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BACKGROUND AND PURPOSE: The aim of this cross-sectional study was to investigate long-term health-related quality of life (HRQoL) in men with prostate cancer treated 2002-2008 with external beam radiotherapy (EBRT) combined with high dose-rate brachytherapy (HDRBT), Cohort A, and to compare these data with age-adjusted normative data. In addition, differences in HRQoL following adjustments of the brachytherapy technique in 2001 were investigated by comparing Cohort A with men treated at the same clinic from 1998-2000, Cohort B. METHODS AND MATERIAL: Cohort A: 1495 men treated with EBRT 2 Gy to 50 Gy and 2 fractions of 10 Gy HDRBT at a single centre, 2002-2008, still alive at five years. As part of routine follow-up, the patients responded to the EORTC QLQ-C30 and PR-25 questionnaires. Cohort B: HRQoL data was retrieved from an earlier study from the original article. RESULTS: In Cohort A, 1046 (70%) men completed the questionnaires at five years, median age 66 years. In general, HRQoL mean scores were high and similar to Swedish age-matched normative data. Concerning disease-specific HRQoL, low levels of bowel and urinary problems were reported, in contrast to a substantial effect on sexual functioning. 'No' or 'A little' problems with faecal incontinence and urinary incontinence were reported by 98% and 93% of patients, respectively. The corresponding figure for sexual functioning was 39%. A difference in the frequency of nocturia in favour of Cohort A was the only statistically significant difference between Cohort A and B found in general and disease-specific HRQOL (p = 0.03), despite modifications in the brachytherapy procedure introduced in 2001. CONCLUSION: Long-term general HRQoL was rated high and comparable to an aged-matched reference population five years after treatment with combined radiotherapy. Disease-specific HRQoL was still affected, foremost in the sexual domain.
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Braquiterapia , Neoplasias de la Próstata , Masculino , Humanos , Anciano , Braquiterapia/métodos , Calidad de Vida , Estudios Transversales , Dosificación Radioterapéutica , Neoplasias de la Próstata/radioterapiaRESUMEN
BACKGROUND AND PURPOSE: To analyse the cumulative incidence of any failure (AF), prostate cancer-specific failure (PCSF), any death (AD), prostate cancer-specific death (PCSD), and local control in 2387 men with prostate cancer (PC), consecutively treated with combined high-dose-rate brachytherapy (HDRBT) and external beam radiotherapy (EBRT) from 1998 to 2010. MATERIAL AND METHODS: A retrospective, single-institution study of men with localised PC. The mean age was 66 years and 54.7% had high-risk PC according to the Cambridge prognostic group (CPG) classification. The treatment was delivered as EBRT (2 Gy × 25) and HDRBT (10 Gy × 2) with combined androgen blockade (CAB). The median follow-up was 10.2 years. RESULTS: The cumulative incidence of PCSD at 10 years was 5% [CI 95% 0.04-0.06]. The 10 years PCSD per risk group were: low (L) 0.4%, intermediate favourable (IF) 1%, intermediate unfavourable (IU) 4.3%, high-risk favourable (HF) 5.8%, and high-risk unfavourable (HU) 13.9%. The PCSF rate at 10 years was 16.5% [CI 95% 0.15-0.18]. The PCSF per risk group at 10 years were: L 2.5%, IF 5.5%, IU 15.9%, HF 15.6%, and HU 38.99%. PCSF occurred in 399 men, of whom 15% were found to have local failure. The estimated frequency of local failure in the entire cohort was 1.2%. CONCLUSIONS: HDRBT combined with EBRT is an effective treatment with long-term overall survival and excellent local control for patients with PC. The low rate of local recurrence among men with relapse suggests that these patients were micro metastasised at time of treatment, which calls for improved methods to detect disseminated disease.
