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BACKGROUND: This study aimed to create a prognostic model to predict disease recurrence among patients with lymph node involvement but no prostate-specific antigen (PSA) persistence and to explore its clinical utility. METHODS: The study analyzed patients with lymph node involvement after pelvic lymph node dissection with radical prostatectomy in whom no PSA persistence was observed between 2006 and 2019 at 33 institutions. Prognostic factors for recurrence-free survival (RFS) were analyzed by the Cox proportional hazards model. RESULTS: Among 231 patients, 127 experienced disease recurrence. The factors prognostic for RFS were PSA level at diagnosis (≥ 20 vs. < 20 ng/mL: hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.09-2.52; P = 0.017), International Society of Urological Pathology grade group at radical prostatectomy (RP) specimen (group ≥ 4 vs. ≤ 3: HR, 1.63; 95% CI 1.12-2.37; P = 0.010), pathologic T-stage (pT3b/4 vs. pT2/3a: HR, 1.70; 95% CI 1.20-2.42; P = 0.0031), and surgical margin status (positive vs. negative: HR, 1.60; 95% CI 1.13-2.28; P = 0.0086). The prognostic model using four parameters were associated with RFS and metastasis-free survival. CONCLUSION: The prognostic model in combination with postoperative PSA value and number of lymph nodes is clinically useful for discussing treatment choice with patients.
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Linfonodos , Metástase Linfática , Recidiva Local de Neoplasia , Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/sangue , Prostatectomia/métodos , Antígeno Prostático Específico/sangue , Pessoa de Meia-Idade , Taxa de Sobrevida , Seguimentos , Prognóstico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/sangue , Idoso , Linfonodos/patologia , Linfonodos/cirurgia , Excisão de Linfonodo , Estudos Retrospectivos , Estadiamento de Neoplasias , Gradação de Tumores , Margens de ExcisãoRESUMO
PURPOSE: The International Bladder Cancer Group designated the subgroup that is resistant to Bacillus Calmette-Guérin (BCG) but does not meet the criteria for BCG-unresponsive NMIBC as "BCG-exposed high-risk NMIBC" to guide optimal trial design. We aimed to investigate the treatment patterns and prognoses of patients with BCG-exposed NMIBC. METHODS: We conducted a retrospective chart review of 3283 patients who received intravesical BCG therapy for NMIBC at 14 participating institutions between January 2000 and December 2019. Patients meeting the criteria for BCG-exposed and BCG-unresponsive NMIBC, as defined by the Food and Drug Administration and International Bladder Cancer Group, were selected. To compare treatment patterns and outcomes, high-risk recurrence occurring more than 24 months after the last dose of BCG was defined as "BCG-treated NMIBC." In addition, we compared prognoses between BCG rechallenge and early cystectomy in patients with BCG-exposed NMIBC. RESULTS: Of 3283 patients, 108 (3.3%), 150 (4.6%), and 391 (11.9%) were classified as having BCG-exposed, unresponsive, and treated NMIBC, respectively. BCG-exposed NMIBC demonstrated intermediate survival curves for intravesical recurrence-free and progression-free survival, falling between those of BCG-unresponsive and treated NMIBC. Among patients with BCG-exposed NMIBC, 48 (44.4%) received BCG rechallenge, which was the most commonly performed treatment, and 19 (17.6%) underwent early cystectomy. No significant differences were observed between BCG rechallenge and early cystectomy in patients with BCG-exposed NMIBC. CONCLUSIONS: The newly proposed definition of BCG-exposed NMIBC may serve as a valuable disease subgroup for distinguishing significant gray areas, except in cases of BCG-unresponsive NMIBC.
