Among its extragonadal effects, follicle-stimulating hormone (FSH) has an impact on body composition and bone metabolism. Since androgen deprivation therapy (ADT) has a profound impact on circulating ...FSH concentrations, this hormone could potentially be implicated in the changes of fat body mass (FBM), lean body mass (LBM), and bone fragility induced by ADT. The objective of this study is to correlate FSH serum levels with body composition parameters, bone mineral density (BMD), and bone turnover markers at baseline conditions and after 12 months of ADT.
Twenty-nine consecutive non-metastatic prostate cancer (PC) patients were enrolled from 2017 to 2019 in a phase IV study. All patients underwent administration of the luteinizing hormone-releasing hormone antagonist degarelix. FBM, LBM, and BMD were evaluated by dual-energy x-ray absorptiometry at baseline and after 12 months of ADT. FSH, alkaline phosphatase, and C-terminal telopeptide of type I collagen were assessed at baseline and after 6 and 12 months. For outcome measurements and statistical analysis,
-test or sign test and Pearson or Spearman tests for continuous variables were used when indicated.
At baseline conditions, a weak, non-significant, direct relationship was found between FSH serum levels and FBM at arms (
= 0.36) and legs (
= 0.33). Conversely, a stronger correlation was observed between FSH and total FBM (
= 0.52, p = 0.006), fat mass at arms (
= 0.54, p = 0.004), and fat mass at trunk (
= 0.45, p = 0.018) assessed after 12 months. On the other hand, an inverse relationship between serum FSH and appendicular lean mass index/FBM ratio was observed (
= -0.64, p = 0.001). This is an ancillary study of a prospective trial and this is the main limitation.
FSH serum levels after ADT could have an impact on body composition, in particular on FBM. Therefore, FSH could be a promising marker to monitor the risk of sarcopenic obesity and to guide the clinicians in the tailored evaluation of body composition in PC patients undergoing ADT.
This research was partially funded by Ferring Pharmaceuticals. The funder had no role in design and conduct of the study, collection, management, analysis, and interpretation of the data and in preparation, review, or approval of the manuscript.
clinicalTrials.gov NCT03202381, EudraCT Number 2016-004210-10.
Background: Relatively few studies investigated the importance of frailty in radical cystectomy (RC) patients. We tested the ability of frailty, using the Johns Hopkins Adjusted Clinical Groups ...indicator, to predict early perioperative outcomes after RC.
Methods: RC patients were identified within the National Inpatient Sample database (2000–2015). The effect of frailty, age and Charlson Comorbidity Index were tested in five separate multivariable models predicting: (1) complications, (2) failure to rescue (FTR), (3) in-hospital mortality, (4) length of stay (LOS) and (5) total hospital charges (THCs). All models were weighted and adjusted for clustering, as well as all available patient and hospital characteristics.
Results: Of 23,967 RC patients, 5833 (24.3%) were frail, 7721 (32.2%) were aged ≥75 years and 2832 (11.8%) had CCI ≥2. Frailty, age ≥75 years and CCI ≥2 were non-overlapping in 86.3% of the cohort. Any two or three of these features were recorded in 12.4 and 1.3%, respectively. Frailty was an independent predictor of all five examined endpoints and the magnitude of its association was stronger or at least equal than that of age ≥75 years and CCI ≥2.
Conclusion: Frailty, advanced age and comorbidities represent non-overlapping patients’ characteristics. Of those, frailty represents the most consistent and strongest predictor of early adverse outcomes after RC. Ideally, all three indicators should be considered in retrospective, as well as prospective analyses. Pre-surgical recognition of frail patients should be ideally incorporate in clinical practice in order to address these patients to multimodal pre-habilitation programs that may potentially improve the perioperative prognosis.
•Age, comorbidities and frailty may worsen perioperative outcomes after radical cystectomy.•However, these three features often represent non-overlapping patients' characteristics.•Frailty represents the strongest predictor of early adverse outcomes after radical cystectomy.•Pre-surgical recognition of frail patients should be ideally incorporate in clinical practice.•Frail patients should be addressed to multimodal pre-habilitation programs.
Purpose
To investigate the prognostic role of the preoperative systemic immune–inflammation index (SII) in patients with upper tract urothelial carcinoma (UTUC) treated with radical ...nephroureterectomy (RNU).
