Advances in the application of radiotherapy for bladder preservation in muscle-invasive bladder cancer_West China Medical Journal

Authors：

MIAO Yandong ^1,2 ,  SHEN Yali ¹

1. Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. The First School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu 730000, P. R. China;

Corresponding author：

SHEN Yali, Email: sylprecious@163.com

Keywords：

Muscular-invasive bladder cancer; Radiotherapy; Bladder preservation; Trimodality therapy

DOI：

10.7507/1002-0179.201907015

Video：

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Abstract Full text Figures/Tables Video References Cited by

Bladder cancer is the most common malignant tumor in the urinary system. The standard treatment of muscle-invasive bladder cancer (MIBC) is the radical cystectomy combined with pelvic lymphadenectomy. In recent years, radiotherapy has played an important role in the MIBC bladder-preserving treatment model. This article will review the advances in the application of radiotherapy for bladder preservation in MIBC, and introduce the application progress of radiotherapy in trimodality therapy of adjuvant radiotherapy and chemotherapy after transurethral resection of bladder tumors, radical radiotherapy, preoperative radiotherapy, radiotherapy combined with immunotherapy, the development and challenges of radiotherapy technology, and radiotherapy-related adverse reactions. The aim of this article is to provide a reference for further exploration of a more scientific and effective comprehensive treatment mode for bladder preservation.

Citation： MIAO Yandong, SHEN Yali. Advances in the application of radiotherapy for bladder preservation in muscle-invasive bladder cancer. West China Medical Journal, 2020, 35(1): 103-109. doi: 10.7507/1002-0179.201907015 Copy

