Skeletal Metastasis of Unknown Primary Origin at the Initial Visit: A Retrospective Analysis of 286 Cases

Abstract

Background: Skeletal metastasis is a common metastatic event for several carcinomas, and the treatment for skeletal metastasis of unknown primary (SMUP) are a critical issue in cancer therapy. Making a diagnosis of the primary site is the most crucial step in the treatment of SMUP; however, the procedures are sometimes difficult and time-consuming, and the primary site often remains unknown. Therefore, to establish optimal diagnostic strategies and elucidate the overall survival rates of SMUP, we conducted this retrospective study.

Methods: We retrospectively analyzed the clinical data for 286 SMUP cases from a total of 2,641 patients with skeletal metastases who were treated between 2002 and 2014 at our initiations.

Results: The primary sites were identified in 254/286 patients (88.8%), while 32 (11.2%) primary sites were not detected by our diagnostic strategies. Lung cancer was identified in 72 (25.2%) cases, and was the most frequently observed primary lesion. The median survival time of the SMUP patients was 20.0 months, while the median survival times of solitary bone metastasis cases and multi-bone metastasis cases were 39.0 months and 16.0 months, respectively. The median survival times of prostate cancer cases was over 120 months, that of patients with primary lung cancers was 9.0 months and the median survival time of cases who were finally diagnosed with an unknown primary was 11.0 months.

Conclusions: We believe that our study would contribute to establishing an optimal strategy for diagnosing the primary site in SMUP patients, and our data provide definite indications for the survival times for different SMUP situations.

Fig 1. The Kaplan-Meier survival curves show the overall survival rates for each primary site of the SMUP cohort.

A: lung cancers, B: blood cell tumors (including multiple myelomas and malignant lymphomas), C: Unknown (still unknown origin after the nine steps) and D: prostate cancers.

Fig 2. The Kaplan-Meier survival curves show the survival rates regarding skeletal metastases and the performance status (PS) at the first visit in the SMUP cohort.

A: The different skeletal metastasis situations (solitary metastases vs. multiple metastases), B: PS (good PS of 0–2 vs. poor PS of 3–4). A, The Kaplan-Meier curve of the overall survival demonstrated that patients with solitary metastases (MST: 16.0 months) had a longer survival than those with multiple metastases (MST: 39.0 months) (p<0.01). B. To elucidate the early survival rates based on the PS, we employed the limited survival data within five years of follow-up in all 286 SMUP cases, and the data were analyzed using the Kaplan-Meier method. The limited data showed that the good PS group had a better prognosis compared to the poor PS group, and there was a significant difference in the survival of the good and poor PS groups (p<0.01). The non-limited survival data with regard to the PS are shown in S2 Fig

Fig 3. The diagnostic abilities of each step for identifying the primary tumors in 286 SMUP cases: The graph shows the diagnostic abilities of each examination step.

We divided the steps into two categories: steps 1~5 as “common examinations”, and steps 6~9 as “advanced examinations”. Almost half of the SMUP cases (53.3%) were diagnosed by “common examinations”. Additionally, Step 9 (PET scan) was not efficient for identifying the primary site in our cohort. The details of these findings are shown in S2 Fig and Supplemental Table A in S1 File.