當代攝護腺癌 精選論文點評導讀集
當代攝護腺癌精選論文點評導讀集 2015 2015 12 Copyright 2015 Taiwan Maple Urological Association 7 ( )886-2-2312-3456 65326 This Collection is the result of a working group of medical professionals from Taiwan, China, Hong Kong and Malaysia. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means including but not limited to electronic, mechanical, photocopying, or recording without written permission of the publisher. / ( ) This publication is sponsored by Astellas Pharma Taiwan Inc. as a service to the medical profession. No responsibility is assumed by Elsevier, its licensors or associates, for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made. Although advertising material is expected to conform to ethical (medical) standards, inclusion in this publication does not constitute a guarantee or endorsement of the quality or value of such product or of the claims made of it by its manufacturer. Produced by Elsevier 14ET022
(2011 5 2015 8 ) 52 38 52 38 33.130.430.329.7 14.810.87.2 5.35.34.23.4 98 (Globocan 2012, IARC) 30% 68 74 80 (, 2010) (PSA 20 ng/ml 50% 1/3) 2011 19% 28% 30% 23% ( ) PSA PSA 33% ( ) 1
當代攝護腺癌精選論文點評導讀集 QR code 2
38 PSA 52 ( ) Asian Journal of Urology 3
當代攝護腺癌精選論文點評導讀集 PSA 52 ( ) mhspc mcrpc 4
2015 7 52 2011 5 2015 8 SCI 36 1 1 38 14 22 1 1 4 (2015-07~2015-11) (Astellas Pharma Taiwan, Inc.) EMBA 5
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Tulane International Journal of Radiation Oncology, Biology, Physics (NCCN) ( ) GKT ( ) (TCOG) ( ) EMBA 7
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( ) Asian Journal of Urology 9
當代攝護腺癌精選論文點評導讀集 10
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1 7 15 文 20 23 1. Screening for Prostate Cancer with the Prostate-Specific Antigen Test - A Review of Current Evidence 23 2. Prevention and Early Detection of Prostate Cancer 24 3. Long-Term Survival of Participants in the Prostate Cancer Prevention Trial 26 4. Prostate Cancer in the Elderly Patient 27 5. Long-Term Follow-Up of a Large Active Surveillance Cohort of Patients with Prostate Cancer 29 6. Gleason 6 Prostate Tumors Diagnosed in the PSA Era Do Not Demonstrate the Capacity for Metastatic Spread at the Time of Radical Prostatectomy 30 7. Vasectomy and Risk of Aggressive Prostate Cancer: A 24-Year Follow-Up Study 31 8. Use of Statins and the Risk of Death in Patients with Prostate Cancer 32 9. Association between Metformin Use and Risk of Prostate Cancer and Its Grade 33 10. Metformin Use and All-Cause and Prostate Cancer Specific Mortality among Men with Diabetes 34 11. Dietary Lycopene, Angiogenesis, and Prostate Cancer: A Prospective Study in the Prostate-Specific Antigen Era 35 15
當代攝護腺癌精選論文點評導讀集 12. Selenium Supplementation and Prostate Cancer Mortality 36 13. Can Urinary PCA3 Supplement PSA in the Early Detection of Prostate Cancer? 37 39 14. Comparison of MR/Ultrasound Fusion Guided Biopsy with Ultrasound Guided Biopsy for the Diagnosis of Prostate Cancer 39 15. Can Clinically Significant Prostate Cancer Be Detected with Multiparametric Magnetic Resonance Imaging? A Systematic Review of the Literature 41 16. High Diagnostic Ability of Multiparametric Magnetic Resonance Imaging to Detect Anterior Prostate Cancer Missed by Transrectal 12-Core Biopsy 42 17. Prevalence of Prostate Cancer on Autopsy: Cross-Sectional Study on Unscreened Caucasian and Asian Men 43 18. Systematic Review of Complications of Prostate Biopsy 44 19. Neuroendocrine Prostate Cancer (NEPC) Progressing from Conventional Prostatic Adenocarcinoma: Factors Associated with Time to Development of NEPC and Survival from NEPC Diagnosis A Systematic Review and Pooled Analysis 46 ( ) 47 20. Radical Prostatectomy versus Observation for Localized Prostate Cancer 47 21. Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer 48 22. Androgen Deprivation with or without Radiation Therapy for Clinically Node-Positive Prostate Cancer 50 16
23. Effectiveness of Androgen-Deprivation Therapy and Radiotherapy for Older Men with Locally Advanced Prostate Cancer 52 24. Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy plus Radiotherapy versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer 54 25. Adjuvant and Salvage Radiotherapy after Prostatectomy: AUA/ASTRO Guideline 56 26. Might Men Diagnosed with Metastatic Prostate Cancer Benefit from Definitive Treatment of the Primary Tumor? A SEER-Based Study 58 27. Proton Beam Therapy (PBT) 60 mhspc 61 28. Effectiveness of Primary Androgen-Deprivation Therapy for Clinically Localized Prostate Cancer 61 29. Intermittent versus Continuous Androgen Deprivation in Prostate Cancer 63 30. Treatment of Prostate Cancer with Intermittent versus Continuous Androgen Deprivation: A Systemic Review of Randomized Trials 65 31. Androgen-Deprivation Therapy alone or with Docetaxel in Non-Castrate Metastatic Prostate Cancer (GETUG-AFU 15): A Randomised, Open-Label, Phase 3 Trial 66 32. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer 67 mcrpc 69 33. Castration-Resistant Prostate Cancer: AUA Guideline Amendment 69 17
當代攝護腺癌精選論文點評導讀集 34. Increased Survival with Enzalutamide in Prostate Cancer after Chemotherapy 71 35. Enzalutamide in Metastatic Prostate Cancer before Chemotherapy (PREVAIL) 73 36. Abiraterone and Increased Survival in Metastatic Prostate Cancer 74 37. Abiraterone Acetate plus Prednisone versus Placebo plus Prednisone in Chemotherapy-Naive Men with Metastatic Castration-Resistant Prostate Cancer (COU-AA-302): Final Overall Survival Analysis of a Randomised, Double-Blind, Placebo-Controlled Phase 3 Study 75 38. Abiraterone Acetate for Patients with Metastatic Castration-Resistant Prostate Cancer Progressing after Chemotherapy: Final Analysis of a Multicentre, Open-Label, Early-Access Protocol Trial 77 39. AR-V7 and Resistance to Enzalutamide and Abiraterone in Prostate Cancer 78 40. Phase III, Randomized, Double-Blind, Multicenter Trial Comparing Orteronel (TAK-700) plus Prednisone with Placebo plus Prednisone in Patients with Metastatic Castration-Resistant Prostate Cancer That Has Progressed during or after Docetaxel-Based Therapy: ELM-PC 5 79 41. Orteronel plus Prednisone in Patients with Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer (ELM-PC 4): A Double-Blind, Multicentre, Phase 3, Randomised, Placebo-Controlled Trial 81 42. Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer 83 85 43. Autonomic Nerve Development Contributes to Prostate Cancer Progression 85 18
44. Conversion of Abiraterone to D4A Drives Anti-Tumor Activity in Prostate Cancer 86 45. Circulating Tumor Cell Biomarker Panel as an Individual-Level Surrogate for Survival in Metastatic Castration-Resistant Prostate Cancer 87 46. Therapeutic Targeting of BET Bromodomain Proteins in Castration-Resistant Prostate Cancer 88 47. The Evolutionary History of Lethal Metastatic Prostate Cancer 89 48. Genome-Wide Association Study in Chinese Men Identifies Two New Prostate Cancer Risk Loci at 9q31.2 and 19q13.4 90 93 49. Randomized Controlled Trial of Early Zoledronic Acid in Men with Castration-Sensitive Prostate Cancer and Bone Metastases: Results of CALGB 90202 (Alliance) 93 50. Prevention of Bone Metastases in Patients with High-Risk Nonmetastatic Prostate Cancer Treated with Zoledronic Acid: Efficacy and Safety Results of the Zometa European Study (ZEUS) 94 51. Denosumab and Bone-Metastasis-Free Survival in Men with Castration-Resistant Prostate Cancer: Results of a Phase 3, Randomised, Placebo-Controlled Trial 95 52. Denosumab for Patients with Persistent or Relapsed Hypercalcemia of Malignancy despite Recent Bisphosphonate Treatment 96 19
