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ESOU18

ESOU18: Radiotherapy Treatment for Oligometastatic Prostate Cancer Disease

Amsterdam, The Netherlands (UroToday.com) Prostate cancer (PC), with an estimated 1.1 million new cases globally, is the second most common cancer among men, with an estimated death of over 300,000 deaths annually. Novel imaging modalities enabled us to better diagnose patients with a limited number of metastases, after they underwent primary curative treatment. This is called the oligometastatic state which is manifested by harboring limited metastatic disease [1]. The improvements in therapeutic techniques have changed clinical practice, allowing for a local treatment (such as surgery or radiotherapy) either with or without systemic approach for this unique state.  Obviously, the distribution and extent of metastases affect the prognosis of oligometastatic castration-sensitive PC. Intuitively, patients with low-volume or oligometastatic disease have improved survival compared with those with high-volume metastases or a widely disseminated metastatic cancer [2].

While chemo-hormonal therapy is the standard of care for men with high-volume metastatic castration-sensitive PC [3], stereotactic body radiotherapy (SBRT) is emerging as a promising low-toxicity treatment option for oligometastatic disease both at diagnosis and recurrence (local consolidative therapy and metastasis-directed therapy) [4]. Small-volume high-dose SBRT limited to metastatic sites could potentially eliminate all macroscopic cancer foci, and thus prolong the progression-free interval and postpone androgen deprivation therapy (ADT). The concept of ADT-free survival, defined as the time to the delayed start of systemic therapy, has emerged as a method to spare the known negative side effect of this treatment, such as the increased occurrence of cardiovascular events and metabolic syndrome, and other effects, significantly affecting patient quality of life (QoL) [5]. 

The aim of SBRT in this setting is to achieve local control, and delay progression, thereby postpone the need for further treatment. Currently, limited studies focus on metastasis-directed SBRT. These studies, despite short follow-up limiting their evaluation of overall survival (OS) and cancer-specific survival (CSS), demonstrated that metastasis-directed SBRT is a safe treatment, achieving high local control (~ 95%) with low-grade toxicity (generally limited to gastro-intestinal effects) [5,6].

A deeper understanding of the predictive role of biomarkers is required for a targeted treatment selection and proper surveillance programs. The limitation associated with the use of PSA as diagnostic and follow-up marker stimulated several investigations of several novel biological markers, such as blood-based parameters, microRNA, and cell-free DNA [7].

Another novel research frontier is the role of imaging in this specific setting of patients. The role of whole-body magnetic resonance imaging (WB-MRI) has been proposed as a suitable solution for tumor detection with performance at least comparable with that of choline positron emission tomography/computed tomography (Ch-PET/CT)[8]. New tracers like prostate specific membrane antigen (PSMA) are being investigated in PET imaging  as well. 

To date, the standard of care for recurrent PC remains ADT, with its associated considerable side effects and worsening of QoL. Randomized clinical trials with homogeneous patient population are needed to better define, and standardize treatment of oligometastatic PC.


Speaker: Barbara Alicja Jereczek-Fossa MD, PhD, Assistant Professor in Radiation Oncology of the University of Milan Senior Deputy Director of the Division of Radiotherapy, European Institute of Oncology, Milan, Italy

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at The 15th Meeting of the EAU Section of Oncological Urology ESOU18 - January 26-28, 2018 - Amsterdam, The Netherlands

References:

1. Weichselbaum RR, Hellman S. Oligometastases revisited. Nat Rev Clin Oncol 2011;8:378–82.

2. Gandaglia G et al. Impact of the site of metastases on survival in patients with metastatic prostate cancer. Eur. Urol. 68, 325–334 (2015).

3. James ND et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016 Mar 19;387(10024):1163-77. doi: 10.1016/S0140-6736(15)01037-5.

4. Tree AC et al. Stereotactic body radiotherapy for oligometastases. Lancet Oncol 2013;14:e28–37.

5. Berkovic P et al. Salvage stereotactic body radiotherapy for patients with limited prostate cancer metastases: deferring androgen deprivation therapy. Clin. Genitourin. Cancer 11, 27–32 (2013).

6. Ahmed KA et al. Stereotactic body radiationtherapy in the treatment of oligometastatic prostate cancer. Front. Oncol. 2, 215 (2013).

7. Gu X et al. Prognostic significance of neutrophil-to-lymphocyte ratio in prostate cancer: evidence from 16,266 patients. Sci Rep. 2016 Feb 25;6:22089. doi: 10.1038/srep22089.

8. Padhani AR et al. METastasis Reporting and Data System for Prostate Cancer: Practical Guidelines for Acquisition, Interpretation, and Reporting of Whole-body Magnetic Resonance Imaging-based Evaluations of Multiorgan Involvement in Advanced Prostate Cancer. Eur Urol. 2017 Jan;71(1):81-92. doi: 10.1016/j.eururo.2016.05.033. Epub 2016 Jun 14.