王宇 1 , 魏強 2 , 曾浩 2 , 羅睿 1 , 劉華渝 1
  • 1. 四川大學(xué)華西臨床醫(yī)學(xué)院（成都 610041）2. 四川大學(xué)華西醫(yī)院泌尿外科;

目的 　系統(tǒng)評價卡介苗聯(lián)合化療藥物交替膀胱灌注與單用卡介苗膀胱灌注預(yù)防表淺性膀胱癌 TURB-t 術(shù)后復(fù)發(fā)的臨床療效和不良反應(yīng)。
方法 　電子檢索PubMed （1950～2006.12）﹑OVID （1966～ 2006.12）﹑EMbase （1984～ 2006.12）﹑Cochrane 圖書館（2006 年第 4 期 )、中國生物醫(yī)學(xué)文獻數(shù)據(jù)庫（1978 ～ 2006）和維普中文科技期刊數(shù)據(jù)庫（1989 ～ 2006），并手工檢索已發(fā)表和未發(fā)表文獻，納入卡介苗聯(lián)合化療藥物交替膀胱灌注預(yù)防表淺性膀胱癌 TURB-t 術(shù)后復(fù)發(fā)的隨機對照試驗，按 Cochrane 系統(tǒng)評價方法對納入研究進行質(zhì)量評價，并采用RevMan4.2.9 軟件進行 Meta 分析。
結(jié)果 　共納入 4 個隨機對照試驗，包括 681例表淺性膀胱癌患者。Meta 分析結(jié)果顯示，卡介苗聯(lián)合化療藥物交替膀胱灌注與單用卡介苗膀胱灌注相比，① 對于 Ta 和 T1 期表淺性膀胱癌，復(fù)發(fā)率差異有統(tǒng)計學(xué)意義［RR合并 0.69，95%CI（0.53，0.90）］；② 對于 Tis期表淺性膀胱癌，復(fù)發(fā)率差異無統(tǒng)計學(xué)意義［RR 1.22， 95%CI（0.97，1.54）］；③ 不良反應(yīng)發(fā)生率差異無統(tǒng)計學(xué)意義［RR合并 0.85，95%CI（0.70， 1.03）］。
結(jié)論 　卡介苗聯(lián)合化療藥物交替膀胱灌注與單用卡介苗膀胱灌注相比，對于 Ta 和 T1 期表淺性膀胱癌，前者能有效降低TURB-t 術(shù)后腫瘤復(fù)發(fā)率；對于Tis 期膀胱癌，兩者在 TURB-t術(shù)后腫瘤復(fù)發(fā)率差異無統(tǒng)計學(xué)意義；在副作用發(fā)生率方面，兩者差異也無統(tǒng)計學(xué)意義。但由于本系統(tǒng)評價納入研究數(shù)量少，且存在選擇偏倚、實施偏倚以及發(fā)表偏倚的中度可能性，很可能影響結(jié)果的可靠性，故應(yīng)謹慎看待以上結(jié)論，期待更多高質(zhì)量的隨機對照試驗提供更可靠的證據(jù)。

引用本文： 王宇,魏強,曾浩,羅睿,劉華渝. 卡介苗聯(lián)合化療藥物交替膀胱灌注預(yù)防表淺性膀胱癌TURB-t術(shù)后復(fù)發(fā)的系統(tǒng)評價. 中國循證醫(yī)學(xué)雜志, 2007, 07(9): 650-657. doi: 復(fù)制

1. Lum BL, Torti FM. Adjuvant intravesical pharmacology for superficial bladder cancer. J Natl Cancer Inst, 1991, 83(10): 682-694.
2. Tolley DA, Hargreave TB, Smith PH, et al. Effect of intravesical mitomycin C on recurrence of newly diagnosed superficial bladder cancer: interim report from the Medical Research Council Subgroup on Superficial Bladder Cancer (Urological Cancer Working Party). Br Med J, 1988, 296(6639): 1759-1761.
3. Melekos MD, Dauaher H, Fokaefs E, et al. Intravesical instillations of 4-epi-doxorubicin (epirubicin) in the prophylactic treatment of superficial bladder cancer: results of a controlled prospective study. J Urol, 1992, 147(2): 371-375.