Materials and methods
We retrospectively analyzed our multi-institutional database to identify 2492 patients. SII was calculated as platelet count × neutrophil/lymphocyte count and evaluated at a cutoff of 485. Logistic regression analyses were performed to investigate the association of SII with muscle-invasive and non-organ-confined (NOC) disease. Cox regression analyses were performed to investigate the association of SII with recurrence-free, cancer-specific, and overall survival (RFS/CSS/OS).
Results
Overall, 986 (41.6%) patients had an SII > 485. On univariable logistic regression analyses, SII > 485 was associated with a higher risk of muscle-invasive (
P
= 0.004) and NOC (
P
= 0.03) disease at RNU. On multivariable logistic regression, SII remained independently associated with muscle-invasive disease (
P
= 0.01). On univariable Cox regression analyses, SII > 485 was associated with shorter RFS (
P
= 0.002), CSS (
P
= 0.002) and OS (
P
= 0.004). On multivariable Cox regression analyses SII remained independently associated with survival outcomes (all
P
< 0.05). Addition of SII to the multivariable models improved their discrimination of the models for predicting muscle-invasive disease (
P
= 0.02). However, all area under the curve and C-indexes increased by < 0.02 and it did not improve net benefit on decision curve analysis.
Conclusions
Preoperative altered SII is significantly associated with higher pathologic stages and worse survival outcomes in patients treated with RNU for UTUC. However, the SII appears to have relatively limited incremental additive value in clinical use. Further study of SII in prognosticating UTUC is warranted before routine use in clinical algorithms.
Background
To compare survival outcomes of metastatic patients harbouring either papillary (pRCC) or clear-cell (ccRCC) renal cell carcinoma in overall population and according to treatment modality.
...Methods
Within the Surveillance, Epidemiology and End Results database (2006–2015), we identified 6800 patients (585 papillary and 6215 clear-cell) with metastatic RCC. Propensity-score (PS) matching, Kaplan–Meier plots and multivariable Cox-regression models (CRMs) were used.
Results
Overall, 585 (8.6%) patients harboured pRCC. Rates of nodal metastases were higher in patients with pRCC (49.7 vs. 23.3%;
p
< 0.001). Median overall survival (OS) was 13 vs. 18 months for pRCC vs. ccRCC patients. After multivariable adjustments, no difference in OS was recorded. Furthermore, after propensity-score matching, virtually the same results were recorded. Median OS of pRCC vs. ccRCC was 8 vs. 4 months for no treatment (NT), 11 vs. 12 months for targeted therapy alone (TT), 17 vs. 35 months for cytoreductive nephrectomy alone (CN) and 18 vs. 25 months for combination of CN with TT.
Conclusions
Metastatic pRCC patients exhibit poor survival, regardless of treatment received. Moreover, pRCC patients are more likely to present nodal metastases, compared to ccRCC patients, as demonstrated by twofold higher rates of lymph node invasion at diagnosis. These observations indicate that papillary variant represents more prognostically unfavorable tumor histology, in the context of metastatic RCC.
Luteinizing hormone-releasing hormone (LHRH)-agonists in prostate cancer (PCa) patients induce sarcopenic obesity. The effect of LHRH-antagonist on body composition has never been explored. We ...evaluated changes in fat (FBM) and lean body mass (LBM) in PCa patients undergoing Degarelix.
This is a single-center prospective study, enrolling 29 non-metastatic PCa patients eligible to LHRH-antagonist from 2017 to 2019. All patients received monthly subcutaneous injection of Degarelix for 12 months. Changes in FBM and LBM between baseline and 12-month Degarelix, as measured by dual-energy x-ray absorptiometry, were the co-primary endpoints. Secondary endpoints were changes in serum lipids, glucose profile and follicle-stimulating hormone (FSH). Appendicular lean mass index (ALMI) and ALMI/FBM ratio were assessed as post-hoc analyses. Linear mixed models with random intercept tested for estimated least squared means differences (EMD).
FBM significantly increased after 12 months (EMD +2920.7, +13.8%, p < 0.001), whereas LBM remained stable (EMD -187.1, -0.3%, p = 0.8). No differences occurred in lipid profile. Glycated hemoglobin significantly increased and serum FSH significantly decreased. A significant inverse relationship was found between serum FSH and ALMI/FBM ratio after 12 month (r = -0.44, p = 0.02).
