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PURPOSE: To evaluate active surveillance (AS) outcomes including overall survival (OS), freedom from distant metastases (FDM), freedom from therapeutic intervention (FTI), and quality of life (QOL) outcomes in prostate cancer patients using transperineal template-guided mapping biopsy (TTMB) for patient selection. METHODS: From April 2005-January 2016, 226 consecutive, prospectively evaluated prostate cancer patients underwent TTMB for either low-grade prostate cancer or persistently elevated prostate-specific antigen (PSA) and/or the presence of ASAP. Evaluated outcomes included OS, FDM, FTI and QOL including urinary, bowel, sexual function and depression. Repeat biopsy was based on PSA kinetics and/or abnormal digital rectal examination. RESULTS: Of the 226 patients, 212 (93.8%) were Gleason 3 + 3 and 14 (6.2%) were Gleason 3 + 4. The median follow-up was 5.0 years (range 0.8-13.0 years). The mean prostate volume was 61.3 cm3 with a mean of 59.5 TTMB cores/patient. At the time of AS enrollment, an average of 72.9 cores (TRUS + TTMB) had been obtained for each patient. At 8 years, OS, FTI and FDM were 92.5, 96.8 and 100%. Two hundred and twenty-two patients (98.2%) had a PSA doubling time of more than 3 years. No statistical changes in urinary function, bowel function or depression were noted. At 8 years, 73% of the patients maintained erectile function. CONCLUSION: Within the confines of the follow-up of this study, the use of TTMB for patient selection identifies a cohort of patients unlikely to develop biochemical or clinical progression and maintain a favorable quality of life.
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Biópsia Guiada por Imagem/métodos , Seleção de Pacientes , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Qualidade de Vida , Conduta Expectante/métodos , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Importance: The optimal treatment for Gleason score 9-10 prostate cancer is unknown. Objective: To compare clinical outcomes of patients with Gleason score 9-10 prostate cancer after definitive treatment. Design, Setting, and Participants: Retrospective cohort study in 12 tertiary centers (11 in the United States, 1 in Norway), with 1809 patients treated between 2000 and 2013. Exposures: Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy, or EBRT plus brachytherapy boost (EBRT+BT) with androgen deprivation therapy. Main Outcomes and Measures: The primary outcome was prostate cancer-specific mortality; distant metastasis-free survival and overall survival were secondary outcomes. Results: Of 1809 men, 639 underwent RP, 734 EBRT, and 436 EBRT+BT. Median ages were 61, 67.7, and 67.5 years; median follow-up was 4.2, 5.1, and 6.3 years, respectively. By 10 years, 91 RP, 186 EBRT, and 90 EBRT+BT patients had died. Adjusted 5-year prostate cancer-specific mortality rates were RP, 12% (95% CI, 8%-17%); EBRT, 13% (95% CI, 8%-19%); and EBRT+BT, 3% (95% CI, 1%-5%). EBRT+BT was associated with significantly lower prostate cancer-specific mortality than either RP or EBRT (cause-specific HRs of 0.38 [95% CI, 0.21-0.68] and 0.41 [95% CI, 0.24-0.71]). Adjusted 5-year incidence rates of distant metastasis were RP, 24% (95% CI, 19%-30%); EBRT, 24% (95% CI, 20%-28%); and EBRT+BT, 8% (95% CI, 5%-11%). EBRT+BT was associated with a significantly lower rate of distant metastasis (propensity-score-adjusted cause-specific HRs of 0.27 [95% CI, 0.17-0.43] for RP and 0.30 [95% CI, 0.19-0.47] for EBRT). Adjusted 7.5-year all-cause mortality rates were RP, 17% (95% CI, 11%-23%); EBRT, 18% (95% CI, 14%-24%); and EBRT+BT, 10% (95% CI, 7%-13%). Within the first 7.5 years of follow-up, EBRT+BT was associated with significantly lower all-cause mortality (cause-specific HRs of 0.66 [95% CI, 0.46-0.96] for RP and 0.61 [95% CI, 0.45-0.84] for EBRT). After the first 7.5 years, the corresponding HRs were 1.16 (95% CI, 0.70-1.92) and 0.87 (95% CI, 0.57-1.32). No significant differences in prostate cancer-specific mortality, distant metastasis, or all-cause mortality (≤7.5 and >7.5 years) were found between men treated with EBRT or RP (cause-specific HRs of 0.92 [95% CI, 0.67-1.26], 0.90 [95% CI, 0.70-1.14], 1.07 [95% CI, 0.80-1.44], and 1.34 [95% CI, 0.85-2.11]). Conclusions and Relevance: Among patients with Gleason score 9-10 prostate cancer, treatment with EBRT+BT with androgen deprivation therapy was associated with significantly better prostate cancer-specific mortality and longer time to distant metastasis compared with EBRT with androgen deprivation therapy or with RP.
