Impact of body composition on clinical outcomes in patients with metastatic hormone sensitive prostate cancer treated with androgen deprivation therapy plus second-generation antiandrogen.
Impact of body composition on clinical outcomes in patients with metastatic hormone sensitive prostate cancer treated with androgen deprivation therapy plus second-generation antiandrogen.
Francesco Farioli; Giuseppe Agresti; Federica Fiocchi; Stefania Pipitone; Roberto Sabbatini; Guido Ligabue; Pietro Torricelli
The management of metastatic hormone-sensitive prostate cancer (mHSPC) has undergone significant evolution over the years, with androgen deprivation therapy (ADT) serving as the cornerstone of treatment. In recent times, there has been a notable paradigm shift in the therapeutic landscape, with the incorporation of second-generation antiandrogens into the standard ADT regimen. These advances have raised intriguing questions about their potential impact not only on disease progression but also on various aspects of patients' overall health. This comprehensive research endeavor seeks to delve deeply into the role played by the combined therapy of ADT and either abiraterone (ABI) or apalutamide (APA) in the context of modifying body composition parameters (BCPs) in individuals who have received a new diagnosis of mHSPC. The choice of ABI and APA as specific agents of interest is particularly noteworthy, given their distinct mechanisms of action and their demonstrated efficacy in clinical trials. To unravel the multifaceted implications of this treatment approach, our investigation will encompass a meticulous assessment of alterations in key body composition parameters, including but not limited to body fat mass, lean muscle mass, and the distribution of body fat. This research investigates the holistic effects of novel treatment approaches in mHSPC, with insights that may guide clinical decision-making and enhance patient-centered care. Our analysis aspires to contribute to the growing body of knowledge surrounding the intricacies of managing this complex disease, ultimately striving for improved therapeutic outcomes and an enhanced quality of life for individuals facing mHSPC.
The present study constitutes an observational retrospective data collection effort, focusing on patients who received a new diagnosis of metastatic hormone-sensitive prostate cancer (mHSPC) and were treated at the Modena Cancer Center within the timeframe spanning from January 2007 to April 2022. This retrospective investigation was initiated following a formal request submitted to the Nucleo Operativo Provinciale (NOP) of Emilia Romagna, Italy, in adherence to stringent ethical and data protection protocols. The primary objective of this meticulously crafted research endeavor was to comprehensively assess and analyze the dynamic changes in a spectrum of body composition parameters (BCPs) over the course of mHSPC treatment, with particular attention to their modification from the time of initial diagnosis to the period characterized by prostate-specific antigen (PSA) nadir. These selected BCPs encompassed a range of metrics, including the total fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA), skeletal muscle area (SMA), and skeletal muscle index (SMI). The choice of these specific parameters was guided by their acknowledged relevance in the context of cancer-related cachexia, treatment response, and overall patient prognosis. To ensure precision and consistency in our measurements, all BCP assessments were conducted at the level of the third lumbar vertebra (L3) utilizing advanced imaging techniques, specifically Computed Tomography (CT). This anatomical landmark was selected due to its well-established utility as a reliable reference point for the assessment of body composition, allowing for accurate and reproducible measurements across the patient cohort.
Semi-automatic Fat Analysis of a patient of the cohort made with Synapse 3D (Fujifilm).
Semi-automatic Muscle Analysis of a patient of the cohort made with Advantage Workstation for Diagnostic Imaging (GE).