當代攝護腺癌精選論文點評導讀集 ( ) ( ) acetylcholine active surveillance (AS) androgen receptor (AR) androgen-deprivation therapy (ADT) anti-androgen cancer specific survival cancer-specific mortality (CSM) cancer-specific survival (CSS) castration-resistant prostate cancer (CRPC) castration-sensitive prostate cancer (CSPC) chemotherapy (chemo) clone combined androgen blockade (CAB) confidence interval (CI) continuous androgen deprivation (CAD) digital rectal examination (DRE) endpoint extended node dissection Gleason score (GS) hazard ratio (HR) hormone-sensitive prostate cancer (HSPC) instrumental variable analysis intermittent androgen deprivation (IAD) leuteinizing hormone releasing hormone agonist (LHRHa) leuteinizing hormone releasing hormone antagonist (LHRHant) life style localized prostate cancer ( hormone therapy ) ( bicalutamide flutamide cyproterone acetate ) ( HSPC) ( CSPC) 20
( ) ( ) locally advanced prostate cancer (LAPC) magnetic resonance imaging (MRI) meta-analysis metastatic CRPC (mcrpc) metastatic CSPC (mcspc) multi-parametric MRI (mpmri) multivariable analyses multivariable Cox proportional hazards models muscarinic receptors neuroendocrine prostate cancer (NEPC) node dissection norepinephrine odds ratio (OR) overall mortality (OM) overall survival (OS) progression-free survival (PFS) propensity score (T3/T4) Cox prostate cancer (PC) ( ) prostate specific antigen (PSA) quality of life (QoL) radical prostatectomy (RP) radiographic progression-free survival (rpfs) radiotherapy (RT) randomized controlled trial (RCT) single nucleotide polymorphism (SNP) subclone subgroup analysis time to progression (TTP) watchful waiting or observation (WW) xenograft 21
當代攝護腺癌精選論文點評導讀集 22
Specific Antigen Test - A Review of Current Evidence JAMA 2014; 311: 1143-9. (review article) 55~69 ( ) (prostate specific antigen, PSA) 11~13 55~69 PSA PSA PSA PSA (PLCO ERSPC) PLCO 76,685 13 (relative risk [RR], 1.12; 95% CI, 1.07~1.17) (RR, 1.09; 95%CI, 0.87~1.36) PSA 7 ERSPC 182,160 11 PSA (RR, 1.63; 95% CI, 1.57~1.69) (RR, 0.79; 95% CI, 0.68~0.91) 37 1 11 PLCO PSA 11 13 1. (US Preventive Services Task Force) 2. (AUA) 55~69 70 10~15 PSA 2 55 3. (ASCO) 50 10 65 45 PSA 65 40 PSA<2.5 ng/ml PSA 2 PSA>2.5 ng/ml PSA>4.0 ng/ ml 4. (American College of Physicians) 50~69 10~15 65 45 65 40 PSA 5. 50 10 40~49 4 6. 40~45 PLCO ERSPC 1. BRCA1 BRCA2 55~69 PSA 2. PSA 4 ng/ ml PSA<1 ng/ml 3~4 3. PSA>4 ng/ml 4. (active surveillance) (watchful waiting) Screening for Prostate Cancer with the Prostate- 1. 23
當代攝護腺癌精選論文點評導讀集 2. Prevention and Early Detection of Prostate Cancer Lancet Oncol 2014; 15: e484-92. (review article) 5 PSA PSA Ki67 (mpmri) ( ) ( ) 58% 144% 65 (relative risk, RR) (RR, 2.48) 65 BRCA2 8.6 HOXB13 G84E RR (3~4 ) -I (IGF-I) 2 PSA PSA PLCO ERSPC ERSPC 11 55~69 PSA 21% 29 62% PSA 38% PSA PSA PSA ( PLCO) 2~4 (ERSPC) PSA 6~10 ng/ml ( PIVOT ) PSA CAP/ProtecT 2016 450,000 PSA 24
(PHI) PSA / PSA (free/total PSA ratio) (Kallikrein protein) hk2 PSA PCA3 PSA TMPRSS2 Ki67 mpmri MRI MRI MRI (PROMOIS) mpmri PLCO PSA mpmri PSA ERSPC 4 26% PSA 6 PIVOT (observation) 6 5 (5- reductase inhibitor) finasteride PCPT dutasteride REDUCE 5 25% 25% 15 PCPT finasteride Dutasteride 38% (REDEEM ) 5 SELECT E E (aspirin) Statins statins (alternative treatment) mpmri 6 (active surveillance) 5 PSA PSA Ki67 mpmri 25
當代攝護腺癌精選論文點評導讀集 3. Long-Term Survival of Participants in the Prostate Cancer Prevention Trial N Engl J Med 2013; 369: 603-10. (PCPT) (randomized controlled trial) 18,882 55 PSA<3.0 ng/ml Finasteride (placebo) 18 Finasteride 1/3 finasteride 18 finasteride Prostate Cancer Prevention Trial (PCPT) finasteride 2003 (NEJM 2003; 349: 215-24) finasteride 7 24.8% finasteride (high grade) 26.9% finasteride PCPT 18 finasteride ( ) 18 finasteride 10.5% 14.9% ( RR, 0.70; 95% CI, 0.65~0.76; P<0.001) 70 finasteride 3.5% 3.0% 7 10 (RR, 1.17; 95% CI, 1.00~1.37; P = 0.05) finasteride 15 78.0% 78.2% (RR, 1.03; 95% CI, 0.98~1.09; P=0.26) (RR, 1.01; P=0.90) 18 finasteride finasteride ( 2 6 ) 43% finasteride " " 26
J Clin Oncol 2014; 32: 2523-30. (review article) (geriatric assessment, GA) (metastatic castration-resistant prostate cancer, mcrpc) (relative life expectancy, RLE) (co-morbidities) RLE (geriatric assessment, GA) GA RLE RLE RLE (expectant management) (The Society of Geriatric Oncology) (1) (2) (3) (adapted treatment) (4) D'Amico RLE RLE 10 SPCG-4 65 ( 21 ) PIVOT (all-cause mortality) 65 PSA>10 65 ( 20 ) 75 (peri-operative) (active surveillance) (androgen deprivation therapy, ADT) ADT ADT (radiation) RLE 10 (adjuvant) ADT (Prostate Cancer Outcome Study) 2 5 6.2 5.1 3.46 1.96 15 Prostate Cancer in the Elderly Patient 4. 27
當代攝護腺癌精選論文點評導讀集 (N Engl J Med 2013; 368: 436-45) (biochemical recurrence, BCR) RLE PSA (doubling time) 2 PSA ADT III (castration-sensitive) ADT ADT ADT 70 ADT ADT ( 29 30 ) taxane docetaxel cabazitaxel COU-AA-301 abiraterone (75 ) ( 36 ) AFFIRM enzalutamide ( 34 ) sipuleucel-t -223 ( 42 ) Zoledronic acid denosumab III denosumab (13% vs 6%) (2% vs 1%) 1/4 75 28
Cohort of Patients with Prostate Cancer J Clin Oncol 2015; 33: 272-7. (prospective single-arm cohort study) 993 1995~1999 [ ( 6 PSA 10)] [70 PSA 15 3+4] 2000 [ ( 6 PSA 10)] [ (PSA 10~20 3+4) 10 ] (active surveillance) 6.4 (0.2~19.8 ) (favorable-risk) 15 2.8% 1.5% (definitive intervention) (favorable risk) (intermediate-risk) 15 PSA (PSA doubling time) 3 993 67.8 (clinical progression) (metastasis) 6.4 266 (26.8%) 10 50 (5.0%) 15 10 15 98.1% 94.3% 28 (2.8%) 149 (15%) 15 (1.5%) 10 15 (overall survival, OS) 80% 62% PSA (definitive treatment) 2009 PSA (mpmri) 3 4 80 PSA (guidelines) PSA mpmri mpmri (multivariable analyses) 70 (HR, 2.87; P<0.001) (HR, 0.983; P=0.001) 6 (HR, 1.70; P=0.010) PSA log-scale values (HR, 1.52; P=0.048) OS 5 10 15 75.7% 63.5% 55.0% (cumulative hazard ratio) 9.2 1 15 OS CSS (cancerspecific survival) Long-Term Follow-Up of a Large Active Surveillance 5. 29
當代攝護腺癌精選論文點評導讀集 6. Gleason 6 Prostate Tumors Diagnosed in the PSA Era Do Not Demonstrate the Capacity for Metastatic Spread at the Time of Radical Prostatectomy Urology 2013; 82: 148-53. (cohort study) (prospective longitudinal outcomes study) 2000 10 2012 6 1,781 6 (Gleason score) 6 (biochemical recurrence, BCR) (local recurrence) 6 PSA PSA 50% 50 30% 3% 6 PSA (salvage) 6 2000 10 2012 6 1,781 857 (48.1%) 6 857 PSA (no BCR, 834 [97.3%]) (significant BCR [sbcr], 16 [1.9%]) (insignificant BCR [ibcr], 7 [0.82%]) PSA PSA (PSA doubling time, PSADT) BCR PSA 0.2 ng/ml 2 PSA 0.14 ng/ ml PSADT 36 PSADT 36 PSA (no BCR, 5.4 ng/ml; ibcr, 4.9 ng/ml; sbcr, 6.2 ng/ ml) (no BCR: T1, 87.8%, T2, 12.2%; ibcr: T1, 85.7%, T2, 14.3%; sbcr: T1, 81.2%, T2, 18.8%) (no BCR: tumor <20%, 87.8%, tumor 20%, 12.2%; ibcr: tumor <20%, 85.7%, tumor 20%, 14.3%; sbcr: tumor <20%, 81.2%, tumor 20%, 18.8%) sbcr (no BCR, 6.1%; ibcr, 28.6%; sbcr, 43.8%; P<0.001) BCR (no BCR, 6.7%; ibcr, 28.6%; sbcr, 12.5%) (P=0.054) sbcr / PSA 0.1 ng/ml (local recurrence) 2 (0.23%) PSA 2 7 6 PSA 6 6 7 (multiparametric MRI, mpmri) 6 7~10 mpmri 12 (12 cores) ( 7~10 ) 98% (negative predictive value) mpmri 6 6 6 mpmri (insignificant) 30
