Real-world cost-effectiveness of targeted therapy in metastatic renal cell carcinoma in Sweden: a population-based retrospective analysis.

OBJECTIVE: To explore cost-effectiveness of targeted therapies (TTs) in the treatment of metastatic renal cell carcinoma (mRCC) in a real-world context using a nationwide population-based approach. METHODS: Data on patients diagnosed with mRCC between 2002 and 2012 were extracted from Swedish national health data registers. To facilitate comparisons of patients diagnosed before and after TT introduction to the market, three cohorts were derived: pre-TT introduction (preTT), patients diagnosed 2002-2005; early TT introduction (TTi), patients diagnosed 2006-2008; and late TT introduction (TTii), which was limited to patients diagnosed 2009-2010 to ensure availability of total health care resource utilization (HCRU) data. Patients were followed until end of 2012. The value of TTs across cohorts was estimated using mean HCRU costs per life-year (LY) gained. Data on HCRU were obtained through national health registers for dispensed medication and inpatient and outpatient care, and the associated costs were estimated using the Lin method to account for censoring. LYs gained were defined as the difference in mean survival over the study period. RESULTS: The preTT, TTi, and TTii cohorts consisted of 1,366, 1,158, and 806 patients, respectively. Mean survival in years from mRCC diagnosis was 1.45 in the preTT cohort, 1.62 in the TTi cohort, and 1.83 in the TTii cohort. The respective mean total HCRU cost per patient over the study period was US$16,894, US$29,922, and US$30,037. The cost per LY gained per cohort was US$78,656 for TTi vs preTT, US$34,132 for TTii vs preTT, and US$523 for TTii vs TTi. CONCLUSION: Given common willingness-to-pay per LY gained thresholds, this study in a real-world population suggests the use of TTs in the Swedish mRCC population is increasingly cost-effective over time.

Promising long-term health-related quality of life after high-dose-rate brachytherapy boost for localized prostate cancer.

PURPOSE: To explore the long-term general and disease-specific health-related quality of life (HRQOL) >5 years after combined radiotherapy for localized prostate cancer, including a high-dose-rate brachytherapy boost and hormonal deprivation therapy. METHODS AND MATERIALS: Of 196 eligible patients with localized prostate cancer (Stage T1-T3a) consecutively treated with curative radiotherapy at our institution between June 1998 and August 2000, 182 (93%) completed the European Organization for Research and Treatment of Cancer Quality of Life questionnaires QLQ-C30 and QLQ-PR25, including specific questions on fecal incontinence >5 years after treatment in September 2005. A comparison with age-matched normative data was done, as well as a longitudinal analysis using HRQOL data from a previous study. RESULTS: The analysis included 158 nonrecurrent patients. Comparisons made with normative data showed that physical and role functioning were significantly better statistically and social functioning was significantly worse. Diarrhea and sleep disturbances were more pronounced and pain less pronounced than in a normal male population. The longitudinal analysis of disease-specific HRQOL showed that urinary urgency and erectile problems persisted 5 years after treatment, and nocturia and hormonally dependent symptoms had declined significantly, with a statistically significant difference. Fecal incontinence was recognized by 25% of patients, of whom 80% considered it a minor problem. CONCLUSION: More than 5 years after combined radiotherapy, irritative urinary problems and erectile dysfunction remain concerns, although severe bowel disturbance and fecal incontinence seem to be minor problems. Longitudinally, a decline mainly in hormonally dependent symptoms was seen. Minor differences in general HRQOL compared with normative data were observed, possibly including "response shift" effects.

Overall survival in Swedish patients with renal cell carcinoma treated in the period 2002 to 2012: Update of the RENCOMP study with subgroup analysis of the synchronous metastatic and elderly populations.

BACKGROUND: This retrospective study investigated overall survival (OS) and factors influencing OS in Swedish patients with metastatic renal cell carcinoma (mRCC) during the pre- (2002-2005), early (2006-2008), and late (2009-2012) targeted therapy (TT) era. METHODS: Three national Swedish registries identified patients with mRCC. Median OS was estimated using the Kaplan-Meier method. Multivariate analysis was performed using Cox proportional hazards regression. Subgroup analysis was conducted for patients with synchronous metastases (M1) and the elderly (aged≥75y). RESULTS: A total of 4,217 patients with mRCC were identified, including 1,533 patients with M1 and 1,275 elderly patients. For patients with mRCC diagnosed in 2002 to 2005, 2006 to 2008, and 2009 to 2012, median OS was 10.0, 13.0, and 18.0 months. Similarly, median OS improved in the M1 and elderly populations. Elderly patients were less likely to be prescribed TT (≥75 vs.<75y): 18.3 vs. 63.5% (in 2006-2008) and 28.6% vs. 55.9% (in 2009-2012). Diagnosis of mRCC in 2009 to 2012, nephrectomy and TT prescription were associated with improved OS in the total mRCC, M1, and elderly populations. CONCLUSION: This real-world study showed continued significant improvement in mRCC OS during the late TT era, including in M1 and elderly populations. TT should be considered for all patients with mRCC based on tolerability, regardless of age.

Health-related quality of life in men after treatment of localized prostate cancer with external beam radiotherapy combined with (192)ir brachytherapy: a prospective study of 93 cases using the EORTC questionnaires QLQ-C30 and QLQ-PR25.