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Braquiterapia , Neoplasias de la Próstata , Anciano , Humanos , Masculino , Recurrencia Local de Neoplasia , Antígeno Prostático Específico , Neoplasias de la Próstata/radioterapia , Dosificación Radioterapéutica , Estudios RetrospectivosRESUMEN
BACKGROUND: The risk stratification currently applied prior to curative treatment for localized prostate cancer (PC) does not take into account comorbidity or age. Therefore, we investigated the impact of comorbidity on overall survival (OS) in PC patients treated with external beam radiotherapy (EBRT) and high-dose rate (HDR) brachytherapy boost. MATERIAL AND METHODS: At a single center, 611 consecutive patients diagnosed with localized PC from 1998 to 2004 underwent definitive EBRT (50 Gy) and HDR brachytherapy boosts (2 × 10 Gy) combined with neoadjuvant total androgen blockade. Comorbidity was assessed with the Charlson comorbidity score. The impact of risk factors on OS and disease-free survival (DFS) was calculated using Cox proportional hazard ratios. Risk groups were defined as follows: low-risk PC: PSA <10, WHO grade 1 and T stage 1; high-risk PC: PSA >20 and/or WHO grade 3 and/or T stage 3a; intermediate-risk PC representing patients who did not fit either the low- or high-risk PC group. RESULTS: Mean age in the study cohort was 66.4 years, and 51% of the patients reported some degree of comorbidity. Divided into risk groups 8.2% were categorized as low-risk, 64% as intermediate-risk and 27.8% as high-risk PC. Overall 10-year survival was 72.2%, and 89% of the patients were relapse-free. In the univariate and multivariate analyses using Cox proportional hazard ratios, age, comorbidity and T stage were statistically significant predictors of OS: hazard ratios 1.56, 1.44 and 1.2 (p-values .002, .04 and .05), respectively. WHO grade, PSA at diagnosis, T stage and comorbidity were also significant predictors of DFS (p-values .0001, .0001, .009 and .003, respectively). CONCLUSION: Comorbidity assessed with the Charlson score predicts OS in patients with localized PC treated with curative intent using combined EBRT and HDR brachytherapy boost, and should be considered when making decisions before radical treatment.
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Adenocarcinoma/mortalidad , Braquiterapia/mortalidad , Neoplasias de la Próstata/mortalidad , Radioterapia Conformacional/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/radioterapia , Anciano , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Dosificación Radioterapéutica , Estudios Retrospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
BACKGROUND: Capture rate and representativity of quality registers need to be assessed in order to ensure that register data are generalizable. MATERIAL AND METHODS: In 1998-2009, 103 047 men had been diagnosed with prostate cancer and registered in the Swedish Cancer Register to which registration is mandated by law and of these men, 100 849 men (98%) had also been registered in The National Prostate Cancer Register (NPCR) of Sweden. We compared demographics, cancer treatment, comorbidity, and mortality in men in NPCR, with those who had only been registered in the Cancer Register, by use of data from the Cause of Death Register, the In-Patient Register and the Prescribed Drug Register. In addition, we identified 1929 men who had prostate cancer as underlying cause of death in the Cause of Death Register who had neither been registered in the Cancer Register nor in NPCR. RESULTS: Compared to men in NPCR, men only registered in the Cancer Register were slightly older, median age 72 versus 71 years, and a lower proportion underwent radical prostatectomy, 15% versus 27%. Ten year prostate cancer mortality was 23% (95% CI 20-25) for men in the Cancer Register only and 24% (95% CI 24-25) in NPCR, while mortality from competing causes was 28% (95% CI 26-31) and 30% (95% CI 30-30), respectively. Men identified with prostate cancer by a death certificate were old and had high comorbidity. CONCLUSION: The capture rate of NPCR is very high and there are only modest differences in demographics, cancer treatment, comorbidity, and mortality between the small proportion of men only registered in the Cancer Register and men registered in NPCR, indicating that information in NPCR can be generalized to all men with prostate cancer in Sweden.