1.	Antoni S, Ferlay J, Soerjomataram I, et al. Bladder cancer incidence and mortality: a global overview and recent trends. Eur Urol, 2017, 71(1): 96-108.
2.	Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin, 2018, 68(1): 7-30.
3.	陈万青, 李贺, 孙可欣, 等. 2014 年中国恶性肿瘤发病和死亡分析. 中华肿瘤杂志, 2018, 40(1): 5-13.
4.	Kulkarni GS, Black PC, Sridhar SS, et al. Canadian urological association guideline: muscle-invasive bladder cancer. Can Urol Assoc J, 2019, 13(8): 230-238.
5.	Sanli O, Dobruch J, Knowles MA, et al. Bladder cancer. Nat Rev Dis Primers, 2017, 3: 17022.
6.	Alfred Witjes J, Lebret T, Compérat EM, et al. Updated 2016 EAU guidelines on muscle-invasive and metastatic bladder cancer. Eur Urol, 2017, 71(3): 462-475.
7.	Reddy AV, Pariser JJ, Pearce SM, et al. Patterns of failure after radical cystectomy for pT3-4 bladder cancer: implications for adjuvant radiation therapy. Int J Radiat Oncol Biol Phys, 2016, 94(5): 1031-1039.
8.	Fonteyne V, Ost P, Bellmunt J, et al. Curative treatment for muscle invasive bladder cancer in elderly patients: a systematic review. Eur Urol, 2018, 73(1): 40-50.
9.	Fuentes J, Ramos E, Truan D, et al. Review of a series of cystectomies in women for bladder cancer: complications and quality of life. Arch Esp Urol, 2014, 67(4): 303-312.
10.	Fahmy O, Khairul-Asri MG, Schubert T, et al. A systematic review and meta-analysis on the oncological long-term outcomes after trimodality therapy and radical cystectomy with or without neoadjuvant chemotherapy for muscle-invasive bladder cancer. Urol Oncol, 2018, 36(2): 43-53.
11.	Kim YJ, Byun SJ, Ahn H, et al. Comparison of outcomes between trimodal therapy and radical cystectomy in muscle-invasive bladder cancer: a propensity score matching analysis. Oncotarget, 2017, 8(40): 68996-69004.
12.	Vashistha V, Wang H, Mazzone A, et al. Radical cystectomy compared to combined modality treatment for muscle-invasive bladder cancer: a systematic review and meta-analysis. Int J Radiat Oncol Biol Phys, 2017, 97(5): 1002-1020.
13.	Kulkarni GS, Hermanns T, Wei Y, et al. Propensity score analysis of radical cystectomy versus bladder-sparing trimodal therapy in the setting of a multidisciplinary bladder cancer clinic. J Clin Oncol, 2017, 35(20): 2299-2305.
14.	Tanaka H, Yoshida S, Koga F, et al. Impact of immunohistochemistry-based subtypes in muscle-invasive bladder cancer on response to chemoradiation therapy. Int J Radiat Oncol Biol Phys, 2018, 102(5): 1408-1416.
15.	Turgeon GA, Souhami L, Cury FL, et al. Hypofractionated intensity modulated radiation therapy in combined modality treatment for bladder preservation in elderly patients with invasive bladder cancer. Int J Radiat Oncol Biol Phys, 2014, 88(2): 326-331.
16.	Russell CM, Lebastchi AH, Borza T, et al. The role of transurethral resection in trimodal therapy for muscle-invasive bladder cancer. Bladder Cancer, 2016, 2(4): 381-394.
17.	Mak KS, Smith AB, Eidelman A, et al. Quality of life in long-term survivors of muscle-invasive bladder cancer. Int J Radiat Oncol Biol Phys, 2016, 96(5): 1028-1036.
18.	Shipley WU, Winter KA, Kaufman DS, et al. Phase Ⅲ trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of radiation therapy oncology group 89-03. J Clin Oncol, 1998, 16(11): 3576-3583.
19.	Kaufman DS, Winter KA, Shipley WU, et al. The initial results in muscle-invading bladder cancer of RTOG 95-06: phase Ⅰ/Ⅱ trial of transurethral surgery plus radiation therapy with concurrent cisplatin and 5-fluorouracil followed by selective bladder preservation or cystectomy depending on the initial response. Oncologist, 2000, 5(6): 471-476.
20.	Hagan MP, Winter KA, Kaufman DS, et al. RTOG 97-06: initial report of a phase Ⅰ-Ⅱ trial of selective bladder conservation using TURBT, twice-daily accelerated irradiation sensitized with cisplatin, and adjuvant MCV combination chemotherapy. Int J Radiat Oncol Biol Phys, 2003, 57(3): 665-672.