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Prostatectomia , Neoplasias da Próstata/terapia , Radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico , Braquiterapia , Causas de Morte , Terapia Combinada , Progressão da Doença , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Pontuação de Propensão , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Radioterapia/métodos , Estudos Retrospectivos , Análise de SobrevidaRESUMO
BACKGROUND: The burden of pulmonary hypertension (PH) among patients with chronic obstructive pulmonary disease (COPD) is not well understood. The present retrospective cohort study aimed to quantify the clinical and economic burden of PH in patients with COPD. METHODS: Adults with COPD were retrospectively identified in the Optum® Clinformatics® Data Mart between July 1, 2016 and June 30, 2021. Those diagnosed with PH were assigned to the PH-COPD cohort and those without a diagnosis of PH were assigned to the COPD cohort. Outcomes, including the number of visits for exacerbations and all-cause and COPD-related healthcare resource utilization (HCRU) and costs per patient per month (PPPM), were compared between cohorts. Baseline and study outcomes were analyzed descriptively. For significance testing, continuous variables were analyzed using Student's t-tests and categorical variables were analyzed using Chi-square tests. RESULTS: A total of 1627 patients with PH-COPD were matched 1:1 to COPD patients without PH. A greater percentage of PH-COPD patients experienced COPD exacerbations vs. the COPD cohort (p < 0.001) and the PH-COPD cohort had more total (p < 0.001) and severe exacerbation-related visits PPPM (p < 0.001). All-cause and COPD-related HCRU PPPM estimates were higher among the PH-COPD cohort vs. the COPD cohort (p < 0.01). Total all-cause (p < 0.001) and COPD-related costs (p < 0.001) were higher among PH-COPD patients than COPD patients. CONCLUSIONS: Patients with PH-COPD had higher rates of severe exacerbations, hospitalizations, and costs compared to COPD patients without PH, underscoring the need for targeted therapies to prevent and manage PH in patients with COPD.
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Hipertensão Pulmonar , Doença Pulmonar Obstrutiva Crônica , Adulto , Humanos , Estados Unidos/epidemiologia , Estudos Retrospectivos , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/terapia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/terapia , Atenção à Saúde , Aceitação pelo Paciente de Cuidados de SaúdeRESUMO
PURPOSE: Very-high-risk (VHR) prostate cancer (PC) is an aggressive subgroup with high risk of distant disease progression. Systemic treatment intensification with abiraterone or docetaxel reduces PC-specific mortality (PCSM) and distant metastasis (DM) in men receiving external beam radiation therapy (EBRT) with androgen deprivation therapy (ADT). Whether prostate-directed treatment intensification with the addition of brachytherapy (BT) boost to EBRT with ADT improves outcomes in this group is unclear. METHODS AND MATERIALS: This cohort study from 16 centers across 4 countries included men with VHR PC treated with either dose-escalated EBRT with ≥24 months of ADT or EBRT + BT boost with ≥12 months of ADT. VHR was defined by National Comprehensive Cancer Network (NCCN) criteria (clinical T3b-4, primary Gleason pattern 5, or ≥2 NCCN high-risk features), and results were corroborated in a subgroup of men who met Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trials inclusion criteria (≥2 of the following: clinical T3-4, Gleason 8-10, or PSA ≥40 ng/mL). PCSM and DM between EBRT and EBRT + BT were compared using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression. RESULTS: Among the entire cohort, 270 underwent EBRT and 101 EBRT + BT. After a median follow-up of 7.8 years, 6.7% and 5.9% of men died of PC and 16.3% and 9.9% had DM after EBRT and EBRT + BT, respectively. There was no significant difference in PCSM (sHR, 1.47 [95% CI, 0.57-3.75]; P = .42) or DM (sHR, 0.72, [95% CI, 0.30-1.71]; P = .45) between EBRT + BT and EBRT. Results were similar within the STAMPEDE-defined VHR subgroup (PCSM: sHR, 1.67 [95% CI, 0.48-5.81]; P = .42; DM: sHR, 0.56 [95% CI, 0.15-2.04]; P = .38). CONCLUSIONS: In this VHR PC cohort, no difference in clinically meaningful outcomes was observed between EBRT alone with ≥24 months of ADT compared with EBRT + BT with ≥12 months of ADT. Comparative analyses in men treated with intensified systemic therapy are warranted.
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Braquiterapia , Neoplasias da Próstata , Masculino , Humanos , Braquiterapia/métodos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/patologia , Estudos de Coortes , Antagonistas de Androgênios/uso terapêutico , Gradação de Tumores , Estudos RetrospectivosRESUMO
IMPORTANCE: Radiotherapy combined with androgen deprivation therapy (ADT) is a standard of care for high-risk prostate cancer. However, the interplay between radiotherapy dose and the required minimum duration of ADT is uncertain. OBJECTIVE: To determine the specific ADT duration threshold that provides a distant metastasis-free survival (DMFS) benefit in patients with high-risk prostate cancer receiving external beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT). DESIGN, SETTINGS, AND PARTICIPANTS: This was a cohort study of 3 cohorts assembled from a multicenter retrospective study (2000-2013); a post hoc analysis of the Randomized Androgen Deprivation and Radiotherapy 03/04 (RADAR; 2003-2007) randomized clinical trial (RCT); and a cross-trial comparison of the RADAR vs the Deprivación Androgénica y Radio Terapía (Androgen Deprivation and Radiation Therapy; DART) 01/05 RCT (2005-2010). In all, the study analyzed 1827 patients treated with EBRT and 1108 patients treated with EBRT+BT from the retrospective cohort; 181 treated with EBRT and 203 with EBRT+BT from RADAR; and 91 patients treated with EBRT from DART. The study was conducted from October 15, 2020, to July 1, 2021, and the data analyses, from January 5 to June 15, 2021. EXPOSURES: High-dose EBRT or EBRT+BT for an ADT duration determined by patient-physician choice (retrospective) or by randomization (RCTs). MAIN OUTCOMES AND MEASURES: The primary outcome was DMFS; secondary outcome was overall survival (OS). Natural cubic spline analysis identified minimum thresholds (months). RESULTS: This cohort study of 3 studies totaling 3410 men (mean age [SD], 68 [62-74] years; race and ethnicity not collected) with high-risk prostate cancer found a significant interaction between the treatment type (EBRT vs EBRT+BT) and ADT duration (binned to <6, 6 to <18, and ≥18 months). Natural cubic spline analysis identified minimum duration thresholds of 26.3 months (95% CI, 25.4-36.0 months) for EBRT and 12 months (95% CI, 4.9-36.0 months) for EBRT+BT for optimal effect on DMFS. In RADAR, the prolongation of ADT for patients receiving only EBRT was not associated with significant improvements in DMFS (hazard ratio [HR], 1.01; 95% CI, 0.65-1.57); however, for patients receiving EBRT+BT, a longer duration was associated with improved DMFS (DMFS HR, 0.56; 95% CI, 0.36-0.87; P = .01). For patients receiving EBRT alone (DART), 28 months of ADT was associated with improved DMFS compared with 18 months (RADAR HR, 0.37; 95% CI, 0.17-0.80; P = .01). CONCLUSIONS AND RELEVANCE: These cohort study findings suggest that the optimal minimum ADT duration for treatment with high-dose EBRT alone is more than 18 months; and for EBRT+BT, it is 18 months or possibly less. Additional studies are needed to determine more precise minimum durations.