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Neoplasias de la Próstata/epidemiología , Sistema de Registros/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Causas de Muerte , Certificado de Defunción , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prostatectomía/estadística & datos numéricos , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/cirugía , Suecia/epidemiologíaRESUMEN
ProBio is the first outcome-adaptive platform trial in prostate cancer utilizing a Bayesian framework to evaluate efficacy within predefined biomarker signatures across systemic treatments. Prospective circulating tumor DNA and germline DNA analysis was performed in patients with metastatic castration-resistant prostate cancer before randomization to androgen receptor pathway inhibitors (ARPIs), taxanes or a physician's choice control arm. The primary endpoint was the time to no longer clinically benefitting (NLCB). Secondary endpoints included overall survival and (serious) adverse events. Upon reaching the time to NLCB, patients could be re-randomized. The primary endpoint was met after 218 randomizations. ARPIs demonstrated ~50% longer time to NLCB compared to taxanes (median, 11.1 versus 6.9 months) and the physician's choice arm (median, 11.1 versus 7.4 months) in the biomarker-unselected or 'all' patient population. ARPIs demonstrated longer overall survival (median, 38.7 versus 21.7 and 21.8 months for taxanes and physician's choice, respectively). Biomarker signature findings suggest that the largest increase in time to NLCB was observed in AR (single-nucleotide variant/genomic structural rearrangement)-negative and TP53 wild-type patients and TMPRSS2-ERG fusion-positive patients, whereas no difference between ARPIs and taxanes was observed in TP53-altered patients. In summary, ARPIs outperform taxanes and physician's choice treatment in patients with metastatic castration-resistant prostate cancer with detectable circulating tumor DNA. ClinicalTrials.gov registration: NCT03903835 .
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BACKGROUND/AIM: The goal of this study was to investigate whether health-related quality of life (HRQoL) was affected in patients with high- or intermediate-risk localized prostate cancer treated with docetaxel following radiation therapy (RT). PATIENTS AND METHODS: A total of 376 patients treated with RT and androgen deprivation were randomized to receive 6 cycles of docetaxel 75 mg/m2 (N=188, Arm A) or surveillance (N=188, Arm B). FACT-P HRQoL questionnaires were gathered at baseline, six months and 1, 2 and 4 years after randomization. The data were analysed using analysis of covariance. RESULTS: FACT-P scores decreased in Arm A at the end of treatment and remained unchanged in Arm B (p<0.0001). The HRQoL scores in Arm A matched Arm B in the 1-year follow-up (p=0.0528) and remained similar in further follow-up. CONCLUSION: Docetaxel transiently decreased HRQoL during chemotherapy but not after treatment for up to four years of follow-up.
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Docetaxel/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Adolescente , Adulto , Anciano , Docetaxel/farmacología , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Adulto JovenRESUMEN
BACKGROUND: Patients with advanced prostate cancer (PCa) typically undergo numerous lines of treatment leading to large amounts of information in Electronic Health Records (EHRs). The Patient-overview Prostate Cancer (PPC) presents clinical information in a graphical overview. The aim of this study was to measure time spent on retrieving clinical information in PPC compared to EHRs, to assess if retrieved data was correct and to explore usability of PPC. MATERIAL AND METHODS: Oncologists, urologists and nurses in three hospitals in Sweden were timed when filling out questionnaires about patients using PPC and two different EHRs; Melior and COSMIC. Time and number of errors were analysed using linear mixed models (LMMs). Usability of PPC was measured with the System Usability Scale. RESULTS: The LMM showed a significantly shorter time to retrieve information in PPC compared to EHRs. The estimated time to complete one questionnaire was 8 minutes (95% CI = 6-10, p < 0.001) in PPC compared to 25 minutes in Melior and 21 minutes in COSMIC. Compared to PPC, the estimated time difference was 17 minutes longer in Melior (95% CI = 14-20, p < 0.001) and 13 minutes longer in COSMIC (95% CI = 10-17, p < 0.001). The LMM showed significantly fewer errors in PPC compared to Melior. No significant difference in the number of errors was found between PPC and COSMIC. The usability of PPC was rated as excellent by oncologists, urologists and nurses. CONCLUSION: A graphical overview of a patient's medical history, as in PPC, gives health staff rapid access to relevant information with a high degree of usability.
