RESUMO
BACKGROUND: Current guidelines suggest adjuvant radiation therapy for men with adverse pathologic features (APFs) at radical prostatectomy (RP). We examine at-risk men treated only with RP until the time of metastasis. OBJECTIVE: To evaluate whether clinicopathologic risk models can help guide postoperative therapeutic decision making. DESIGN, SETTING, AND PARTICIPANTS: Men with National Comprehensive Cancer Network intermediate- or high-risk localized prostate cancer undergoing RP in the prostate-specific antigen (PSA) era were identified (n=3089). Only men with initial undetectable PSA after surgery and who received no therapy prior to metastasis were included. APFs were defined as pT3 disease or positive surgical margins. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Area under the receiver operating characteristic curve (AUC) for time to event data was used to measure the discrimination performance of the risk factors. Cumulative incidence curves were constructed using Fine and Gray competing risks analysis to estimate the risk of biochemical recurrence (BCR) or metastasis, taking censoring and death due to other causes into consideration. RESULTS AND LIMITATIONS: Overall, 43% of the cohort (n=1327) had APFs at RP. Median follow-up for censored patients was 5 yr. Cumulative incidence of metastasis was 6% at 10 yr after RP for all patients. Cumulative incidence of metastasis among men with APFs was 7.5% at 10 yr after RP. Among men with BCR, the incidence of metastasis was 38% 5 yr after BCR. At 10 yr after RP, time-dependent AUC for predicting metastasis by Cancer of the Prostate Risk Assessment Postsurgical or Eggener risk models was 0.81 (95% confidence interval [CI], 0.72-0.97) and 0.78 (95% CI, 0.67-0.97) in the APF population, respectively. At 5 yr after BCR, these values were lower (0.58 [95% CI, 0.50-0.66] and 0.70 [95% CI, 0.63-0.76]) among those who developed BCR. Use of risk model cut points could substantially reduce overtreatment while minimally increasing undertreatment (ie, use of an Eggener cut point of 2.5% for treatment of men with APFs would spare 46% from treatment while only allowing for metastatic events in 1% at 10 yr after RP). CONCLUSIONS: Use of risk models reduces overtreatment and should be a routine part of patient counseling when considering adjuvant therapy. Risk model performance is significantly reduced among men with BCR. PATIENT SUMMARY: Use of current risk models can help guide decision making regarding therapy after surgery and reduce overtreatment.
Assuntos
Técnicas de Apoio para a Decisão , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Área Sob a Curva , Humanos , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasia Residual , Valor Preditivo dos Testes , Antígeno Prostático Específico/sangue , Prostatectomia/efeitos adversos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Curva ROC , Radioterapia Adjuvante , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoAssuntos
Doenças Cardiovasculares/prevenção & controle , Suplementos Nutricionais , Neoplasias/prevenção & controle , Vitamina D/administração & dosagem , Distribuição por Idade , Idoso , Doenças Cardiovasculares/epidemiologia , Intervalos de Confiança , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Prevenção Primária/métodos , Probabilidade , Valores de Referência , Medição de Risco , Distribuição por Sexo , Análise de Sobrevida , Falha de TratamentoAssuntos
Antagonistas de Androgênios/uso terapêutico , Androgênios/fisiologia , Recidiva Local de Neoplasia/terapia , Neoplasias Hormônio-Dependentes/terapia , Orquiectomia , Neoplasias da Próstata/terapia , Antagonistas de Androgênios/efeitos adversos , Terapia Combinada , Análise Custo-Benefício , Humanos , Masculino , Metástase Neoplásica , Recidiva Local de Neoplasia/economia , Neoplasias Hormônio-Dependentes/economia , Orquiectomia/economia , Cuidados Paliativos/economia , Neoplasias da Próstata/economia , Ensaios Clínicos Controlados Aleatórios como AssuntoAssuntos
Androgênios/fisiologia , Antineoplásicos Fitogênicos/administração & dosagem , Dietilestilbestrol/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Fitoterapia , Neoplasias da Próstata/tratamento farmacológico , Biomarcadores Tumorais/sangue , Estudos Cross-Over , Progressão da Doença , Contaminação de Medicamentos , Seguimentos , Humanos , Masculino , Neoplasias Hormônio-Dependentes/patologia , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Resultado do TratamentoRESUMO
OBJECTIVES: To evaluate familial aggregation and the mode of inheritance of bothersome benign prostatic hyperplasia (BPH). METHODS: During an extension of the North American Finasteride Trial, 301 of 895 patients and 158 spousal controls completed a family history questionnaire. Segregation analysis was performed to examine the mode of inheritance in first-degree relatives of the 301 probands. RESULTS: The lifetime cumulative probability of bothersome BPH was similar in relatives of those with BPH (0.35; 95% confidence interval [CI] 0.28 to 0.44) and spousal controls (0.36; 95% CI 0.22 to 0.56), but the age of onset was significantly earlier in relatives of cases than controls (P = 0.001). Fathers of those with BPH had a significantly elevated risk of bothersome BPH (unadjusted odds ratio [OR] 2.1; 95% CI 1.2 to 3.8) and brothers had a significantly elevated risk of both bothersome BPH (OR 3.5; 95% CI 1.7 to 7.3) and transurethral resection of the prostate (OR 3.6; 95% CI 1.4 to 8.8). After adjusting for family size, the risk of bothersome BPH increased approximately twofold with each additional affected first-degree relative (0 relatives, OR 1.0; 1 relative, OR 1.7; 2 relatives, OR 4.7). Segregation analysis suggested a rare autosomal codominant allele (frequency 0.0004). CONCLUSIONS: These findings confirm previous findings that family history and early age of onset are associated with an increased risk of BPH and that the most likely mode of inheritance is autosomal dominant or codominant. Bothersome BPH appears to have a weaker genetic component than more restrictive definitions of hereditary BPH. Thus, linkage studies are more likely to be successful if they focus on stricter definitions of hereditary BPH (eg, early onset, large volume, strong family history) rather than symptomatic or clinical BPH.