21.	Kaufman DS, Winter KA, Shipley WU, et al. Phase Ⅰ-Ⅱ RTOG study (99-06) of patients with muscle-invasive bladder cancer undergoing transurethral surgery, paclitaxel, cisplatin, and twice-daily radiotherapy followed by selective bladder preservation or radical cystectomy and adjuvant chemotherapy. Urology, 2009, 73(4): 833-837.
22.	Shipley WU, Kaufman DS, Zehr E, et al. Selective bladder preservation by combined modality protocol treatment: long-term outcomes of 190 patients with invasive bladder cancer. Urology, 2002, 60(1): 62-67.
23.	Krasnow RE, Drumm M, Roberts HJ, et al. Clinical outcomes of patients with histologic variants of urothelial cancer treated with trimodality bladder-sparing therapy. Eur Urol, 2017, 72(1): 54-60.
24.	Michaelson MD, Hu C, Pham HT, et al. A phase 1/2 Trial ofa combination of paclitaxel and trastuzumab with daily irradiation or paclitaxel alone with daily irradiation after transurethral surgery for noncystectomy candidates with muscle-invasive bladder cancer (trial NRG oncology RTOG 0524). Int J Radiat Oncol Biol Phys, 2017, 97(5): 995-1001.
25.	Mitin T, Hunt D, Shipley WU, et al. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol, 2013, 14(9): 863-872.
26.	Michaelson MD, Hu C, Pham HT, et al. The initial report of RTOG 0524: Phase Ⅰ/Ⅱ trial of a combination of paclitaxel and trastuzumab with daily irradiation or paclitaxel alone with daily irradiation following transurethral surgery for noncystectomy candidates with muscle-invasive bladder cancer. J Clin Oncol, 2014, 32(4).
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28.	Giacalone NJ, Shipley WU, Clayman RH, et al. Long-term outcomes after bladder-preserving tri-modality therapy for patients with muscle-invasive bladder cancer: an updated analysis of the massachusetts general hospital experience. Eur Urol, 2017, 71(6): 952-960.
29.	Efstathiou JA, Spiegel DY, Shipley WU, et al. Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the MGH experience. Eur Urol, 2012, 61(4): 705-711.
30.	Ritch CR, Balise R, Prakash NS, et al. Propensity matched comparative analysis of survival following chemoradiation or radical cystectomy for muscle-invasive bladder cancer. BJU Int, 2018, 121(5): 745-751.
31.	Gofrit ON, Nof R, Meirovitz A, et al. Radical cystectomy vs. chemoradiation in T2-4aN0M0 bladder cancer: a case-control study. Urol Oncol, 2015, 33(1): 19.e1-19.e5.
32.	Teramukai S, Nishiyama H, Matsui Y, et al. Evaluation for surrogacy of end points by using data from observational studies: tumor downstaging for evaluating neoadjuvant chemotherapy in invasive bladder cancer. Clin Cancer Res, 2006, 12(1): 139-143.
33.	Thompson C, Joseph N, Sanderson B, et al. Tolerability of concurrent chemoradiation therapy with gemcitabine (GemX), with and without prior neoadjuvant chemotherapy, in muscle invasive bladder cancer. Int J Radiat Oncol Biol Phys, 2017, 97(4): 732-739.
34.	Coen JJ, Zhang P, Saylor PJ, et al. Bladder Preservation with twice-a-day radiation plus fluorouracil/cisplatin or once daily radiation plus gemcitabine for muscle-invasive bladder cancer: NRG/RTOG 0712-a randomized phase Ⅱ trial. J Clin Oncol, 2019, 37(1): 44-51.
35.	Bellmunt J, von der Maase H, Mead GM, et al. Randomized phase Ⅲ study comparing paclitaxel/cisplatin/gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy: EORTC intergroup study 30987. J Clin Oncol, 2012, 30(10): 1107-1113.
36.	Chiang Y, Cheng JC, Huang CY, et al. A role of multimodality bladder-preserving therapy in patients with muscle-invasive bladder cancer plus hydronephrosis with or without pelvic nodal involvement. J Formos Med Assoc, 2017, 116(9): 689-696.
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40.	Hayter CR, Paszat LF, Groome PA, et al. A population-based study of the use and outcome of radical radiotherapy for invasive bladder cancer. Int J Radiat Oncol Biol Phys, 1999, 45(5): 1239-1245.
41.	Blandy JP, England HR, Evans SJ, et al. T3 bladder cancer--the case for salvage cystectomy. Br J Urol, 1980, 52(6): 506-510.