The BLADE study prospectively evaluated changes in body composition after LHRH-antagonist. LHRH-antagonist therapy is associated to an increased risk of obesity and diabetes, but lean body mass and serum lipids are not affected. This may represent an additional evidence supporting the reduced cardiovascular risk associated with LHRH-antagonist. The role of FSH in influencing sarcopenic obesity in PCa after androgen deprivation deserves to be further explored.
Purpose
To test the association between African-American race and overall mortality (OM) rates in patients with metastatic renal cell carcinoma (mRCC).
Methods
Within the Surveillance, Epidemiology, ...and End Results registry (2006–2015), we identified patients with clear cell (ccmRCC) and non-clear cell mRCC (non-ccmRCC). African-Americans, Caucasians, and Hispanics were identified. Stratification was made according to histology and treatments: (1) no treatment, (2) systemic therapy (ST), (3) cytoreductive nephrectomy (CNT), (4) CNT + ST. Kaplan–Meier plots and multivariable Cox regression analyses were used.
Results
Of ccmRCC patients, 410 (7%), 4353 (75%), and 1005 (17%) were African-American, Caucasian, and Hispanic, respectively. Of non-ccmRCC patients, 183 (25%), 479 (65%), and 77 (10%) were African-American, Caucasian, and Hispanic, respectively. In ccmRCC, African-Americans were associated with higher OM rates (HR 1.20; 95% CI 1.05–1.37). Conversely, in non-ccmRCC, African-Americans were associated with lower OM rates (HR 0.75; 95% CI 0.59–0.97).
Conclusion
African-American race is associated with prolonged survival in non-ccmRCC, but it is also associated with lower survival rates in ccmRCC. The exception to these observations consisted of patients treated with combination of CNT + ST for either ccmRCC or non-ccmRCC.
Our objective was to investigate age- and sex-related differences in the distribution of metastases in patients with metastatic bladder cancer.
Within the National Inpatient Sample database ...(2008-2015), we identified 7040 patients with metastatic bladder cancer. Trend test and Chi-square test analyses were used to evaluate the relationship between age and site of metastases, according to sex.
Of 7040 patients with metastatic bladder cancer, 5226 (74.2%) were men and 1814 (25.8%) were women. Thoracic, abdominal, bone and brain metastases were present in 19.5 vs. 23.0%, 43.6 vs. 46.9%, 23.9 vs. 18.7% and 2.4 vs. 2.9% of men vs. women, respectively. Bone was the most common metastatic site in men (23.9%) vs. lung in women (22.4%). Increasing age was associated with decreasing rates of abdominal (from 44.9 to 40.2%) and brain (from 3.2 to 1.4%) metastases in men vs. decreasing rates of bone (from 21.0 to 13.3%) and brain (from 5.1 to 2.0%) metastases in women (all P < 0.05). Finally, rates of metastases in multiple organs also decreased with age, in both men and women.
The distribution of metastases in bladder cancer varies according to sex. Moreover, differences exist according to patient age and these differences are also sex-specific. In consequence, patient age and sex should be considered in the interpretation of imaging, especially when findings are indeterminate.
Purpose
To test the effect of tumor location (urachal vs. non-urachal) on cancer-specific mortality (CSM) in patients with adenocarcinoma of the urinary bladder (ADKUB).
Materials and methods
Within ...the Surveillance, Epidemiology, and End Results registry (2004–2016), we identified patients with non-metastatic (≤ T4N0M0) ADKUB. Stratification was made according to tumor location: urachal vs. non-urachal ADKUB. Kaplan–Meier plots and multivariable Cox regression models were fitted before and after 1:3 propensity score (PS) matching and separate Cox regression models were refitted before and after inverse probability of treatment weighting (IPTW).