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Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Humanos , Vacina BCG/uso terapêutico , Estudos Retrospectivos , Adjuvantes Imunológicos/uso terapêutico , Prognóstico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Análise de Dados , Administração Intravesical , Invasividade Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/tratamento farmacológicoRESUMO
BACKGROUND: This retrospective observational study explored the therapeutic potential of combined androgen blockade (CAB) with bicalutamide (Bic-CAB) as an initial treatment for metastatic hormone-sensitive prostate cancer (mHSPC) in Japan. METHODS: The electronic health records of 159 patients with mHSPC from three Japanese institutions who received initial treatment with Bic-CAB between 2007 and 2017 were analyzed. The time to prostate-specific antigen (PSA) progression, duration of Bic-CAB treatment, and overall survival (OS), with various definitions for PSA progression, were assessed. A multivariate Cox proportional hazards model was constructed using clinical parameters to predict time to the end of Bic-CAB treatment and OS. RESULTS: The median observation period was 46.4 months, and the median age of patients at diagnosis was 71 years. A total of 46.5% patients experienced PSA progression with a median survival duration of 29 months (according to Prostate Cancer Clinical Trials Working Group 3 criteria), and 49.1% patients achieved a PSA nadir < 0.2 ng/mL in a median time of 4.7 months. When stratified by PSA nadir and PSA change, patients at low risk for disease progression with a small PSA change due to low initial PSA had a 5-year OS of 100% and a 10-year OS of 75%. The OS during the observation period was 72.9 months. CONCLUSION: These findings highlight the potential effect of Bic-CAB in patients with mHSPC who were at low risk for disease progression. Initial treatment with Bic-CAB and adjusting treatment early based on PSA dynamics may be a reasonable treatment plan for these patients.
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BACKGROUND: The therapeutic role of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) for prostate cancer is not established. In clinical practice, PLND is primarily performed in cases of high-risk prostate cancer. The detection of lymph node metastasis plays a crucial role in determining the need for subsequent treatments. This study aims to evaluate the prognosis of prostate cancer patients with lymph node involvement (LNI) by stratifying them based on postoperative prostate-specific antigen (PSA) levels to identify biomarkers that can guide postoperative treatment strategies. METHODS: Analysis was conducted on 383 patients, selected from 572 initially eligible, who underwent RP with LNI across 33 Japanese Urological Oncology Group institutions from 2006 to 2019. Patients were grouped according to postoperative PSA levels and salvage treatments received. Follow-up focused on castration resistance-free survival (CRFS), metastasis-free survival (MFS), and overall survival (OS). RESULTS: In the persistent PSA group (PSA ≥ 0.1 ng/mL), CRFS and MFS were significantly shorter compared to the non-persistent PSA group (PSA < 0.1 ng/mL), and there was a tendency for shorter OS. In the persistent PSA group, patients with postoperative PSA values above the median (PSA ≥ 0.52 ng/mL) showed shorter CRFS and MFS. Furthermore, in the PSA ≥ 0.52 group, androgen deprivation therapy (ADT) plus radiotherapy (RT) combination had prolonged CRFS and MFS compared with ADT alone. CONCLUSIONS: This study provides valuable insights into stratifying patients based on postoperative PSA levels to tailor postoperative treatment strategies, potentially improving the prognosis of prostate cancer patients with LNI.
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Benign prostatic hyperplasia, a prevalent condition in aging men, is characterized by the proliferation of prostatic epithelial and stromal cells, which leads to bladder outlet obstruction and the exacerbation of lower urinary tract symptoms. There is increasing evidence that chronic prostatic inflammation contributes to the pathogenesis and progression of benign prostatic hyperplasia. This review explores the complex relationship between chronic inflammation and benign prostatic hyperplasia, focusing on the underlying mechanisms, clinical implications, and current therapeutic approaches. The pathophysiology of benign prostatic hyperplasia is multifaceted, involving factors such as hormonal changes, hypoxia, urine reflux into prostatic ducts and stroma, autoimmune responses, and infection-induced inflammation. Inflammatory cytokines, particularly interleukin-17 and interleukin-8, may play key roles in tissue remodeling and smooth muscle contraction within the prostate, thereby influencing benign prostatic hyperplasia progression. Current therapies for benign prostatic hyperplasia include α1-blockers, phosphodiesterase 5 inhibitors, 5α-reductase inhibitors, and plant-based treatments (e.g., pollen extract). These therapies aim to alleviate symptoms by reducing prostatic inflammation, improving blood flow, and inhibiting hormonal pathways involved in prostatic enlargement. However, patients with chronic prostatic inflammation often experience more severe lower urinary tract symptoms and may be resistant to conventional treatments. This resistance has prompted the exploration of alternative therapies targeting inflammation. Chronic prostatic inflammation plays a central role in the pathogenesis and severity of benign prostatic hyperplasia. An understanding of its mechanisms will enable the development of more effective treatments to improve the quality of life among patients with benign prostatic hyperplasia.