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Braquiterapia , Neoplasias da Próstata , Antagonistas de Androgênios/efeitos adversos , Androgênios , Braquiterapia/efeitos adversos , Análise de Dados , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Estudos RetrospectivosRESUMO
Objectives: To evaluate the impact of age on overall survival (OS), freedom from distant metastasis (FDM), rates of therapeutic intervention (TI), and quality of life (QOL) in active surveillance (AS) prostate cancer patients. Materials and methods: Three hundred and five consecutive, prospectively evaluated AS patients who underwent a staging transperineal template-guided mapping biopsy (TTMB) prior to enrollment on AS were evaluated and stratified by age. Evaluated outcomes included OS, FDM, TI, and QOL to include urinary, bowel, sexual function, and depression. Post void residual (PVR) urine measurements were also followed. Repeat biopsy was based on PSA kinetics, abnormal digital rectal examination or patient preference. Results: Of the 305 patients, 290 (95.1%) were Gleason 3 + 3 and 15 patients (4.9%) were Gleason 3 + 4. The median follow-up was 5.5 years (range 1-14 years). At 10 years, TI was 0%, 1.0%, and 11.4% for patients ≤59, 60-69, and ≥70 years of age (P < .001). No patient has developed distant metastasis. The median time to TI was 4.71 years. No statistical differences in urinary function, bowel function, or depression were noted. Potency preservation was dependent on patient age. Conclusion: Within the confines of the follow-up of our series, younger patients were less likely to proceed to therapeutic intervention. In addition, patient age did not adversely impact QOL outcomes.
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OBJECTIVE: The objective of this study was to evaluate the impact of body mass index (BMI) on overall survival, freedom from distant metastases, rates of therapeutic intervention (TI), and quality of life (QOL) in active surveillance (AS) prostate cancer patients. MATERIALS AND METHODS: Three hundred forty consecutive, prospectively evaluated AS patients underwent a staging transperineal template-guided mapping biopsy before AS enrollment and were stratified by BMI (<25, 25 to 29.9, 30 to 34.9, and >35 kg/m2). Evaluated outcomes included overall survival, freedom from distant metastases, TI, QOL to include urinary, bowel, sexual function and depression and serial postvoid residual urine measurements. The relationship between BMI and anterior prostate cancer distribution was evaluated. Repeat biopsy was based on prostate specific antigen kinetics, abnormal digital rectal examination and patient preference. RESULTS: Of the 340 patients, 323 (95%) were Gleason 3+3 and 17 patients (5.0%) were Gleason 3+4. The median follow-up was 5.2 years (range: 1 to 14 y). At 10 years, TI was instituted in 4.7%, 2.2%, 9.5%, and 25.0% of patients in BMI cohorts <25, 25 to 29.9, 30 to 34.9, and ≥35 (P=0.075). No patient has developed distant metastases. The median time to TI was 4.86 years. In multivariate analysis, TI was most closely predicted by prostate specific antigen density (P=0.071). At 8 years, no statistical differences in urinary function, bowel function, depression or postvoid residual were noted. However, a trend for erectile dysfunction was identified (P=0.106). CONCLUSION: At 10 years, BMI did not statistically predict for TI, geographic distribution of prostate cancer or QOL parameters.
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Índice de Massa Corporal , Neoplasias da Próstata , Qualidade de Vida , Conduta Expectante , Idoso , Depressão/etiologia , Disfunção Erétil/etiologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/análise , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Taxa de SobrevidaRESUMO
The natural history of radiorecurrent high-risk prostate cancer (HRPCa) is not well-described. To better understand its clinical course, we evaluated rates of distant metastases (DM) and prostate cancer-specific mortality (PCSM) in a cohort of 978 men with radiorecurrent HRPCa who previously received either external beam radiation therapy (EBRT, n = 654, 67%) or EBRT + brachytherapy (EBRT + BT, n = 324, 33%) across 15 institutions from 1997 to 2015. In men who did not die, median follow-up after treatment was 8.9 yr and median follow-up after biochemical recurrence (BCR) was 3.7 yr. Local and systemic therapy salvage, respectively, were delivered to 21 and 390 men after EBRT, and eight and 103 men after EBRT + BT. Overall, 435 men developed DM, and 248 were detected within 1 yr of BCR. Measured from time of recurrence, 5-yr DM rates were 50% and 34% after EBRT and EBRT + BT, respectively. Measured from BCR, 5-yr PCSM rates were 27% and 29%, respectively. Interval to BCR was independently associated with DM (p < 0.001) and PCSM (p < 0.001). These data suggest that radiorecurrent HRPCa has an aggressive natural history and that DM is clinically evident early after BCR. These findings underscore the importance of further investigations into upfront risk assessment and prompt systemic evaluation upon recurrence in HRPCa. PATIENT SUMMARY: High-risk prostate cancer that recurs after radiation therapy is an aggressive disease entity and spreads to other parts of the body (metastases). Some 60% of metastases occur within 1 yr. Approximately 30% of these patients die from their prostate cancer.
