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The Role of Systemic Chemotherapy in Management of Upper Tract Urothelial Cancer

  • Urothelial Cancer (A Sagalowsky, Section Editor)
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Abstract

Upper tract urothelial cancer (UTUC) accounts for roughly 5 % of all urothelial cancers. At presentation, 30 % of patients demonstrate invasive and/or locally advanced disease, 30–40 % have regional lymph node involvement, and 20 % harbor metastatic disease. Systemic recurrence and progression rates after surgery for patients with advanced disease range between 45–60 %. Five-year cancer specific survival rates for pT2 and pT3 tumors are 73 % and 40 %, respectively. Median survival for patients with pT4 disease is approximately 6 months. Nonetheless, there is a lack of improvement in the rates of systemic recurrence and progression in patients with advanced UTUC. Extrapolating evidence obtained from experience with multi-modal therapy of patients with urothelial bladder cancer, additional improvements in oncological outcomes for patients with UTUC can be achieved through integration of effective systemic chemotherapy with local tumor control. We provide an overview of the rationale and utilization strategies of peri-operative systemic chemotherapy in patients with UTUC.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Raman JD, Messer J, Sielatycki JA, et al. Incidence and survival of patients with carcinoma of the ureter and renal pelvis in the USA, 1973–2005. BJU Int. 2011;107(7):1059–64.

    Article  PubMed  Google Scholar 

  2. Ozsahin M, Zouhair A, Villa S, et al. Prognostic factors in urothelial renal pelvis and ureter tumours: a multicentre Rare Cancer Network study. Eur J Cancer. 1999;35(5):738–43.

    Article  PubMed  CAS  Google Scholar 

  3. •• Margulis V, Shariat SF, Matin SF, et al. Outcomes of radical nephroureterectomy: a series from the Upper Tract Urothelial Carcinoma Collaboration. Cancer. 2009;115(6):1224–33. This article reports the outcomes of extripartive therapy of UTUC from a large multicenter collaborative group.

    Article  PubMed  Google Scholar 

  4. •• Vassilakopoulou M, de la Motte Rouge T, Colin P, et al. 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. 2011;117(24):5500–8. A retrospective study evaluating the effects of adjuvant chemotherapy on patients with high risk disease.

    Article  PubMed  Google Scholar 

  5. von der Maase H, Hansen SW, Roberts JT, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000;18(17):3068–77.

    PubMed  Google Scholar 

  6. Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003;349(9):859–66.

    Article  PubMed  CAS  Google Scholar 

  7. 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. 2005 Aug;48(2):202–5; discussion 5–6.

  8. • Adibi M, Youssef R, Shariat SF, et al. Oncological outcomes after radical nephroureterectomy for upper tract urothelial carcinoma: comparison over the three decades. Int J Urol. 2012;19(12):1060–6. This article highlights the temporal trends of the management of UTUC.

    Article  PubMed  Google Scholar 

  9. Raman JD, Scherr DS. Management of patients with upper urinary tract transitional cell carcinoma. Nat Clin Pract Urol. 2007;4(8):432–43.

    Article  PubMed  Google Scholar 

  10. McCarron JP, Mills C, Vaughn Jr ED. Tumors of the renal pelvis and ureter: current concepts and management. Semin Urol. 1983;1(1):75–81.

    PubMed  CAS  Google Scholar 

  11. Chen GL, El-Gabry EA, Bagley DH. Surveillance of upper urinary tract transitional cell carcinoma: the role of ureteroscopy, retrograde pyelography, cytology and urinalysis. J Urol. 2000;164(6):1901–4.

    Article  PubMed  CAS  Google Scholar 

  12. Xia TL. [Cytologic diagnostic value of voided urine in 60 cases of primary transitional cell carcinoma of the renal pelvis and ureter]. Zhonghua Wai Ke Za Zhi. 1989 Dec;27(12):753–5, 82.

  13. Smith AK, Stephenson AJ, Lane BR, et al. Inadequacy of biopsy for diagnosis of upper tract urothelial carcinoma: implications for conservative management. Urology. 2011;78(1):82–6.