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OBJECTIVE: To evaluate and compare the voting results of Japanese urologists with the global panel at the Advanced Prostate Cancer Consensus Conference (APCCC) 2022. METHODS: Among the 198 questions discussed at the APCCC 2022, the APCCC-JAPAN 2023 focused on 14 key questions related to the management of advanced prostate cancer with insufficient high-level evidence based on their relevance to the Japanese cohort. A panel of six prostate cancer experts addressed these 14 questions and presented the latest evidence to Japanese urologists who voted on-site using a web-based system. The results were compared with those of APCCC 2022. RESULTS: This study found significant differences in the voting results between Japanese urologists and the global panel regarding several crucial issues related to advanced prostate cancer management. These differences were those observed in treatment preferences, monitoring strategies, and treatment choices in specific clinical scenarios. These findings highlight the need for a nuanced approach tailored to the unique challenges with considerations of the Japanese healthcare environment. CONCLUSIONS: APCCC-JAPAN 2023 provides valuable insights into the current clinical issues surrounding the management of advanced prostate cancer in Japan. The partial divergence in the consensus between Japanese urologists and the global panel underscores the importance of a context-specific approach. The results of this study provide practical guidance for physicians facing complex challenges and should be used to inform decision-making in the management of advanced prostate cancer.
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OBJECTIVES: To compare the effectiveness and safety of gonadotropin-releasing hormone (GnRH) antagonist monotherapy to combined androgen blockade (CAB) with a GnRH agonist and bicalutamide in patients with advanced hormone-sensitive prostate cancer (HSPC). METHODS: The study was conducted as KYUCOG-1401 trial (UMIN000014243) and enrolled 200 patients who were randomly assigned to either group A (GnRH antagonist monotherapy followed by the addition of bicalutamide) or group B (CAB by a GnRH agonist and bicalutamide). The primary endpoint was PSA progression-free survival. The secondary endpoints were the time to CAB treatment failure, radiographic progression-free survival, overall survival, changes in serum parameters, including PSA, hormones, and bone and lipid metabolic markers, and adverse events. RESULTS: PSA progression-free survival was significantly longer in group B (hazard ratio [HR], 95% confidence interval [CI]; 1.40, 1.01-1.95, p = 0.041). The time to CAB treatment failure was slightly longer in group A (HR, 95% CI; 0.80, 0.59-1.08, p = 0.146). No significant differences were observed in radiographic progression-free survival or overall survival. The percentage of patients with serum testosterone that did not reach the castration level was higher at 60 weeks (p = 0.046) in group A. No significant differences were noted in the serum levels of bone metabolic or lipid markers between the two groups. An injection site reaction was more frequent in group A. CONCLUSIONS: The present results support the potential of CAB using a GnRH agonist and bicalutamide as a more effective treatment for advanced HSPC than GnRH antagonist monotherapy.
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Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Antagonistas de Androgênios/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Anilidas/efeitos adversos , Nitrilas/efeitos adversos , Compostos de Tosil/efeitos adversos , Hormônio Liberador de Gonadotropina , Lipídeos/uso terapêuticoRESUMO
Genetic variations represented by single-nucleotide polymorphisms (SNPs) could be helpful for choosing an effective treatment for patients with prostate cancer. This study investigated the prognostic and predictive values of SNPs associated with the prognoses of pharmacotherapy for prostate cancer through their pharmacological mechanisms. Patients treated with docetaxel or androgen receptor pathway inhibitors (ARPIs), such as abiraterone and enzalutamide, for castration-resistant prostate cancer were included. The SNPs of interest were genotyped for target regions. The prognostic and predictive values of the SNPs for time to progression (TTP) were examined using the Cox hazard proportional model and interaction test, respectively. Rs1045642 in ABCB1, rs1047303 in HSD3B1, rs1856888 in HSD3B1, rs523349 in SRD5A2, and rs34550074 in SLCO2A1 were differentially associated with TTP between docetaxel chemotherapy and ARPI treatment. In addition to rs4775936 in CYP19A1, rs1128503 in ABCB1 and rs1077858 in SLCO2B1 might be differentially associated with TTP between abiraterone and enzalutamide treatments. Genetic predictive models using these SNPs showed a differential prognosis for treatments. This study identified SNPs that could predict progression as well as genetic models that could predict progression when patients were treated with docetaxel versus ARPI and abiraterone versus enzalutamide. The use of genetic predictive models is expected to be beneficial in selecting the appropriate treatment for the individual patient.
