Biochemical Recurrence in Patients with Prostate Cancer after Primary Definitive Therapy: Next-Generation Imaging and Treatment Based on Risk Stratification - Beyond the Abstract

Biochemical recurrence (BCR) following primary definitive interventional treatment (e.g., radical prostatectomy [RP] or radiotherapy [RT]) occurs in approximately one-third of patients with prostate cancer.1,2 In general, BCR is defined as a rise in serum prostate-specific antigen (PSA) levels post-RP to ≥0.2 ng/mL, and a PSA increase ≥2 ng/mL above nadir post-RT.3

Historically, conventional imaging techniques have been used for the assessment of clinical progression in BCR. However, these imaging technologies have limited sensitivity at low PSA values (<10 ng/mL).4 Next-generation imaging (NGI) technologies may overcome the sensitivity limitations associated with low PSA values and offer improved diagnostic accuracy for identifying BCR compared with conventional imaging technologies.5 For patients with BCR, there is a lack of consensus among guideline associations and medical societies regarding the most effective treatments.3,6 Thus, these patients are best managed using a treatment strategy involving risk stratification. In companion reviews, we presented the latest clinical evidence for patients with BCR focusing on patient identification with NGI and treatment approaches.7,8

NGI technologies, including positron emission tomography (PET) radiotracers have demonstrated increased sensitivity and selectivity for diagnosing BCR at PSA concentrations <2.0 ng/mL.9-11 Detection rates range between 46% and 50%, with decreasing PSA levels for choline (1–3 ng/mL), fluciclovine (0.5–1 ng/mL), and prostate-specific membrane antigen (0.2–0.49 ng/mL) PET radiotracers.12-14 Radiographic Assessments for Detection of Advanced Recurrence III group suggests NGI for patients with rising PSA (≥0.2 ng/mL) after primary treatment, including patients with PSA levels below the Phoenix definition.15 European and US medical societies recommend NGI for patients with BCR after primary treatment and negative upon conventional imaging who are candidates for salvage therapy.6,16

Earlier detection of metastasis in the BCR setting enables a broader discussion of treatment strategies. As outlined above, available data support the improved detection performance and selectivity of NGI modalities versus conventional imaging techniques for patients with BCR; however, there is limited clinical evidence regarding the application of NGI to treatment decision-making and its impact on patient outcomes.3

European and US guidelines support the risk-stratified management of BCR.3,6 Post-RP, salvage EBRT (with or without androgen deprivation therapy [ADT]) is an accepted treatment option for patients with BCR.3 When local therapies are not an option, guidelines vary regarding systemic therapies, such as ADT, and certainly promote observation, when appropriate, as well as clinical trial enrollment. Nonetheless, patients often receive ADT, with varying guidance for intermittent ADT versus continuous ADT, due to considerations of quality of life effects.3,17 Post-EBRT, salvage RP, cryotherapy, high-intensity focused ultrasound, stereotactic body radiotherapy, low–dose-rate, and high–dose-rate brachytherapy have all demonstrated relatively comparable relapse-free survival rates but differing adverse event profiles, both short- and long-term.18

The emergence of highly sensitive NGI and displacement of conventional imaging may require a reexamination of the current definitions of BCR that alter our understanding of early recurrence. Redefining the BCR disease state by formalizing the role of NGI in patient management decisions will facilitate greater alignment across research efforts and better reflect the published literature. Despite a current lack of consensus for BCR treatment among guideline associations and medical societies, risk stratification of patients is essential for a personalized treatment approach, as it allows for an informed selection of clinically effective therapeutic strategies and estimation of adverse events. The results from ongoing prospective clinical studies of patients with BCR should elucidate evidence-based options for the improved management of patients with BCR.

Written by:
Judd W. Moul, MD, Duke Cancer Institute, Duke University, Durham, NC
Neal D. Shore, MD, Carolina Urologic Research Center, Myrtle Beach, SC


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  • Dr. Moul reports stock or other ownership with Pfizer, Johnson & Johnson, Bavarian Nordic, Eli Lilly, Procter & Gamble, Walgreens, AstraZeneca, Novartis, and Theralogix; honoraria from AbbVie, Bayer, Ferring, Dendreon, Janssen, Astellas Pharma, Sanofi, Genomic Health, GenomeDx, and Pfizer; consulting or advisory role with AbbVie, Bayer, Theralogix, Tolmar, and Blue Earth Diagnostics; speakers' bureau for Bayer, Ferring, Dendreon, Janssen, Sanofi, Genomic Health, and GenomeDx; research funding from Astellas Pharma (Inst) and Pfizer (Inst).
  • Dr Shore reports grant support and consulting fees from AbbVie, Amgen, Astellas Pharma, AstraZeneca, Bayer, Dendreon, Ferring, Janssen Oncology, Merck, Sumitomo Pharma America Inc. (formerly Myovant Sciences, Inc.), Pfizer, Sanofi–Genzyme, and Tolmar Pharmaceuticals.
  • Medical writing support was provided by Julie B. Stimmel, PhD, ISMPP CMPP of Onyx (a Prime Global agency) and funded by Pfizer Inc. and Astellas Pharma Inc., the co-developers of enzalutamide.