4. Oosterl inck W, Kurth KH, Schroder F, et al. A prospective European Organization for Research and Treatment of Cancer Genitourinary Group. Randomized trial comparing transurethral resection followed by a single intravesical instillation of epirubicin or water in single stage Ta, T1 papillary carcinoma of the bladder. J Urol, 1993, 149(4): 749-752.
5. Martinez-Pineiro JA, Leon J, Martinez-Pineiro LJr. Bacillus Calmette-Guerin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer. J Urol, 1990, 143(3): 502-506.
6. Carl L, Bo Johan N, Peter E, et al. A randomized prospective study comparing long-term intravesical instillations of mitomycin C and bacillus Calmette-Guerin in patients with superficial bladder carcinoma. J Urol, 1996, 156(2): 368-376.
7. Adrian PM, van der Meijden, Brausi M, et al. Intravesical instillation of epirubicin, bacillus Calmette-Guerin and bacillus Calmette-Guerin plus isoniazid for intermediate and high risk Ta, T1 papillary carcinoma of the bladder: a European Organization for Researchand Treatment of Cancer Genitourinary Group Randomized Phase III Trial. J Urol, 2001, 166: 476-481.
8. Lamm DL, van der Meijden PM, Morales A, et al. Incidence and treatment of complications of bacillus Calmette-Guerin intravesical therapy in superficial bladder cancer. J Urol, 1992, 147(3): 596-600.
9. Koya MP, Simon MA, Soloway MS. Complications of intravesical therapy for urothelial cancer of the bladder. J Urol, 2006, 175(6): 2004-2010.
10. Higgins J, Green S, editors. Cochrane Handbook for SystematicReviews of Interventions 4.2.6[updated month year]. In: The Cochrane Library, Issue 4, 2006. Chichester: Wiley. Updated quarterly.
11. Montie JE. Sequential BCG and electromotive mitomycin versus BCG alone for high-risk superficial bladder cancer: a randomised controlled trial. J Urol, 2006, 176(2): 507-508.
12. Di Stasi SM, Giannantoni A, Giuriol i A, et al. Sequential BCG and electromotive mitomycin versus BCG alone for high-risk superficial bladder cancer: a randomised controlled trial. Urologic Oncology, 2006, 24(3): 271-272.
13. Kamat AM, Col in PN. A combination of intravesical and BCG electromotive mitomycin for high-risk superficial bladder cancer. Nat Clin Pract Urol, 2006, 3(9): 472-473.
14. Rintala E, Jauhiainen K, Rajala P, et al. Alternating mitomycin C and bacillus Calmette-Guerin instillation therapy for carcinoma in situ of the bladder. The Finnbladder Group. J Urol, 1995, 154(6): 2050-2053.
15. Jauhiainen K, Rintala E. Superficial urinary bladder cancer. Results from the Finnbladder studies and a review on instillation treatments. Ann Chir Gynaecol Suppl, 1993, 206: 31-38.
16. Jauhiainen KE, Alfthan OS. Instillation therapy in superficial urinary bladder cancer. Finnbladder Group. Scand J Urol Nephrol Suppl, 1991, 138: 179-185.
17. Al i-El-Dein B, Sarhan O, Hinev A, et al Superficial bladder tumors: analysis of prognostic factors and construction of a predictive index. BJU International, 2003, 92: 393-399.
18. Witjes JA, Caris CTM, Mungan NA, et al. Results of a randomized phase III trial of sequential intravesical therapy with mitomycin C and bacillus Calmette-Guerin versus mitomycin C alone in patients with superficial bladder cancer. J Urol, 1998, 160(5): 1668-1671.
19. Rintala E, Jauhiainen K, Rajala P, et al. Alternating mitomycin C and bacillus Calmette-Guerin instillation therapy for caicinoma in situ of the bladder. J Urol, 1995, 154(6): 2050-2053.
20. Rintala E, Jauhiainen K, Kaasinen E, et al. Alternating mitomycin C and bacillus Calmette-Guerin instillation prophylaxis for recurrent papillary (stages Ta to T1) superficial bladder cancer. J Urol, 1996, 156(1): 56-59.