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Registros Electrónicos de Salud , Neoplasias de la Próstata , Humanos , Masculino , Encuestas y Cuestionarios , SueciaRESUMEN
OBJECTIVE: To investigate time spent in hormone-sensitive and castration-resistant disease states in men with advanced prostate cancer in Sweden, and the associated health economic impact. MATERIALS AND METHODS: Registry study (NCT03619980) of the Prostate Cancer data Base Sweden with data from the National Prostate Cancer Register, including the Patient-overview Prostate Cancer (PPC) and other national healthcare registries. The primary endpoint was time in each disease state. Secondary endpoints were co-medications, comorbidities and healthcare resource utilization (HRU) and cost in each disease state. RESULTS: In total, 1,869 men with advanced prostate cancer registered in PPC between 2014 and 2016, with data on the start of androgen deprivation therapy, were identified. Median time to progression and median survival were 4 and 11 years, respectively, for men with non-metastatic (nm) hormone-sensitive prostate cancer (HSPC); 1 and 7 years for men with metastatic (m) HSPC; and 1 and 8.5 years for men with nm castration-resistant prostate cancer (CRPC). Median survival for men with mCRPC was 4 years. Total annual mean costs for HRU per patient increased with increasing severity of disease, from 41,064 Swedish krona (SEK) for nmHSPC to 288,242 SEK for mCRPC. CONCLUSION: Progression time from mHSPC and nmCRPC to the mCRPC state was short and survival in the mCRPC state was approximately 4 years. Survival times were longer than expected, likely due to the selection of long-term survivors among prevalent cases. Healthcare costs were high for men with mCRPC. Further studies are needed to confirm our pilot study findings.
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Costo de Enfermedad , Duración de la Terapia , Neoplasias de la Próstata/economía , Neoplasias de la Próstata/terapia , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Proyectos Piloto , Neoplasias de la Próstata/patología , Neoplasias de la Próstata Resistentes a la Castración/economía , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/terapia , Sistema de Registros , SueciaRESUMEN
BACKGROUND: Multiple therapies exist for patients with metastatic castration-resistant prostate cancer (mCRPC). However, their improvement on progression-free survival (PFS) remains modest, potentially explained by tumor molecular heterogeneity. Several prognostic molecular biomarkers have been identified for mCRPC that may have predictive potential to guide treatment selection and prolong PFS. We designed a platform trial to test this hypothesis. METHODS: The Prostate-Biomarker (ProBio) study is a multi-center, outcome-adaptive, multi-arm, biomarker-driven platform trial for tailoring treatment decisions for men with mCRPC. Treatment decisions in the experimental arms are based on biomarker signatures defined as mutations in certain genes/pathways suggested in the scientific literature to be important for treatment response in mCRPC. The biomarker signatures are determined by targeted sequencing of circulating tumor and germline DNA using a panel specifically designed for mCRPC. DISCUSSION: Patients are stratified based on the sequencing results and randomized to either current clinical practice (control), where the treating physician decides treatment, or to molecularly driven treatment selection based on the biomarker profile. Outcome-adaptive randomization is implemented to early identify promising treatments for a biomarker signature. Biomarker signature-treatment combinations graduate from the platform when they demonstrate 85% probability of improving PFS compared to the control arm. Graduated combinations are further evaluated in a seamless confirmatory trial with fixed randomization. The platform design allows for new drugs and biomarkers to be introduced in the study. CONCLUSIONS: The ProBio design allows promising treatment-biomarker combinations to quickly graduate from the platform and be confirmed for rapid implementation in clinical care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03903835. Date of registration: April 4, 2019. Status: Recruiting.