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Braquiterapia , Neoplasias da Próstata , Braquiterapia/efeitos adversos , Humanos , Masculino , Gradação de Tumores , Próstata , Neoplasias da Próstata/radioterapia , Terapia de SalvaçãoRESUMO
Importance: The optimal management strategy for high-risk prostate cancer and additional adverse clinicopathologic features remains unknown. Objective: To compare clinical outcomes among patients with high-risk prostate cancer after definitive treatment. Design, Setting, and Participants: This retrospective cohort study included patients with high-risk prostate cancer (as defined by the National Comprehensive Cancer Network [NCCN]) and at least 1 adverse clinicopathologic feature (defined as any primary Gleason pattern 5 on biopsy, clinical T3b-4 disease, ≥50% cores with biopsy results positive for prostate cancer, or NCCN ≥2 high-risk features) treated between 2000 and 2014 at 16 tertiary centers. Data were analyzed in November 2020. Exposures: Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT), or EBRT plus brachytherapy boost (BT) with ADT. Guideline-concordant multimodal treatment was defined as RP with appropriate use of multimodal therapy (optimal RP), EBRT with at least 2 years of ADT (optimal EBRT), or EBRT with BT with at least 1 year ADT (optimal EBRT with BT). Main Outcomes and Measures: The primary outcome was prostate cancer-specific mortality; distant metastasis was a secondary outcome. Differences were evaluated using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression models. Results: A total of 6004 men (median [interquartile range] age, 66.4 [60.9-71.8] years) with high-risk prostate cancer were analyzed, including 3175 patients (52.9%) who underwent RP, 1830 patients (30.5%) who underwent EBRT alone, and 999 patients (16.6%) who underwent EBRT with BT. Compared with RP, treatment with EBRT with BT (subdistribution hazard ratio [sHR] 0.78, [95% CI, 0.63-0.97]; P = .03) or with EBRT alone (sHR, 0.70 [95% CI, 0.53-0.92]; P = .01) was associated with significantly improved prostate cancer-specific mortality; there was no difference in prostate cancer-specific mortality between EBRT with BT and EBRT alone (sHR, 0.89 [95% CI, 0.67-1.18]; P = .43). No significant differences in prostate cancer-specific mortality were found across treatment cohorts among 2940 patients who received guideline-concordant multimodality treatment (eg, optimal EBRT alone vs optimal RP: sHR, 0.76 [95% CI, 0.52-1.09]; P = .14). However, treatment with EBRT alone or EBRT with BT was consistently associated with lower rates of distant metastasis compared with treatment with RP (eg, EBRT vs RP: sHR, 0.50 [95% CI, 0.44-0.58]; P < .001). Conclusions and Relevance: These findings suggest that among patients with high-risk prostate cancer and additional unfavorable clinicopathologic features receiving guideline-concordant multimodal therapy, prostate cancer-specific mortality outcomes were equivalent among those treated with RP, EBRT, and EBRT with BT, although distant metastasis outcomes were more favorable among patients treated with EBRT and EBRT with BT. Optimal multimodality treatment is critical for improving outcomes in patients with high-risk prostate cancer.
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Terapia Combinada/normas , Neoplasias da Próstata/terapia , Radioterapia/normas , Idoso , California/epidemiologia , Estudos de Coortes , Terapia Combinada/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Prostatectomia/métodos , Prostatectomia/estatística & dados numéricos , Neoplasias da Próstata/complicações , Neoplasias da Próstata/mortalidade , Radioterapia/métodos , Radioterapia/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
Importance: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) can detect low-volume, nonlocalized (ie, regional or metastatic) prostate cancer that was occult on conventional imaging. However, the long-term clinical implications of PSMA PET/CT upstaging remain unclear. Objectives: To evaluate the prognostic significance of a nomogram that models an individual's risk of nonlocalized upstaging on PSMA PET/CT and to compare its performance with existing risk-stratification tools. Design, Setting, and Participants: This cohort study included patients diagnosed with high-risk or very high-risk prostate cancer (ie, prostate-specific antigen [PSA] level >20 ng/mL, Gleason score 8-10, and/or clinical stage T3-T4, without evidence of nodal or metastatic disease by conventional workup) from April 1995 to August 2018. This multinational study was conducted at 15 centers. Data were analyzed from December 2020 to March 2021. Exposures: Curative-intent radical prostatectomy (RP), external beam radiotherapy (EBRT), or EBRT plus brachytherapy (BT), with or without androgen deprivation therapy. Main Outcomes and Measures: PSMA upstage probability was calculated from a nomogram using the biopsy Gleason score, percentage positive systematic biopsy cores, clinical T category, and PSA level. Biochemical recurrence (BCR), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall survival (OS) were analyzed using Fine-Gray and Cox regressions. Model performance was quantified with the concordance (C) index. Results: Of 5275 patients, the median (IQR) age was 66 (60-72) years; 2883 (55%) were treated with RP, 1669 (32%) with EBRT, and 723 (14%) with EBRT plus BT; median (IQR) PSA level was 10.5 (5.9-23.2) ng/mL; 3987 (76%) had Gleason grade 8 to 10 disease; and 750 (14%) had stage T3 to T4 disease. Median (IQR) follow-up was 5.1 (3.1-7.9) years; 1221 (23%) were followed up for at least 8 years. Overall, 1895 (36%) had BCR, 851 (16%) developed DM, and 242 (5%) died of prostate cancer. PSMA upstage probability was significantly prognostic of all clinical end points, with 8-year C indices of 0.63 (95% CI, 0.61-0.65) for BCR, 0.69 (95% CI, 0.66-0.71) for DM, 0.71 (95% CI, 0.67-0.75) for PCSM, and 0.60 (95% CI, 0.57-0.62) for PCSM (P < .001). The PSMA nomogram outperformed existing risk-stratification tools, except for similar performance to Staging Collaboration for Cancer of the Prostate (STAR-CAP) for PCSM (eg, DM: PSMA, 0.69 [95% CI, 0.66-0.71] vs STAR-CAP, 0.65 [95% CI, 0.62-0.68]; P < .001; Memorial Sloan Kettering Cancer Center nomogram, 0.57 [95% CI, 0.54-0.60]; P < .001; Cancer of the Prostate Risk Assessment groups, 0.53 [95% CI, 0.51-0.56]; P < .001). Results were validated in secondary cohorts from the Surveillance, Epidemiology, and End Results database and the National Cancer Database. Conclusions and Relevance: These findings suggest that PSMA upstage probability is associated with long-term, clinically meaningful end points. Furthermore, PSMA upstaging had superior risk discrimination compared with existing tools. Formerly occult, PSMA PET/CT-detectable nonlocalized disease may be the main driver of outcomes in high-risk patients.