A 24-Year Follow-Up Study J Clin Oncol 2014; 32: 3033-8. (prospective cohort study) 49,405 40~75 24 8~10 Giovannucci 1993 (JAMA 1993; 269: 873-7) 1993 1.66 (P=0.0004) (PSA ) 49,405 40~75 1986 2010 24 12,321 (25%) 6,023 732 ( 8~10) 811 (lethal cancer) (RR, 1.10; 95% CI, 1.04~1.17; P=0.001) 7 (RR, 1.18; 95% CI, 1.06~1.31; P=0.002) 8~10 (RR, 1.22; 95% CI, 1.03~1.45; P=0.02) 2~6 (RR, 1.09; 95% CI, 1.02~1.17; P=0.02) ( T3B T4 N1 M1 ; RR, 1.20; 95% CI, 1.03~1.40; P=0.02) PSA PSA (RR, 1.56; 95% CI, 1.03~2.36; P=0.04) 8~10 (P=0.15) (P=0.12) ( ) β1 β3 (transforming growth factors, TGF-β1/TGF-β3) (J Proteome Res 2011; 10: 941-53) TGF-β1/TGF-β3 (in vitro) 56%24 1.6% " " (exposure time) (causal relationship) Vasectomy and Risk of Aggressive Prostate Cancer: 7. 31
當代攝護腺癌精選論文點評導讀集 8. Use of Statins and the Risk of Death in Patients with Prostate Cancer J Clin Oncol 2014; 32: 5-11. 1998 4 2009 12 statins 4.4 statins statins 2012 Nielsen SF NEJM statins statins Clinical Practice Research Datalink (CPRD) Hospital Episode Statistics (HES) Office for National Statistics (ONS) 1998 4 2009 12 (ICD code: C61) (cohort) statins (pravastatin, rosuvastatin) (atorvastatin, simvastatin, fluvastatin, cerivastatin) statins Cox (time-dependent Cox proportional hazards models) (confounders) 11,772 71.3 4.4 34.8/1,000 / (1,791 ) statins statins 24% statins 23% statins 35% 14% statins (HR, 0.55) statins (HR, 0.77) statins statins statins 32
Prostate Cancer and Its Grade J Natl Cancer Inst 2013; 105: 1123-31. (case-control study) 66 5 2.89 metformin metformin metformin metformin 4 (1) ( ) (2) ( 8) (3) ( 6) (4) ( ) 5 metformin 3 1994 3 2008 3 160,867 66 119,315 5,306 26,530 1,104 1,719 3,524 5 5,520 8,595 17,620 metformin (OR, 0.95; 95% CI, 0.85~1.07) 5 metformin (OR, 0.99; 95% CI, 0.90~1.10) 3 metformin ( : aor [adjusted OR], 1.13; 95% CI, 0.96~1.32 : aor, 1.03; 95% CI, 0.99~1.1) ( : aor, 0.94; 95% CI, 0.82~1.06 : aor, 0.97; 95%CI, 0.95~1.1) ( : aor, 0.98; 95% CI, 0.84~1.02 : aor, 0.98; 95% CI, 0.95~1.1) metformin metformin metformin 10 metformin metformin metformin Association between Metformin Use and Risk of 9. 33
當代攝護腺癌精選論文點評導讀集 10. Metformin Use and All-Cause and Prostate Cancer Specific Mortality among Men with Diabetes J Clin Oncol 2013; 31: 3069-75. 66 (3,837 ) Metformin 4.64 metformin metformin 1997 3 2008 3 105,245 66 3,837 75 4.64 1,343 (35%) 291 (7.6%) metformin 6 metformin 24% (aor [adjustedor], 0.76; 95% CI, 0.64~0.89; P=0.001) 24% (aor, 0.76; 95% CI, 0.70~0.82; P<0.001) 0~6 6~12 12~18 18~24 24~30 HR 0.76 0.88 0.91 0.92 0.93 metformin metformin 34% 38% (Oncologist 2013; 18: 1245-7; Oncologist 2013; 18: 1248-55) metformin (chemo-naive) (mcrpc) PSA (Eur Urol 2014; 66: 468-74) Metformin metformin metformin 9 metformin metformin metformin 34
A Prospective Study in the Prostate-Specific Antigen Era J Natl Cancer Inst 2014; 106: doi:10.1093/jnci/djt430. (prospective cohort study) 1986 49,898 5 24 (1986 2010 ) (PSA) (The Health Professionals Follow-up Study, HPFS) 1986 49,898 1986 2010 1 2 4 (tissue microarrays) (microenvironment) ( ) 5 (BMI) 2008 PSA (HR) 0.91 (95% CI, 0.84~1.00; P=0.009) 0.72 (95% CI, 0.56~0.94; P=0.04) 28% 1994 PSA 0.85 (95% CI, 0.72~1.00; P=0.07) 28% (HR, 0.72; 95% CI, 0.51~1.00; P=0.07) PSA 28% ( HR, 0.72; 95% CI, 0.49~1.10; P=0.10) PSA PSA (HR, 0.48; 95% CI, 0.30~0.78; P=0.009) (HR, 0.47; 95% CI, 0.29~0.75; P=0.009) (aggressive cancers) (indolent cancers) PSA Dietary Lycopene, Angiogenesis, and Prostate Cancer: 11. 35
當代攝護腺癌精選論文點評導讀集 12. Selenium Supplementation and Prostate Cancer Mortality J Natl Cancer Inst 2015; 107: doi: 10.1093/jnci/dju360. (prospective cohort study) 4,459 ( T3a) 4 ( 1~24 μg/ 25~139 μg/ 140 μg/ ) 1988 2010 22 140 μg/ (The Health Professionals Follow-up Study, HPFS) 1986 51,529 40 75 (non-metastatic) PSA 4 1~24 μg/ 25~139 μg/ 140 μg/ Cox PSA 8.9 965 226 (23.4%) 267 (27.7%) 7.8 762 PSA 140 μg/ ( ) 1,000 (person-year) 10.5 5.6 3 1.18 1.33 2.6 PSA 140 μg/ E 36
Detection of Prostate Cancer? J Clin Oncol 2014; 32: 4066-72. (prospective randomized open blinded end point compliant study) 859 562 297 PCA3 PCA3>60 (PPV) PCA3<20 (NPV) PCA3<20 PCA3>60 PSA 3 (prostate cancer antigen 3, PCA3) (non-coding longchain) RNA PCA3 PSA FDA 2012 PCA3 (prospective randomized open blinded end point compliant study) (Blood Press 1992; 1: 113-19) PCA3 PSA 11 859 562 297 PCA3 PCA3 (DRE) PSA (primary endpoint) (secondary endpoint) ( > 6 ) PCA3 PCA3 mrna PSA mrna (Cancer Lett 2011; 301: 1-6) PCA3 PPV 80% (95% CI, 72~86%) PCA3>60 42% (95% CI, 0.36~0.48) 91% (95% CI, 0.87~0.94) PCA3 NPV 88% (95% CI, 81~93%) PCA3<20 76% (95% CI, 0.64~0.86) 52% (95% CI, 0.45~0.58) PCA3 <20 20~60 >60 PCA3 PCA3 PCA3>60 PCA3<20 PCA3 PCA3<20 12% 3% 13% PCA3<20 NPV PCA3>60 PCA3<20 PSA PCA3 Can Urinary PCA3 Supplement PSA in the Early 13. 37
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14. Comparison of MR/Ultrasound Fusion Guided Biopsy with Ultrasound Guided Biopsy for the Diagnosis of Prostate Cancer (prospective cohort study) 2007 2014 1,003 (targeted biopsy) (standard biopsy) 30% (173 vs 122 ; P<0.001) 17% (213 vs 258 ; P=0.002) (systematic biopsy) 6 (sextant biopsy) 10 12 (targeted biopsy) (clinically significant cancer) 2007 2014 (National Cancer Institute) 1,003 690 (69%) (461 ) (469 ) 30% (173 vs 122 ; P<0.001) 17% (213 vs 258 ; P=0.002) 112 (67%) ( ) ; 60 (41%) ( ) (P<0.001) 103 (22%) (83% 12% 5% ) (sensitivity) 77% 53% (specificity) ( 68% vs 66%) AUC (area under curve) 0.73 (0.59; P=0.005) (0.67; P=0.04) 2015; 313: 390-7. JAMA 39
當代攝護腺癌精選論文點評導讀集 癌 6 攝護腺癌 3+4 ( ) 攝護腺癌 3+4 ( ) 攝護腺癌 4+3 439 74 12 12 5 542 6 3+4 ( ) 3+4 ( ) 4+3 38 84 12 10 3 147 17 14 9 19 7 66 14 21 7 29 4 75 26 13 12 19 103 173 534 206 52 89 122 1,003 40
15. Can Clinically Significant Prostate Cancer Be Detected with Multiparametric Magnetic Resonance Imaging? A Systematic Review of the Literature (systematic review) MRI PSA mpmri mpmri (non-systematic) (targeted) (multiparametric MRI, mpmri) (clinically significant prostate cancer) MRI (mpmri) ( ) Radboud University Nijmegen Medical Centre Fütterer mpmri mpmri MRI MRI T1WI (T1 weighted image) + T2WI MRI (diffusion-weighted MRI, DW-MRI) (dynamic contrastenhanced MRI, DCE-MRI) (MR spectroscopy imaging, MRSI) Fütterer Pubmed Embase Cochrane 2000 2014 9 MRI 1,729 (Quality Assessment of Diagnostic Accuracy Studies, QUADAS-2) 12 62~65 (PSA) 5.1~13.4 ng/ml 6~10 T2WI 2 MRI (DW-MRI DCE- MRI MRSI) PSA mpmri 44~87% 58~96% 23~87 mpmri ( negative predictive value, NPV) 63~98% 34~68% mpmri 63~98% mpmri mpmri (nonsystematic) (targeted) mpmri T1WI + T2WI + DW-MRI MRI T1WI + T2WI + DW-MRI + DCE-MRI mpmri MRI PC 12 MRI MRI MRI Urol 2015; 68: 1045-53. Eur 41
當代攝護腺癌精選論文點評導讀集 16. High Diagnostic Ability of Multiparametric Magnetic Resonance Imaging to Detect Anterior Prostate Cancer Missed by Transrectal 12-Core Biopsy J Urol 2013; 190: 867-73. ( ) (prospective study) PSA 2.5 20 ng/ml 75 324 (mpmri) mpmri (significant cancer) 324 (mpmri) 12 (TR12PBx) 14 (TP14PBx) 26 ( ) (significant cancer) 4+3 20% 5 mm 39% (128/324 ) 28% (N=36) TR12PBx TP14PBx 20% (65/324) mpmri 36 31 mpmri 26 12 11 mpmri TR12PBx mpmri TP14PBx mpmri 46% (31 of 67) 100% (12/12) mpmri 74% (26 of 35) 91.7% (11/12) MRI TR12PBx mpmri mpmri 圖一 病人分佈圖 有 PC (N=128) 受試者族群 (N=324) TR12PBx TP14PBx (30) (26) TR12PBx (+) 無 PC (N=196) MRI(+)-AP(+) TP-AP(26/26) (27) Sig. (11/26) MRI(+)-AP(-) (5) MRI(+)-AP(-) (38) TP-AP(2/5) Sig. (1/5) (5) MRI (-) (24) (160) TP-AP(2/5) MRI (-) Sig. (0/5) TR12PBx (-) (9) MRI(+)-AP(+) MRI(+)-AP(-) MRI(-) TR12PBx 12 TP14PBx 14 TP-AP (26/26) ( ) Sig. (11/26) ( ) MRI(+)-AP(+) 42