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Biomarcadores de Tumor/genética , Medicina de Precisión , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/terapia , Ensayos Clínicos Fase III como Asunto , Análisis Mutacional de ADN , Mutación de Línea Germinal , Humanos , Masculino , Estudios Multicéntricos como Asunto , Metástasis de la Neoplasia , Supervivencia sin Progresión , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
Introduction: Novel drugs have been shown to prolong life in men with metastatic prostate cancer (PCa) and castration resistant Pca (CRPC). The aim of Patient-overview Prostate cancer (PPC) is to register and report these treatments and their effect.Material and methods: In PPC, a new part of the National Prostate Cancer Register of Sweden data on start and stop of treatments, imaging, prostate specific antigen, clinical assessment of progression and patient reported outcome measures (PROM) are registered from initiation of hormonal treatment. Data are displayed in a graph to inform clinical decisions for individual patients. For research, data in PPC are linked to PCBaSe with information from NPCR and a number of health care registers.Results: In December 2019, 7 882 men had been registered in PPC out of whom 3 912 had reached the CRPC state. Median time to start of androgen receptor targeted drugs (ART) from start of ADT was 4 years (interquartile range IQR 6) for men with primary ADT, and 9 years (IQR 6) and for men with secondary ADT. Out of all men in PCBaSe with a prescription for ART in 2016-2017, PPC captured 1 480/4 055 (36%). There were small differences between men registered/not registered in PPC for cancer characteristics, primary treatment, comorbidity, and time on ADT before start of ART.Conclusion: In PPC, use and effects of novel therapies for advanced Pca are assessed in a real-life setting. PPC data are used as a decision aid, for quality assurance, and in research.
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Neoplasias de la Próstata/terapia , Sistema de Registros , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/patología , SueciaRESUMEN
BACKGROUND: Docetaxel combined with androgen deprivation therapy (ADT) has improved patient survival for advanced prostate cancer (PCa). OBJECTIVE: This randomised trial aimed to evaluate whether six courses of docetaxel improved biochemical disease-free survival (BDFS) after radical radiotherapy (RT) for intermediate- or high-risk PCa patients. DESIGN, SETTING, AND PARTICIPANTS: A total of 376 patients were randomised in this multinational phase III study, and received either six cycles of adjuvant docetaxel 75â¯mg/m2 every 3 wk without continuous prednisone (arm A, nâ¯=â¯188) or surveillance (arm B, nâ¯=â¯188) after RT (NTC006653848). Neoadjuvant/adjuvant ADT was mandatory for all the patients. The primary endpoint was rising prostate-specific antigen (PSA) ≥2â¯ng/ml above the nadir PSA value. Intermediate- or high-risk PCa was defined as T2 with a Gleason score (GS) of 4â¯+â¯3, PSAâ¯>â¯10; T2, GS 8-10, ≤â¯70â¯ng/ml; or any T3. The patients were followed for 5â¯yr by assessing PSA levels every 3 mo for 2â¯yr and every 6 mo thereafter. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The study power was 89% to detect a difference in BDFS between groups, and the sample size calculation accounted for the T2/T3 distribution, where a 12%/15% difference in BDFS was assumed for the T2/T3 patients. RESULTS AND LIMITATIONS: All six cycles were completed in 147 (78%) of the patients in arm A. The median age was 67â¯yr in both treatment groups, 75% had T3 disease, and 47% had GS 8-10. The median follow-up was 59 mo (range 1-111â¯mo). The primary endpoint was observed for 58 patients in arm A (docetaxel) and for 57 patients in arm B (surveillance). The Kaplan-Meier analysis showed no difference in the BDFS curves (pâ¯=â¯0.6) between the treatment groups. The 5-yr estimated biochemical progression rates were 31% for arm A and 28% for arm B. Febrile neutropenia occurred in 16% of the docetaxel patients. No deaths were related to the docetaxel treatment. There were 43 deaths during the trial, including 20 in arm A and 23 in arm B, of which nine and seven, respectively, were due to PCa. The hazard ratio from Cox multivariate analysis for PSA progression of arm A (docetaxel) versus arm B (surveillance) was 1.14 (95% confidence interval 0.79-1.64, pâ¯=â¯0.5). CONCLUSIONS: Adjuvant docetaxel without prednisone did not improve BDFS after radical RT with ADT for intermediate- or high-risk PCa. PATIENT SUMMARY: We compared six cycles of adjuvant docetaxel given after radical external radiotherapy plus androgen deprivation therapy to surveillance in intermediate- and high-risk localised prostate cancer. We found no overall benefit in this setting.