    Article  PubMed  Google Scholar 

  14. • Matin SF, Kamat AM, Grossman HB. High-frequency endoluminal ultrasonography as an aid to the staging of upper tract urothelial carcinoma: imaging findings and pathologic correlation. J Ultrasound Med. 2010;29(9):1277–84. This article focuses on new emerging technologies in the diagnosis of UTUC.

    PubMed  Google Scholar 

  15. • Brien JC, Shariat SF, Herman MP, et al. Preoperative hydronephrosis, ureteroscopic biopsy grade and urinary cytology can improve prediction of advanced upper tract urothelial carcinoma. J Urol. 2010;184(1):69–73. This authors discuss the utility of a model incorporting preoperative hydronephrosis, biopsy, and urine cytology to predict advanced disease in patients with UTUC.

    Article  PubMed  Google Scholar 

  16. Favaretto RL, Shariat SF, Savage C, et al. Combining imaging and ureteroscopy variables in a preoperative multivariable model for prediction of muscle-invasive and non-organ confined disease in patients with upper tract urothelial carcinoma. BJU Int. 2012;109(1):77–82.

    Article  PubMed  Google Scholar 

  17. • Margulis V, Youssef RF, Karakiewicz PI, et al. Preoperative multivariable prognostic model for prediction of nonorgan confined urothelial carcinoma of the upper urinary tract. J Urol. 2010;184(2):453–8. This article reports the results of a prognostic model for predicting locally advanced disease.

    Article  PubMed  Google Scholar 

  18. Kikuchi E, Margulis V, Karakiewicz PI, et al. Lymphovascular invasion predicts clinical outcomes in patients with node-negative upper tract urothelial carcinoma. J Clin Oncol. 2009;27(4):612–8.

    Article  PubMed  Google Scholar 

  19. Novara G, Matsumoto K, Kassouf W, et al. Prognostic role of lymphovascular invasion in patients with urothelial carcinoma of the upper urinary tract: an international validation study. Eur Urol. 2010;57(6):1064–71.

    Article  PubMed  Google Scholar 

  20. •• Cha EK, Shariat SF, Kormaksson M, et al. Predicting clinical outcomes after radical nephroureterectomy for upper tract urothelial carcinoma. Eur Urol. 2012;61(4):818–25. This article studied the prognostic value of pathological features and predicting oncologlocal outcomes after RNU.

    Article  PubMed  Google Scholar 

  21. Shariat SF, Tokunaga H, Zhou J, et al. p53, p21, pRB, and p16 expression predict clinical outcome in cystectomy with bladder cancer. J Clin Oncol. 2004;22(6):1014–24.

    Article  PubMed  CAS  Google Scholar 

  22. • Bagrodia A, Youssef RF, Kapur P, et al. Prospective evaluation of molecular markers for the staging and prognosis of upper tract urothelial carcinoma. Eur Urol. 2012;62(1):e27–9. This article reports on the feasibility of using molecular markers in determine prognosis in patients with UTUC treated with RNU.

    Article  PubMed  Google Scholar 

  23. •• Roupret M, Zigeuner R, Palou J, et al. European guidelines for the diagnosis and management of upper urinary tract urothelial cell carcinomas: 2011 update. Eur Urol [Consensus Development Conference]. 2011;59(4):584–94. European guidelines on the management of UTUC.

    Article  Google Scholar 

  24. •• Colin P, Ouzzane A, Pignot G, et al. Comparison of oncological outcomes after segmental ureterectomy or radical nephroureterectomy in urothelial carcinomas of the upper urinary tract: results from a large French multicentre study. BJU Int. 2012;110(8):1134–41. This article concludes that the oncological outcomes of segmental resection mirror that of RNU.

    Article  PubMed  Google Scholar 

  25. Lehmann J, Suttmann H, Kovac I, et al. Transitional cell carcinoma of the ureter: prognostic factors influencing progression and survival. Eur Urol. 2007;51(5):1281–8.