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Docetaxel , Transportadores de Ânions Orgânicos , Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Antagonistas de Receptores de Andrógenos/uso terapêutico , Androgênios , Docetaxel/uso terapêutico , Variação Genética , Proteínas de Membrana/genética , Nitrilas/uso terapêutico , Transportadores de Ânions Orgânicos/genética , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Taxoides , Resultado do TratamentoRESUMO
BACKGROUND: In men undergoing upfront active surveillance, predictors of adverse pathology in radical prostatectomy specimens, including intraductal carcinoma of the prostate and cribriform patterns, remain unknown. Therefore, we aimed to examine whether adverse pathology in radical prostatectomy specimens could be predicted using preoperative patient characteristics. METHODS: We re-reviewed available radical prostatectomy specimens from 1035 men prospectively enrolled in the PRIAS-JAPAN cohort between January 2010 and September 2020. We defined adverse pathology on radical prostatectomy specimens as Gleason grade group ≥3, pT stage ≥3, pN positivity or the presence of intraductal carcinoma of the prostate or cribriform patterns. We also examined the predictive factors associated with adverse pathology. RESULTS: All men analyzed had Gleason grade group 1 specimens at active surveillance enrolment. The incidence of adverse pathologies was 48.9% (with intraductal carcinoma of the prostate or cribriform patterns, 33.6%; without them, 15.3%). The addition of intraductal carcinoma of the prostate or cribriform patterns to the definition of adverse pathology increased the incidence by 10.9%. Patients showing adverse pathology with intraductal carcinoma of the prostate or cribriform patterns had lower biochemical recurrence-free survival (log-rank P = 0.0166). Increasing age at active surveillance enrolment and before radical prostatectomy was the only predictive factor for adverse pathology (odds ratio: 1.1, 95% confidence interval: 1.02-1.19, P = 0.0178; odds ratio: 1.12, 95% confidence interval: 1.02-1.22, P = 0.0126). CONCLUSIONS: Increasing age could be a predictive factor for adverse pathology. Our findings suggest that older men could potentially derive advantages from adhering to the examination schedule in active surveillance.
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Carcinoma Intraductal não Infiltrante , Neoplasias da Próstata , Masculino , Humanos , Idoso , Próstata/patologia , Carcinoma Intraductal não Infiltrante/patologia , Conduta Expectante , Neoplasias da Próstata/patologia , Prostatectomia , Gradação de TumoresRESUMO
OBJECTIVE: This study investigated the efficacy of docetaxel (DOC) and cabazitaxel (CBZ) and examined the factors associated with the prognosis of patients with castration-resistant prostate cancer (CRPC) receiving DOC-CBZ sequential treatment in Japanese real-world data. METHODS: We retrospectively evaluated data for 146 patients who received DOC followed by CBZ. The correlations of prostate specific antigen (PSA) decrease rate and time to progression between DOC and CBZ treatment were examined. Combined progression-free survival (PFS) of DOC-CBZ and overall survival (OS) from the initiation of DOC and the diagnosis of CRPC were evaluated and compared between patients with high and low PSA levels at the start of DOC and CBZ treatment. RESULTS: No correlations of PSA decrease rate and time to progression were observed between DOC and CBZ. The patients for whom DOC was started in higher PSA levels had significantly shorter combined PFS (p = 0.003) and OS from the initiation of DOC (p = 0.002). In patients who started DOC at high PSA levels, those who switched to CBZ at low PSA levels had longer OS than those who switched at high PSA levels (p = 0.048). The OS from CRPC of patients who started DOC at low PSA levels was significantly longer than those that started at high PSA levels (p = 0.030). CONCLUSIONS: For patients for whom DOC was not effective, sequential CBZ might have change to be effective. The PSA levels at the start of DOC and CBZ might be a potential prognostic biomarker.
