World Journal of Urology

, Volume 31, Issue 1, pp 77–82 | Cite as

Oncologic outcomes obtained after neoadjuvant and adjuvant chemotherapy for the treatment of urothelial carcinomas of the upper urinary tract: a review

  • Jan Cordier
  • Guru Sonpavde
  • Christian G. Stief
  • Derya TilkiEmail author
Topic paper



Nephroureterectomy with excision of a bladder cuff is the gold standard in the treatment of upper urinary tract carcinomas (UTUC). But especially for patients suffering from advanced tumor stages, life expectancy has not improved over the years with local recurrence or distant metastases being the main reasons for treatment failure. Chemotherapy in an adjuvant or neoadjuvant setting seems therefore to be a promising approach.


The literature of the last 20 years was searched using Medline. Articles were chosen by using the given abstracts. Only articles written in English and not older than 20 years were considered.


Most information concerning chemotherapy of urothelial carcinomas is gained from studies comprising patients suffering from lower urinary tract carcinomas. The combination of methotrexate, adriamycin, vinblastine and cisplatin as well as the combination of gemcitabine and cisplatin are the most used chemotherapy regimens in advanced UCC and have shown beneficial results. The summarized data of studies for UTUC contained no level one information. Down staging effects as well as prolongation of survival have been shown for some patients treated with neoadjuvant chemotherapy, but because of the small study groups and the retrospective design, no definite conclusions can be drawn from these results. In addition, there exists an uncertainty for preoperative staging. Results for adjuvant chemotherapy are lacking.


No definite recommendations for peri-operative chemotherapy in UTUC can be derived from the current literature. Current therapy is largely based on extrapolation from the bladder cancer literature. Prospective studies dedicated to UTUC are needed.


Upper urinary tract carcinoma Adjuvant chemotherapy Neoadjuvant chemotherapy Transitional cell carcinoma 


Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Raman JD, Messer J, Sielatycki JA, et al (1973–2005) Incidence and survival of patients with carcinoma of the ureter and renal pelvis in the USA.BJU Int 107:1059–1064Google Scholar
  2. 2.
    Roupret M, Zigeuner R, Palou J et al (2011) European guidelines for the diagnosis and management of upper urinary tract urothelial cell carcinomas: 2011 update. Eur Urol 59:584–594PubMedCrossRefGoogle Scholar
  3. 3.
    Colin P, Koenig P, Ouzzane A et al (2009) Environmental factors involved in carcinogenesis of urothelial cell carcinomas of the upper urinary tract. BJU Int 104:1436–1440PubMedCrossRefGoogle Scholar
  4. 4.
    Hall MC, Womack S, Sagalowsky AI et al (1998) Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract: a 30-year experience in 252 patients. Urology 52:594–601PubMedCrossRefGoogle Scholar
  5. 5.
    Brown GA, Busby JE, Wood CG et al (2006) Nephroureterectomy for treating upper urinary tract transitional cell carcinoma: time to change the treatment paradigm? BJU Int 98:1176–1180PubMedCrossRefGoogle Scholar
  6. 6.
    Bellmunt J, von der Maase H, Mead GM et al (2012) 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 30:1107–1113PubMedCrossRefGoogle Scholar
  7. 7.
    von der Maase H, Sengelov L, Roberts JT et al (2005) Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol 23:4602–4608PubMedCrossRefGoogle Scholar
  8. 8.
    Sternberg CN, de Mulder P, Schornagel JH et al (2006) Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Cancer 42:50–54PubMedCrossRefGoogle Scholar
  9. 9.
    Saxman SB, Propert KJ, Einhorn LH et al (1997) Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol 15:2564–2569PubMedGoogle Scholar
  10. 10.
    Griffiths G, Hall R, Sylvester R et al (2011) International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol 29:2171–2177PubMedCrossRefGoogle Scholar
  11. 11.
    Grossman HB, Natale RB, Tangen CM et al (2003) Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 349:859–866PubMedCrossRefGoogle Scholar
  12. 12.
    Vale CL (2005) Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol 48:202–205; discussion 205–206Google Scholar
  13. 13.
    Calabro F, Sternberg CN (2009) Neoadjuvant and adjuvant chemotherapy in muscle-invasive bladder cancer. Eur Urol 55:348–358PubMedCrossRefGoogle Scholar
  14. 14.
    Kaag MG, O’Malley RL, O’Malley P et al (2010) Changes in renal function following nephroureterectomy may affect the use of perioperative chemotherapy. Eur Urol 58:581–587PubMedCrossRefGoogle Scholar
  15. 15.
    Williams SK, Denton KJ, Minervini A et al (2008) Correlation of upper-tract cytology, retrograde pyelography, ureteroscopic appearance, and ureteroscopic biopsy with histologic examination of upper-tract transitional cell carcinoma. J Endourol 22:71–76PubMedCrossRefGoogle Scholar
  16. 16.
    Hellenthal NJ, Shariat SF, Margulis V et al (2009) Adjuvant chemotherapy for high risk upper tract urothelial carcinoma: results from the Upper Tract Urothelial Carcinoma Collaboration. J Urol 182:900–906PubMedCrossRefGoogle Scholar
  17. 17.
    Brien JC, Shariat SF, Herman MP et al (2010) Preoperative hydronephrosis, ureteroscopic biopsy grade and urinary cytology can improve prediction of advanced upper tract urothelial carcinoma. J Urol 184:69–73PubMedCrossRefGoogle Scholar
  18. 18.
    Margulis V, Youssef RF, Karakiewicz PI et al (2010) Preoperative multivariable prognostic model for prediction of nonorgan confined urothelial carcinoma of the upper urinary tract. J Urol 184:453–458PubMedCrossRefGoogle Scholar
  19. 19.
    Igawa M, Urakami S, Shiina H et al (1995) Neoadjuvant chemotherapy for locally advanced urothelial cancer of the upper urinary tract. Urol Int 55:74–77PubMedCrossRefGoogle Scholar
  20. 20.
    Matin SF, Margulis V, Kamat A et al (2010) Incidence of downstaging and complete remission after neoadjuvant chemotherapy for high-risk upper tract transitional cell carcinoma. Cancer 116:3127–3134PubMedCrossRefGoogle Scholar
  21. 21.
    Youssef RF, Shariat SF, Lotan Y et al (2011) Upper urinary tract urothelial carcinoma with loco-regional nodal metastases: insights from the Upper Tract Urothelial Carcinoma Collaboration. BJU Int 108:1286–1291PubMedCrossRefGoogle Scholar
  22. 22.
    Rajput MZ, Kamat AM, Clavell-Hernandez J et al (2011) Perioperative outcomes of laparoscopic radical nephroureterectomy and regional lymphadenectomy in patients with upper urinary tract urothelial carcinoma after neoadjuvant chemotherapy. Urology 78:61–67PubMedCrossRefGoogle Scholar
  23. 23.
    Skinner DG, Daniels JR, Russell CA, et al (1991) The role of adjuvant chemotherapy following cystectomy for invasive bladder cancer: a prospective comparative trial. J Urol 145:459–464; discussion 464–457Google Scholar
  24. 24.
    Stockle M, Meyenburg W, Wellek S et al (1995) Adjuvant polychemotherapy of nonorgan-confined bladder cancer after radical cystectomy revisited: long-term results of a controlled prospective study and further clinical experience. J Urol 153:47–52PubMedCrossRefGoogle Scholar
  25. 25.
    Lehmann J, Franzaring L, Thuroff J et al (2006) Complete long-term survival data from a trial of adjuvant chemotherapy vs control after radical cystectomy for locally advanced bladder cancer. BJU Int 97:42–47PubMedCrossRefGoogle Scholar
