Skeletal Metastases of Unknown Primary: Biological Landscape and Clinical Overview

Abstract

Skeletal metastases of unknown primary (SMUP) represent a clinical challenge dealing with patients diagnosed with bone metastases. The management have improved significantly in the past years, however fraught with lack of evidences, approach to these patients held out hope for more systematic and tailored treatment—and some patients can achieve impressive gains. Nevertheless, in real-life practice the outlook at the beginning of the take in charge of SMUP is decidedly more somber. An incomplete translational relevance of pathological and clinical data on the mortality and morbidity rate has had unsatisfactory consequences for SMUP patients and their physicians. We examined several approaches to confront the available evidences and highlighted three key points that emerge. The characterization of the SMUP biologic profile is essential to drive clinical decisions, integrating genetic and molecular profile into a multi-step diagnostic work-up. Nonetheless, pragmatic investigation plan and therapy of SMUP cannot follow a single template; it must be adapted to different pathophysiological dynamics and coordinated with efforts of a systematic algorithm and high-quality data derived from statistically powered clinical trials within. This review argues that greater efforts are required to face the unmet need dealing with SMUP patients in oncology. Finally, we provide an original functional network analysis, identifying novel therapeutic targets.

Clinical characteristics and surgical treatment of spinal metastases from pancreatic cancer: a single-center retrospective study

“…Spinal metastases of unknown primary (SMUP) are challenging in the treatment of patients with malignant spinal metastases, and the concepts of systematics and translational medicine are crucial in clinical and scientific research practices (31). Over the past few years, managing these patients has partially become easier due to a better understanding of the biological characteristics of SMUP (31). The improvements in knowledge facilitated clinical decision-making by integrating genetic and molecular characteristics of SMUP into a multi-step diagnostic process.…”

“…The improvements in knowledge facilitated clinical decision-making by integrating genetic and molecular characteristics of SMUP into a multi-step diagnostic process. In this regard, Argentiero and coworkers postulated that a pragmatic investigation plan and therapy for SMUP could not follow a single template (31). The treatment must reflect different pathophysiological dynamics and should be based on systematic methodology and high-quality data derived from clinical trials (31).…”

Perioperative mortality of metastatic spinal disease with unknown primary: A case report and review of literature

“…Metastatic tumors from unknown sources are likely to retain the characteristics of their putative primary origins, therefore large differences in clinical manifestations are usually observed among patients with spinal metastases from UPT[ 24 ]. Nonetheless, several common signatures can be retrieved from the reported literature to depict this peculiar group of diseases: (1) Rapid progression and early dissemination, which contribute to the unidentified origin and aggressive presentation[ 24 ]; (2) Diversity of clinical and biological profiles due to the difference in origin[ 25 ]; (3) Relatively poor prognosis as non-selective empirical therapy rather than targeted management is conducted[ 26 ]; and (4) Traditional diagnostic indicators including tumor markers and immunohistochemical activity may be raised without any diagnostic or predictive value, and new methods such as NGS (next generation sequencing) may be suggested to improve diagnosis and prognosis[ 27 ].…”

State-of-the-art imaging for diagnosis of metastatic bone disease

“…Bone metastases occur in 50% of patients with cancer, and among these, 40–70% are vertebral lesions [ 23 ], with unknown primary in 10% of patients [ 24 ]. In adults the primary tumors causing vertebral involvement are in the breast (22%), lung (15%), prostate (10%), lymphatic system (10%), connective tissue (9%), kidney (7%), and gastrointestinal tract (5%).…”

“…Most often, CT is performed as part of the routine staging protocol during the initial work-up of any cancer diagnosis, and thus it is commonly the first imaging modality to detect the bone lesion suspected of representing MBD. Staging imaging examinations in the case of malignant bone tumors are usually performed after obtaining a histological diagnosis or when investigating malignancy of unknown origin [ 24 ]. Magnetic resonance imaging has superior sensitivity and specificity for tissue characterization; however, when MRI is not available or contraindicated, CT can provide similar information about the extent of the tumor.…”