ESMO 2017: Case Studies in mCRPC – Navigating the Increasingly Busy Waters

Madrid, Spain (UroToday.com) Dr. Omlin and Dr. O’Sullivan provided several complex case presentations for patients with mCRPC at the Targeted Alpha Therapy in mCRPC lunch symposium. The first case was a 76-year-old presented by Dr. Omlin who was diagnosed with bone and lymph node metastases cT3bN2M1(bone), Gleason 5+5 disease, and PSA 39.1 ng/mL. He was initially started on ADT and denosumab, however within nine months his PSA was increasing in the setting of castrate testosterone and he was started on six weeks of docetaxel with a subsequent >50% PSA response.

A further 9 months after chemotherapy his PSA was increasing (in the setting of new pelvic pain) and restaging demonstrated stable disease. Through an expanded access program he was started on radium-223. Dr. Omlin then showed results of the Advanced Prostate Cancer Consensus Conference (APCCC 2017) survey recently published [1]. Specifically, when the expert panel was queried as to how frequently they recommend PSA testing in men with mCRPC being treated with radium-223, 40% reported every 3-4 weeks and 40% reported every 2-4 months. When asked whether they recommend ALP testing in men with mCRPC being treated with radium-223, the consensus was that 47% recommended every 3-4 weeks and 35% every 2-4 months. After 3 doses of radium-223 this patient’s PSA increased, as well as the ALP (although still normal). When the APCCC panel was asked what kind of imaging for staging and treatment monitoring they recommended for those being treated with radium-223, 75% recommended CT and bone scintigraphy. When asked about the frequency of imaging for those on radium-223, the most common response (41%) was every 3-4 months during and after treatment initiation with radium-223.

This patient subsequently had continued PSA progression, in addition to increasing disease burden in the bone and osteonecrosis of the jaw. When the APCCC panel was queried about treatment practices for patients treated with radium-223 who progress outside of the bone, the majority (52%) of respondents recommended completing treatment with radium-223 plus adding abiraterone or enzalutamide. The patient was started on abiraterone with improved imaging, PSA, and ALP parameters. Finally, this patient continued with abiraterone for a period of time and was subsequently given cabazitaxel.

Dr. Omlin concluded with several important points: (i) men with bone metastases and hormone naïve prostate cancer should not be treated with denosumab, (ii) monitoring for men on radium-223 should include PSA, ALP and imaging should be considered after 3 doses of radium-223 in case of soft tissue progression, and (iii) the combination of radium-223 with abiraterone or enzalutamide is not yet standard of care, however phase III trials are ongoing (ERA 223; PEACE-III).

Dr. O’Sullivan then presented a case of a 67-year-old male that presented with increasing nocturia and worsening back pain. His workup demonstrated a PSA of 2,000 ng/mL, ALP 6,000 U/L, Gleason 9 prostate cancer in 14/15 cores, and widespread metastasis. He was started on an LHRH analogue + bicalutamide and zoledronic, however he refused docetaxel. After three-months his PSA nadir was 50 ng/mL although ALP was rising. Within 4 months his PSA was increasing again and he was started on enzalutamide and radiotherapy to the hip metastases. After two months of enzalutamide his disease continued to progress (but remain bone only) and he was started on radium-223 and continued on enzalutamide. Although he had an initial adequate response, over 12 months his disease progressed and he eventually passed 12 months after starting radium-223.

For Dr. O’Sullivan’s second case, he presented a 61 year-old-male diagnosed with T3N0M1b prostate cancer with a PSA of 500 ng/mL started on an LHRH analogue. He eventually went on to develop CRPC after 9 years and then underwent 8 cycles of docetaxel prior to disease progression and development of bone-only metastasis. He had an initial response to enzalutamide, however he once again had disease progression after 6 months. Dr. O’ Sullivan kept the patient on enzalutamide and started him on radium-223 and denosumab, for which he had an excellent PSA response. Dr. O’Sullivan concluded his talk with highlighting several important points (i) radium-223 can be used in combination with best standard of care at first sign of clinical progression, (ii) layering of radium-223 treatment onto ongoing enzalutamide therapy shows clinical benefit, and (iii) patients have more opportunity to benefit from using radium-223 earlier rather than later in the disease process.

Speaker: Aurelius Omlin, Kantonsspital St. Gallen, St. Gallen, Switzerland; Joe O’Sullivan, Queen’s University Belfast, Belfast, United Kingdom

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain

Reference:

1. Gillessen S, Attard G, Beer TM, et al. Management of patients with advanced prostate cancer: The Report of the Advanced Prostate Cancer Consensus Conference APCCC 2017. Eur Urol 2017 [Epub ahead of print].