Emergence of more sensitive imaging modalities and novel tumor biomarker assays combined with new therapies promise to improve management approaches for men with non-metastatic castration-resistant prostate cancer (nmCRPC) who experience rising PSA levels, according to a new review published in European Urology.1

A key component of managing these patients is earlier detection of metastatic disease, which might be possible with the current progress being made in positron emission tomography (PET) and multi-parametric and whole-body magnetic resonance imaging, as well as the development of sensitive assays for measuring circulating tumor cells. Identification of “molecularly detectable residual disease” from circulating tumor material or bone micrometastases in patients with nmCRPC “could help stratify nmCRPC patients based on the risk of relapse and for treatment intensification,” Joaquin Mateo, MD, PhD, from the Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and colleagues wrote.

Although observation might be an option for selected patients, the review noted, the novel anti-androgen medications enzalutamide and apalutamide could be appropriate treatment for nmCRPC patients with a PSA doubling time of 10 months or less. In the landmark phase 3 randomized, controlled PROSPER and SPARTAN trials, enzalutamide and apalutamide treatment demonstrated increased metastasis-free survival among nmCRPC patients with a PSADT of 10 months or less. The agents also have been shown to increase time to detectable metastases by bone scan and computed tomography (CT) scans.

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The FDA approved enzalutamide and apalutamide for nmCRPC on July 13 and February 14, respectively, based on the findings from the PROSPER and SPARTAN trials, respectively.

For their review, the authors conducted a literature search up to July 2018. The review included clinical trials and clinical practice guidelines from National Comprehensive Cancer Network, European Association of Urology, Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence, European Society for Medical Oncology, and Prostate Cancer Clinical Trials Working Group.

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Tomasz M. Beer, MD, Deputy Director of the Knight Cancer Institute and Professor of Medicine at Oregon Health and Sciences University in Portland, Oregon, said the new review provides a solid summary of the current state of knowledge. Still, many unanswered questions remain. “I do think that there is enough evidence to evolve the standard of care, but I would note that it is not 1 standard of care for all patients,” he told Renal & Urology News. “The PROSPER and SPARTAN trials demonstrated an improvement in metastases-free survival but have not demonstrated overall survival.”

Overall survival may be similar if patients with nmCRPC are treated early or when they have the first signs of metastatic CPRC, he said, adding that the PROSPER and SPARTAN trials only included men with shorter PSA doubling times.

In addition, adverse effects vary from patient to patient and treatment costs are an important consideration, he pointed out. “So I think that the review does a fine job, and it needs to be understood as discussing a new standard of care that can be deployed in nmCRPC, but need not be deployed in every patient. There is room for individualizing therapy decisions in this setting,” Dr Beer said.

Amar Kishan, MD, Assistant Professor in the Department of Radiation Oncology at the University of California, Los Angeles, agrees with Dr Beer. “The new PET-imaging technologies, including fluciclovine and especially prostate-specific membrane antigen-based imaging, will likely allow us to identify metastases in many of these men. What to do with that information is unclear,” Dr Kishan said.



1.     Mateo J, Fizazi K, Gillessen S, et al. Managing nonmetastatic castration-resistant prostate cancer. Eur Urol. 2018; published online ahead of print.                                         #