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Antineoplásicos/uso terapéutico , Docetaxel/uso terapéutico , Neoplasias de la Próstata/terapia , Espera Vigilante , Anciano , Antagonistas de Andrógenos/uso terapéutico , Terapia Combinada , Supervivencia sin Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Medición de RiesgoRESUMEN
OBJECTIVES: The aim of this study was to examine the use of abiraterone and enzalutamide, two oral novel antiandrogens (NOVAs), in men with prostate cancer (PCa) in Sweden. MATERIALS AND METHODS: This cross-sectional study investigated filled prescriptions for NOVAs recorded in the Swedish Prescribed Drug Register between July 2015 and April 2016. Associations between age, comorbidity, educational level, marital status and county of residence and filled prescriptions were analyzed in the National Prostate Cancer Register (NPCR) and other health population-based registers, using multivariable logistic regression. RESULTS: Of 91,209 men, 1650 (2%) had at least one prescription filled for NOVAs, of whom 1350 (82%) had high-risk or metastatic PCa at diagnosis.. Of 1914 men with M1 disease and a high probability of castration-resistant prostate cancer (CRPC), 22% had a prescription for NOVAs at a median 3 years after the date of diagnosis. At multivariable logistic regression analysis,, the likelihood of NOVA use was lower in older men [age >80 vs <70 years: odds ratio (OR) 0.23, 95% confidence interval (CI) 0.15-0.35] and in men with lower educational level (high vs low education: OR 1.64, 95% CI 1.23-2.20). There was up to a five-fold difference in the use of NOVAs between county councils. CONCLUSIONS: Less than one-third of potentially eligible men with CRPC received NOVAs in 2015-2016. There were large differences in use according to age and region of residence, indicating that efforts are needed to improve equal access to novel cancer drugs.
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Antagonistas de Andrógenos/uso terapéutico , Androstenos/uso terapéutico , Antineoplásicos/uso terapéutico , Feniltiohidantoína/análogos & derivados , Neoplasias de la Próstata/tratamiento farmacológico , Factores de Edad , Anciano , Anciano de 80 o más Años , Benzamidas , Estudios Transversales , Prescripciones de Medicamentos/estadística & datos numéricos , Escolaridad , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Nitrilos , Feniltiohidantoína/uso terapéutico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Sistema de Registros , Características de la Residencia/estadística & datos numéricos , Suecia , Factores de TiempoRESUMEN
Purpose In patients with metastatic castration-resistant prostate cancer (mCRPC), overall survival (OS) is significantly improved with cabazitaxel versus mitoxantrone after prior docetaxel treatment. FIRSTANA ( ClinicalTrials.gov identifier: NCT01308567) assessed whether cabazitaxel 20 mg/m2 (C20) or 25 mg/m2 (C25) is superior to docetaxel 75 mg/m2 (D75) in terms of OS in patients with chemotherapy-naïve mCRPC. Patients and Methods Patients with mCRPC and Eastern Cooperative Oncology Group performance status of 0 to 2 were randomly assigned 1:1:1 to receive C20, C25, or D75 intravenously every 3 weeks plus daily prednisone. The primary end point was OS. Secondary end points included safety; progression-free survival (PFS); tumor, prostate-specific antigen, and pain response; pharmacokinetics; and health-related quality of life. Results Between May 2011 and April 2013, 1,168 patients were randomly