Developments in oligometastatic hormone-sensitive prostate cancer

Abstract

“Suddenly a solitary horseman appeared on the horizon, then another, and another, and then six. In a few moments a whole crowd of solitary horsemen swooped down upon him.” This quote by Stephen Leacock was in included in the Introduction for the first definitive work on low-volume metastatic cancer by Philip Rubin and Jerold Green, entitled Solitary Metastases, and encompasses the fears of all those who endeavor to understand and treat patients with what is now termed oligometastatic disease [1]. Formally hypothesized by Hellman and Weichselbaum, the oligometastatic state is an intermediate state along a spectrum of cancer metastasis whereby local therapies may alter the natural history of patients with metastatic disease [2]. With the recent coalescence of developments in biology, imaging and metastasis-directed therapies (MDT) such as stereotactic ablative radiotherapy (SABR), this state has become an area of growing biologic and clinical interest [3, 4]. It is in this context we are pleased to present a special issue in the Journal on Developments in oligometastatic hormone-sensitive prostate cancer. Briefly, we preview and highlight the work covered in this issue and place them in a cohesive picture of we believe are key future big picture outstanding biological and clinical questions that will be important in the field of primarily hormone-sensitive oligometastatic prostate cancer. First, what is oligometastatic prostate cancer? Then, how do we best treat this condition? Taking the lead is Christopher Hovens and his group who produce a cogent review of the multiple molecular and clinical studies in support of this meta-stable metastatic state [5]. They argue as we develop greater understanding of oligometastases in prostate cancer we will be able to molecularly define the oligometastatic state and depart from our current simple clinical numerical definition with hopefully significant clinical benefits [6]. We do include an original investigative report by Dhondt et al. who chronicle the failed validation of a miRNA serum signature as a biomarker for oligometastatic prostate cancer [7]. Preliminary data suggest that tissue microRNAs (miRNAs), small 18–24 nucleotide RNAs that regulate gene expression, may drive metastatic competency by adaptive communication between cancer cells and their local and distant environment [8, 9], but unfortunately this did not hold true in this case for the serum miRNAs profiled in prostate cancer. Consequently, until we have such a molecular definition, work that includes clinical models will be needed. Along this vein, Buelens et al. then describe their development of a pragmatic and prognostic clinical model comprised of tumor burden using the CHAARTED metastatic volume definition (high-volume = visceral metastasis or ≥ 4 bone metastases with ≥ 1 appendicular lesion) and alkaline phosphatase to stratify metastatic hormone-naive prostate cancer (mHNPC) [10]. These data support the prognostic significance of the lowvolume or oligometastatic state in prostate cancer. Newer and highly sensitive imaging modalities for prostate cancer cannot be ignored and will be a critical bridge towards a molecular definition of oligometastatic prostate cancer [11]. We have two specific contributions to this imaging work in this special issue, the first by Jurgen J. Futterer and company describe a level setting review of imaging modalities that sheds light on the role of conventional and functional imaging in the setting of synchronous oligometastatic prostate cancer [12]. Pasoglou et al. then present some original work using whole-body magnetic resonance imaging (WB-MRI) to assess the anatomical distribution of oligometastatic and polymetastatic prostate cancer and the impact of the initial treatment on metastatic distribution [13]. They found that oligometastatic men showed different distribution of bone metastases * Piet Ost [email protected]