Results
Of 1681 patients, 226 (13.5%) vs. 1455 (86.5%) harboured urachal vs. non-urachal ADKUB, respectively. Five-year cancer-specific survival (CSS) rates were, respectively, 75 vs. 67% for urachal vs. non-urachal ADKUB (
p
= 0.001). In subgroup analyses of ≤ T2N0M0 patients, 5-year CSS rates were, respectively, 84 vs. 73% for urachal vs. non-urachal ADKUB (
p
= 0.006). In subgroup analyses of T3-4N0M0 patients, 5-year CSS rates were, respectively, 68 vs. 49% for urachal vs. non-urachal ADKUB (
p
< 0.001). In multivariable Cox regression models, urachal ADKUB was associated with lower CSM rates (HR 0.6;
p
= 0.01). Virtually, the same findings were recorded after 1:3 PS matching (HR 0.6;
p
= 0.009) as well as when Cox regression models were refitted after IPTW (HR 0.7;
p
= 0.01).
Conclusion
The distinction between urachal vs. non-urachal ADKUB indicates better prognosis when the origin of the tumor is urachal, regardless of methodological approach used for the comparison.
Purpose
To test the effect of age on cancer-specific mortality (CSM) in most contemporary prostate cancer (PCa) patients of all stages and across all treatment modalities.
Methods
Within the ...Surveillance, Epidemiology, and End Results database (2004–2016), we identified 579,369 PCa patients. Cumulative incidence plots and multivariable competing-risks regression analyses (MCR) were used. Subgroup analyses were performed according to ethnicity (African-Americans), clinical stage (T1-2N0M0, T3-4N0M0, TanyN1M0, and TanyNanyM1), as well as treatment modalities.
Results
Patient distribution was as follows: 142,338 (24.6%) < 60 years; 113,064 (19.5%) 60–64 years; 127,158 (21.9%) 65–69 years; 94,782 (16.4%) 70–74 years; and 102,027 (17.6%) ≥ 75 years. Older patients harbored worse tumor characteristics and more frequently received no local treatment. Overall, 10-year CSM rates were 4.8, 5.3, 5.9, 7.6, and 14.6%, respectively, in patients aged < 60, 60–64, 65–69, 70–74 ,and ≥ 75 years (
p
< 0.001). In MCR focusing on the overall cohort and T1-2N0M0 patients, older age independently predicted higher CSM, but not in T3-4N0-1M0-1 patients.
Conclusions
Older age was associated with higher grade and stage and independently predicted higher CSM in T1-2N0M0 patients, but not in higher stages. Differences in diagnostics and therapeutics seem to affect elderly patients within T1-2N0M0 PCa and should be avoided if possible.
Purpose
To test the effect of perioperative chemotherapy (CHT) on overall mortality (OM) and cancer-specific mortality (CSM) in patients with locally advanced or metastatic squamous cell carcinoma of ...the urinary bladder (SCC UB).
Methods
Within the Surveillance, Epidemiology and End Results database (1988–2016), we identified 1,018 SCC UB patients (664 T
3–4a
N
0
M
0
, 197 TanyN
1–3
M
0
and 156 T
4b
N
0–3
or M
1
), who underwent radical cystectomy with or without perioperative chemotherapy administration. Inverse probability of treatment-weighting (IPTW), Kaplan–Meier plots and Cox-regression models (CRMs) were used.
Results
CHT was administrated in 116 (17.5%) T
3–4a
N
0
M
0
, 77 (39.1%) TanyN
1–3
M
0
and 47 (30.1%) T
4b
N
0–3
or M
1
patients. IPTW-adjusted 2-year cancer-specific survival (CSS) was 66.5 vs. 71.5% (
p
= 0.19), 60.9 vs. 29.5% (
p
< 0.001) and IPTW-adjusted 1-year CSS was 46.2 vs. 31.1% (
p
= 0.03) for CHT vs. no CHT administration in T
3–4a
N
0
M
0
, TanyN
1–3
M
0
and T
4b
N
0–3
or M
1
, respectively. In multivariable IPTW-adjusted CRMs, chemotherapy was an independent predictor of lower CSM in TanyN
1–3
M
0
(HR 0.44) and in T
4b
N
0–3
or M
1
(HR 0.60), but not in T
3–4a
N
0
M
0
(
p
= 0.6) patients. Virtually the same results were obtained on OM, as well as without IPTW-adjustment and after stratification according to age and gender.
Conclusions
The use of perioperative CHT in patients with SCC UB confers survival benefit in the presence of T4b disease, lymph node or distant metastases. Conversely, patients with locally advanced disease but negative lymph node invasion do not benefit from its use. Pending higher quality data from prospective trials, these data should encourage the use of perioperative CHT in those high-risk patient groups.
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