Sectional Study on Unscreened Caucasian and Asian Men J Natl Cancer Inst 2013; 105: 1050-58. (prospective cross-sectional study) 320 ( ) 220 ( ) 100 (37% vs 35%) 50% 7 25% (clinically significant prostate cancer) 2009 10 30 (indolent or latent PC) 2008 2011 220 100 (68.5 vs 62.5 ; P<0.001) (2.23 0.42 g vs 3.54 1.59 g; P=0.001) (35.0% vs 37.3%; P=0.70) 83 (70.9%) (unifocal) 27 (23.1%) (multifocal) 31.6% 7 (51.4% vs 23.1%; P=0.003) 7 (P=0.03) 60 40% 80 60% 0.303 cm 3 13 (11.1%) (extra-prostatic extension; P=0.94) 59 (59%) 26 (11.8%) (P<0.001) (62.9% vs 12.2%) (56.9% vs 11.6%) (high grade prostate intraepithelial neoplasia, HGPIN) (P=0.21) 50% 7 25% 7 7 Prevalence of Prostate Cancer on Autopsy: Cross- 17. 43
當代攝護腺癌精選論文點評導讀集 18. Systematic Review of Complications of Prostate Biopsy Eur Urol 2013; 64: 896-92. (systematic review) 2002-2013 213 25% 2% (<1%) (10~84%) (18G vs 16G) 20 8 TURP (transurethral resection of the prostate) 1.3~45% 0~6% (UTI) 24 ( ) lidocaine (LUTS) 25% LUTS 2% IPSS (α-blockers) (ED) ED 6 44
UTI 0~1.6% 36.7~100% 0~5.2% 1.6~8.8% 20.6% 22,175 120 1.3% 1,778 120 0.3% SEER Medicare 30 0.31% 30 1.09% 30 30 (OR, 0.29; 95% CI, 0.22~0.38; P<0.0001) 30 30 12 (95% CI, 8.59~16.80; P<0.0001) α ED 45
當代攝護腺癌精選論文點評導讀集 19. Neuroendocrine Prostate Cancer (NEPC) Progressing from Conventional Prostatic Adenocarcinoma: Factors Associated with Time to Development of NEPC and Survival from NEPC Diagnosis A Systematic Review and Pooled Analysis J Clin Oncol 2014; 32: 3383-90. (meta-analysis) 54 (treatment-related neuroendocrine prostate cancer, tnepc) NEPC (time to NEPC, TTNEPC) NEPC 123 tnepc NEPC 20 TTNEPC NEPC 7 (castrationresistant prostate cancer, CRPC) (neuroendocrine prostate cancer, NEPC) NEPC (treatment-related NEPC, tnepc) tnepc (PSA) (lytic bone lesions) PSA 34,000 25% tnepc (meta-analysis) 2013 10 MEDLINE EMBASE Chinese CNKI and Wanfang Japanese KURENAI and J-STAGE ASCO 82 tnepc 54 123 tnepc NEPC (TTNEPC) NEPC NEPC 20 TTNEPC (HR, 1.66; 95% CI, 1.04~2.64; P=0.032) NEPC 7 (0.5~63 ) NEPC (HR, 3.31; 95% CI, 1.62~6.76; P=0.001) 3 3 (biologic progression) (disseminated disease) (oligometastatic disease) NEPC (HR, 0.66; 95% CI, 0.45~0.96; P=0.034) (HR, 0.38; 95% CI, 0.17~0.85; P=0.018) (HR, 0.29; 95% CI, 0.11~0.76; P=0.012) ( ) tnepc NEPC NEPC 46
) ( ) Localized Prostate Cancer N Engl J Med 2012; 367: 203-13. 文 (PIVOT study) (open label randomized controlled trial) (T1/T2) 731 (RP) (observation, Obs) (1:1) 10.0 論 Obs (OS) (CSS) PSA>10 RP CSS 20. Radical Prostatectomy versus Observation for ( SPCG-4 (localized) (RP) (Obs) 731 T1/T2 (RP) (Obs) 10.0 RP (N=364) Obs (N=367) 171 (47.0%) 183 (49.9%) (HR, 0.88; 95% CI, 0.71~1.08; P=0.22; 2.9 ) 21 (5.8%) 31 (8.4%) (HR, 0.63; 95% CI, 0.36~1.09; P=0.09; 2.6 ) (subgroup analysis) PSA>10 RP (CSS) (P=0.12) (P=0.54) PSA<10 (P=0.82) RP CSS (Obs) (OS) RP (P<0.05) RP (P=0.16) RP Obs 15% RP (4.7%) Obs (10.6%) PSA<10 2 RP OS CSS PIVOT 12 PSA OS CSS SPCG-4 ( 21 ) (watchful waiting Obs) RP OS CSS ( 21 ) 47
當代攝護腺癌精選論文點評導讀集 21. Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer N Engl J Med 2014; 370: 932-42. 文 論 (SPCG-4 study) (open label randomized controlled trial) (T1/T2) 695 (RP) (watchful waiting, WW) 13.4 RP (OS) (CSS) WW 65 (intermediate risk) RP OS CSS PIVOT ( 20 ) (localized) (RP) (WW) OS 695 T1/T2 (RP) (WW) 13.4 23 RP (N=347) WW (N=348) 200 247 63 (18.1%) 99 (28.4) RP WW 44% (95% CI, 23%~59%; P=0.001) (subgroup analysis) RP 65 (P=0.002) (intermediate risk, P<0.001) 65 (P=0.19) (low risk, P=0.17) (high risk, P=0.84) RP WW (CSS) PIVOT ( 20 ) RP WW OS CSS SPCG-4 1989 ( ) 10 (1989~1999) PIVOT PSA PSA SPCG-4 (highrisk) PIVOT (24% vs 20%) 24% SPCG-4 95% PSA DRE (88% ) 24% (intermediate risk) SPCG-4 RP WW (micro-metastasis) (RP 45.9% vs WW 50.8%; P=0.39) ( ) 65 RP WW (PIVOT ) RP WW RP (active surveillance, AS) RCT "ProtecT Trial" 1999 2009 48
) RP AS 2015 AS WW AS WW WW RP WW PIVOT SPCG-4 65 RP WW RP WW 65 18 RP 15 RP RP WW PIVOT SPCG-4 ( PSA testing era Pre-PSA testing SPCG-4 1994.11~2002.1 1989~1999 SPCG-4 (2012 ) 77 ( ) 67 65 80~81 ( ) 65 35% 46% PSA (ng/ml) 7.8 (median) 10.1 (mean) 12.9 (mean) PSA>10 34% 47% (SPCG-4) (SPCG-4) (SPCG-4) PSA (SPCG-4) PSA (SPCG-4) PSA 76% 5% PSA (PIVOT) (GS) 7 25% (48% central review) 32% Stage T1c 50% 12% Stage T2 45% 69% 20% 24% RP 5.8% Obs 8.4% Total: 7.1% P=0.09 RP 18.1% WW 28.4% Total: 19.6% P=0.001 GS (SPCG-4) T1c (PIVOT) (SPCG-4) (SPCG-4) SPCG-4 49
當代攝護腺癌精選論文點評導讀集 22. Androgen Deprivation with or without Radiation Therapy for Clinically Node-Positive Prostate Cancer J Natl Cancer Inst 2015; 107: djv119. doi:10.1093/jnci/djv119. 文 (retrospective study on national cancer data base) (cn+) (M0) 636 (ADT + RT) (ADT) 5.2 ( ) 論 ADT ADT + RT cn+m0 (OS) 50.3% (clinical stage) (cn+) (M0) T4N0M0 (M1) T4N0M0 (locally advanced) (ADT + RT) (ADT) ADT + RT ADT (curative) (local treatment, RT) (pn+) ADT RT (randomized) ( / ) (Eur Urol 2011; 59: 832-40; Urol 2001; 58: 233-39) (cn+) ADT + RT ADT cn+m0 (NCDB) 2004 2011 3,540 cn+m0 (high-risk feature) 61.7% 8~10 46.2% PSA 20 ng/ml 39.4% ct3-4 2004 2006 ADT RT (595 ) ADT (388 ) 318 ADT + RT 50
) ADT 50.3% (HR, 0.50; 95% CI, 0.37~0.67; P<0.001) ( T stage PSA level) (P<0.05) P (0.05~0.07) cn+m0 ADT + RT ( 51.4% ADT + RT) ADT cn+m0 ( 51
當代攝護腺癌精選論文點評導讀集 23. Effectiveness of Androgen-Deprivation Therapy and Radiotherapy for Older Men with Locally Advanced Prostate Cancer J Clin Oncol 2015; 33: 716-22. 文 論 (nonrandomized effectiveness studies) (cohort) (locally advanced PC, LAPC) [ (ADT) + (RT)] [ (ADT)] 7 ADT + RT RT ADT Bekelman (cohort) (locally advanced prostate cancer, LAPC) (high risk) (androgen deprivation therapy, ADT) (radiation therapy, RT) ADT ADT + RT ADT (Lancet 2009; 373: 301-8; Lancet 2011; 378: 2104-11) SEER Medicare 1995 2007 LAPC 2009 12 31 7 ( ) (randomized clinical trial cohort) 65~75 4,642 ADT 8,282 ADT + RT ( ) (elderly cohort) 75 8,694 ADT 5,646 ADT + RT ( ) (screen-detected cohort) (high risk) 2,017 ADT 2,060 ADT + RT Cox (multivariable Cox proportional hazards models) ADT ADT + RT (propensity score) (instrumental variable analysis) ADT + RT (overall mortality) (cause-specific mortality) (OS) (CSS) ADT ADT + RT (1) ADT 9 LHRH agonist ( one dose LHRHa) ADT LHRH agonist (2) RT Bolla 1997 RT ADT 3 RT ADT RT (N Engl J Med 1997; 337: 295-300; Lancet Oncol 2010; 11: 1066-73) ADT RT ADT LAPC ADT + RT (time to progression) (prostate cancer specific outcome) (J Clin Oncol 2015; 10: 2143-9 24 ) 52
) (micro-metastasis) 20~60% (20% in high risk, 60% in very high risk) ADT RTOG 85-31 (N Engl J Med 2010; 341: 1781-8) ADT + RT ADT RT (Eur Urol 2014; 65: 1058-66; Pract Radiat Oncol 2013; 3: 234-40; Int J Radiat Oncol Biol Phys 2014; 88: 1064-73; Crit Rev Oncol Hematol 2015; 93: 136-48; Eur Urol 2015; 67: 3-6) (J Clin Oncol 2014; 32: 3939-47) ADT + RT ADT ADT NCCN 30% PSA ADT 2~3 RT ADT 10 15 82% 78% LAPC ( ) ADT RT LAPC ADT + RT RT ADT + ADT (extended node dissection) (cytoreduction) (adjuvant) ( 53
