전이성 전립선암 환자의 치료 편집하기 (부분)

== 근거표 ==
{| class="wikitable"
!KQ17
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!Reference
|1. Pagliarulo V, Bracarda S, Eisenberger MA et al. Contemporary role of androgen deprivation therapy for prostate cancer. Eur Urol 2012;61:11-25.
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!Study type
|Systematic review
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!Patients
|48 studies
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!Purpose of Study
|To evaluate whether adding short-term ADT to radiotherapy would improve survival among patients with nonbulky localized prostate adenocarcinomas and an initial PSA level of 20 ng per milliliter or less.
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!Study Results
|Data from randomized controlled trials and population-based studies were analyzed in different clinical paradigms. Specifically, the role of ADT was evaluated in patients with nonmetastatic disease as the primary and sole treatment, in combination with radiation therapy (RT) or after surgery, and in patients with metastatic disease. The data suggest that in men with nonmetastatic disease, the use of primary ADT as monotherapy has not shown a benefit and is not recommended, while ADT combined with conventional-dose RT (<72Gy) for patients with high-risk disease may delay progression and prolong survival. The postoperative use of ADT remains poorly evaluated in prospective studies. Likewise, there are no trials evaluating the role of ADT in patients with biochemical relapses after surgery or RT. In patients with metastatic disease, there is a clear benefit in terms of quality of life, reduction of disease-associated morbidity, and possibly survival. Treatment with bilateral orchiectomy, luteinizing hormone-releasing hormone agonist therapy, with and without antiandrogens has been associated with various serious adverse events, including cardiovascular disease, diabetes, and skeletal complications that may also affect mortality.
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!Level of Study
|1
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!Reference
|2. Kunath F, Grobe HR, Rucker G, et al. Non-steroidal antiandrogen monotherapy compared with luteinising hormone-releasing hormone agonists or surgical castration monotherapy for advanced prostate cancer. Cochrane Database Syst Rev 2014:CD009266.
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!Study type
|Systematic review
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!Patients
|11 studies, 3,060 patients
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!Purpose of Study
|To assess the effects of non-steroidal antiandrogen monotherapy compared with luteinising hormone-releasing hormone agonists or surgical castration monotherapy for treating advanced stages of prostate cancer.
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!Study Results
|Eleven studies involving 3060 randomly assigned participants were included in this review. The quality of evidence is hampered by risk of bias. Use of non-steroidal antiandrogens decreased overall survival (hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.05 to 1.48, six studies, 2712 participants) and increased clinical progression (one year: risk ratio (RR) 1.25, 95% CI 1.08 to 1.45, five studies, 2067 participants; 70 weeks: RR 1.26, 95% CI 1.08 to 1.45, six studies, 2373 participants; two years: RR 1.14, 95% CI 1.04 to 1.25, three studies, 1336 participants), as well as treatment failure (one year: RR 1.19, 95% CI 1.02 to 1.38, four studies, 1539 participants; 70 weeks: RR 1.27, 95% CI 1.05 to 1.52, five studies, 1845 participants; two years: RR 1.14, 95% CI 1.05 to 1.24, two studies, 808 participants), compared with medical or surgical castration. The quality of evidence for overall survival, clinical progression and treatment failure was rated as moderate according to GRADE. Predefined subgroup analyses showed that use of non-steroidal antiandrogens, compared with castration, was less favourable for overall survival, clinical progression (at one year, 70 weeks, two years) and treatment failure (at one year, 70 weeks, two years) in men with metastatic disease. Use of non-steroidal antiandrogens also increased the risk for treatment discontinuation due to adverse events (RR 1.82, 95% CI 1.13 to 2.94, eight studies, 1559 participants), including events such as breast pain (RR 22.97, 95% CI 14.79 to 35.67, eight studies, 2670 participants), gynaecomastia (RR 8.43, 95% CI 3.19 to 22.28, nine studies, 2774 participants) and asthenia (RR 1.77, 95% CI 1.36 to 2.31, five studies, 2073 participants). The risk of other adverse events, such as hot flashes (RR 0.23, 95% CI 0.19 to 0.27, nine studies, 2774 participants), haemorrhage (RR 0.07, 95% CI 0.01 to 0.54, two studies, 546 participants), nocturia (RR 0.38, 95% CI 0.20 to 0.69, one study, 480 participants), fatigue (RR 0.52, 95% CI 0.31 to 0.88, one study, 51 participants), loss of sexual interest (RR 0.50, 95% CI 0.30 to 0.83, one study, 51 participants) and urinary frequency (RR 0.22, 95% CI 0.11 to 0.47, one study, 480 participants) was decreased when non-steroidal antiandrogens were used. The quality of evidence for breast pain, gynaecomastia and hot flashes was rated as moderate according to GRADE. The effects of non-steroidal antiandrogens on cancer-specific survival and biochemical progression remained unclear.
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!Level of Study
|1
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!Reference
|3. Seidenfeld J, Samson DJ, Hasselblad V et al. Single-therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis. Ann Intern Med 2000;132:566-77.