42.	Goffinet DR, Schneider MJ, Glatstein EJ, et al. Bladder cancer: results of radiation therapy in 384 patients. Radiology, 1975, 117(1): 149-153.
43.	Goodman GB, Hislop TG, Elwood JM, et al. Conservation of bladder function in patients with invasive bladder cancer treated by definitive irradiation and selective cystectomy. Int J Radiat Oncol Biol Phys, 1981, 7(5): 569-573.
44.	龚虹云, 宋启斌, 胡伟国, 等. 根治性放疗与根治性手术治疗肌层浸润性膀胱癌的 Meta 分析. 中国肿瘤, 2013, 22(8): 671-675.
45.	Chahal R, Sundaram SK, Iddenden R, et al. A study of the morbidity, mortality and long-term survival following radical cystectomy and radical radiotherapy in the treatment of invasive bladder cancer in Yorkshire. Eur Urol, 2003, 43(3): 246-257.
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1. Antoni S, Ferlay J, Soerjomataram I, et al. Bladder cancer incidence and mortality: a global overview and recent trends. Eur Urol, 2017, 71(1): 96-108.
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin, 2018, 68(1): 7-30.
3. 陈万青, 李贺, 孙可欣, 等. 2014 年中国恶性肿瘤发病和死亡分析. 中华肿瘤杂志, 2018, 40(1): 5-13.
4. Kulkarni GS, Black PC, Sridhar SS, et al. Canadian urological association guideline: muscle-invasive bladder cancer. Can Urol Assoc J, 2019, 13(8): 230-238.
5. Sanli O, Dobruch J, Knowles MA, et al. Bladder cancer. Nat Rev Dis Primers, 2017, 3: 17022.
6. Alfred Witjes J, Lebret T, Compérat EM, et al. Updated 2016 EAU guidelines on muscle-invasive and metastatic bladder cancer. Eur Urol, 2017, 71(3): 462-475.
7. Reddy AV, Pariser JJ, Pearce SM, et al. Patterns of failure after radical cystectomy for pT3-4 bladder cancer: implications for adjuvant radiation therapy. Int J Radiat Oncol Biol Phys, 2016, 94(5): 1031-1039.
8. Fonteyne V, Ost P, Bellmunt J, et al. Curative treatment for muscle invasive bladder cancer in elderly patients: a systematic review. Eur Urol, 2018, 73(1): 40-50.
9. Fuentes J, Ramos E, Truan D, et al. Review of a series of cystectomies in women for bladder cancer: complications and quality of life. Arch Esp Urol, 2014, 67(4): 303-312.
10. Fahmy O, Khairul-Asri MG, Schubert T, et al. A systematic review and meta-analysis on the oncological long-term outcomes after trimodality therapy and radical cystectomy with or without neoadjuvant chemotherapy for muscle-invasive bladder cancer. Urol Oncol, 2018, 36(2): 43-53.
11. Kim YJ, Byun SJ, Ahn H, et al. Comparison of outcomes between trimodal therapy and radical cystectomy in muscle-invasive bladder cancer: a propensity score matching analysis. Oncotarget, 2017, 8(40): 68996-69004.
12. Vashistha V, Wang H, Mazzone A, et al. Radical cystectomy compared to combined modality treatment for muscle-invasive bladder cancer: a systematic review and meta-analysis. Int J Radiat Oncol Biol Phys, 2017, 97(5): 1002-1020.
13. Kulkarni GS, Hermanns T, Wei Y, et al. Propensity score analysis of radical cystectomy versus bladder-sparing trimodal therapy in the setting of a multidisciplinary bladder cancer clinic. J Clin Oncol, 2017, 35(20): 2299-2305.
14. Tanaka H, Yoshida S, Koga F, et al. Impact of immunohistochemistry-based subtypes in muscle-invasive bladder cancer on response to chemoradiation therapy. Int J Radiat Oncol Biol Phys, 2018, 102(5): 1408-1416.
15. Turgeon GA, Souhami L, Cury FL, et al. Hypofractionated intensity modulated radiation therapy in combined modality treatment for bladder preservation in elderly patients with invasive bladder cancer. Int J Radiat Oncol Biol Phys, 2014, 88(2): 326-331.
16. Russell CM, Lebastchi AH, Borza T, et al. The role of transurethral resection in trimodal therapy for muscle-invasive bladder cancer. Bladder Cancer, 2016, 2(4): 381-394.
17. Mak KS, Smith AB, Eidelman A, et al. Quality of life in long-term survivors of muscle-invasive bladder cancer. Int J Radiat Oncol Biol Phys, 2016, 96(5): 1028-1036.
18. Shipley WU, Winter KA, Kaufman DS, et al. Phase Ⅲ trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of radiation therapy oncology group 89-03. J Clin Oncol, 1998, 16(11): 3576-3583.