assigned. Baseline characteristics were similar across cohorts. Median OS was 24.5 months with C20, 25.2 months with C25, and 24.3 months with D75. Hazard ratio for C20 versus D75 was 1.01 (95% CI, 0.85 to 1.20; P = .997), and hazard ratio for C25 versus D75 was 0.97 (95% CI, 0.82 to 1.16; P = .757). Median PFS was 4.4 months with C20, 5.1 months with C25, and 5.3 months with D75, with no significant differences between treatment arms. Radiographic tumor responses were numerically higher for C25 (41.6%) versus D75 (30.9%; nominal P = .037, without multiplicity test adjustment). Rates of grade 3 or 4 treatment-emergent adverse events were 41.2%, 60.1%, and 46.0% for C20, C25, and D75, respectively. Febrile neutropenia, diarrhea, and hematuria were more frequent with C25; peripheral neuropathy, peripheral edema, alopecia, and nail disorders were more frequent with D75. Conclusion C20 and C25 did not demonstrate superiority for OS versus D75 in patients with chemotherapy-naïve mCRPC. Tumor response was numerically higher with C25 versus D75; pain PFS was numerically improved with D75 versus C25. Cabazitaxel and docetaxel demonstrated different toxicity profiles, with overall less toxicity with C20.
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Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Taxoides/uso terapéutico , Anciano , Antineoplásicos/uso terapéutico , Supervivencia sin Enfermedad , Docetaxel , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Prednisona/administración & dosificación , Neoplasias de la Próstata Resistentes a la Castración/patología , Tasa de SupervivenciaRESUMEN
Effects on long-term health-related quality of life (HRQoL) were evaluated in patients treated for localized prostate cancer by two standard modalities: radical retropubic prostatectomy (RP) and external beam radiotherapy combined with a high-dose-rate brachytherapy boost (HDRBT-EBRT). The HRQoL data were compared with age-adjusted normative data. Men diagnosed with localized prostate cancer and treated with curative intent in Gothenburg, Sweden, 1988-1997 were included. HRQoL was measured in October 2000 using the EORTC QLQ-C30 and EORTC QLQ-PR25 questionnaires, with a response rate of 82% (n=347). No differences in patient characteristics were found between the two treatment groups, except regarding tumor stage and PSA recurrence at the time of the questionnaires. In the RP group, 42% had T1 and 6% had T3-4 tumors; corresponding proportions in the HDRBT-EBRT group were 29% and 13% (p=0.01). PSA recurrence was detected in 44% of RP patients and 9% of HDRBT-EBRT patients. In most domains, mean HRQoL scores were high and similar to the scores for the age-adjusted normative sample. However, patients reported better role and physical function compared to the normal population. We also observed more sleeping disturbances but less pain among patients than in the normal population. The disease-specific questionnaires showed statistically significant higher levels of bowel and urinary problems in the irradiated group than in the RP group, and the absolute difference between the groups was small and had minor clinical significance. We conclude that overall the general quality of life was rated high by the patients irrespective of curative treatment modality and in agreement with age-adjusted normative data. Statistically significant differences in bowel and urinary symptoms were found between the two treatment groups in favor of the RP group, but the clinical significance was small.