Baseline clinical Characteristics of patients
This study encompassed a meticulously selected cohort of 20 Caucasian men who were diagnosed with metastatic hormone-sensitive prostate cancer (mHSPC). The patients were divided into two distinct groups, with ten individuals receiving androgen deprivation therapy (ADT) in combination with abiraterone (ABI), and the remaining ten patients undergoing ADT in conjunction with apalutamide (APA). This deliberate division allowed for a comparative analysis of the effects of these two second-generation antiandrogen treatments on both clinical and body composition outcomes. One of the primary outcomes under scrutiny was the Body Mass Index (BMI) of these patients during the course of treatment, particularly at the time of prostate-specific antigen (PSA) nadir. While the overall analysis revealed no statistically significant modification in BMI across the patient cohort, it is noteworthy that four patients exhibited a substantial reduction in BMI, exceeding the clinically relevant threshold of 10%. These findings prompt further investigation into the potential underlying mechanisms and clinical implications of such changes in body composition. Another pivotal aspect of our study pertained to the clinical progression of the disease, with six patients (30%) experiencing progression during the course of treatment. Importantly, this progression was evenly distributed between the two treatment groups, with three patients from each group (ABI and APA) manifesting progression. Intriguingly, our data unveiled divergent trends in BCPs among patients who experienced disease progression during their treatment journey. Notably, those receiving APA and encountering progression disease exhibited reductions in both total fat area (TFA) and visceral fat area (VFA). In contrast, patients undergoing ABI treatment and experiencing progression disease demonstrated an increase in both TFA and VFA. These contrasting trends underscore the complexity of body composition dynamics and their potential association with treatment response in mHSPC. Furthermore, our investigation revealed notable alterations in skeletal muscle area (SMA) and skeletal muscle index (SMI) among patients who experienced disease progression. Five patients, irrespective of the specific second-generation antiandrogen treatment they received, displayed reductions in SMA and SMI. However, one patient who received ABI treatment and exhibited disease progression demonstrated a unique increase in both SMA and SMI, concurrent with a substantial increase in BMI. All patients treated with APA displayed a remarkable and clinically significant ≥50% decline in PSA levels within a mere four weeks of initiating treatment, underscoring the rapid and potent antiandrogen effects of this therapeutic agent.
Body compositions parameters of the cohort at baseline and at PSA nadir.
The outcomes of our comprehensive analysis have unveiled a thought-provoking and potentially clinically relevant association, indicating that a reduction in skeletal muscle area (SMA) and skeletal muscle index (SMI) could potentially be linked to a more favorable therapeutic response when androgen deprivation therapy (ADT) is combined with either abiraterone (ABI) or apalutamide (APA) in the management of metastatic hormone-sensitive prostate cancer (mHSPC). This novel finding suggests that the modulation of skeletal muscle composition may indeed play an integral role in influencing treatment outcomes and patient prognosis in the context of mHSPC. The implications of this observation extend into several intriguing avenues of investigation. First and foremost, elucidating the underlying mechanisms driving the observed relationship between SMA/SMI reduction and improved therapeutic response is of paramount importance. Further research into the biological, hormonal, and molecular pathways that connect skeletal muscle alterations with the efficacy of ADT plus ABI or APA is warranted. Such insights could potentially inform the development of targeted therapeutic interventions aimed at optimizing this response and enhancing patient outcomes. Moreover, this finding raises the compelling prospect of utilizing changes in skeletal muscle composition as a predictive or prognostic biomarker in the clinical management of mHSPC. If confirmed through further research and validation studies, monitoring SMA and SMI alterations during the course of treatment could offer valuable clinical insights. Clinicians may be able to identify patients who are more likely to benefit from ADT plus ABI or APA, potentially enabling more precise treatment decision-making and individualized therapeutic approaches. The clinical implications of our findings also extend to the broader domain of supportive care in mHSPC. Given the recognized impact of skeletal muscle composition on overall functional status and quality of life, strategies for preserving or enhancing muscle mass during treatment may warrant exploration. In conclusion, our study contributes valuable insights into the complex interplay between skeletal muscle composition and the therapeutic response in mHSPC, underscoring the need for further investigation into the underlying mechanisms and clinical implications of these findings. The potential utility of SMA and SMI as biomarkers and the prospect of personalized treatment strategies offer promising avenues for improving the management and outcomes of patients facing this challenging disease. Additional research endeavors and prospective studies are essential to validate and build upon these initial observations, ultimately advancing the field of mHSPC management and enhancing the well-being of affected individuals.
