A Systematic Review of Contemporary Management of Oligometastatic Prostate Cancer: Fighting a Challenge or Tilting at Windmills? - Beyond the Abstract
Since the implementation of the latest imaging techniques such as whole-body MRI and PSMA PET/CT, detection rates for this subgroup of patients has increased exponentially.
By this review of contemporary literature, we aim to summarize all the currently available evidence on the most appropriate management of oligometastatic prostate cancer while evaluating the feasibility of ongoing trials. In particular, we analyze the role of cytoreductive prostatectomy, definitive prostatic radiation therapy and metastasis directed therapy in the setting of oligometastatic PCa.
In light of the results obtained through this paper, it seems that we lack quality evidence justifying the use of local surgical excision in oligometastatic patients.
Fortunately, the scientific community has become aware of the problem and a number of RCTs are underway: of note, the ongoing trial at UT MD Anderson Cancer Center, entitled “Best Systemic Therapy or Best Systemic Therapy (BST) Plus Definitive Treatment (Radiation or Surgery)” (M1 NCT01751438). This first surgical trial is actually a phase II study comparing best systemic therapy to best systemic therapy plus CRP or RT. Promoters are eager for the data to mature to be able to provide us with preliminary results.
Other surgical trials include the g-RAMPP trial (NCT02454543) entitled « Impact of Radical Prostatectomy as Primary Treatment in Patients With Prostate Cancer With Limited Bone Metastases ». It is a German trial, investigating the role of radical prostatectomy with extended lymphadenectomy in patients with mPCa limited to bones. Recruitment is likely to end in April 2020
Similarly, TroMbone: « Testing Radical prostatectomy in men with prostate cancer and oligometastases to the bone » (ISRCTN15704862) is a UK randomized controlled feasibility trial promoted by Freddie Hamdy of the Oxford University Hospitals in London. The design of this study is Radical prostatectomy with extended lymph node dissection with standard of care versus standard of care alone.
On the other hand, encouraging findings have been reported from prostatic radiotherapy in metastatic patients. In the STAMPEDE Trial radiation therapy was well tolerated, as there were only 5% adverse effects during radiotherapy and 4% at a later stage. The trial suggests that the addition of radiation therapy to standard therapy improves survival without failure (hazard ratio [HR] = 0.76, 95% confidence interval [CI], 0.68-0.84; <0.0001), but does not improve overall survival (HR = 0.92, 95% CI, 0.80-1.06, p = 0.2266). Subgroup analysis showed that for patients with a low metastatic burden overall survival was improved ((HR 0·68, 95% CI 0·52–0·90; p=0·007; 3-year survival 73% in control vs 81% with radiotherapy). Radiotherapy gave a three-year survival of 81% in these men, compared to 73% in the standard treatment group.
Finally, the role of metastasis directed therapy is the subject of several ongoing trials. They are very different in terms of inclusion criteria and primary outcome. One could mention the Sunnybrook trial which is focused on the toxicity of patients with prostate cancer classified M1a-b≤5 and having received 35-40 Gy / 5 fx on the prostate, 25-35 Gy / 5 fx on the nodes and 30-40 gy7 5 fx on metastases with androgen deprivation therapy for 1 year.
Ongoing trials data are eagerly awaited to draw reliable recommendations.
Written by: Amine Slaoui, Urology B Department, Ibn Sina Hospital, Mohammed V, University, Rabat, Morocco, Urology Department, Jules Bordet Institute, ULB, Brussels, Belgium, and of the Laboratory of Genetics, NeuroEndocrinology and Biotechnology, Faculty of Sciences, University Ibn Tofail, Kenitra, Morocco
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