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Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Docetaxel/uso terapêutico , Estudos Retrospectivos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Antígeno Prostático Específico , Japão , Resultado do TratamentoRESUMO
The treatment for lymph node involvement (LNI) after radical prostatectomy (RP) has not been established. This study aimed to reveal the outcomes of various management strategies among patients with LNI after RP. Retrospectively, 561 patients with LNI after pelvic lymph node dissection (PLND) with RP treated between 2006 and 2019 at 33 institutions participating in the Japanese Urological Oncology Group were investigated. Metastasis-free survival (MFS) was the primary outcome. Patients were stratified by prostate-specific antigen (PSA) persistence after RP. Cox regression models were used to analyze the relationships between clinicopathological characteristics and survival. Survival analyses were conducted using the Kaplan-Meier method and log-rank test with or without propensity score matching. Prognoses, including MFS and overall survival, were prominently inferior among patients with persistent PSA compared with those without persistent PSA. In multivariate analysis, androgen deprivation therapy (ADT) plus radiotherapy (RT) was associated with better MFS than ADT alone among patients with persistent PSA (hazard ratio = 0.37; 95% confidence interval = 0.15-0.93; p = 0.034). Similarly, MFS and overall survival were significantly better for ADT plus RT than for ADT alone among patients with persistent PSA after propensity score matching. This study indicated that PSA persistence in LNI prostate cancer increased the risk of poor prognoses, and intensive treatment featuring the addition of RT to ADT might improve survival.
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Antagonistas de Androgênios , Neoplasias da Próstata , Antagonistas de Androgênios/uso terapêutico , Androgênios , Humanos , Linfonodos/patologia , Masculino , Antígeno Prostático Específico , Prostatectomia/métodos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Estudos RetrospectivosRESUMO
BACKGROUND: The prognostic significance of germline variants in homologous recombination repair genes in advanced prostate cancer (PCa), especially with regard to hormonal therapy, remains controversial. METHODS: Germline DNA from 549 Japanese men with metastatic and/or castration-resistant PCa was sequenced for 27 cancer-predisposing genes. The associations between pathogenic variants and clinical outcomes were examined. Further, for comparison, DNA from prostate biopsy tissue samples from 80 independent patients with metastatic PCa were analysed. RESULTS: Forty-four (8%) patients carried germline pathogenic variants in one of the analysed genes. BRCA2 was most frequently altered (n = 19), followed by HOXB13 (n = 9), PALB2 (n = 5) and ATM (n = 5). Further, the BRCA1, BRCA2, PALB2 and ATM variants showed significant association with a short time to castration resistance and overall survival (hazard ratio = 1.99 and 2.36; 95% CI, 1.15-3.44 and 1.23-4.51, respectively), independent of other clinical variables. Based on log-rank tests, the time to castration resistance was also significantly short in patients with BRCA1, BRCA2, PALB2 or ATM somatic mutations and TP53 mutations. CONCLUSIONS: Germline variants in BRCA1, BRCA2, PALB2 or ATM are independent prognostic factors of the short duration of response to hormonal therapy in advanced PCa.
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Mutação em Linhagem Germinativa , Neoplasias da Próstata , Masculino , Humanos , Prognóstico , Proteína BRCA2/genética , Genes BRCA2 , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Mutação , Predisposição Genética para Doença , Proteína BRCA1/genética , Proteína do Grupo de Complementação N da Anemia de Fanconi/genética , Proteínas Mutadas de Ataxia Telangiectasia/genéticaRESUMO
The role of local treatment in patients with de novo metastatic prostate cancer is controversial. In population-based retrospective studies, metastatic prostate cancer patients who received local treatment with prostate radiotherapy showed a better prognosis than those who did not. In addition, several prospective randomized studies demonstrated that prostate radiotherapy achieves a survival benefit for patients with oligo-metastasis. Moreover, the efficacy of metastasis-directed radiotherapy was evaluated, revealing a potential benefit for patients with oligo-metastasis. Importantly, these radiotherapies may reduce the occurrence of symptomatic local events. In this review, the rationale, efficacy and future perspectives for local prostate and metastasis-directed radiotherapy in the treatment of metastatic prostate cancer were described and summarized.