當代攝護腺癌精選論文點評導讀集 24. Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy plus Radiotherapy versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer J Clin Oncol 2015; 33: 2143-50. 文 論 (unmasked, randomized controlled trial) (T3-4, N0/NxM0, LAPC) 1,205 (lifelong androgen deprivation therapy, ADT) (ADT + RT) 8.0 LAPC (overtreatment) (undertreatment) (LAPC) (ADT) LAPC ADT (RT) NCIC Clinical Trial Group PR.3/Medical Research Council PR07/intergroup T94-0110 Eastern Cooperative Oncology Group Southwest Oncology Group (T3-4, N0/NxM0, LAPC) (T1-2 + PSA>40 ng/ml or PSA 20~40 ng/ml + (GS) 8~10) ADT ADT (RT) (Lancet 2011; 378: 2104-11) ADT RT ADT (OS; HR, 0.77; 95% CI, 0.61~0.98; P=0.033) (CSS DSS) RT (four-field box technique) RT 45 Gy 20~24 Gy 64~69 Gy 88% 65~69 Gy 1,205 (T3-4, 87%; PSA>20 ng/ml, 63%; GS>8, 18%) ADT ADT + RT 8.0 ADT (N=602) ADT + RT (N=603) 260 205 199 (OS) ADT + RT 30% (HR, 0.70; 95% CI, 0.57~0.85; P<0.001) (HR, 0.74; 95%CI, 0.61~0.87) PSA (>50 vs <20) (8~10 vs <8) OS (disease-specific survival, DSS) ADT + RT (HR, 0.46; 95% CI, 0.34~0.61; P<0.001) (Phoenix criteria PSA + 2 ng/ml ) ADT + RT (HR, 0.31; 95% CI, 0.27~0.37) ADT + RT (2/589) (N=420, 72%) (N=166, 28%) (HR, 0.70; 95% CI, 0.45~1.09; P=0.12) 1995 2005 RT ADT LAPC ADT 54
) ADT RT (median OS) ADT 9.7 (95% CI, 8.8~10.5 ) RT ADT + RT 10.9 (95% CI, 10.0~12.8 ) (10-year OS) 49% (95% CI, 44~54%) 55% (95% CI, 49~60%) (10-yr biochemical progression free rate, Phoenix criteria) 27% (95% CI, 23~32%) 63% (95% CI, 57~68%) ( 55
當代攝護腺癌精選論文點評導讀集 25. Adjuvant and Salvage Radiotherapy after Prostatectomy: AUA/ASTRO Guideline J Urol 2013; 190: 441-9. 文 論 (adjuvant) (salvage) PSA (AUA) (ASTRO) 1990 2012 PubMed Embase Cochrane 294 (adjuvant) PSA (salvage) ( PSA ) PSA PSA ( ) PSA 0.2 ng/ml PSA 9 1. ( ) 2. PSA 3. PSA (SWOG8794 EORTC22911 ARO96-02) PSA ( ) SWOG PSA 0.2 ng/ml PSA 4. PSA PSA PSA 56
) PSA ( ) 5. PSA 0.2 ng/ml PSA 0.2 ng/ml 0.2 ng/ml PSA PSA PSA 8.8% 0.2 ng/ml PSA PSA PSA 6. ( ) 7. PSA SWOG 8794 EORTC 22911 PSA (0.2 ng/ml) PSA PSA 90% 75% T PSA PSA PSA PSA PSA 8. PSA PSA PSA 0.1 ng/ml 2.6% PSA 1 ng/ml 18.1% SWOG 8794 PSA 1 ng/ml PSA 9. 5% 90 (IMRT) 16.8% 4% PSA ( 57
當代攝護腺癌精選論文點評導讀集 26. Might Men Diagnosed with Metastatic Prostate Cancer Benefit from Definitive Treatment of the Primary Tumor? A SEER-Based Study Eur Urol 2014; 65: 1058-66. 文 論 2004~2010 SEER 8,185 M1a~M1c (metastatic prostate cancer) (radical prostatectomy, RP) (N=245) (brachytherapy, BT) (N=129) (no surgery or radiation therapy, NSR) (N=7,811) 16 (RP BT RP) NSR PSA ( ) (metastatic prostate cancer) 2004~2010 SEER 8,185 M1a~M1c (radical prostatectomy, RP) (N=245) (brachytherapy, BT) (N=129) (no surgery or radiation therapy, NSR) (N=7,811) 16 RP BT PSA RP BT NSR 5 (OS) 67.4% 52.6% 22.5% (P<0.001) 5 (predicted diseasespecific survival, DSS) 75.8% 61.3% 48.7% (P<0.001) BT RP (HR) (RP BT) PSA 2 NSR 3 NSR ( RP) NSR 2 SEER RP BT (intensity-modulated radiation therapy, IMRT) (Cancer Epidemiol 2014; 38: 435-41; J Urol 2015; 194: 378-85) SEER 61 RP (ADT) (PFS) (CSS) OS (J Urol 2015; 193: 832-8) SWOG 9346 ADT (minimal metastatic disease) (extensive metastatic disease) 6.9 4.4 5 58
) 50~60% (N Engl J Med 2013; 368: 1314-60~70% 25) ADT SEER ( 59
當代攝護腺癌精選論文點評導讀集 27. Proton Beam Therapy (PBT) ASTRO Model Policies 2014; May 20. 文 論 (ASTRO) (PBT) PBT (ASTRO) (model policies) (PBT) PBT ( ) PBT (photon beam) PBT PBT (Bragg peak) PBT PBT PBT PBT (scattering) (scanning) PBT PBT PBT X PBT PBT PBT 1. 2. PBT 3. PBT 4. PBT PBT PBT PBT PBT PBT PBT (brachytherapy) PBT PBT 60
mhspc 28. Effectiveness of Primary Androgen-Deprivation Therapy for Clinically Localized Prostate Cancer J Clin Oncol 2014; 32: 1324-30. 文 論 (retrospective cohort study) 15,170 (primary androgen deprivation therapy, PADT) 61 PADT PADT 65 PADT PADT Medicare (Surveillance, Epidemiology, and End Results, SEER) PADT PADT HMO 1995~2008 ( ) 61 15,170 PADT (allcause mortality) (prostate cancerspecific mortality) (cancer mortality) (cardiovascular mortality) (subgroup analysis) 34 PADT GnRH (N=3,435) PADT (N=11,735) PADT PADT PSA>20 (42% vs 10%) 8 (26% vs 7%) (58% vs 18%) (31% vs 24%) (propensity score) 4,921 1,048 PADT (49% vs 28%; HR, 1.96; 95% CI, 1.85~2.08; P<0.001) (13% vs 5%; HR, 2.91; 95% CI, 2.57~3.28; P<0.001) (propensity score adjusted estimates using standardized mortality ratio weighting) PADT (HR, 0.98; 95% CI, 0.91~1.06) (HR, 1.01; 95% CI, 0.86~1.16) (HR, 1.02; 95% CI, 0.90~1.14) (HR, 1.04; 95% CI, 0.88~1.20) PADT (HR, 0.88; 95% CI, 61 mhspc
當代攝護腺癌精選論文點評導讀集 0.78~0.97; P=0.02) PADT (HR, 1.41; 95% CI, 0.99~1.82; P=0.02) PSA (doubling time) PADT (delay PADT) PADT PADT PADT PADT 62
29. Intermittent versus Continuous Androgen Deprivation in Prostate Cancer N Engl J Med 2013; 368: 1314-25. 文 1,535 (IAD) (CAD) (1:1) 9.8 論 CAD IAD IAD (ADT) ADT (castration resistance) 2.5 3 IAD CAD IAD CAD (non-inferiority) SWOG ECOG CALGB NCIC-CTG (the National Cancer Institute of Canada Clinical Trials Group) EORTC 6 (induction) (LHRHa antiandrogen) PSA 6 7 4 ng/ml IAD CAD 6 7 PSA 4 ng/ml IAD ADT (off period) PSA 20 ng/ml PSA ADT PSA 10 ng/ml ADT ADT 7 PSA 4 ng/ml ADT 7 PSA 4 ng/ml ADT off period 3 PSA ADT ADT 1995 5 2008 9 3,040 7 ADT 1,535 19 17 (IAD vs CAD) IAD 47% ADT (30.4% vs 32.7%; P=0.53) 3.7 (1.8~7.9 ) ( 6 7 PSA 4 ng/ml ) 1.7 (1.0~3.2 ) 928 IAD CAD 483 445 5.1 5.8 IAD CAD 10% (HR, 1.10 90% CI, 0.99~1.23) 90% 1.20 1.23 Piaggio (JAMA 2006; 295: 1152-60) " IAD CAD " 0.99 1.00 "IAD CAD " minimal disease ( ) extensive disease ( ) IAD extensive disease 4.9 CAD 4.4 IAD HR 1.02 (95% CI, 0.85~1.22) minimal disease IAD 5.4 CAD 6.9 IAD HR 1.19 (95% CI, 0.98~1.43) Docetaxel (2004) (P=0.54) CAD 73% IAD 80% 3 9 15 63 mhspc
當代攝護腺癌精選論文點評導讀集 IAD IAD CAD (P<0.001) (P=0.04) (mental health, P=0.003) 15 IAD CAD 64
30. Treatment of Prostate Cancer with Intermittent versus Continuous Androgen Deprivation: A Systemic Review of Randomized Trials J Clin Oncol 2013; 31: 2029-36. 文 ( ) (locally advanced) (IAD) (CAD) Medline EMBASE Cochrane Library (Proceedings) 2012 9 IAD CAD (OS) / (TTP) 9 5,508 25 100 OS TTP IAD 論 CAD IAD ADT ADT IAD (ADT) ADT (castration resistance) (CAD) (IAD) 1986 IAD IAD CAD IAD CAD (OS) (TTP) (QoL) IAD 1948 2012 9 MEDLINE 1980 2012 9 EMBASE Cochrane Library 2012 9 review articles meeting proceedings ADT ( LHRH agonist LHRH agonist antiandrogen) 6 PSA <4 ng/ml 1,323 ( 1,311 12 proceedings) 9 5,019 IAD CAD 3 OS (endpoint) 4 OS 5 TTP 3 CAD OS IAD HRs 1.02 (95% CI, 0.93~1.11) TTP HRs 0.96 (95% CI, 0.76~1.20) IAD CAD IAD QoL ( ) IAD QoL Pharmacy's Reference Red Book GnRH agonists antiandrogens IAD CAD 48.5% (US$ 5,685 vs $11,710) ( ) OS TTP IAD CAD IAD ADT ADT IAD (US Preventive Services Task Force Grade B recommendation) 65 mhspc
當代攝護腺癌精選論文點評導讀集 31. Androgen-Deprivation Therapy alone or with Docetaxel in Non-Castrate Metastatic Prostate Cancer (GETUG-AFU 15): A Randomised, Open-Label, Phase 3 Trial Lancet Oncol 2013; 14: 149-58. 文 (GETUG-AFU 15) (randomized, open-label, phase 3 study) 30 ( 29 1 ) 385 docetaxel 192 193 (1:1) 50 論 Docetaxel (non-castrate) docetaxel (androgendeprivation therapy, ADT) (non-castrate) 358 1:1 ADT (N=193) ADT docetaxel ( 21 75 mg/m² N=192) (OS) (intention to treat) 50 (39~63) PSA (bpfs) (cpfs) PSA ADT docetaxel ADT ADT + docetaxel 58.9 (95% CI, 50.8~69.1) ADT 54.2 (42.2 ; HR, 1.01; 95% CI, 0.75~1.36; P=0 955) docetaxel ADT ADT + docetaxel 72 (40 [21%]) (6 [3%]) (3 [2%]) (2 [1%]) ADT + docetaxel 4 (2 ) (granulocyte colony-stimulating factor) + + (chemohormonal therapy) 4 10% ( ) ADT docetaxel (CHAARTED Study, 32 ) 66
