate Cancer. Eur Urol 2017;71(4):630-642.

Speaker(s): Philip Cornford, Royal Liverpool and Broadgreen Hospitals NHS Trust, Liverpool, UK

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto
Twitter: @zklaassen_md

at the #EAU17 - March 24-28, 2017- London, England
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