19. Kaufman DS, Winter KA, Shipley WU, et al. The initial results in muscle-invading bladder cancer of RTOG 95-06: phase Ⅰ/Ⅱ trial of transurethral surgery plus radiation therapy with concurrent cisplatin and 5-fluorouracil followed by selective bladder preservation or cystectomy depending on the initial response. Oncologist, 2000, 5(6): 471-476.
20. Hagan MP, Winter KA, Kaufman DS, et al. RTOG 97-06: initial report of a phase Ⅰ-Ⅱ trial of selective bladder conservation using TURBT, twice-daily accelerated irradiation sensitized with cisplatin, and adjuvant MCV combination chemotherapy. Int J Radiat Oncol Biol Phys, 2003, 57(3): 665-672.
21. Kaufman DS, Winter KA, Shipley WU, et al. Phase Ⅰ-Ⅱ RTOG study (99-06) of patients with muscle-invasive bladder cancer undergoing transurethral surgery, paclitaxel, cisplatin, and twice-daily radiotherapy followed by selective bladder preservation or radical cystectomy and adjuvant chemotherapy. Urology, 2009, 73(4): 833-837.
22. Shipley WU, Kaufman DS, Zehr E, et al. Selective bladder preservation by combined modality protocol treatment: long-term outcomes of 190 patients with invasive bladder cancer. Urology, 2002, 60(1): 62-67.
23. Krasnow RE, Drumm M, Roberts HJ, et al. Clinical outcomes of patients with histologic variants of urothelial cancer treated with trimodality bladder-sparing therapy. Eur Urol, 2017, 72(1): 54-60.
24. Michaelson MD, Hu C, Pham HT, et al. A phase 1/2 Trial ofa combination of paclitaxel and trastuzumab with daily irradiation or paclitaxel alone with daily irradiation after transurethral surgery for noncystectomy candidates with muscle-invasive bladder cancer (trial NRG oncology RTOG 0524). Int J Radiat Oncol Biol Phys, 2017, 97(5): 995-1001.
25. Mitin T, Hunt D, Shipley WU, et al. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol, 2013, 14(9): 863-872.
26. Michaelson MD, Hu C, Pham HT, et al. The initial report of RTOG 0524: Phase Ⅰ/Ⅱ trial of a combination of paclitaxel and trastuzumab with daily irradiation or paclitaxel alone with daily irradiation following transurethral surgery for noncystectomy candidates with muscle-invasive bladder cancer. J Clin Oncol, 2014, 32(4).
27. Mak RH, Hunt D, Shipley WU, et al. Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: a pooled analysis of Radiation Therapy Oncology Group protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol, 2014, 32(34): 3801-3809.
28. Giacalone NJ, Shipley WU, Clayman RH, et al. Long-term outcomes after bladder-preserving tri-modality therapy for patients with muscle-invasive bladder cancer: an updated analysis of the massachusetts general hospital experience. Eur Urol, 2017, 71(6): 952-960.
29. Efstathiou JA, Spiegel DY, Shipley WU, et al. Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the MGH experience. Eur Urol, 2012, 61(4): 705-711.
30. Ritch CR, Balise R, Prakash NS, et al. Propensity matched comparative analysis of survival following chemoradiation or radical cystectomy for muscle-invasive bladder cancer. BJU Int, 2018, 121(5): 745-751.
31. Gofrit ON, Nof R, Meirovitz A, et al. Radical cystectomy vs. chemoradiation in T2-4aN0M0 bladder cancer: a case-control study. Urol Oncol, 2015, 33(1): 19.e1-19.e5.
32. Teramukai S, Nishiyama H, Matsui Y, et al. Evaluation for surrogacy of end points by using data from observational studies: tumor downstaging for evaluating neoadjuvant chemotherapy in invasive bladder cancer. Clin Cancer Res, 2006, 12(1): 139-143.
33. Thompson C, Joseph N, Sanderson B, et al. Tolerability of concurrent chemoradiation therapy with gemcitabine (GemX), with and without prior neoadjuvant chemotherapy, in muscle invasive bladder cancer. Int J Radiat Oncol Biol Phys, 2017, 97(4): 732-739.
34. Coen JJ, Zhang P, Saylor PJ, et al. Bladder Preservation with twice-a-day radiation plus fluorouracil/cisplatin or once daily radiation plus gemcitabine for muscle-invasive bladder cancer: NRG/RTOG 0712-a randomized phase Ⅱ trial. J Clin Oncol, 2019, 37(1): 44-51.
