Managing Nonmetastatic Castration-resistant Prostate Cancer

Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) have rising prostate-specific antigen (PSA) and castrate testosterone levels, with no radiological findings of metastatic disease on computed tomography and bone scan. Given recent drug approvals for nmCRPC, with many other therapeutics and imaging modalities being developed, management of nmCRPC is a rapidly evolving field that merits detailed investigation.

To review current nmCRPC management practices and identify opportunities for improving care of nmCRPC patients.

A literature search up to July 2018 was conducted, including clinical trials and clinical practice guidelines (National Comprehensive Cancer Network, European Society for Medical Oncology, European Association of Urology, Prostate Cancer Clinical Trials Working Group, Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence). Keywords included prostate cancer, nonmetastatic, castration resistance, rising PSA, and biochemical relapse.

Recommendations regarding indications for, and frequency of, imaging and PSA testing, as well as for initiating systemic therapy in nmCRPC are based on PSA rise kinetics and symptoms. Both enzalutamide and apalutamide have been shown to significantly increase metastasis-free survival in phase III placebo-controlled randomised trials in nmCRPC patients with PSA doubling time (DT) ≤10 mo. The expected impact of new imaging techniques in the assessment of nmCRPC is also reviewed.

nmCRPC is a heterogeneous disease; while observation may be an option for some patients, enzalutamide and apalutamide may be appropriate to treat nmCRPC patients with PSA-DT ≤10 mo. The emergence of more accurate imaging modalities as well as circulating tumour biomarker assays will likely redefine the assessment of nmCRPC in the near future.

Herein, we review key literature and clinical practice guidelines to summarise the optimal management of patients with prostate cancer and rising prostate-specific antigen despite castrate testosterone levels, but with no evidence of distant metastasis on traditional imaging. New drugs are being developed for this disease setting; novel imaging and tumour biomarker blood tests are likely to define this disease state more accurately.

European urology. 2018 Aug 14 [Epub ahead of print]

Joaquin Mateo, Karim Fizazi, Silke Gillessen, Axel Heidenreich, Raquel Perez-Lopez, Wim J G Oyen, Neal Shore, Matthew Smith, Christopher Sweeney, Bertrand Tombal, Scott A Tomlins, Johann S de Bono

Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain., Institut Gustave Roussy and University of Paris Sud, Villejuif, France., Department of Oncology and Hematology, Kantonsspital St. Gallen, Switzerland., University Hospital Aachen, Cologne, Germany., The Royal Marsden Hospital and The Institute of Cancer Research, London, UK., Carolina Urologic Research Center and Atlantic Urology Clinics, Myrtle Beach, SC, USA., Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA., Cliniques Universitaires Saint Luc, Brussels, Belgium., Michigan Center for Translational Pathology, Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA., The Royal Marsden Hospital and The Institute of Cancer Research, London, UK. Electronic address: .