Docetaxel-based chemotherapy is one of the standard first-line agents used to treat CRPC patients, specifically in those with increasing symptoms, such as bone pain and general fatigue, due to disease progression. However, there are concerns regarding its toxicity, particularly in men with age- and ADT-related low skeletal muscle mass or sarcopenia. In addition to being linked to chemotherapy toxicity, body composition parameters (BCP) have been shown to be prognostic among CRPC patients.
Studies have reported that obesity is prognostically favorable when resistance to castration arises. Patients with a high SAT volume have longer overall survival (OS) than those with a low SAT volume, while sarcopenia has been shown to independently predict worse survival in PC patients. Despite these studies, the effect of BCP on survival outcomes of CRPC patients remains unclear.
The present study assessed the prevalence of sarcopenia in CRPC patients and evaluated whether muscle, visceral and SAT are correlated with tumor progression and/or OS in CRPC patients treated with docetaxel. Furthermore, we studied the value of BCP as prognostic factors for OS after docetaxel chemotherapy in CRPC patients.
Consequently, we analyzed data from 186 consecutive patients who received chemo-hormonal treatment between 2005 and 2016 for CRPC at our institution. Specific Hounsfield units were measured from cross-sectional areas of subcutaneous fat, visceral fat, and skeletal muscle from CT scans before initiation of chemotherapy at the level of the 3rd lumbar vertebra.
Overall, 154 (82.8%) patients met the criteria for sarcopenia and 118 (63.4%) for sarcopenic obesity. Sarcopenic patients were significantly older and had a lower body mass index (BMI) at chemotherapy initiation. A total of 139 (74.7%) out of 186 patients completed at least six cycles of docetaxel, while the remaining discontinued chemotherapy due to adverse events. Within a median follow-up of 24.1 months, 156 (83.9%) patients experienced disease progression.
Multiple parameters such as ECOG performance status, age, high PSA, low SMV, and the presence of liver metastasis were associated with disease progression. A total of 93 (50%) patients died during follow-up whereby the median OS was 26.2 months. Visceral to subcutaneous fat area ratio (VSR), LDH, BMI, and presence of liver metastases were associated with a shorter OS. Median SMV did not differentiate the docetaxel treated CRPC patients regarding OS.
We found that low SMV is an independent factor associated with tumor progression and the presence of liver metastases an adverse prognosticator for OS. A high volume of visceral fat was also independently associated with reduced OS. Despite the absence of sarcopenia, a high VSR tends to be a predictor of shorter survival in CRPC patients treated with chemo-hormonal therapy.
In conclusion, BMI is an inaccurate measure of sarcopenia and obesity based on its inability to distinguish between lean muscle mass, subcutaneous fat, and visceral fat. Assessing individual patients' BCP can provide custom-made strategies so that systemic therapy can be tailored for unfit patents and allow for improved patient stratification in future clinical trials to facilitate risk-stratified treatment selection and dosage.
Written by: Rodrigo Suarez-Ibarrola, BSc, MD, Department of Urology,
University of Freiburg;
Judith Stangl-Kremser, MD, Department of Urology,
Medical University of Vienna;
and Shahrokh F. Shariat, MD, PhD, Professor of Urology, Weill Cornell Medicine.Read the Abstract