PURPOSE: To describe prospectively the long-term health-related quality of life (HRQOL) and treatment-related symptoms in patients with localized prostate cancer treated with neoadjuvant androgen deprivation therapy and radical radiotherapy (RT), including external beam RT and iridium high-dose-rate brachytherapy, and to compare them with age-matched normative data. METHODS AND MATERIALS: A total of 93 patients with T1-T3a tumors consecutively treated with definitive RT at our institution completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ)-C30 and QLQ-prostate specific 25-item (PR25) module twice at an 18-month interval 0-18 months after RT. Subgroups were analyzed regarding acute and late effects on symptoms and quality of life. RESULTS: The main analysis included 80 patients who were disease free at the final assessment. The levels of HRQOL were generally high, did not change over time, and were comparable to the normative data. Symptom development (urinary, bowel, and sexual) correlated well with the known acute and late effects of radical RT and neoadjuvant androgen deprivation therapy. CONCLUSION: Combining external beam RT and HDR brachytherapy when treating prostate cancer did not appear to impair HRQOL and was comparable to that of other brachytherapy methods. The negative contribution from late neoadjuvant androgen deprivation therapy on symptom development seemed to be substantial but mostly transitory. Additional research is needed to determine the long-term HRQOL (3-5 years), and interventional randomized studies are suggested.

Use of the Charlson combined comorbidity index to predict postradiotherapy quality of life for prostate cancer patients.

PURPOSE: To determine the impact of pretreatment comorbidity on late health-related quality of life (HRQoL) scores after patients have undergone combined radiotherapy for prostate cancer, including high-dose rate brachytherapy boost and hormonal deprivation therapy. METHODS AND MATERIALS: Results from the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire survey of 158 patients 5 years or more after completion of therapy were used from consecutively accrued subjects treated with curative radiotherapy at our institution, with no signs of disease at the time of questionnaire completion. HRQoL scores were compared with the Charlson combined comorbidity index (CCI), using analysis of covariance and multivariate regression models together with pretreatment factors including tumor stage, tumor grade, pretreatment prostate-specific antigen level, neoadjuvant hormonal treatment, diabetes status, cardiovascular status, and age and Charlson score as separate variables or the composite CCI. RESULTS: An inverse correlation between the two HRQoL domains, long-term global health (QL) and physical function (PF) scores, and the CCI score was observed, indicating an impact of comorbidity in these function areas. Selected pretreatment factors poorly explained the variation in functional HRQoL in the multivariate models; however, a statistically significant impact was found for the CCI (with QL and PF scores) and the presence of diabetes (with QL and emotional function). Cognitive function and social function were not statistically significantly predicted by any of the pretreatment factors. CONCLUSIONS: The CCI proved to be valid in this context, but it seems useful mainly in predicting long-term QL and PF scores. Of the other variables investigated, diabetes had more impact than cardiovascular morbidity on HRQoL outcomes in prostate cancer.

Clinical outcome in patients with prostate cancer treated with external beam radiotherapy and high dose-rate iridium 192 brachytherapy boost: a 6-year follow-up.

To report the long-term results for treatment of localized carcinoma of the prostate using high dose rate (HDR) brachytherapy, conformal external beam radiotherapy (3D EBRT) and neo-adjuvant hormonal therapy (TAB). From 1998 through 1999, 154 patients with localized prostate cancer were entered in the trial. Biologically no evidence of disease (bNED) was defined at PSA levels < 2 microg/l. In order to compare the results of this treatment with other treatment modalities, the patient's pre-treatment data were used to calculate the estimated 5-year PSA relapse free survival using Kattan's nomograms for radical prostatectomy (RP) and 3D EBRT. After 6 years of follow-up, 129 patients remain alive. The actual 5-year relapse-free survival is 84%. None of the patients demonstrated clinical signs of local recurrence. The median PSA at follow-up among the relapse-free patients was 0.05 microg/l. Among the 80 patients who presented with clinical stage T3 tumours, 55 (68%) were relapse-free. The expected 5-year relapse-free survival using nomograms for RP and 3D EBRT was 54% and 70%, respectively. Late rectal toxicity RTOG grade 3 occurred in 1% of the patients. Late urinary tract toxicity RTOG grade 3 developed in 4% of the patients. Combined treatment, utilizing HDR, 3D EBRT and TAB, produces good clinical results. Rectal toxicity is acceptable. Urinary tract toxicity, most likely can be explained by the fact that during the first years of this treatment, no effort was made to localize the urethra, which was assumed to be in the middle of the prostate.

Combined curative radiotherapy including HDR brachytherapy and androgen deprivation in localized prostate cancer: a prospective assessment of acute and late treatment toxicity.

Self-reported symptoms including urinary, bowel and sexual side effects were investigated prospectively at multiple assessment points before and after combined radiotherapy of prostate cancer including HDR brachytherapy and neoadjuvant androgen deprivation therapy. Between April 2000 and June 2003, patients with predominantly advanced localized prostate tumours subjected to this treatment were asked before treatment and on follow-up visits to complete a questionnaire covering urinary, bowel and sexual problems. The mainly descriptive analyses included 525 patients, responding to at least one questionnaire before or during the period 2-34 months after radiotherapy. Adding androgen deprivation before radiotherapy significantly worsened sexual function. During radiotherapy, urinary, bowel and sexual problems increased and were reported at higher levels up to 34 months, although there seemed to be a general tendency to less pronounced irritative bowel and urinary tract symptoms over time. No side effects requiring surgery were reported. Classic late irradiation effects such as mucosal bleeding were demonstrated mainly during the second year after therapy, but appear less pronounced in comparison with dose escalated EBRT series. In conclusion, despite the high radiation dose given, the toxicity seemed comparable with that of other series but long term (5-10 years) symptom outcome has to be determined.