21. Al i-El-Dein B, Nabeeh A, Ismail EH, et al. Sequential bacillus Calmette-Guerin and epirubicin versus bacillus Calmette-Guerin alone for superficial bladder tumors: a randomized prospective study. J Urol, 1999, 162(2): 339-342.
22. Bilen CY, Ozen H, Aki FT, et al. Clinical experience with BCG alone versus BCG plus epirubicin. Int J Urol, 2000, 7(6): 206-209.
23. Kaasinen E, Wijkstrom H, Malmstrom PU, et al. Alternating mitomycin C and BCG instillations versus BCG alone in treatment of carcinoma in situ of the urinary bladder: a nordic study. Eur Urol, 2003, 43(6): 637-645.
24. Di Stasi SM, Giannantoni A, Giuriol i A, et al. Sequential BCG and electromotive mitomycin versus BCG alone for high-risk superficial bladder cancer: a randomised controlled trial. The lancet oncology, 2006, 7(1): 43-51.
25. Bohle A, Brandau S. Immune mechanisms in bacillus Calmette-Guerin immunotherapy fou superficial bladder cancer. J Urol, 2003, 170: 964-969.
26. Wolf H, Melsen F, Pedersen SE, et al. Natural history of carcinoma in situ of the urinary bladder. Scand J Urol Nephrol, 1994, 157(suppl): 147.
27. Sarosdy MF. Management of high grade superficial bladder cancer: role of BCG. AUA Update Series, 1998, 17(12): 90.
28. Utz DC, Hanash K A, Farrow GM. The pl ight of the patient with carcinoma of the bladder. Trans Am Assoc Genitourin Surg, 1969, 61: 90-100.
  1. 1. Lum BL, Torti FM. Adjuvant intravesical pharmacology for superficial bladder cancer. J Natl Cancer Inst, 1991, 83(10): 682-694.
  2. 2. Tolley DA, Hargreave TB, Smith PH, et al. Effect of intravesical mitomycin C on recurrence of newly diagnosed superficial bladder cancer: interim report from the Medical Research Council Subgroup on Superficial Bladder Cancer (Urological Cancer Working Party). Br Med J, 1988, 296(6639): 1759-1761.
  3. 3. Melekos MD, Dauaher H, Fokaefs E, et al. Intravesical instillations of 4-epi-doxorubicin (epirubicin) in the prophylactic treatment of superficial bladder cancer: results of a controlled prospective study. J Urol, 1992, 147(2): 371-375.
  4. 4. Oosterl inck W, Kurth KH, Schroder F, et al. A prospective European Organization for Research and Treatment of Cancer Genitourinary Group. Randomized trial comparing transurethral resection followed by a single intravesical instillation of epirubicin or water in single stage Ta, T1 papillary carcinoma of the bladder. J Urol, 1993, 149(4): 749-752.
  5. 5. Martinez-Pineiro JA, Leon J, Martinez-Pineiro LJr. Bacillus Calmette-Guerin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer. J Urol, 1990, 143(3): 502-506.
  6. 6. Carl L, Bo Johan N, Peter E, et al. A randomized prospective study comparing long-term intravesical instillations of mitomycin C and bacillus Calmette-Guerin in patients with superficial bladder carcinoma. J Urol, 1996, 156(2): 368-376.
  7. 7. Adrian PM, van der Meijden, Brausi M, et al. Intravesical instillation of epirubicin, bacillus Calmette-Guerin and bacillus Calmette-Guerin plus isoniazid for intermediate and high risk Ta, T1 papillary carcinoma of the bladder: a European Organization for Researchand Treatment of Cancer Genitourinary Group Randomized Phase III Trial. J Urol, 2001, 166: 476-481.
  8. 8. Lamm DL, van der Meijden PM, Morales A, et al. Incidence and treatment of complications of bacillus Calmette-Guerin intravesical therapy in superficial bladder cancer. J Urol, 1992, 147(3): 596-600.
  9. 9. Koya MP, Simon MA, Soloway MS. Complications of intravesical therapy for urothelial cancer of the bladder. J Urol, 2006, 175(6): 2004-2010.
  10. 10. Higgins J, Green S, editors. Cochrane Handbook for SystematicReviews of Interventions 4.2.6[updated month year]. In: The Cochrane Library, Issue 4, 2006. Chichester: Wiley. Updated quarterly.
