Novel Insights into the Management of Oligometastatic Prostate Cancer: A Comprehensive Review
Introduction
Patients with metastatic prostate cancer (mPCa) are currently best treated with palliative treatments such as androgen deprivation therapy (ADT) plus either docetaxel or abiraterone [1]. However, we hypothesise that oligometastatic PCa is a different clinical entity to widely disseminated mPCa and presents an interesting opportunity to explore novel treatment approaches. The term “oligometastasis” refers to an intermediate cancer state between locally confined and widely disseminated disease [2], in which patients develop only a limited number of metastatic lesions (defined as 1–5 lesions in most studies) [3]. For example, multiple studies have shown that, in mPCa, an increasing number of metastatic lesions are associated with poorer outcomes [2], [3], [4], [5]. Within the subgroup of patients exhibiting oligometastatic disease, different oligometastatic entities (summarised in the Supplementary material) have different prognoses, which justifies considering these disease states as separate entities that are likely to require different therapeutic approaches [6]. In addition, some studies have provided more insight into the molecular underpinnings of oligometastatic PCa. Lussier and colleagues [7] studied micro-RNA profiles of primary tumour and metastatic sites in patients with oligometastatic cancer, treated with stereotactic body radiation therapy (SBRT). Patients who failed to develop polymetastases during follow-up were characterised by unique features in the microRNA-200 family. More recently, the same group demonstrated that patients with metastatic colorectal cancer who have metastases exhibiting MSI-independent immune activation, experience the most favourable survival [8].
The main prognostic factor in oligometastatic PCa is the status of the primary lesion; active primary lesions (as in the case of synchronous oligometastases) confer a worse prognosis than controlled primary lesions (as in oligorecurrent PCa) [9]. This is not surprising given the complex patterns of metastatic seeding involving crosstalk between the primary tumour and metastatic sites. Moreover, PCa metastases can be seeded not only from the primary tumour, but also from other metastatic sites [10]. It is therefore reasonable to hypothesise that metastasis-directed therapy (MDT) or treatment of the primary tumour in oligometastatic disease might break the vicious cycle of tumour seeding.
Ablation of limited metastases using surgery or SBRT may slow disease progression, delay or avoid the need for systemic therapy, and improve survival [11]. Although this paradigm shift in treatment is not accepted by all, such MDT could theoretically lead to cure. In addition to MDT, ablation of the primary tumour may have a role in slowing disease progression in patients with synchronous oligometastatic PCa [12].
Despite the emerging data described, there is absence of high-level evidence to direct oligometastatic PCa management. Until robust evidence is available to guide treatment decisions, physicians are challenged with how best to manage patients with PCa oligometastases. The aim of this review was to collate the available evidence on the role of MDT (including salvage lymph node dissection [sLND]) and/or prostate-targeted therapy in the setting of oligometastatic PCa, and to outline ongoing trials in this setting.
Section snippets
Evidence acquisition
We searched PubMed for the combination of “prostate cancer” and “oligometastatic”, “oligometastases”, “oligometastasis”, “solitary metastases”, “stereotactic body radiotherapy”, “SBRT”, “stereotactic ablative radiotherapy”, “SABR”, “salvage lymphadenectomy”, or “metastasectomy” until January 2018. To complete the picture about oligometastatic PCa, we also searched ClinicalTrials.gov for “prostate cancer” and “oligometastatic” for the most relevant ongoing trials.
Evidence analysis
The studies were categorised into synchronous and metachronous according to the timing of metastasis, and into prostate-targeted treatment or MDT (including sLND) according to treatment modality. For MDT of synchronous/metachronous metastases, we included 14 completed studies (Table 1). For sLND for nodal recurrence after primary treatment with curative intent, we included 11 completed studies (Table 2). For MDT of synchronous/metachronous metastases, we included 11 ongoing prospective studies (
Conclusions
In selected patients with oligorecurrent disease, early detection and aggressive treatment of metastatic lesions with surgery or RT appear to be a feasible strategy. However, current evidence supporting a role for MDT in oligometastatic PCa largely derives from retrospective case series [11]. In general, absence of control groups, selection bias, and use of adjuvant ADT at different time periods hinder the ability to draw firm conclusions from these studies [31]. Although many patients achieve
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