32. Chemohormonal Therapy in Metastatic Hormone- Sensitive Prostate Cancer N Engl J Med 2015; 373: 737-46. 文 論 (E3805) (Phase III open label randomized trial) 790 (ADT + 6 (cycles) docetaxel ) (ADT) 28.9 (57.6 vs 44.0 ) (high volume) 2004 TAX327 SWOG9916 docetaxel 2.5 120 (ADT) 790 ADT 6 75 mg/m 2 docetaxel 28.9 (57.6 vs 44.0 ) (hazard ratio, HR) 0.61 (95% CI, 0.47~0.80; P<0.001) PSA (20.2 vs 11.7 ) HR 0.61 (95% CI, 0.51~0.72; P<0.001) 12 PSA 0.2 ng/ml 27.7% 16.8% 6.2% 0.5% ( ) (high volume) (49.2 vs 32.2 ) HR 0.60 (95% CI, 0.45~0.81; P<0.001) (low volume) GETUG-AFU 15 (ADT + 9 docetaxel) (ADT) 385 (58.9 vs 54.2 ) HR 1.01 (95% CI, 0.75~1.36) (Lancet Oncol 2013; 14: 149-58) GETUG- AFU 15 (54.2 vs 44.0 ) GETUG-AFU 15 2015 (ASCO) STAMPEDE 477 ADT + docetaxel ADT (65 vs 43 ) HR 0.73 (95% CI, 0.59~0.89; P=0.002) (E3805) E3805 docetaxel 67 mhspc
當代攝護腺癌精選論文點評導讀集 68
mcrpc 33. Castration-Resistant Prostate Cancer: AUA Guideline Amendment J Urol 2015; 193: 491-9. (AUA) (meta-analysis) 37 (CRPC) 2013 2 2014 2 (performance status) docetaxel 6 (index patient) (mcrpc) 2004 (ADT) 2004 docetaxel mcrpc 2010 enzalutamide abiraterone sipuleucel-t cabazitaxel -223 (radium-223) mcrpc (OS) CRPC (AUA) 1996 1 2013 2 2013 CRPC (J Urol 2013; 190: 429-38) 2014 CRPC 2013 2 2014 2 CRPC PSA / AUA (performance status) docetaxel 6 (index patient) CRPC AUA (standard) (recommendation) (option) (clinical principle) (expert opinion) 6 1 (M0) CRPC 2014 ADT (flutamide, bicalutamide, nilutamide) (ketoconazole + steroid) 2 docetaxel mcrpc 2014 abiraterone + prednisone ( 37 ) docetaxel sipuleucel-t ketoconazole + steroid PREVAIL ( 35 ) enzalutamide 3 docetaxel mcrpc docetaxel -223 abiraterone + prednisone 6969 mcrpc
當代攝護腺癌精選論文點評導讀集 estramustine sipuleucel-t ketoconazole + steroid mitoxantrone -153-89 2014-223 ( 42 ) -223 DNA docetaxel mcrpc -223 (14.9 vs 11.3 ; HR, 0.695; P=0.00007) -223 3 4 docetaxel mcrpc sipuleucel-t abiraterone + prednisone ketoconazole + steroid -153-89 docetaxel mitoxantrone -223 2014-223 5 docetaxel mcrpc abiraterone + prednisone enzalutamide cabazitaxel -223 ketoconazole + steroid docetaxel docetaxel 2014-223 6 docetaxel mcrpc abiraterone + prednisone enzalutamide ketoconazole + steroid : 2014 ( vitamin D) CRPC denosumab zoledronic acid CRPC (skeletal-related events) CRPC http://www.auanet. org/education/guidelines/castration-resistantprostate-cancer.cfm 70
34. Increased Survival with Enzalutamide in Prostate Cancer after Chemotherapy N Engl J Med 2012; 367: 1187-97. (AFFIRM) (randomized, double-blind, placebo-controlled study) (mcrpc) 1,199 Enzalutamide (ENZ) 160 mg QD (placebo) (2:1) 14.4 ENZ placebo docetaxel mcrpc (OS) (PFS) PSA 1,199 docetaxel mcrpc 15 156 2:1 enzalutamide (ENZ) 160 mg (N=800) placebo (N=399) ENZ (progression) (primary endpoint) (OS) ( PSA QoL) ( PSA radiographic PFS SRE ) 520 ENZ 8.3 3 14.4 ENZ 18.4 13.6 ENZ 4.8 37% (HR, 0.63; 95% CI, 0.53~0.75; P<0.001) ENZ ( ) ENZ P <0.001 ( SRE HRQoL ) ENZ SRE (16.7 vs 13.3 ; P=0.0001) (Lancet Oncol 2014; 15: 1147-56) (post-hoc) ENZ ( 75 <75 ) OS (Ann Oncol 2014; 25: 429-34) ENZ (, N=684;, N=395) (OS ) (BJU Int 2015; 115: 41-9) PSA (<40 40~<110 111~<406 >406) ENZ OS radiographic PFS PSA (Eur Urol 2015; 67: 223-30) ENZ 3 (SAE) (45.3% vs 53.1%) SAE 8.4 (12.6 vs 4.2) ENZ 0.6% (5/800) (dose-dependent) GABA A - ENZ abiraterone acetate (AA) ENZ mcrpc docetaxel PSA PSA radiographic PFS ENZ AA COU-AA-301 ( 36 ) prednisone AFFIRM ENZ 7171 mcrpc
當代攝護腺癌精選論文點評導讀集 AA docetaxel mcrpc (SRE) cabazitaxel radium-223 abiraterone enzalutamide AA ( ) ENZ 72
35. Enzalutamide in Metastatic Prostate Cancer before Chemotherapy (PREVAIL) N Engl J Med 2014; 371: 424-33. (PREVAIL) (double-blind randomized controlled trial) (mcrpc) 1,717 Enzalutamide (160 mg once daily) (placebo) 22 ( ) enzalutamide (radiographic progression) Enzalutamide AFFIRM ( 34 ) (metastatic castration-resistant prostate cancer, mcrpc) enzalutamide mcrpc mcrpc enzalutamide enzalutamide (radiographic progression-free survival, rpfs) (overall survival, OS) mcrpc (ECOG) 0~1 ketoconazole abiraterone acetate 1,717 mcrpc enzalutamide 160 mg (N=872) (N=845) enzalutamide Enzalutamide rpfs 65% 14% (enzalutamide [HR] 0.19 95% [95% CI] 0.15~0.23; P<0.001) 72% enzalutamide 63% (HR for enzalutamide, 0.71; 95%CI, 0.60~0.84; P<0.001) Enzalutamide (32.4 ) (30.2 ) 2.2 (HR, 0.35) (HR, 0.72) (59% vs 5%) PSA (HR, 0.17) PSA>50% (78% vs 3%) enzalutamide PREVAIL mcrpc enzalutamide 2.2 (rpfs) abiraterone acetate COU-AA 302 ( 37 ) abiraterone acetate mcrpc 37 7373 mcrpc
當代攝護腺癌精選論文點評導讀集 36. Abiraterone and Increased Survival in Metastatic Prostate Cancer N Engl J Med 2011; 364: 1995-2005. (COU-AA-301) (randomized, double-blind, placebo-controlled study) docetaxel (mcrpc) 1,195 [Abiraterone acetate (AA) 1,000 mg + prednisone 5 mg BID] [ (placebo) + prednisone 5 mg BID] (2:1) 12.8 docetaxel mcrpc AA + prednisone (OS) 1,195 mcrpc docetaxel 13 147 2:1 abiraterone acetate (AA) 1,000 mg + prednisone 5 mg BID (N=797) placebo + prednisone 5 mg BID (N=398) 4 250 mg AA placebo 1 2 prednisone 5 mg BID (progression) PSA 25% (primary endpoint) (OS) PSA PSA (radiographic PFS) (interim analysis) AA 8 4 12.8 AA 14.8 10.9 AA 35% (HR, 0.65; 95% CI, 0.54~0.77; P<0.001) AA AA PSA (29% vs 6%; P < 0.001) PSA (10.2 vs 6.6 ; P<0.001) radiographic PFS (5.6 vs 3.6 ; P<0.001) 20.2 AA (15.8 vs 11.2 ; HR, 0.74; 95% CI, 0.64~0.86; P<0.0001) PSA (29.5% vs 5.5%) PSA (8.5 vs 6.6 ) radiographic PFS (5.6 vs 3.6 ) AA P <0.0001 (Lancet Oncol 2012; 13: 983-2) (post-hoc) AA (pain relief, delayed pain progression) (skeletal-related events, SRE) (45.0% vs 28.8%; P=0.0005) SRE (25.0 vs 20.3 months; P=0.0001) (Lancet Oncol 2012; 13: 1210-17) AA (HRQoL) FACT-P (Functional Assessment of Cancer Therapy-Prostate) (48% vs 32%; P<0.0001) (Eur J Cancer 2013; 49: 3648-57) AA ( 4.6 4.8 ) 21% (HR, 0.79; 95% CI, 0.60~1.05; P=0.102) 31% (HR, 0.79; 95% CI, 0.60~1.05; P=0.102) AA P AA (Prostate Cancer Prostatic Dis 2014; 17: 34-9) AA CYP17 ( ) (mineralocorticoid excess) (31% vs 22%; P=0.04) (17% vs 8%; P<0.001) (13% vs 11%; P=0.14) (10% vs 8%) (19% vs 23%; P=0.09) (12% vs 15%) AFFIRM study ( 34 ) 74
37. Abiraterone Acetate plus Prednisone versus Placebo plus Prednisone in Chemotherapy-Naive Men with Metastatic Castration-Resistant Prostate Cancer (COU-AA-302): Final Overall Survival Analysis of a Randomised, Double-Blind, Placebo-Controlled Phase 3 Study Lancet Oncol 2015; 16: 152-60. (COU-AA-302) (double-blind randomized controlled trial) (mcrpc) 1,088 Abiraterone acetate prednisone (placebo) prednisone 49.2 ( ) abiraterone acetate (radiographic progression) PREVAIL ( 35 ) COU-AA-301 ( 36 ) abiraterone acetate (metastatic castration-resistant prostate cancer, mcrpc) abiraterone mcrpc mcrpc abiraterone prednisone prednisone (radiographic progression-free survival, rpfs) (overall survival, OS) mcrpc (ECOG) 0~1 ketoconazole 7 1,088 mcrpc abiraterone 1,000 mg prednisone 5 mg (N=546) prednisone 5 mg (N=542) COU- AA-302 49.2 abiraterone 354 (65%) 387 (71%) 238 (44%) abiraterone Abiraterone (, abiraterone 34.7, 30.3 ; [HR], 0.81; 95% CI, 0.71~0.93; P=0.0033) Abiraterone (rpfs) ( N Engl J Med 2013; 368: 138-48, abiraterone 16.5, 8.3 ; HR, 0.53; P=0.01) (abiraterone 8% vs 4%) (abiraterone 6% vs 1%) (abiraterone 5% vs 3%) COU-AA-302 mcrpc abiraterone prednisone 4.4 (rpfs) abiraterone abiraterone enzalutamide COU-AA-301 AFFIRM ( 34 ) mcrpc COU-AA-302 PREVAIL abiraterone enzalutamide abiraterone enzalutamide mcrpc PREVAIL 7575 mcrpc