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Próstata , Neoplasias da Próstata , Humanos , Masculino , Metástase Neoplásica/patologia , Pelve/patologia , Estudos Prospectivos , Próstata/patologia , Neoplasias da Próstata/patologia , Estudos RetrospectivosRESUMO
OBJECTIVES: The US Food and Drug Administration recently defined the clinical term "bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer" as a disease state resistant to adequate bacillus Calmette-Guérin therapy. There is a significant lack of prognostication for this disease even in patients who have undergone early radical cystectomy. This study aimed to identify the clinical outcomes and prognostic factors in Japanese patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer who underwent early radical cystectomy. METHODS: Data from a large-scale multicenter retrospective study included 2879 patients with highest-risk or high-risk non-muscle-invasive bladder cancer who received intravesical bacillus Calmette-Guérin induction therapy between January 2000 and December 2019. A total of 141 patients (4.3%) met the criteria for bacillus Calmette-Guérin-unresponsive disease, of whom 47 (33.3%) underwent early radical cystectomy. Prognostic factors for three clinical endpoints, namely, unresectable lesion-free survival, cancer-specific survival, and overall survival, were identified. RESULTS: The highest-risk status at induction bacillus Calmette-Guérin was associated with short unresectable lesion-free survival (hazard ratio 7.85; P < 0.05), cancer-specific survival (hazard ratio 12.24; P < 0.05), and overall survival (hazard ratio 9.25; P < 0.01). Moreover, extravesical tumors (pathological T3 or T4) on the radical cystectomy specimens were associated with poor prognosis and were found at a higher rate in patients with the highest-risk status at induction bacillus Calmette-Guérin than in those with high-risk status (35.7% vs 21.2%). CONCLUSIONS: The highest-risk status among the pre-bacillus Calmette-Guérin factors was associated with upstaging to extravesical tumors and poor prognosis despite early radical cystectomy procedures. Appropriate decision-making and the correct timing of radical cystectomy are vital to avoid treatment delays and improve outcomes.
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Vacina BCG , Neoplasias da Bexiga Urinária , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Vacina BCG/uso terapêutico , Cistectomia/métodos , Humanos , Japão/epidemiologia , Invasividade Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
OBJECTIVE: This study aimed to assess survival outcomes in older patients with de novo metastatic prostate cancer who initially received androgen deprivation therapy. METHODS: The retrospective multicenter study included 2784 men with metastatic prostate cancer who were treated with androgen deprivation therapy between 2008 and 2017. Patients were classified into <75, 75-79, and ≥80 age groups. Propensity score matching was conducted to assess the cancer-specific survival of the groups. The 5-year net overall survival of each group was derived to evaluate relative survival compared with the general population using the Pohar-Perme estimator and the 2019 Japan Life Table. RESULTS: During the follow-up (median, 34 months), 1014 patients died, of which 807 died from metastatic prostate cancer progression. Compared with the <75 group, the cancer-specific survival of the 75-79 group was similar (hazard ratio 1.07; 95% confidence interval 0.84-1.37; P = 0.580), whereas that of the ≥80 group was significantly worse (hazard ratio 1.41; 95% confidence interval 1.10-1.80; P = 0.006). The 5-year net overall survival of the <75, 75-79, and ≥80 age groups were 0.678, 0761, and 0.718, respectively. The 5-year net overall survival of patients aged ≥80 years with low- and high-volume disease were 0.893 and 0.586, respectively, which was comparable with those in patients aged <75 years (0.872 and 0.586, respectively). CONCLUSIONS: Older metastatic prostate cancer patients aged ≥80 years had poorer cancer-specific survival compared with younger patients. Conversely, 5-year net overall survival in older patients aged ≥80 years was comparable with that in younger patients aged <75 years.
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Neoplasias da Próstata , Idoso , Antagonistas de Androgênios/uso terapêutico , Androgênios , Humanos , Masculino , Modelos de Riscos Proporcionais , Neoplasias da Próstata/patologia , Estudos RetrospectivosRESUMO
OBJECTIVE: To determine the effect of combined androgen blockade with a first-generation anti-androgen on the prognoses of metastatic hormone-sensitive prostate cancer patients stratified by tumor burden. METHODS: We retrospectively analyzed the cases of metastatic hormone-sensitive prostate cancer patients who were treated with androgen deprivation therapy in 2008-2017 at 30 institutions in Japan. To compare the overall survival and progression-free survival rates of the patients treated with castration monotherapy and combined androgen blockade, we carried out a Cox proportional hazards regression analysis using both inverse probability of treatment weighting and instrumental variables methods. High-burden disease was defined as the presence of four or more bone metastases and/or visceral metastasis. RESULTS: Of 2048 patients, 702 (34.3%) and 1346 (65.7%) patients were classified as the low- and high-burden groups, respectively. In each group, >80% of the patients were treated with combined androgen blockade. Although there was no significant between-group difference in the overall survival according to the androgen deprivation therapy method, in the high-burden group the progression-free survival of the combined androgen blockade-treated patients was significantly better than that of patients treated with castration monotherapy: inverse probability of treatment weighting method, hazard ratio 0.49, 95% confidence interval 0.34-0.71; instrumental variables method, hazard ratio 0.80, 95% confidence interval 0.60-0.98. CONCLUSION: In the high-burden group, combined androgen blockade with a first-generation anti-androgen resulted in superior progression-free survival compared with castration monotherapy. For well-selected metastatic hormone-sensitive prostate cancer patients, the use of combined androgen blockade might still have some suitable scenarios.
