Unfortunately, there is no clear definition of oligometastatic prostate cancer, and a recent review by Tosoian et al. (Nature Reviews Urology 2017), highlights the difficulty with having so many variable definitions – comparisons are all but impossible. More importantly, the imaging modality utilized is rapidly changing – and it is unclear if increased identification of smaller metastases at lower PSA levels actually translates to a cancer-specific and overall survival benefit.
Next, he highlighted the key rationale for the treatment of the primary tumor with radical prostatectomy (RP) or radiation therapy (RT) in men with oligometastatic prostate cancer:
The STAMPEDE study,1 specifically the arm focused on radiation of the primary tumor, has been a game-changer in this disease space. In this study, they identified that men with the low-volume metastatic burden (based on CHAARTED criteria) had significantly better PFS, MFS and OS than men with a higher metastatic burden. Specifically, OS was better in men treated with radiation who had low volume metastases (HR 0.68, p = 0.007). This has established radiation as a viable treatment option in this setting.
But, what about radical prostatectomy? He outlines below why he thinks RP could be useful as a first-line therapy in these patients:
Unfortunately, there is no level 1 evidence to support this … yet. In his mind, ideal patients for this are men with no visceral metastases and, if they were pretreated with systemic therapy, a low PSA nadir with systemic therapy. A study by Fossati et al. (EU 2015), using the SEER registry, attempted to address this question – and they found that, men with a 3-year cancer-specific mortality risk < 40% benefited from treatment of the primary (CSM calculated from age, PSA, Gleason grade, cT stage, and cN stage). The number needed to treat was 30-40 – but increased exponentially if the mortality risk was > 40%.
While there is also simultaneously increasing evidence of benefit from treating low-volume metastases with radiation or surgery (rather than systemic therapy), as seen in the study by Piet Ost and colleagues (EU 2015), these lend credence to the concept of maximal tumor eradication.
There are 4 ongoing trials or completed assessing this question of local therapy in this setting, which are summarized below:
The SUO study and the TROMBONE study both assess RP and will both take some time to report – so, unfortunately, unlikely to have prospective Level 1 data in the near future. In the meantime, beware that radiation therapy may become the standard – and it may become difficult to convince patients and other physicians to recruit to or even try RP in this setting.
His take-home slide, which segues nicely to the later talks:
- Stampede (radiation) – overall negative study, but positive for low-volume M1 (prespecified subset analysis)
- HORRAD (radiation) – overall negative study; oligomets not prespecified, so underpowered – but post-hoc analysis suggested some benefit.
- RP (surgery) – retrospective series are sparse and biased. But they do support RP as a local therapy.
- Surgical complications are higher than radiation, but not intolerable
- Await surgical RCTs
Presented by: Judd Moul, MD, Urologic Oncologist, Duke University, Durham, North Carolina, USA
Written by: Thenappan Chandrasekar, MD. Clinical Instructor, Thomas Jefferson University, Twitter: @tchandra_uromd, @TjuUrology, at the 16th Meeting of the European Section of Oncological Urology, #ESOU19, January 18-20, 2019, Prague, Czech Republic
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