當代攝護腺癌精選論文點評導讀集 docetaxel 24% cabazitaxel 7% 32% COU-AA-302 13% mcrpc abiraterone enzaluatmide docetaxel mcrpc PREVAIL COU-AA-302 docetaxel abiraterone enzalutamide mcrpc PREVAIL 8 mcrpc enzalutamide (Azira D, et al. ASCO GU 2012) abiraterone 8 mcrpc TAX- 327 docetaxel 7-10 mcrpc ( ) PSA (AR V7 variant) mcrpc abiraterone enzalutamide mcrpc enzalutamide abiraterone COU- AA-302 PREVAIL enzalutamide 29% 3% 73% 0% enzalutamide rpfs (Poster 767P, ESMO 2014 Congress) enzalutamide mcrpc abiraterone mcrpc COU-AA-302 PREVAIL COU-AA-302 PREVAIL 49.2 22 Abiraterone + prednisone Placebo + prednisone Enzalutamide Placebo 67% 80% 44% 76% Docetaxel 57% 61% 33% 57% Cabazitaxel 18% 19% 6% 13% Abiraterone 13% 44% 21% 46% Ketoconazole 8% 13% - - Sipuleucel-T 8% 6% 1% 1% Radium-223 4% 1% - - Enzalutamide - - 1% 4% 76
38. Abiraterone Acetate for Patients with Metastatic Castration- Resistant Prostate Cancer Progressing after Chemotherapy: Final Analysis of a Multicentre, Open-Label, Early-Access Protocol Trial Lancet Oncol 2014; 15: 1263-8. (multicentre, open-label, early-access protocol trial) (mcrpc) abiraterone acetate prednisone 2,314 abiraterone acetate prednisone 5.4 COU-AA-301 abiraterone abiraterone acetate COU-AA-301 ( 36 ) docetaxel (mcrpc) abiraterone prednisone prednisone (15.8 vs 11.2 ) COU-AA-301 (multicentre, open-label, early-access protocol trial) abiraterone prednisone mcrpc early-access protocol (EAP) ( abiraterone) 2010 11 2013 9 23 2,314 mcrpc 5.4 (IQR, 3.5~10.6 ) abiraterone (1,000 mg QD) prednisone (5 mg BID) 28 abiraterone 30 (PSA ) 952 (41%) 366 (16%) 585 (25%) 167 (7%) (188 [8%]) (99 [4%]) (52 [2%]) (31 [1%]) (28 [1%]) (23 [1%]) 172 (7%) 64 (3%) 171 (7%) 85 (4%) 72 (3%) 14 (1%) 86 18 (<1%) PSA 8.5 (95% CI, 8.3~9.7) 12.7 (95% CI, 11.8~13.8) COU-AA-301 abiraterone prednisone COU-AA-301 54% ( 41%) 38% ( 25%) 13% ( 7%) 3% ( 7%) PSA 8.5 COU-AA-301 abiraterone abiraterone acetate 7777 mcrpc
當代攝護腺癌精選論文點評導讀集 39. AR-V7 and Resistance to Enzalutamide and Abiraterone in Prostate Cancer N Engl J Med 2014; 371:1028-38. (prospective study) enzalutamide abiraterone 62 (circulating tumor cells) AR-V7 (androgen-receptor splice variant 7) mrna Enzalutamide 5.4 abiraterone 4.6 AR-V7 mrnaenzalutamide abiraterone Enzalutamide abiraterone (mcrpc) Enzalutamide (androgen receptor, AR) AR abiraterone 62 CRPC 31 enzalutamide 31 abiraterone Enzalutamide 5.4 (1.4~9.9 ) abiraterone 4.6 (0.9~8.2 ) - (quantitative RT-PCR) (circulating tumor cells) AR-V7 mrna PSA PSA (OS) AR-V7 PSA PSA OS enzalutamide 12 (39%) abiraterone 6 (19%) AR-V7 mrna AR-V7 AR-V7 enzalutamide abiraterone PSA (enzalutamide, 0% vs 53%; P=0.004; abiraterone, 0% vs 68%; P=0.004) PSA (enzalutamide, 1.4 vs 6.0 ; P<0.001; abiraterone, 1.3 vs ; P<0.001) (enzalutamide, 2.1 vs 6.1 ; P<0.001; abiraterone, 2.3 vs ; P<0.001) (enzalutamide, 5.5 vs ; P=0.002; abiraterone, 10.6 vs ; P=0.006) AR-V7 PSA mrna (full-length androgen receptor mrna) AR-V7 PSA PSA mrna enzalutamide abiraterone AR-V7 PSA AR-V7 AR AR Enzalutamide abiraterone mcrpc AR-V7 enzalutamide abiraterone CRPC abiraterone III abiraterone 55.2% 8% AR (splice variant) AR-V7 AR-V7 CRPC 78
40. Phase III, Randomized, Double-Blind, Multicenter Trial Comparing Orteronel (TAK-700) plus Prednisone with Placebo plus Prednisone in Patients with Metastatic Castration-Resistant Prostate Cancer That Has Progressed during or after Docetaxel-Based Therapy: ELM-PC 5 J Clin Oncol 2015; 33: 723-31. (ELM-PC 5) III (double-blind, multicenter, phase 3, randomized control trial) Docetaxel (metastatic castration-resistant prostate cancer, mcrpc) 1,099 Orteronel + prednisone ( ) (placebo) + prednisone ( ) (2:1) 10.7 orteronel + prednisone docetaxel mcrpc PSA 50% PSA Orteronel TAK-700 (cytochrome) 17,20- (lyase) (partially selective reversible inhibitor) abiraterone abiraterone orteronel 17 -hydroxylase ( ) ELM-PC 4 ( 41 ) mcrpc orteronel + prednisone prednisone (ELM- PC 5) docetaxel mcrpc ELM-PC 4 (chemonaive) mcrpc 1,099 docetaxel mcrpc 400 mg orteronel + 5 mg prednisone (N=734) + 5 mg prednisone (N=365) (OS) 10.7 OS 17.0 15.2 (HR, 0.886; 95% CI, 0.739~1.062; P=0.190) OS (HR, 0.709; 95% CI, 0.53~0.95; P=0.019) OS (rpfs) 8.3 5.7 (HR, 0.760; 95% CI, 0.653~0.885; P<0.001) rpfs PSA >50 ng/ml 8 rpfs PSA 5.5 2.9 (HR, 0.698; 95% CI, 0.602~0.809; P<0.001) 12 PSA 50% 25% 10% (P<0.001) orteronel + prednisone OS (, 42% vs 7979 mcrpc
當代攝護腺癌精選論文點評導讀集 26%;, 36% vs 17%;, 29% vs 23%) (, 30%;, 24%) ELM-PC 5 mcrpc rpfs PSA 50% PSA OS Orteronel CYP17 mcrpc OS orteronel (, 5.7 ;, 4.6 ) abiraterone (COU-AA 301, 36 ) 8 Orteronel Abiraterone orteronel (19% vs 30%) abiraterone mcrpc orteronel CYP17 (abiraterone) OS OS mcrpc ELM-PC 4 orteronel + prednisone rpfs OS docetaxel mcrpc ELM-PC 4 orteronel mcrpc docetaxel mcrpc 34 (enzalutamide, AFFIRM ) 80
41. Orteronel plus Prednisone in Patients with Chemotherapy- Naive Metastatic Castration-Resistant Prostate Cancer (ELM-PC 4): A Double-Blind, Multicentre, Phase 3, Randomised, Placebo-Controlled Trial Lancet Oncol 2015; 16: 338-48. (ELM-PC 4) III (double-blind, multicenter, phase 3, randomized control trial) (metastatic castration-resistant prostate cancer, mcrpc) 1,560 Orteronel + prednisone ( ) + prednisone ( ) (1:1) 20.7 orteronel + prednisone mcrpc ELM-PC 5 ( 40 ) mcrpc orteronel + prednisone prednisone ( ) mcrpc ELM-PC 5 docetaxel ( ) mcrpc 1,560 mcrpc 400 mg orteronel + 5 mg prednisone (N=781) + 5 mg prednisone (N=779) (rpfs) (OS) (rpfs) 8.4 rpfs 13.8 (95% CI, 13.1~14.9) 8.7 (95%, CI 8.3~10.9) (HR, 0.71; 95% CI, 0.63~0.80; P<0.0001) PSA rpfs 20.7 OS 31.4 29.5 (HR, 0.92; 95% CI, 0.79~1.08; P=0.31) PSA >50 ng/ml OS (HR, 0.81; 95% CI, 0.67~0.99) orteronel + prednisone OS 18% ( 41% vs 59%) 28% (14% vs 42%) 8% (38% vs 46%) ELM-PC 4 mcrpc orteronel + prednisone rpfs OS ELM-PC 4 mcrpc abiraterone enzalutamide Abiraterone + prednisone mcrpc 8.3 rpfs (HR, 0.52; P<0.0001) 4.4 OS (HR, 0.80; P=0.0027) (COU-AA-302, 37 ) abiraterone enzalutamide mcrpc rpfs (HR, 0.19; P<0.001) OS (HR, 0.71; P<0.001)(PREVAIL study, 35 ) docetaxel mcrpc 8181 mcrpc
當代攝護腺癌精選論文點評導讀集 (ELM-PC 5) ( 40 ) orteronel mcrpc orteronel mcrpc orteronel mcrpc 82
42. Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer N Engl J Med 2013; 369: 213-23. (ALSYMPCA study) (randomized double-blind, placebo-controlled trial) (castration-resistant prostate cancer, CRPC) 921-223 (radium-233) (placebo) (2:1) 3.0-223 mcrpc -223 (radium-233) α DNA -223 α (<100 μm) III (CRPC) -223-223 921 docetaxel CRPC 2:1 6-223 ( 50 kbq/kg 4 1 ) 3 (OS) (symptomatic skeletal events, SSE) ( ) ( (alkaline phosphatase, ALP) PSA ) (interim analysis, 314 ) -223 (N=541) (N=268) 2.8 (14.0 vs 11.2 ) -223 191 (35%) 123 (46%) (HR, 0.70; 95% CI, 0.55~0.88; P=0.002) (Data & Safety Monitoring Committee) -223-223 (528 ) -223 3.6 (14.9 vs 11.3 ) -223 (N=614) (N=307) 333 (54%) 195 (64%) (HR, 0.70; 95% CI, 0.58~0.83; P<0.001) 809 921-223 -223-223 α -223-223 -223 5% -223-223 ( ) -223-223 mcrpc docetaxel mcrpc -223 8383 mcrpc
當代攝護腺癌精選論文點評導讀集 84
43. Autonomic Nerve Development Contributes to Prostate Cancer Progression (xenograft) (transgenic mouse models) (autonomic nerve system) (TGF-β) TGF-β (neoneurogenesis) (sympathetic nervous system, SNS) (norepinephrine) (stromal cells) β 2 β 3 (adrenergic β 2 and β 3 receptors) (parasympathetic nervous system, PNS) (acetylcholine) (muscarinic receptors) 43 SNS PNS β 2013; 341: 1236361-1-10. Science 85