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Antígenos de Superfície/metabolismo , Biomarcadores Tumorais/metabolismo , Regras de Decisão Clínica , Glutamato Carboxipeptidase II/metabolismo , Nomogramas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/terapia , Estudos Retrospectivos , Medição de Risco , Programa de SEER , Análise de SobrevidaRESUMO
BACKGROUND: Many elderly localized prostate cancer patients could benefit from conservative management (CM). This retrospective cohort study examined the associations of patient-reported access to care and multimorbidity on CM use patterns among Medicare Fee-for-Service (FFS) beneficiaries with localized prostate cancer. METHODS: We used linked Surveillance, Epidemiology, and End Results cancer Registry, Medicare Claims, and the Medicare Consumer Assessment of Healthcare Providers and Systems (MCAHPS) survey files. We identified FFS Medicare Beneficiaries (age ≥ 66; continuous enrollment in Parts A & B) with incident localized prostate cancer from 2003 to 2013 and a completed MCAHPS survey measuring patient-reported experiences of care within 24 months after diagnosis (n = 496). We used multivariable models to examine MCAHPS measures (getting needed care, timeliness of care, and doctor communication) and multimorbidity on CM use. RESULTS: Localized prostate cancer patients with multimorbidity were less likely to use CM (adjusted odds ratio (AOR)=0.42 (0.27- 0.66), P < .001); those with higher scores on timeliness of care (AOR = 1.21 (1.09, 1.35), P < .001), higher education attainment (3.21 = AOR (1.50,6.89), P = .003), and impaired mental health status (4.32 = AOR (1.86, 10.1) P < .001) were more likely to use CM. CONCLUSION(S): Patient-reported experience with timely care was significantly and positively associated with CM use. Multimorbidity was significantly and inversely associated with CM use. Addressing specific modifiable barriers to timely care along the cancer continuum for elderly localized prostate cancer patients with limited life expectancy could reduce the adverse effects of overtreatment on health outcomes and costs.
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Tratamento Conservador/estatística & dados numéricos , Multimorbidade , Medidas de Resultados Relatados pelo Paciente , Neoplasias da Próstata/terapia , Idoso , Escolaridade , Planos de Pagamento por Serviço Prestado/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Humanos , Expectativa de Vida , Masculino , Medicare/estatística & dados numéricos , Saúde Mental , Análise Multivariada , Razão de Chances , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Programa de SEER/estatística & dados numéricos , Fatores Socioeconômicos , Estados UnidosRESUMO
BACKGROUND: The role of elective whole-pelvis radiotherapy (WPRT) remains controversial. Few studies have investigated it in Gleason grade group (GG) 5 prostate cancer (PCa), known to have a high risk of nodal metastases. OBJECTIVE: To assess the impact of WPRT on patients with GG 5 PCa treated with external-beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT). DESIGN, SETTING, AND PARTICIPANTS: We identified 1170 patients with biopsy-proven GG 5 PCa from 11 centers in the United States and one in Norway treated between 2000 and 2013 (734 with EBRT and 436 with EBRT+BT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific survival (PCSS) were compared using Cox proportional hazards models with propensity score adjustment. RESULTS AND LIMITATIONS: A total of 299 EBRT patients (41%) and 320 EBRT+BT patients (73%) received WPRT. The adjusted 5-yr bRFS rates with WPRT in the EBRT and EBRT+BT groups were 66% and 88%, respectively. Without WPRT, these rates for the EBRT and EBRT+BT groups were 58% and 78%, respectively. The median follow-up was 5.6yr. WPRT was associated with improved bRFS among patients treated with EBRT+BT (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.2-0.9, p=0.02), but no evidence for improvement was found in those treated with EBRT (HR 0.8, 95% CI 0.6-1.2, p=0.4). WPRT was not significantly associated with improved DMFS or PCSS in the EBRT group (HR 1.1, 95% CI 0.7-1.7, p=0.8 for DMFS and HR 0.7, 95% CI 0.4-1.1, p=0.1 for PCSS), or in the EBRT+BT group (HR 0.6, 95% CI 0.3-1.4, p=0.2 for DMFS and HR 0.5 95% CI 0.2-1.2, p=0.1 for PCSS). CONCLUSIONS: WPRT was not associated with improved PCSS or DMFS in patients with GG 5 PCa who received either EBRT or EBRT+BT. However, WPRT was associated with a significant improvement in bRFS among patients receiving EBRT+BT. Strategies to optimize WPRT, potentially with the use of advanced imaging techniques to identify occult nodal disease, are warranted. PATIENT SUMMARY: When men with a high Gleason grade prostate cancer receive radiation with external radiation and brachytherapy, the addition of radiation to the pelvis results in a longer duration of prostate-specific antigen control. However, we did not find a difference in their survival from prostate cancer or in their survival without metastatic disease. We also did not find a benefit for radiation to the pelvis in men who received radiation without brachytherapy.