  26. 26.
    Freiha F, Reese J Torti FM (1996) A randomized trial of radical cystectomy versus radical cystectomy plus cisplatin, vinblastine and methotrexate chemotherapy for muscle invasive bladder cancer. J Urol 155:495–499; discussion 499–500Google Scholar
  27. 27.
    Studer UE, Bacchi M, Biedermann C et al (1994) Adjuvant cisplatin chemotherapy following cystectomy for bladder cancer: results of a prospective randomized trial. J Urol 152:81–84PubMedGoogle Scholar
  28. 28.
    Vale CL, Collaboration ABCAM-a (2005) Adjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis of individual patient data Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. European Urology 48:189–199; discussion 199–201Google Scholar
  29. 29.
    Cognetti F, Ruggeri EM, Felici A, et al (2011) Adjuvant chemotherapy with cisplatin and gemcitabine versus chemotherapy at relapse in patients with muscle-invasive bladder cancer submitted to radical cystectomy: an Italian, multicenter, randomized phase III trial. Ann Oncol 23:695–700PubMedCrossRefGoogle Scholar
  30. 30.
    Paz-Ares L, Solsona E Esteban E (2010) Randomized phase III trial comparing adjuvant paclitaxel/gemcitabine/cisplatin (PGC) to observation in patients with resected invasive bladder cancer: results of the Spanish Oncology Genitourinary Group (SOGUG) 99/01 study. J Clin Oncol 28:18s (suppl; abstr LBA4518)Google Scholar
  31. 31.
    David KA, Milowsky MI, Ritchey J et al (2007) Low incidence of perioperative chemotherapy for stage III bladder cancer 1998 to 2003: a report from the National Cancer Data Base. J Urol 178:451–454PubMedCrossRefGoogle Scholar
  32. 32.
    Feifer A TJ, Shouery M, et al (2011) Multi-institutional quality-of-care initiative for nonmetastatic, muscle-invasive, transitional cell carcinoma of the bladder. J Clin Oncol 29 (suppl 7; abstr 240)Google Scholar
  33. 33.
    Kikuchi E, Margulis V, Karakiewicz PI et al (2009) Lymphovascular invasion predicts clinical outcomes in patients with node-negative upper tract urothelial carcinoma. J Clin Oncol 27:612–618PubMedCrossRefGoogle Scholar
  34. 34.
    Kim DS, Lee YH, Cho KS et al (2010) Lymphovascular invasion and pT stage are prognostic factors in patients treated with radical nephroureterectomy for localized upper urinary tract transitional cell carcinoma. Urology 75:328–332PubMedCrossRefGoogle Scholar
  35. 35.
    Novara G, Matsumoto K, Kassouf W et al (2010) Prognostic role of lymphovascular invasion in patients with urothelial carcinoma of the upper urinary tract: an international validation study. Eur Urol 57:1064–1071PubMedCrossRefGoogle Scholar
  36. 36.
    Lane BR, Smith AK, Larson BT et al (2010) Chronic kidney disease after nephroureterectomy for upper tract urothelial carcinoma and implications for the administration of perioperative chemotherapy. Cancer 116:2967–2973PubMedCrossRefGoogle Scholar
  37. 37.
    Suzuki S, Shinohara N, Harabayashi T et al (2004) Impact of adjuvant systemic chemotherapy on postoperative survival in patients with high-risk urothelial cancer. Int J Urol 11:456–460PubMedCrossRefGoogle Scholar
  38. 38.
    Kwak C, Lee SE, Jeong IG et al (2006) Adjuvant systemic chemotherapy in the treatment of patients with invasive transitional cell carcinoma of the upper urinary tract. Urology 68:53–57PubMedCrossRefGoogle Scholar
  39. 39.
    Lee SE, Byun SS, Park YH et al (2006) Adjuvant chemotherapy in the management of pT3N0M0 transitional cell carcinoma of the upper urinary tract. Urol Int 77:22–26PubMedCrossRefGoogle Scholar
  40. 40.
    Hirano D, Okada Y, Nagane Y, et al (2012) Intravesical Recurrence after Surgical Management of Urothelial Carcinoma of the Upper Urinary Tract. Urol Int 89:71–77PubMedCrossRefGoogle Scholar
  41. 41.
    Vassilakopoulou M, de la Motte Rouge T, Colin P et al (2011) Outcomes after adjuvant chemotherapy in the treatment of high-risk urothelial carcinoma of the upper urinary tract (UUT-UC): results from a large multicenter collaborative study. Cancer 117:5500–5508PubMedCrossRefGoogle Scholar
  42. 42.
    Kawashima A, Nakai Y, Nakayama M, et al (2011) The result of adjuvant chemotherapy for localized pT3 upper urinary tract carcinoma in a multi-institutional study. World J Urol. doi: 10.1007/s00345-011-0775-z
  43. 43.
    Siefker-Radtke AO KA, Corn PG, et al Neoadjuvant chemotherapy with DD-MVAC and bevacizumab in high-risk urothelial cancer: Results from a phase II trial at the M. D. Anderson Cancer Center. J Clin Oncol 30 (suppl 5; abstr 261)Google Scholar
  44. 44.
    Birtle AJ, Lewis R, Johnson M et al (2012) Time to define an international standard of postoperative care for resected upper urinary tract transitional cell carcinoma (TCC)—opening of the peri-operative chemotherapy versus surveillance in upper tract urothelial cancer (POUT) Trial. BJU Int 110:919–921PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Jan Cordier
    • 1
  • Guru Sonpavde
    • 2
  • Christian G. Stief
    • 1
  • Derya Tilki
    • 1
    Email author
  1. 1.Department of Urology, University Hospital GrosshadernLudwig-Maximilians-University MunichMunichGermany
  2. 2.Urologic Medical OncologyUAB Comprehensive Cancer CenterBirminghamUSA

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