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!Study type
|Meta-analysis
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!Patients
|10 studies, 1,908 patients
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!Purpose of Study
|To compare luteinizing hormone-releasing hormone (LHRH) agonists with orchiectomy or diethylstilbestrol, and to compare antiandrogens with any of these three alternatives.
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!Study Results
|Ten trials of LHRH agonists involving 1908 patients reported no significant difference in overall survival. The hazard ratio showed LHRH agonists to be essentially equivalent to orchiectomy (hazard ratio, 1.1262 [corrected] [95% CI, 0.915 to 1.386]). There was no evidence of difference in overall survival among the LHRH agonists, although CIs were wider for leuprolide (hazard ratio, 1.0994 [CI, 0.207 to 5.835]) and buserelin (hazard ratio, 1.1315 [CI, 0.533 to 2.404]) than for goserelin (hazard ratio, 1.1172 [CI, 0.898 to 1.390]). Evidence from 8 trials involving 2717 patients suggests that nonsteroidal antiandrogens were associated with lower overall survival. The CI for the hazard ratio approached statistical significance (hazard ratio, 1.2158 [CI, 0.988 to 1.496]). Treatment withdrawals were less frequent with LHRH agonists (0% to 4%) than with nonsteroidal antiandrogens (4% to 10%).
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!Level of Study
|1
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!Reference
|4. Sun M, Choueiri TK, Hamnvik OP, et al. Comparison of Gonadotropin-Releasing Hormone Agonists and Orchiectomy: Effects of Androgen-Deprivation Therapy. JAMA Oncol 2016;2:500-7.
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!Study type
|Case-control study
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!Patients
|A population-based cohort of 3,295 men with metastatic PCa between January 1995 and December 2009 66 years or older was selected from the Surveillance, Epidemiology, and End Results (SEER) Medicare-linked database
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!Purpose of Study
|To provide a comparative effectiveness analysis of the adverse effects of gonadotropin- releasing hormone agonists (GnRHa) vs bilateral orchiectomy in a homogeneous population.
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!Study Results
|Overall, 3295 men with a primary diagnosis of metastatic PCa treated with GnRHa or orchiectomy were identified between years 1995 and 2009, and in adjusted analyses, patients who received a bilateral orchiectomy had significantly lower risks of experiencing any fractures (hazard ratio [HR], 0.77; 95% CI, 0.62-0.94; P=.01), peripheral arterial disease (HR, 0.65; 95% CI, 0.49-0.87; P=.004), and cardiac-related complications (HR, 0.74; 0.58-0.94; P=.01) compared with those treated with GnRHa. No statistically significant difference was noted between orchiectomy and GnRHa for diabetes and cognitive disorders. In individuals treated with GnRHa for 35 months or more, the increased risk for GnRHa compared with orchiectomy was noted for fractures (HR, 1.80), peripheral arterial disease (HR, 2.25), venous thromboembolism (HR, 1.52), cardiac-related complications (HR, 1.69), and diabetes mellitus (HR, 1.88) (P≤.01 for all). At 12 months after PCa diagnosis, the median total expenditures was not significantly different between GnRHa and orchiectomy.
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!Level of Study
|3
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!Reference
|5. Chen DY, See LC, Liu JR, et al. Risk of Cardiovascular Ischemic Events After Surgical Castration and Gonadotropin-Releasing Hormone Agonist Therapy for Prostate Cancer: A Nationwide Cohort Study. J Clin Oncol 2017;35:3697-705.
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!Study type
|Case-control study
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!Patients
|By using the Taiwan National Health Insurance Research Database, we analyzed data from 14,715 patients with PCa diagnosed from January 1, 1997, through December 31, 2011
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!Purpose of Study
|Our aim was to determine whether cardiovascular (CV) risk in patients with prostate cancer (PCa) differs between those who receive androgen-deprivation therapy by surgical castration and those who receive gonadotropin-releasing hormone agonist (GnRHa) therapy.
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!Study Results
|Overall, 3,578 patients with PCa (24.3%) underwent bilateral orchiectomy and 11,137 patients (75.7%) received GnRHa therapy. Both groups had a similar risk of CV ischemic events (ie, MI or IS; hazard ratio, 1.16; 95% CI, 0.97 to 1.38) during a median follow- up time of 3.3 years. However, during the first 1.5 years of follow-up, there were higher CV ischemic events in the orchiectomy group than in the GnRHa group (hazard ratio, 1.40; 95% CI, 1.04 to 1.88), particularly in patients who were ≥65 years of age, had hypertension, had a Charlson comorbidity index score ≥3, and had a previous history of MI, IS, or coronary heart disease. Conclusion Compared with bilateral orchiectomy, use of GnRHa does not increase the risk of CV ischemic events in patients with PCa. Nonetheless, orchiectomy is associated with higher rates of CV ischemic events in older patients and those with a history of CV comorbidities within 1.5 years of initiating androgen-deprivation therapy. These findings can help clinicians decide on the optimal castration strategy for individual patients.
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!Level of Study
|3
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