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Braquiterapia , Irradiação Hemicorpórea , Neoplasias da Próstata/radioterapia , Idoso , Humanos , Masculino , Gradação de Tumores , Pelve , Próstata , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
PURPOSE: Gleason score (GS) 10 disease is the most aggressive form of clinically localized prostate adenocarcinoma (PCa). The long-term clinical outcomes and overall prognosis of patients presenting with GS 10 PCa are largely unknown because of its rarity. METHODS AND MATERIALS: The study included 112 patients with biopsy-determined GS 10 PCa who received treatment with radical prostatectomy (RP, n = 26), external beam radiation therapy (EBRT, n = 48), or EBRT with a brachytherapy boost (EBRT-BT, n = 38) between 2000 and 2013. Propensity scores were included as covariates for comparative analysis. Overall survival, prostate cancer-specific survival, and distant metastasis-free survival (DMFS) were estimated by the Kaplan-Meier method with inverse probability of treatment weighting to control for confounding. RESULTS: The median follow-up period was 4.9 years overall (3.9 years for RP, 4.8 years for EBRT, and 5.7 years for EBRT-BT). Significantly more EBRT patients than EBRT-BT patients received upfront androgen deprivation therapy (98% vs 79%, P < .01 by χ2 test), though the durations were similar (median, 24 months vs 22.5 months). Of the RP patients, 34% received postoperative EBRT, and 35% received neoadjuvant systemic therapy. The propensity score-adjusted 5-year overall survival rate was 80% for the RP group, 73% for the EBRT group, and 83% for the EBRT-BT group. The corresponding adjusted 5-year prostate cancer-specific survival rates were 87%, 75%, and 94%, respectively. The EBRT-BT group trended toward superior DMFS when compared with the RP group (hazard ratio, 0.3; 95% confidence interval 0.1-1.06; P = .06) and had superior DMFS when compared with the EBRT group (hazard ratio, 0.4; 95% confidence interval 0.1-0.99; P = .048). CONCLUSIONS: To our knowledge, this is the largest series ever reported on the clinical outcomes of patients with biopsy-determined GS 10 PCa. These data provide useful prognostic benchmark information for physicians and patients. Aggressive therapy with curative intent is warranted, as >50% of patients remain free of systemic disease 5 years after treatment.
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Adenocarcinoma/patologia , Adenocarcinoma/terapia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico , Benchmarking , Braquiterapia , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Pontuação de Propensão , Prostatectomia/métodos , Neoplasias da Próstata/mortalidade , Taxa de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVES: Active surveillance (AS) is increasingly utilized for low-grade prostate cancer with the greatest risk being the possibility of missing a high-grade cancer. We evaluate the role of transperineal template-guided mapping biopsy (TTMB) to select patients for AS. METHODS: A total of 131 consecutive, prospectively evaluated men with transrectal ultrasound-guided needle biopsy (TRUS)-diagnosed very low risk (Gleason score ≤6, ≤2 positive biopsies, prostate-specific antigen [PSA] density <0.15, and ≤50% involvement on any core) and low risk (Gleason score ≤6, clinical stage T1c, and PSA ≤10 ng/mL) underwent TTMB as a staging procedure. Biopsies were obtained corresponding to 24 regional biopsy locations. For each patient, the location of each positive biopsy core, the number of positive cores, and the percentage involvement of each core were reported. RESULTS: After TTMB, TRUS-detected very-low-risk prostate cancer patients were less likely to be diagnosed with higher Gleason score, were less likely to have bilateral involvement, and had statistically fewer number of positive biopsy cores on TTMB. After TTMB, no cancer, very-low-risk, or low-risk prostate cancer was detected in 60 of 72 (83.3%) and 19 of 59 (32.2%) of patients with very low and low risk, respectively. In multivariate analysis, older age and low risk predicted for higher Gleason score at the time of TTMB. CONCLUSIONS: Very-low-risk prostate cancer patients have a significantly lower incidence of Gleason score upgrading than those with low-risk disease. After TTMB, 83.3% of patients with very-low-risk and 32.2% of patients with low-risk disease appear to be outstanding candidates for AS.