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Antagonistas de Androgênios , Neoplasias da Próstata , Antagonistas de Androgênios/uso terapêutico , Androgênios , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Estudos Retrospectivos , Carga TumoralRESUMO
The metastatic burden is a critical factor for decision-making in the treatment of metastatic hormone-sensitive prostate cancer (HSPC). This study aimed to develop and validate a novel risk model for survival in patients with de novo low- and high-burden metastatic HSPC. The retrospective observational study included men with de novo metastatic prostate cancer who were treated with primary androgen-deprivation therapy at 30 institutions across Japan between 2008 and 2017. We created a risk model for overall survival (OS) in the discovery cohort (n = 1449) stratified by the metastatic burden (low vs high) and validated its predictive ability in a separate cohort (n = 951). Based on multivariate analyses, lower hemoglobin levels, higher Gleason grades, and higher clinical T-stage were associated with poor OS in low-burden disease. Meanwhile, lower hemoglobin levels, higher Gleason grade group, liver metastasis, and higher extent of disease scores in bone were associated with poor OS in patients with high-burden disease. In the discovery and validation cohorts, the risk model using the aforementioned parameters exhibited excellent discriminatory ability for progression-free survival and OS. The predictive ability of this risk model was superior to that of previous risk models. Our novel metastatic burden-stratified risk model exhibited excellent predictive ability for OS, and it is expected to have several clinical uses, such as precise prognostic estimation.
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Adenocarcinoma/tratamento farmacológico , Antagonistas de Androgênios/uso terapêutico , Modelos Estatísticos , Neoplasias da Próstata/tratamento farmacológico , Adenocarcinoma/sangue , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Hemoglobinas/análise , Humanos , Japão/epidemiologia , Masculino , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Intervalo Livre de Progressão , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Medição de RiscoRESUMO
Metastatic burden is a critical factor for therapy decision-making in metastatic hormone-sensitive prostate cancer. The present study aimed to identify prognostic factors in men with high- or low-metastatic burden treated with primary androgen-deprivation therapy. The study included 2450 men with de novo metastatic prostate cancer who were treated with primary androgen-deprivation therapy at 30 institutions across Japan between 2008 and 2017. We investigated the prognostic value of various clinicopathological parameters for progression-free survival (PFS) and overall survival (OS) in patients stratified by low- or high-metastatic burden. Among the 2450 men, 841 (34.3%) and 1609 (65.7%) were classified as having low- and high-metastatic burden, respectively. Median PFS of the low- and high-burden groups were 44.5 and 16.1 months, respectively, and the median OS was 103.2 and 62.7 months, respectively. Percentage of biopsy-positive core, biopsy Gleason grade group, T-stage, and N-stage were identified to be differentially prognostic. M1a was associated with worse PFS than was M1b in the low-burden group, whereas lung metastasis was associated with better PFS and OS than was M1b in the high-burden group. Differential prognostic factors were identified for patients with low- and high-burden metastatic prostate cancer. These results may assist in decision-making to select the optimal therapeutic strategies for patients with different metastatic burdens.