當代攝護腺癌精選論文點評導讀集 44. Conversion of Abiraterone to D4A Drives Anti- Tumor Activity in Prostate Cancer Nature 2015; 523: 347-51. (letter) (castration-resistant prostate cancer, CRPC) Abiraterone D4A ( 4 -abiraterone) abiraterone D4A abiraterone 2011 4 FDA abiraterone acetate prednisone (mcrpc) docetaxel 2012 12 FDA abiraterone acetate mcrpc Abiraterone P450 17A1 (CYP17A1) abiraterone D4A abiraterone abiraterone mcrpc D4A ( 3βHSD, 3β-hydroxysteroid dehydrogenase isoenzymes) 3 HSD LAPC4 D4A abiraterone 3βHSD D4A abiraterone CYP17A1 3βHSD SRD5A (steroid-5a-reductase) enzalutamide (androgen receptor, AR) AR (PSA) (mouse xenograft model) D4A 3βHSD AR abiraterone abiraterone D4A abiraterone D4A abiraterone D4A abiraterone mcrpc abiraterone abiraterone D4A abiraterone mcrpc enzalutamide D4A abiraterone abiraterone 86
45. Circulating Tumor Cell Biomarker Panel as an Individual-Level Surrogate for Survival in Metastatic Castration-Resistant Prostate Cancer (COU-AA-301) (circulating tumor cell, CTC) Docetaxel Abiraterone + prednisone + prednisone CTC LDH (CRPC) COU-AA-301 ( 36 ) docetaxel mcrpc abiraterone acetate prednisone prednisone (15.8 vs 11.2 ) (circulating tumor cell, CTC) 4 8 12 CTC 12 711 12 CTC PSA (lactate dehydrogenase, LDH) (ALP) 12 CTC LDH 3 (CTC 5 cells/7.5 ml LDH>250 U/L) (CTC 5 cells/7.5 ml LDH 250 U/L) (CTC<5 cells/7.5 ml LDH ) 2 46% 10% 2% 12 CTC LDH CTC LDH CTC LDH CRPC Clin Oncol 2015; 33: 1348-55. J 87
當代攝護腺癌精選論文點評導讀集 46. Therapeutic Targeting of BET Bromodomain Proteins in Castration-Resistant Prostate Cancer Nature 2014; 510: 278-82. (CRPC) (bromodomain) (xenograft) BET (bromodomain and extraterminal proteins) JQ1 CRPC (androgen receptor, AR) (coactivators) (CRPC) BRD4 BET RNA (polymerase) II BRD4 (bromodomain) BD1 BD2 JQ1 I-BET762 RNA polymerase II JQ1 CRPC JQ1 AR (AR signaling) JQ1 BRD2 3 4 JQ1 AR G 0 -G 1 BCL-XL ( BCL2L1) JQ1 AR JQ1 AR TMPRSS2-ERG PSA ERG AR (DHT) JQ1 MDV3100 ( enzalutamide) AR JQ1 DHT BRD4 AR- BRD4 VCaP ( ) JQ1 MDV3100 MYC (de-repression) MDV3100 JQ1 VCaP JQ1 50% JQ1 AR AR (splice variant) 88
47. The Evolutionary History of Lethal Metastatic Prostate Cancer (clinical molecular autopsy study) 10 (mcrpc) (whole genome sequencing) (bioinformatics) Battenberg algorithm (phylogenetic trees) (monoclonal seeding) (multiple clones) (metastasisto-metastasis seeding) (evolution) (tumor suppressor genes) (cancer evolution) Peter C. Nowell (Science, 1976) (subclonal selection) (Darwinian theory) (selective pressure) 10 (metastatic castration-resistant prostate cancer, mcrpc) (primary) (5 5 ) (whole genome sequencing) (copy number changes) (insertions and deletions) (mutation clustering) (subclones) (clonal seeding) (Fig. 2) (Fig. 3) " " ( ) (50%) (polyclonal seeding) (primary tumor) (clones) (AR signaling pathway) ( ) AR A21 A24 A21 AR (large tandem duplication)a24 truncal AR T878A A22 MYC (amplification) AR (T878A) (castration-resistance) CTNNB1 FOXA1 CRPC (monoclonal metastasis-to-metastasis seeding) 2015; 520: 353-7. Nature 89
當代攝護腺癌精選論文點評導讀集 48. Genome-Wide Association Study in Chinese Men Identifies Two New Prostate Cancer Risk Loci at 9q31.2 and 19q13.4 Nat Genet 2012; 44: 1231-5. 4,488 8,934 (genome-wide association studies, GWAS) GWAS GWAS 4,484 8,934 1,497 1,008 Illumina Human OmniExpress BeadChips 731,458 (single nucleotide polymorphism, SNP) SNP SNP (association test) P<5 10 3 ( 4,323 SNP ) γ 2 <0.5 ( 166 SNP ) (P 0.02) 43 SNP SNP 9q31.2 (rs817826, P=5.45 10 14 ) 19q13.4 (rs103294, P=5.34 10 16 ) rs103294 LILRA3 7 (exon) 6 LILRA3 T LILRA3 (P<1 10 4 ) SNP (case-control series) SNP PSA SNP PSA Cancer Genetic Markers of Susceptibility (CGEMS) United States and Cancer Prostate in Sweden rs103294 rs817826 rs817826 LIR (leukocyte immunoglobulin-like receptor) (major histocompatibility complex antigens) UCSC LILRA3 80 LILRA3 T eqtl GWAS 90
LILRA3 T LILRA3 SNP rs103294 91
當代攝護腺癌精選論文點評導讀集 92
49. Randomized Controlled Trial of Early Zoledronic Acid in Men with Castration-Sensitive Prostate Cancer and Bone Metastases: Results of CALGB 90202 (Alliance) (CALGB 90202 Alliance Study) (metastatic castration-sensitive prostate cancer, mcspc; M1) 645 zoledronic acid (ZA) (placebo) (1:1) 84 mcspc ZA (SRE) (OS) (AE) (mcspc) ADT 6 CRPC zoledronic acid (ZA) (SRE) ZA mcspc SRE (OS) (AE) 645 mcspc 1:1 ZA (CRPC) ZA SRE 84 ZA SREZA (N=323) (N=322) SRE 31.9 (95% CI, 24.2~40.3) 28.8 (95% CI, 25.3~37.2) HR 0.97 (95% CI, 0~1.174; P=0.385) ZA 37.9 36.0 HR 0.88 (95% CI, 0.70~1.12; P=0.29) SRE ZA SRE 17.6 (95% CI, 14.5~33.3) ZA 31.9 (95% CI, 24.2~NR; P<0.054) ZA SRE SRE SRE (ZA 31.8 30.6 ) ZA (PFS) 10.6 (95% CI, 8.5~15.4) 9.2 (95% CI, 8.0~11.9) PSA 70% (22%) (8%) 618 (96%) (AE) ZA 65 38 AE AE (ZA 3% 3%) (ZA 3% 2%) (ZA 3% 2%) (ZA 3% 1%) ZA 10 (3.2%) 6 Alliance mcspc ZA SRE ZA mcrpc SRE Clin Oncol 2014; 32: 1143-50. J 93
當代攝護腺癌精選論文點評導讀集 50. Prevention of Bone Metastases in Patients with High- Risk Nonmetastatic Prostate Cancer Treated with Zoledronic Acid: Efficacy and Safety Results of the Zometa European Study (ZEUS) Eur Urol 2015; 67: 482-91. (open label randomized controlled trial) 1,393 zoledronic acid + ( ) (1:1) 4 0.5 zoledronic acid zoledronic acid 4 mg 8~10 PSA>20 ng/ml (EAU) 13 1,393 zoledronic acid (ZAG, N=694) (CG, N=699) (ADT) 872 (63%) ADT 37% ADT 872 (45%) (curative treatment) 4 0.5 1,040 ZAG 17.1% (88/515) CG 17.0% (89/525; chi-square test, P=0.95) (subgroup analysis) ADT zoledronic acid 4 51 94
51. Denosumab and Bone-Metastasis-Free Survival in Men with Castration-Resistant Prostate Cancer: Results of a Phase 3, Randomised, Placebo-Controlled Trial (randomized double-blind placebo-controlled) 1,432 denosumab 120 mg (1:1) 24 (microenvironment) (OS) Denosumab (Dmab, Xgeva ) RANK ligand (osteoclast) Dmab (mcrpc) (SRE) (M0 CRPC) Amgen 30 319 1,432 M0 CRPC (PSA 8.0 ng/ml PSA doubling time 10.0 ) 1:1 Dmab Dmab (bone-metastasis-free survival, BMFS) 4.2 (, 29.5 vs 25.2 ; HR, 0.85; 95% CI, 0.73~0.98; P=0.028) Dmab (33.2 vs 29.5 ; HR, 0.84; 95% CI, 0.71~0.98; P=0.032) (OS) (43.9 vs 44.8 ; HR, 1.01; 95% CI, 0.85~1.20; P=0.91) Dmab (osteonecrosis of the jaw, ONJ; 5% vs 0%) (hypocalcaemia; 2% vs <1%) (microenvironment) Dmab M0 CRPC zoledronic acid (ZEUS study, Eur Urol 2015; 67: 482-91) (N=1,397 CRPC 37% ) 3 4 mg zoledronic acid FDA 2012 2 Xgeva " M0 CRPC " 1. Dmab 15% BMFS 73% 2. (OS) (PFS) (patient reported outcomes) Dmab 3. Dmab 6% ONJ 2012; 379: 39-46. Lancet 95
當代攝護腺癌精選論文點評導讀集 52. Denosumab for Patients with Persistent or Relapsed Hypercalcemia of Malignancy despite Recent Bisphosphonate Treatment J Natl Cancer Inst 2013; 105: 1417-20. (open label, single-arm) (bisphosphonate) ( 15 ) denosumab 26 denosumab denosumab RANKL (receptor activator of nuclear factor kappa-b ligand) (osteoclasts) denosumab 2009 11 2011 6 7 30 (albumin-corrected serum calcium) 12.5 mg/ dl 1 8 15 29 denosumab 120 mg 4 4 57 12.5 mg/dl denosumab 10 11.5 mg/dl (response duration) 11.5 mg/dl (complete response)10 10.8 mg/dl 63 10 5 13.6 mg/dl 15 12 (80%) 11.5 mg/dl 8 26 10 10 (67%) 10 2.7 mg/dl Denosumab 26 denosumab (<1%) denosumab denosumab denosumab D 3 96
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由全球華人中 數十位第一線治療攝護腺癌的頂尖醫學專家 為52篇當代有巨大影響力的論文 撰寫中文點評導讀 將大幅 提升華人世界對攝護腺癌病人的醫療水平! 臺灣楓城泌尿學會 學會地址 臺灣台北市中山南路7號 (臺大醫院泌尿部) 連絡電話 886-2-2312-3456 分機 65326 傳真電話 886-2-2321-9145 E-mail tmua@tmua.org.tw http www.tmua.org.tw