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Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Conduta Expectante , Idoso , Biópsia com Agulha de Grande Calibre , Humanos , Biópsia Guiada por Imagem , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Seleção de Pacientes , Períneo , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico por imagem , Medição de Risco , UltrassonografiaRESUMO
PURPOSE: To evaluate the impact of supplemental external beam radiation therapy (EBRT) prior to permanent prostate brachytherapy on long term urinary, bowel, and erectile function. MATERIAL AND METHODS: Patient administered urinary, bowel, and erectile quality of life (QoL) instrument were obtained prior to treatment and following brachytherapy. The study population was comprised of the 457 patients who were alive as of June 2016, had been randomized to two markedly different supplemental EBRT dose regimens and a third arm without supplemental EBRT, and had completed the June 2016 QoL survey. The need for urinary or bowel surgical intervention was prospectively recorded during routine follow-up. Multiple parameters were evaluated for effect on outcomes. RESULTS: The urinary catheter was removed on day 0 in 92.1% of patients and 0.4% required a post-implant transurethral prostatic resection (TURP). On average, the International Prostate Symptom Score (IPSS) normalized at week 14. The 10-year rate of urethral strictures was 5.3%. No significant differences were discerned between baseline and post-implant rectal function assessment score (RFAS), and no patient developed a rectal ulcer or fistula. The 10-year potency preservation rate was 50.3%. Supplemental EBRT did not affect urinary, bowel, or erectile function. Urethral strictures were most closely related to bulbomembranous urethral brachytherapy doses, post-implant rectal function to pre-implant hemorroidal bleeding, and RFAS and erectile function to pre-brachytherapy international index of erectile function and age. CONCLUSIONS: Supplemental EBRT did not significantly effect catheter dependency, IPSS resolution, urethral stricture rate, the need for post-implant TURP, bowel, or erectile function. Careful attention to brachytherapy dose distributions appears to be most important in minimizing post-brachytherapy morbidity.
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PURPOSE: To evaluate prostate-cancer specific mortality (PCSM) in a cohort of high-risk patients treated with a permanent prostate brachytherapy approach, stratified by pre-treatment PSA. MATERIAL AND METHODS: 448 high-risk patients (NCCN criteria) underwent permanent prostate brachytherapy. High risk patients were stratified by pre-treatment PSA (≤ 10.0, 10.1-20, and > 20 ng/ml). Biochemical failure (BF), prostate cancer-specific mortality (PCSM), distant failure (DM), and overall mortality (OM) were assessed as a function of prognostic group. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on outcome. RESULTS: The 10-year OM, BF, and PCSM for the entire cohort were 28.5%, 13.3%, and 4.9%, respectively. At 10 years, PCSM was 2.5%, 10.7%, and 4.5% in the PSA ≤ 10, 10.1-20, and > 20 ng/ml groups, respectively. No statistically significant differences in BF or overall survival (OS) were noted when stratified by pre-treatment PSA. DF was the most common in the 10.1-20 ng/ml cohort (8.6% at 10 years). In multivariate analysis, PCSM was most closely related to percent positive biopsies (p = 0.001) and tobacco (p = 0.042). CONCLUSIONS: High-risk prostate cancer treated with permanent prostate brachytherapy and supplemental external beam radiotherapy resulted in excellent long-term biochemical control and PCSM. Overall, PCSM was low in all cohorts but highest in the intermediate PSA group (10.1-20 ng/ml).
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OBJECTIVE: To report the incidence of prostate cancer diagnosis and quality of life outcomes following transperineal prostate biopsy. METHODS: Forty-six consecutive patients underwent office-based transperineal prostate biopsy for an elevated prostate-specific antigen and a normal digital rectal examination without prior prostate biopsy. Prior to biopsy, a repeat prostate-specific antigen was obtained to ensure persistent elevation. Silodosin (8 mg daily) was initiated the day prior to biopsy and continued for 1 week. A total of 18-20 biopsy cores were obtained per patient. All patients responded to a visual analog scale ranging from 0 to 10 immediately following the completion of both the local anesthesia and the biopsy procedure. In addition, an International Prostate Symptom Score (IPSS), Rectal Function Assessment Score, International Index of Erectile Function, Center for Epidemiologic Studies Depression Scale, and postvoid residual were obtained at baseline and 30 days following biopsy, except IPSS which was also obtained at day 7. RESULTS: The mean patient age was 63.3 years with a mean prostate volume of 41.8 cm(3). The mean visual analog scale was 4.2 for the local anesthesia and 3.0 for the biopsy. Thirty-one patients (67.4%) were diagnosed with prostate cancer, with 18 having a Gleason score ≥ 7. Compared to baseline, no adverse changes in IPSS, Rectal Function Assessment Score, International Index of Erectile Function, Center for Epidemiologic Studies Depression Scale, or postvoid residual were detected at day 30. No patient required catheterization, developed sepsis, or required hospitalization. CONCLUSION: Office-based transperineal prostate biopsy was well tolerated with reasonable treatment-related discomfort, a high rate of prostate cancer diagnosis, and the absence of significant morbidity including sepsis.