Assuntos
Hormônios/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Idoso , Antagonistas de Androgênios/uso terapêutico , Biópsia/métodos , Humanos , Japão , Masculino , Estadiamento de Neoplasias/métodos , Prognóstico , Intervalo Livre de Progressão , Neoplasias da Próstata/tratamento farmacológico , Estudos RetrospectivosRESUMO
BACKGROUND: To explore possible solutions to overcome chronic Bacillus Calmette-Guérin (BCG) shortage affecting seriously the management of non-muscle invasive bladder cancer (NMIBC) in Europe and throughout the world, we investigated whether non-maintenance eight-dose induction BCG (iBCG) was comparable to six-dose iBCG plus maintenance BCG (mBCG). METHODS: This observational study evaluated 2669 patients with high- or highest-risk NMIBC who treated with iBCG with or without mBCG during 2000-2019. The patients were classified into five groups according to treatment pattern: 874 (33%) received non-maintenance six-dose iBCG (Group A), 405 (15%) received six-dose iBCG plus mBCG (Group B), 1189 (44%) received non-maintenance seven-/eight-dose iBCG (Group C), 60 (2.2%) received seven-/eight-dose iBCG plus mBCG, and 141 (5.3%) received only ≤5-dose iBCG. Recurrence-free survival (RFS), progression-free survival, and cancer-specific survival were estimated and compared using Kaplan-Meier analysis and the log-rank test, respectively. Propensity score-based one-to-one matching was performed using a multivariable logistic regression model based on covariates to obtain balanced groups. To eliminate possible immortal bias, 6-, 12-, 18-, and 24-month conditional landmark analyses of RFS were performed. RESULTS: RFS comparison confirmed that mBCG yielded significant benefit following six-dose iBCG (Group B) in recurrence risk reduction compared to iBCG alone (groups A and C) before (P < 0.001 and P = 0.0016, respectively) and after propensity score matching (P = 0.001 and P = 0.0074, respectively). Propensity score-matched sequential landmark analyses revealed no significant differences between groups B and C at 12, 18, and 24 months, whereas landmark analyses at 6 and 12 months showed a benefit of mBCG following six-dose iBCG compared to non-maintenance six-dose iBCG (P = 0.0055 and P = 0.032, respectively). There were no significant differences in the risks of progression and cancer-specific death in all comparisons of the matched cohorts. CONCLUSIONS: Although non-maintenance eight-dose iBCG was inferior to six-dose iBCG plus mBCG, the former might be an alternative remedy in the BCG shortage era. To overcome this challenge, further investigation is warranted to confirm the real clinical value of non-maintenance eight-dose iBCG.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Vacina BCG/administração & dosagem , Quimioterapia de Indução/métodos , Recidiva Local de Neoplasia/epidemiologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Seguimentos , Humanos , Quimioterapia de Indução/estatística & dados numéricos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Quimioterapia de Manutenção/estatística & dados numéricos , Masculino , Recidiva Local de Neoplasia/prevenção & controle , Intervalo Livre de Progressão , Estudos Retrospectivos , Bexiga Urinária/imunologia , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologiaRESUMO
OBJECTIVES: To prospectively evaluate the detection rate of prostate cancer, and to identify the risk factors of prostate cancer detection after a 1-year administration of dutasteride and first negative prostate biopsy. METHODS: Patients with benign prostatic hyperplasia who presented high prostate-specific antigen levels after the first negative prostate biopsy were administered 0.5 mg dutasteride daily for 1 year. They underwent a repeat prostate biopsy after 1 year. The primary end-point was the detection rate of prostate cancer. The secondary end-point was the ability of prostate-specific antigen kinetics to predict prostate cancer detection. Prostate-specific antigen was measured before the initial prostate biopsy and at 6, 9 and 12 months after starting dutasteride. Patients were classified into a prostate cancer and a non-prostate cancer group. RESULTS: Prostate cancer was detected in 15 of 149 participants (10.1%). The total prostate-specific antigen change between the prostate cancer and non-prostate cancer group at 1 year was significantly different (P = 0.002). Although prostate-specific antigen levels at baseline did not significantly differ between study groups (P = 0.102), prostate-specific antigen levels at 6, 9 and 12 months were significantly different (P = 0.002, P = 0.001 and P < 0.001, respectively). The mean reduction rate of prostate-specific antigen density between the prostate cancer and non-prostate cancer group at 1 year was significantly different (-4.25 ± 76.5% vs -38.0 ± 28.7%, P = 0.001). Using a multivariate analysis, a >10% increase of prostate-specific antigen density at 1 year post-dutasteride treatment was the only predictive risk factor for prostate cancer after the first negative prostate biopsy (odds ratio 11.238, 95% confidence interval 3.112-40.577, P < 0.001). CONCLUSION: In the present study cohort, >10% increase in prostate-specific antigen density represented the only significant predictive risk factor for prostate cancer diagnosis in patients with elevated prostate-specific antigen after the first negative prostate biopsy.