  11. 11. Montie JE. Sequential BCG and electromotive mitomycin versus BCG alone for high-risk superficial bladder cancer: a randomised controlled trial. J Urol, 2006, 176(2): 507-508.
  12. 12. Di Stasi SM, Giannantoni A, Giuriol i A, et al. Sequential BCG and electromotive mitomycin versus BCG alone for high-risk superficial bladder cancer: a randomised controlled trial. Urologic Oncology, 2006, 24(3): 271-272.
  13. 13. Kamat AM, Col in PN. A combination of intravesical and BCG electromotive mitomycin for high-risk superficial bladder cancer. Nat Clin Pract Urol, 2006, 3(9): 472-473.
  14. 14. Rintala E, Jauhiainen K, Rajala P, et al. Alternating mitomycin C and bacillus Calmette-Guerin instillation therapy for carcinoma in situ of the bladder. The Finnbladder Group. J Urol, 1995, 154(6): 2050-2053.
  15. 15. Jauhiainen K, Rintala E. Superficial urinary bladder cancer. Results from the Finnbladder studies and a review on instillation treatments. Ann Chir Gynaecol Suppl, 1993, 206: 31-38.
  16. 16. Jauhiainen KE, Alfthan OS. Instillation therapy in superficial urinary bladder cancer. Finnbladder Group. Scand J Urol Nephrol Suppl, 1991, 138: 179-185.
  17. 17. Al i-El-Dein B, Sarhan O, Hinev A, et al Superficial bladder tumors: analysis of prognostic factors and construction of a predictive index. BJU International, 2003, 92: 393-399.
  18. 18. Witjes JA, Caris CTM, Mungan NA, et al. Results of a randomized phase III trial of sequential intravesical therapy with mitomycin C and bacillus Calmette-Guerin versus mitomycin C alone in patients with superficial bladder cancer. J Urol, 1998, 160(5): 1668-1671.
  19. 19. Rintala E, Jauhiainen K, Rajala P, et al. Alternating mitomycin C and bacillus Calmette-Guerin instillation therapy for caicinoma in situ of the bladder. J Urol, 1995, 154(6): 2050-2053.
  20. 20. Rintala E, Jauhiainen K, Kaasinen E, et al. Alternating mitomycin C and bacillus Calmette-Guerin instillation prophylaxis for recurrent papillary (stages Ta to T1) superficial bladder cancer. J Urol, 1996, 156(1): 56-59.
  21. 21. Al i-El-Dein B, Nabeeh A, Ismail EH, et al. Sequential bacillus Calmette-Guerin and epirubicin versus bacillus Calmette-Guerin alone for superficial bladder tumors: a randomized prospective study. J Urol, 1999, 162(2): 339-342.
  22. 22. Bilen CY, Ozen H, Aki FT, et al. Clinical experience with BCG alone versus BCG plus epirubicin. Int J Urol, 2000, 7(6): 206-209.
  23. 23. Kaasinen E, Wijkstrom H, Malmstrom PU, et al. Alternating mitomycin C and BCG instillations versus BCG alone in treatment of carcinoma in situ of the urinary bladder: a nordic study. Eur Urol, 2003, 43(6): 637-645.
  24. 24. Di Stasi SM, Giannantoni A, Giuriol i A, et al. Sequential BCG and electromotive mitomycin versus BCG alone for high-risk superficial bladder cancer: a randomised controlled trial. The lancet oncology, 2006, 7(1): 43-51.
  25. 25. Bohle A, Brandau S. Immune mechanisms in bacillus Calmette-Guerin immunotherapy fou superficial bladder cancer. J Urol, 2003, 170: 964-969.
  26. 26. Wolf H, Melsen F, Pedersen SE, et al. Natural history of carcinoma in situ of the urinary bladder. Scand J Urol Nephrol, 1994, 157(suppl): 147.
  27. 27. Sarosdy MF. Management of high grade superficial bladder cancer: role of BCG. AUA Update Series, 1998, 17(12): 90.
  28. 28. Utz DC, Hanash K A, Farrow GM. The pl ight of the patient with carcinoma of the bladder. Trans Am Assoc Genitourin Surg, 1969, 61: 90-100.