Assuntos
Próstata/patologia , Neoplasias da Próstata/patologia , Qualidade de Vida , Biópsia com Agulha de Grande Calibre/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Períneo , Complicações Pós-Operatórias/epidemiologia , Estudos ProspectivosRESUMO
PURPOSE: To evaluate biochemical failure (BF) and prostate cancer specific mortality (PCSM) in intermediate-risk (IR) brachytherapy patients stratified into favorable and unfavorable cohorts, and to compare those outcomes to patients with low (LR) and high-risk (HR) disease. MATERIAL AND METHODS: From March 1995 till February 2012, 2,502 consecutive patients underwent permanent interstitial brachytherapy for clinically localized prostate cancer. Patients were stratified into risk groups as per the NCCN guidelines with further stratification of the intermediate risk cohort into unfavorable (primary Gleason pattern 4, ≥ 50% positive biopsies or ≥ 2 IR features) and favorable cohorts. Median follow-up was 8.5 years. The brachytherapy prescription dose was prescribed to the prostate gland with generous periprostatic margins. Biochemical failure was defined as a PSA > 0.40 ng/ml after nadir. Patients with metastatic prostate cancer or non-metastatic castrate resistant disease who died of any cause were classified as dead of prostate cancer. Multiple parameters were evaluated for effect on outcomes. RESULTS: Fifteen year BF for LR, favorable IR, unfavorable IR, and HR were 1.4%, 2.2%, 7.1%, and 11.1% (p < 0.001), respectively. At 15 years, PCSM for LR, favorable IR, unfavorable IR, and HR was 0.3%, 0.6%, 2.2% and 4.6% (p < 0.001), respectively. In multivariate analysis, BF was best predicted by risk group, pre-implant PSA, percent positive biopsies, prostate volume, and ADT duration, while PCSM was most closely related to risk group, percent positive biopsies and prostate volume. CONCLUSIONS: Patients with favorable IR disease have biochemical and PCSM outcomes comparable to those of patients with LR disease. Although unfavorable IR has greater than a 3-fold increased risk of BF and PCSM when compared to favorable IR, the outcomes remain superior to those men with HR disease.
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PURPOSE: To determine the necessity and/or dose of supplemental external beam radiotherapy (EBRT) in conjunction with palladium-103 ((103)Pd) brachytherapy for high-risk prostate cancer patients. METHODS AND MATERIALS: Trial 44/20 randomized patients to 44 Gy plus 90 Gy (103)Pd vs. 20 Gy with 115 Gy (103)Pd, and the subsequent trial randomized patients to the 20 Gy arm vs. 125 Gy (103)Pd without EBRT (20/0 trial). Eligibility criteria included clinically organ-confined disease with Gleason scores 7-9 and/or a pretreatment prostate-specific antigen (PSA) 10-20 ng/mL. The brachytherapy prescription dose was prescribed to the prostate gland with generous periprostatic margins. Biochemical failure (BF) was defined as a PSA >0.40 ng/mL after nadir. Median Day 0 minimum dose covering 90% of the prostate volume (D90) was >121.0% of the prescription dose. Multiple parameters were evaluated for effect on outcomes. RESULTS: In 44/20 trial, 13-year BF, prostate cancer-specific mortality (PCSM), and overall mortality (OM) were 8.2%, 4.0%, and 42.8% vs. 8.0%, 1.0%. and 40.3% for the 44 and 20 Gy arms. In 20/0 trial, 8-year BF, PCSM, and OM were 2.1%, 0%, and 14.4% vs. 3.6%, 0%, and 16.1% in the 20 vs. 0 Gy arms. When stratified by either pretreatment PSA or by Gleason score, supplemental EBRT dose did not impact BF, PCSM, or OM. In multivariate analysis, BF was most closely related to percent positive biopsies and prostate volume. In both trials, patients with biochemically controlled disease had a median PSA of <0.02 ng/mL. CONCLUSIONS: With high-quality brachytherapy dose distributions, supplemental EBRT did not influence BF or PCSM for patients with intermediate-risk disease. The number of patients with Gleason score 8-9 was too small to determine the role of supplemental EBRT in that cohort.
Assuntos
Braquiterapia , Paládio/uso terapêutico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/radioterapia , Radioisótopos/uso terapêutico , Idoso , Biópsia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Prospectivos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Fatores de Risco , Taxa de Sobrevida , Falha de TratamentoRESUMO
PURPOSE: To evaluate multi-institutional prostate brachytherapy dosimetric quality using multisector analysis. METHODS AND MATERIALS: In the database, 4547 patients underwent brachytherapy (3094 for (125)I, 1437 for (103)Pd, and 16 for (131)Cs). The original prostate postimplant dosimetry was reported using the maximum dose covering 90% of the prostate volume (D90) and the percentage of the prostate volume covered by the prescription dose (V100). Retrospectively, the dosimetry of all implants was recalculated after segmenting the prostate into 12 sectors (anterior, left and right lateral and posterior, about the center of gravity, and subdivided lengthwise into three-base, midgland, and apex). The dosimetric quality of each sector and combinations of sectors was compared across radionuclides. RESULTS: For each radionuclide, there was no significant difference between monotherapy and boost in terms of V100 or D90. When classified as excellent (V100 ≥ 90%), standard (V100 ≥ 80%), or minimal (V100 < 80%), 33.0%, 4.6%, and 10.5% of all base, midgland, and apical sectors, respectively, were of minimal quality. Specifically, 59.2% of the anterior base and 30.3% of the posterior base sectors were minimal. At the anterior midgland and apex, 22% and 19% of sectors were minimal. Excellent quality was observed in more than 90% of lateral and posterior midgland sectors and in >70% of lateral and posterior sectors. When stratified by (103)Pd vs. (125)I, sector analysis did not result in clinically significant dosimetric differences. CONCLUSIONS: Coverage of base sectors was inferior to midgland and apical sectors, and coverage of anterior sectors was notably inferior to lateral and posterior sectors. Further critique of brachytherapy planning and intraoperative technique is necessary for brachytherapists to minimize these dosimetric differences.