Abstract

Simple SummaryAs sarcopenia is recognized as a poor prognostic factor in various type of cancers, we hypothesized that sarcopenia may also have adverse impact in patients with metastatic hormone-sensitive prostate cancer (mHSPC). In this study, we found that sarcopenia is an independent prognostic factor for poor failure-free survival and time to prostate-specific antigen progression in patients with mHSPC who receive early docetaxel or abiraterone acetate treatment. In addition, we performed RNA sequencing of primary tumors to further understand the biological perspective of the presence of sarcopenia in mHSPC. Transcriptomic differences were found between primary tumors with and without sarcopenia, which may have a potential to link between sarcopenia and poor clinical outcomes in these patients.The clinical value of sarcopenia has not been determined yet in metastatic hormone-sensitive prostate cancer (mHSPC). We retrospectively evaluated data of 70 consecutive patients with mHSPC receiving treatment with either early docetaxel (n = 42) or abiraterone acetate (n = 28) between July 2018 and April 2021. Skeletal muscle index was calculated from cross-sectional areas of skeletal muscle on baseline computed tomography (CT), defining sarcopenia as a skeletal muscle index of ≤52.4 cm2/m2. Failure-free survival (FFS), radiographic progression-free survival, and time to prostate-specific antigen (PSA) progression were estimated using the Kaplan–Meier method, and differences in survival probability were compared using the log-rank test. Cox proportional hazards regression analysis was conducted to identify the predictors of clinical outcomes. Patients with sarcopenia (n = 47) had shorter FFS than those without sarcopenia (n = 23) (median, 20.1 months vs. not reached; log-rank p < 0.001). Sarcopenia was independently associated with shorter FFS (hazard ratio (HR), 6.69; 95% confidence interval (CI), 1.57–28.49; p = 0.010) and time to PSA progression (HR, 12.91; 95% CI, 1.08–153.85; p = 0.043). In conclusion, sarcopenia is an independent prognostic factor for poor FFS and time to PSA progression in patients with mHSPC who receive early docetaxel or abiraterone acetate treatment.

Highlights

  • Prostate cancer is the second most common cancer in men and the fifth leading cause of death worldwide [1]

  • Androgen deprivation therapy (ADT) has historically been the mainstay of therapy for metastatic hormone-sensitive prostate cancer showing an initial response, castration-resistant prostate cancer eventually develops within a median of approximately 2–3 years [2]

  • The mechanism underlying the association between sarcopenia and adverse clinical outcomes in cancer patients remains uncertain, given that the majority of studies on sarcopenia had focused on the clinical relevance without exploring its biological perspective [14]

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Summary

Introduction

Prostate cancer is the second most common cancer in men and the fifth leading cause of death worldwide [1]. To provide better treatment strategies in cancer patients, an increased understanding of the underlying mechanism of sarcopenia regarding its impact would be necessary. In this context, recent studies that investigated gene expression status and found its relationship with body composition and clinical outcomes may suggest an interesting way to find a potential link between sarcopenia and its adverse outcomes [15,16]. We conducted this study to explore whether sarcopenia determined by cross-sectional imaging has prognostic value in patients with mHSPC receiving treatment with either early docetaxel (chemohormonal treatment) or abiraterone acetate. We performed RNA sequencing of tumor samples and compared the transcriptomic features of those with and without sarcopenia

Patients
Clinical Data Collection
RNA Sequencing Pre-Process and Gene Set Enrichment Analysis
Endpoints
Statistical Analysis
Results
Radiographic Progression-Free Survival and Time to PSA PPrrooggrreessssiioonn
The Characteristics of Transcript between Samples with and without Sarcopenia
Conclusions
Full Text
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