In 2018 it was estimated that approximately 30 million prostate-specific antigen (PSA) tests were ordered in the US, with about 600,000 biopsies performed, 164,690 newly diagnosed cases, and 29,340 deaths. There has been a decline in the number of newly diagnosed cases (6% decrease in incidence rate per year since 2009), with stable death rates. The “relaxation” in screening recommendation between 2008 and 2012 has changed the scope of whom we are now seeing with prostate cancer, resulting in more men with an advanced disease being diagnosed.
Data from large population-based studies have shown that in men older than 75, there has been an increase in high-grade disease (58% to 72%) and an increase in metastatic disease (6.6% to 12%). This has also been demonstrated in men younger than 75, with an increase in high-grade disease (46% to 56%) and an increase in metastatic disease (2.7% to 4%).1,2
Dr. Schaeffer continued by stating that there is a need to define the oligometastatic concept and define an oligometastatic state for prostate cancer. We need to understand and use the right imaging modalities for metastatic prostate cancer and ascertain the implications for patients.
The concept of oligometastatic disease was originally proposed in 1995 by S. Hellman and R. Weichselbaum. This was originally developed based on data from gastrointestinal associated liver metastases and lung metastases. Their message was that treatment of the metastatic lesion could be curative. In both cases of gastrointestinal and lung lesions, several factors contribute to improved 5- and 10-year survival. These include complete resection of the metastatic site, reduced number of metastatic lesions, mildly elevated tumor markers, and increased time between the treatment of the primary tumor and emergence of metastatic lesions.
The idea behind treating and curing the oligometastatic disease is to control the primary tumor + control the single or limited metastatic lesions (with local therapy). Importantly, oligometastatic cancer should not require systemic therapy, and its definition is agnostic of timing (synchronous vs. metachronous).
Dr. Schaeffer moved on to specifically discuss the state of oligometastatic prostate cancer. The oligometastatic state in prostate cancer was first defined by Soloway et al. who noted differences in survival based on the number of metastatic sites, with a lower number correlating with a higher survival rate.3 This was later shown in a more recent publication by Ost et al., showing that one single metastasis conferred a 90% five-year cancer-specific survival, while more than one metastasis conferred a 32% 5-year cancer-specific survival rate.4 There are various definitions of oligometastatic disease in prostate cancer, and currently, there is no consensus. Most studies define it as a limited number of metastatic sites, typically less than 5, and excluding liver, lung, and brain lesions, and typically axial (vs. appendicular) skeleton. Importantly, the imaging used so far for the identification of these lesions has been conventional, and the diagnosis can be synchronous or metachronous.
A consensus definition must be formulated, and it should take into account the timing of the oligometastasis (synchronous vs. metachronous), the location (axial vs. appendicular, and bony vs. visceral), and the imaging used (conventional vs. advanced). To date, the National Comprehensive Cancer Network guidelines recommend using conventional bone scan, computerized tomography, or magnetic resonance imaging for metastases diagnosis. Recently, the use of PET/CTs has also been added, including F-18 PET/CT, and C-11 choline (Figure 1). There are currently several FDA approved radiotracers for diagnosing metastatic prostate cancer, including Technetium-methylene diphosphate, F-Sodium fluoride, F-Fludeoxyglucose, C-Choline, and F-Fluciclovine. These newer imaging agents seem to offer improved detection rates of metastatic cancer.
Figure 1 - The National Comprehensive Cancer Network guidelines recommendations regarding staging and risk assessment after initial treatment incorporating PET-based options:
Summarizing his talk, Dr. Schaeffer concluded that the oligometastatic concept exists in prostate cancer, but it is quite rare. However, it is captured more in studies today than in the past. Earlier detection of metastatic disease can undoubtedly improve survival.5 To correctly implement the concept of oligometastatic disease and treat this entity appropriately, we must:
- Completely resect the primary tumor
- Completely resect the metastatic site
- The number of metastatic sites must be limited
- Tumor markers must be only mildly elevated
- The time between the treatment of the primary tumor and emergence of the metastatic lesion must be increased
- Most importantly, we must develop a consensus definition of oligometastatic disease in prostate cancer
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA
- Weiner et al. National Trends in the Management of Low and Intermediate Risk Prostate Cancer in the United States. J. UROL 2015
- Hu et al. J UROL 2016
- Soloway et al. Stratification of patients with metastatic prostate cancer based on extent of disease on initial bone scan. CANCER 1988
- Ost P. et al. Progression-free Survival Following Stereotactic Body Radiotherapy for Oligometastatic Prostate Cancer Treatment-naive Recurrence: A Multi-institutional Analysis. Eur Urol 2016.
- Tabgen et al. Improved overall survival trends of men with newly diagnosed M1 prostate cancer: a SWOG phase III trial experience (S8494, S8894 and S9346). J Urol. 2012