The relationship between body fat distribution and survival remains unclear in patients with castration resistant prostate cancer treated with docetaxel and androgen receptor axis targeted agents. We investigated whether body composition parameters could predict radiographic progression-free and cancer specific survival in patients with castration resistant prostate cancer. In this multicenter retrospective study we evaluated data on 282 consecutive patients diagnosed with castration resistant prostate cancer between September 2009 and March 2017. The subcutaneous fat index, the visceral fat index and the skeletal muscle index at the diagnosis of castration resistant prostate cancer were determined by computerized tomography data. Survival analyses were performed using the subcutaneous fat, visceral fat and skeletal muscle indexes dichotomized at 39.9, 58 and 52.4 cm2/m2, respectively. At the diagnosis of castration resistant prostate cancer, cancer specific survival was independently predicted using prostate specific antigen levels, Gleason score 8 or greater, performance status, a shorter interval from androgen deprivation therapy to castration resistant prostate cancer and a subcutaneous fat index of less than 39.9 cm2/m2. During the median followup of 16.0 months patients with a subcutaneous fat index of 39.9 cm2/m2 or greater received more docetaxel cycles than patients with a subcutaneous fat index of less than 39.9 cm2/m2. Compared to patients with a subcutaneous fat index of less than 39.9 cm2/m2 those with an index of 39.9 cm2/m2 or greater had better 1-year progression-free and 2-year cancer specific survival (p = 0.009 and 0.021, respectively). Patients with a subcutaneous fat index of 39.9 cm2/m2 or greater at the diagnosis of castration resistant prostate cancer showed higher progression-free and cancer specific survival rates than those with a subcutaneous fat index of less 39.9 cm2/m2 at diagnosis. The subcutaneous fat index determined by computerized tomography data could serve as a useful objective prognostic factor to discuss patient therapeutic options. Further studies are needed to define the roles of each body composition parameter in relation to pharmacokinetics and oncologic outcome.
Platinum-based neoadjuvant chemotherapy (NAC) is widely used for treating muscle-invasive bladder cancer (MIBC). A systematic review was performed following PRISMA guidelines. PubMed, Embase, and the Cochrane Library were searched up to December 2020. We conducted a meta-analysis to compare the oncologic outcomes of ddMVAC (dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin) and GC (gemcitabine and cisplatin), which are the most widely used NAC regimens. Endpoints included pathologic complete response (pCR), pathologic downstaging (pDS), overall survival (OS), and cancer-specific survival (CSS). Five studies, with a total of 1206 patients, were included for meta-analysis. pCR was observed in 35.2% of the ddMVAC arm and in 25.1% of the GC arm, and pCR was significantly higher in ddMVAC than in GC (odds ratio (OR), 1.45; 95% confidence interval (CI), 1.11–1.89; p = 0.006). There was no significant difference in pDS (OR, 1.37; CI, 0.84–2.21; p = 0.20). OS was significantly higher in ddMVAC than in GC (hazard ratio, 2.16; CI, 1.42–3.29; p = 0.0004). Only one study reported CSS outcomes. The results of this analysis indicate that ddMVAC is superior to GC in terms of pCR and OS, suggesting that ddMVAC is more effective than GC in NAC for MIBC. However, this should be interpreted with caution because of the inherent limitations of retrospective studies.
1 January 2023 in Investigative and Clinical Urology
We evaluated the risk of osteoporosis and fractures associated with androgen deprivation therapy (ADT) use and duration in men with prostate cancer. From the nationwide claims database in South Korea, a total of 218,203 men with prostate cancer were identified between 2008 and 2017. After applying the inclusion and exclusion criteria, a total of 144,670 patients were included in the analysis. To adjust for comorbidities between cohorts, 1:1 propensity score matching was used. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of events associated with ADT, after controlling for potential confounding factors. In the matched cohort, there were differences in the incidence of newly developed osteoporosis (8.79% in the ADT group vs. 7.08% in the non-ADT group, p < 0.0001) and fractures (8.12% in the ADT group vs. 5.04% in the non-ADT group, p < 0.0001). Age-adjusted Cox regression analysis revealed that the ADT group had a significantly higher risk of osteoporosis (HR, 1.381; 95% CI, 1.305–1.461; p < 0.0001) and fractures (HR, 1.815; 95% CI, 1.703–1.935; p < 0.0001) compared to the non-ADT group. Furthermore, the risk of osteoporosis and fractures increased as the duration of ADT increased. The ADT was associated with an increased risk of osteoporosis and fractures in prostate cancer patients. Clinicians who administer ADT for patients with prostate cancer should always be mindful of the risk of osteoporosis and fracture, avoid unnecessary ADT, and perform regular bone health check-ups.
Non-metastatic castration-resistant prostate cancer (nmCRPC) is defined by a progressively rising prostate-specific antigen level, despite a castrate level of testosterone, in the absence of obvious radiologic evidence of metastatic disease on conventional imaging modalities. As a significant proportion of patients with nmCRPC develop metastatic diseases, the therapeutic goals of physicians for these patients are to delay metastasis development, preserve quality of life, and increase overall survival (OS). Since 2018, the treatment of nmCRPC has changed dramatically with the introduction of second-generation androgen receptor inhibitors, such as enzalutamide (ENZA), apalutamide (APA), and darolutamide (DARO). These drugs demonstrated substantial improvements in metastasis-free survival (MFS) and OS in phase III randomized clinical trials. In addition, these drugs have an excellent safety profile, preserve quality of life, and can delay disease-related symptoms. A recently published indirect meta-analysis reported that APA and ENZA showed better findings in MFS and that DARO had relatively fewer adverse effects. However, in the absence of a direct comparison, careful interpretation is required. Thus, APA, ENZA, and DARO should be considered the new standard drugs for treating nmCRPC.