Impact of age and comorbidities on health-related quality of life for patients with prostate cancer: evaluation before a curative treatment

<p>Abstract</p> <p>Background</p> <p>Interpretation of comparative health-related quality of life (HRQOL) studies following different prostate cancer treatments is often difficult due to differing patient ages. Furthermore, age-related changes can hardly be discriminated from therapy-related changes. The evaluation of age-and comorbidity-related changes was in focus of this study.</p> <p>Methods</p> <p>HRQOL of 528 prostate cancer patients was analysed using a validated questionnaire (Expanded Prostate Cancer Index Composite) before a curative treatment. Patients were divided into age groups ≤65, 6670, 7175 and >75 years. The impact of specific comorbidities and the Charlson Comorbidity Index (CCI) were evaluated. The questionnaire comprises 50 items concerning the urinary, bowel, sexual and hormonal domains for function and bother. For assessment of sexual and hormonal domains, only patients without prior hormonal treatment were included (n = 336).</p> <p>Results</p> <p>Urinary incontinence was observed increasingly with higher age (mean function scores of 92/88/85/87 for patients ≤65, 6670, 7175 and >75 years) complete urinary control in 78%/72%/64%/58% (p < 0.01). Sexual function scores decreased particularly (48/43/35/30), with erections sufficient for intercourse in 68%/50%/36%/32% (p < 0.01) a decrease of more than a third comparing patients ≤65 vs. 6670 (36%) and 6670 vs. 7175 years (39%). The percentage of patients with comorbidities was lowest in the youngest group (48% vs. 66%/68%/63% for ages 6670/7175/>75 years; p < 0.05). A multivariate analysis revealed an independent influence of both age and comorbidities on urinary incontinence, specifically diabetes on urinary bother, and both age and diabetes on sexual function/bother. Rectal domain scores were not significantly influenced by age or comorbidities. A CCI>5 particularly predisposed for lower urinary and sexual HRQOL scores.</p> <p>Conclusion</p> <p>Urinary continence and sexual function are the crucial HRQOL domains with age-related and independently comorbidity-related decreasing scores. The results need to be considered for the interpretation of comparative studies or longitudinal changes after a curative treatment.</p

HCC recurrence in HCV-infected patients after liver transplantation: SiLVER Study reveals benefits of sirolimus in combination with CNIs - a post-hoc analysis

Factors affecting outcomes in liver transplant (LTx) recipients with hepatocellular carcinoma (HCC) and hepatitis C viral (HCV) infection include the choice of immunosuppression. Here, we analyzed the HCV+ subgroup of patients from the randomized controlled, international SiLVER Study. We performed a post hoc analysis of 166 HCV+ SiLVER Study patients regarding HCC outcome after LTx. Control patients (group A: n&nbsp;=&nbsp;88) received mTOR inhibitor (mTORi)-free, calcineurin inhibitor (CNI)-based versus sirolimus-based immunosuppression (group B: n&nbsp;=&nbsp;78). We found no significant difference regarding HCV-RNA titers between group A and B. Since no effect in group B could be due to variable sirolimus dosing, we split group B into patients receiving sirolimus-based immunosuppression&nbsp;+&nbsp;CNIs for &gt;50% (B1; n&nbsp;=&nbsp;44) or &lt;50% (B2; n&nbsp;=&nbsp;34) of the time. While there remained no difference in HCV-RNA titer between groups, HCC recurrence-free survival in group B1 (81.8%) was markedly better versus both group A (62.7%; P&nbsp;=&nbsp;0.0136) and group B2 (64.7%; P&nbsp;=&nbsp;0.0326); Interestingly, further subgroup analysis revealed an increase (P&nbsp;=&nbsp;0.0012) in liver enzyme values in group B2. Taken together, in HCV-infected patients with HCC and LTx, mTORi immunosuppression&nbsp;+&nbsp;CNIs yields excellent outcomes. Unexpectedly, higher levels of liver inflammation and poorer outcomes occur with mTORi monotherapy in the HCV+ subgroup

Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma : A Randomized, Multicenter, Open-Label Phase 3 Trial

Background We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). Methods In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor-free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor-free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. Results Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age 60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874). Conclusions Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC.Peer reviewe

Pretreatment Total Testosterone Level Predicts Pathological Stage in Patients With Localized Prostate Cancer Treated With Radical Prostatectomy

Purpose In the last decade numerous groups have shown that low levels of pretreatment serum total testosterone consistently predict more aggressive disease, worse prognosis and worse treatment response in patients with metastatic prostate cancer. Prior studies have not demonstrated this same correlation in patients with known localized disease. We rigorously tested pretreatment total testosterone levels as a potential staging and prognostic marker in a large cohort of 879 patients with localized cancer treated with radical prostatectomy. Materials and Methods We retrospectively reviewed the clinical records of 879 patients treated with radical prostatectomy between January 1, 1986 and June 30, 2002 from 9 hospital sites. Nonparametric tests were used to compare the relationship of pretreatment testosterone to other variables. Multivariate logistic regression analysis was used to assess clinical predictors of extraprostatic disease. Kaplan-Meier survival methods and Cox regressionanalysis were used to assess predictors of biochemical recurrence. Results Patients with nonorgan confined prostate cancer (pT3–T4) showed significantly lower pretreatment total testosterone levels than those with organ confined cancer (pT1–T2) (nonparametric p =0.041). In multivariate analysis pretreatment total testosterone emerged as a significant independent predictor of extraprostatic disease (p =0.046). Total testosterone was not a significant predictor of biochemical (prostate specific antigen) recurrence (p =0.467). Conclusions Pretreatment total testosterone was an independent predictor of extraprostatic disease in patients with localized prostate cancer. As testosterone decreases patients have an increased likelihood of nonorgan confined disease. Low testosterone was not predictive of biochemical recurrence, although trends observed dictate study in larger cohorts with mature followup

Pretreatment Total Testosterone Level Predicts Pathological Stage in Patients With Localized Prostate Cancer Treated With Radical Prostatectomy

Purpose In the last decade numerous groups have shown that low levels of pretreatment serum total testosterone consistently predict more aggressive disease, worse prognosis and worse treatment response in patients with metastatic prostate cancer. Prior studies have not demonstrated this same correlation in patients with known localized disease. We rigorously tested pretreatment total testosterone levels as a potential staging and prognostic marker in a large cohort of 879 patients with localized cancer treated with radical prostatectomy. Materials and Methods We retrospectively reviewed the clinical records of 879 patients treated with radical prostatectomy between January 1, 1986 and June 30, 2002 from 9 hospital sites. Nonparametric tests were used to compare the relationship of pretreatment testosterone to other variables. Multivariate logistic regression analysis was used to assess clinical predictors of extraprostatic disease. Kaplan-Meier survival methods and Cox regressionanalysis were used to assess predictors of biochemical recurrence. Results Patients with nonorgan confined prostate cancer (pT3–T4) showed significantly lower pretreatment total testosterone levels than those with organ confined cancer (pT1–T2) (nonparametric p =0.041). In multivariate analysis pretreatment total testosterone emerged as a significant independent predictor of extraprostatic disease (p =0.046). Total testosterone was not a significant predictor of biochemical (prostate specific antigen) recurrence (p =0.467). Conclusions Pretreatment total testosterone was an independent predictor of extraprostatic disease in patients with localized prostate cancer. As testosterone decreases patients have an increased likelihood of nonorgan confined disease. Low testosterone was not predictive of biochemical recurrence, although trends observed dictate study in larger cohorts with mature followup