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Estado de Salud , Neoplasias de la Próstata/terapia , Calidad de Vida , Anciano , Anciano de 80 o más Años , Braquiterapia/estadística & datos numéricos , Estudios Transversales , Humanos , Masculino , Persona de Mediana Edad , Prostatectomía/estadística & datos numéricos , Neoplasias de la Próstata/epidemiología , Dosificación Radioterapéutica , Inducción de Remisión , Encuestas y CuestionariosRESUMEN
BACKGROUND: Many elderly men with high-risk nonmetastatic prostate cancer (HRnMPCa) do not receive radical treatment, despite the high mortality associated with conservative management. OBJECTIVE: To investigate how age and comorbidity affect treatment of men with HRnMPCa. DESIGN, SETTING, AND PARTICIPANTS: This was an observational nationwide register study during 2001-2012. We identified 19 190 men of <80 yr of age diagnosed with HRnMPCa in the National Prostate Cancer Register of Sweden and 95 948 age-matched men without prostate cancer in the register of the total population. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcome was the proportion of men with HRnMPCa receiving radical treatment (radical prostatectomy or radiotherapy). Vital status and the Charlson comorbidity index (CCI) were obtained from nationwide registers. The 10-yr survival of men without prostate cancer, stratified by age and CCI, was used as a measure of the life expectancy of the men with prostate cancer. RESULTS AND LIMITATIONS: The proportions receiving radical treatment varied with life expectancy among men younger than 70 yr, whereas use of these treatments did not match the long life expectancy of men in their seventies with CCI 0-1. Only 10% of men aged 75-80 yr with CCI 0 received radical treatment despite 52% probability of 10-yr life expectancy, compared with approximately half of the men younger than 70 yr with a similar life expectancy. The use of radical treatment for HRnMPCa increased with time in all Swedish counties, but a threefold difference between counties remained in 2009-2012 for patients aged 70-80 yr with CCI 0-1. Uncertain external validity is a study limitation, and the impact of physician versus patient preferences on treatment selection could not be assessed. CONCLUSIONS: Otherwise healthy men in their seventies with HRnMPCa were less likely to receive radical treatment than younger men with a similar life expectancy, although increasing use of radical treatment was observed during the study period. Our findings highlight the need for improved methods for clinical decision-making, including improved assessment of life expectancy. PATIENT SUMMARY: We performed a nationwide register study that showed that many healthy men in their seventies live for at least another 10 yr. Despite this long life expectancy, men in their seventies with high-risk nonmetastatic prostate cancer were often not treated with radical prostatectomy or radiotherapy, possibly because their life expectancy was underestimated. Our study highlights the need for improved clinical decision-making, which should incorporate an assessment of the patient's life expectancy.
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Toma de Decisiones Clínicas , Esperanza de Vida , Prostatectomía/estadística & datos numéricos , Neoplasias de la Próstata/terapia , Radioterapia/estadística & datos numéricos , Sistema de Registros , Factores de Edad , Anciano , Comorbilidad , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente , Neoplasias de la Próstata/patología , Calidad de la Atención de Salud , Riesgo , SueciaRESUMEN
INTRODUCTION: In 2007 ESTRO proposed a revision and harmonisation of the core curricula for radiation oncologists, medical physicists and RTTs to encourage harmonised education programmes for the professional disciplines, to facilitate mobility between EU member states, to reflect the rapid development of the professions and to secure the best evidence-based education across Europe. MATERIAL AND METHODS: Working parties for each core curriculum were established and included a broad representation with geographic spread and different experience with education from the ESTRO Educational Committee, local representatives appointed by the National Societies and support from ESTRO staff. RESULTS: The revised curricula have been presented for the ESTRO community and endorsement is ongoing. All three curricula have been changed to competency based education and training, teaching methodology and assessment and include the recent introduction of the new dose planning and delivery techniques and the integration of drugs and radiation. The curricula can be downloaded at http://www.estro-education.org/europeantraining/Pages/EuropeanCurricula.aspx. CONCLUSION: The main objective of the ESTRO core curricula is to update and harmonise training of the radiation oncologists, medical physicists and RTTs in Europe. It is recommended that the authorities in charge of the respective training programmes throughout Europe harmonise their own curricula according to the common framework.