35. Bellmunt J, von der Maase H, Mead GM, et al. Randomized phase Ⅲ study comparing paclitaxel/cisplatin/gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy: EORTC intergroup study 30987. J Clin Oncol, 2012, 30(10): 1107-1113.
36. Chiang Y, Cheng JC, Huang CY, et al. A role of multimodality bladder-preserving therapy in patients with muscle-invasive bladder cancer plus hydronephrosis with or without pelvic nodal involvement. J Formos Med Assoc, 2017, 116(9): 689-696.
37. Smith ZL, Christodouleas JP, Keefe SM, et al. Bladder preservation in the treatment of muscle-invasive bladder cancer (MIBC):a review of the literature and a practical approach to therapy. BJU Int, 2013, 112(1): 13-25.
38. Gakis G, Efstathiou J, Lerner SP, et al. ICUD-EAU International consultation on bladder cancer 2012: radical cystectomy and bladder preservation for muscle-invasive urothelial carcinoma of the bladder. Eur Urol, 2013, 63(1): 45-57.
39. Duncan W, Quilty PM. The results of a series of 963 patients with transitional cell carcinoma of the urinary bladder primarily treated by radical megavoltage X-ray therapy. Radiother Oncol, 1986, 7(4): 299-310.
40. Hayter CR, Paszat LF, Groome PA, et al. A population-based study of the use and outcome of radical radiotherapy for invasive bladder cancer. Int J Radiat Oncol Biol Phys, 1999, 45(5): 1239-1245.
41. Blandy JP, England HR, Evans SJ, et al. T3 bladder cancer--the case for salvage cystectomy. Br J Urol, 1980, 52(6): 506-510.
42. Goffinet DR, Schneider MJ, Glatstein EJ, et al. Bladder cancer: results of radiation therapy in 384 patients. Radiology, 1975, 117(1): 149-153.
43. Goodman GB, Hislop TG, Elwood JM, et al. Conservation of bladder function in patients with invasive bladder cancer treated by definitive irradiation and selective cystectomy. Int J Radiat Oncol Biol Phys, 1981, 7(5): 569-573.
44. 龚虹云, 宋启斌, 胡伟国, 等. 根治性放疗与根治性手术治疗肌层浸润性膀胱癌的 Meta 分析. 中国肿瘤, 2013, 22(8): 671-675.
45. Chahal R, Sundaram SK, Iddenden R, et al. A study of the morbidity, mortality and long-term survival following radical cystectomy and radical radiotherapy in the treatment of invasive bladder cancer in Yorkshire. Eur Urol, 2003, 43(3): 246-257.
46. Bajaj A, Martin B, Bhasin R, et al. The impact of academic facility type and case volume on survival in patients undergoing curative radiation therapy for muscle-invasive bladder cancer. Int J Radiat Oncol Biol Phys, 2018, 100(4): 851-857.
47. Canyilmaz E, Yoney A, Serdar L, et al. Long-term results ofa concomitant boost radiotherapy technique for elderly patients with muscle-invasive bladder cancer. J Geriatr Oncol, 2015, 6(4): 316-323.
48. Reddy AV, Christodouleas JP, Wu T, et al. External validation and optimization of international consensus clinical target volumes for adjuvant radiation therapy in bladder cancer. Int J Radiat Oncol Biol Phys, 2017, 97(4): 740-746.
49. EI-Monim HA, EI-Baradie MM, Younis A, et al. A prospective randomized trial for postoperative vs. preoperative adjuvant radiotherapy for muscle-invasive bladder cancer. Urol Oncol, 2013, 31(3): 359-365.
50. Zaghloul MS. Adjuvant and neoadjuvant radiotherapy for bladder cancer: revisited. Future Oncol, 2010, 6(7): 1177-1191.
51. Pollack A, Zagars GK, Cole CJ, et al. Significance of downstaging in muscle-invasive bladder cancer treated with preoperative radiotherapy. Int J Radiat Oncol Biol Phys, 1997, 37(1): 41-49.
52. Diaz DA, Pollack A, Reis IM, et al. Neoadjuvant radiotherapy improves survival in patients with T2b/T3 bladder cancer:a population-based analysis. Clin Genitourin Cancer, 2015, 13(4): 378-384.
53. Granfors T, Tomic R, Ljungberg B. Downstaging and survival benefits of neoadjuvant radiotherapy before cystectomy for patients with invasive bladder carcinoma. Scand J Urol Nephrol, 2009, 43(4): 293-299.
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