    Article  PubMed  Google Scholar 

  26. Bagrodia A, Kuehhas, F, Gayed, BA, Wood, CG. Comparative analysis of oncologic outcomes of partial ureterectomy versus radical nephroureterectomy in upper tract urothelial carcinoma. urology, In Press. 2013.

  27. Huang WC, Elkin EB, Levey AS, et al. Partial nephrectomy versus radical nephrectomy in patients with small renal tumors–is there a difference in mortality and cardiovascular outcomes? J Urol [Comparative Study]. 2009;181(1):55–61. discussion -2.

    Article  Google Scholar 

  28. Cutress ML, Stewart GD, Wells-Cole S, et al. Long-term endoscopic management of upper tract urothelial carcinoma: 20-year single-centre experience. BJU international. 2012 May 7.

  29. Huang WC, Levey AS, Serio AM, et al. Chronic kidney disease after nephrectomy in patients with renal cortical tumours: a retrospective cohort study. Lancet Oncol. 2006;7(9):735–40.

    Article  PubMed  Google Scholar 

  30. •• Lane BR, Smith AK, Larson BT, et al. Chronic kidney disease after nephroureterectomy for upper tract urothelial carcinoma and implications for the administration of perioperative chemotherapy. Cancer. 2010;116(12):2967–73. The authors report on the high prevlance of CKD following RNU and the implications it has on multimodal therapy.

    Article  PubMed  Google Scholar 

  31. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002 Feb;39(2 Suppl 1):S1–266.

  32. Sternberg CN, Donat SM, Bellmunt J, et al. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer. Urology. 2007;69(1 Suppl):62–79.

    Article  PubMed  Google Scholar 

  33. • Audenet F, Yates DR, Cussenot O, et al. The role of chemotherapy in the treatment of urothelial cell carcinoma of the upper urinary tract (UUT-UCC). Urologic oncology. 2010 Sep 28. A review of chemotherapy in the treatment of patients with UTUC.

  34. •• Hellenthal NJ, Shariat SF, Margulis V, et al. Adjuvant chemotherapy for high risk upper tract urothelial carcinoma: results from the Upper Tract Urothelial Carcinoma Collaboration. J Urol. 2009;182(3):900–6. This article is a large international multicenter retrospective study evaluating the use of adjuvant chemotherapy in high risk patients.

    Article  PubMed  Google Scholar 

  35. • Bamias A, Deliveliotis C, Fountzilas G, et al. Adjuvant chemotherapy with paclitaxel and carboplatin in patients with advanced carcinoma of the upper urinary tract: a study by the Hellenic Cooperative Oncology Group. J Clin Oncol. 2004;22(11):2150–4. Only prospective study evaluating adjuvant chemotherapy.

    Article  PubMed  CAS  Google Scholar 

  36. Millikan R, Dinney C, Swanson D, et al. Integrated therapy for locally advanced bladder cancer: final report of a randomized trial of cystectomy plus adjuvant M-VAC versus cystectomy with both preoperative and postoperative M-VAC. J Clin Oncol. 2001;19(20):4005–13.

    PubMed  CAS  Google Scholar 

  37. •• Matin SF, Margulis V, Kamat A, et al. Incidence of downstaging and complete remission after neoadjuvant chemotherapy for high-risk upper tract transitional cell carcinoma. Cancer. 2010;116(13):3127–34. This article emphasizes the signficance and importance of administering neoadjuvant chemotherapy.

    Article  PubMed  Google Scholar 

  38. Kitamura H, Igarashi M, Tanaka T, et al. A role for preoperative systemic chemotherapy in node-positive upper tract urothelial carcinoma treated with radical nephroureterectomy. Jpn J Clin Oncol. 2012 Oct 16.

  39. • Youssef RF, Shariat SF, Lotan Y, et al. Upper urinary tract urothelial carcinoma with loco-regional nodal metastases: insights from the Upper Tract Urothelial Carcinoma Collaboration. BJU Int. 2011;108(8):1286–91. This article reports on the treatment of Node positive disease in patients with UTUC from a large multicenter collaborative group.

    Article  PubMed  Google Scholar 

  40. Rai BP, Shelley M, Coles B, et al. Surgical management for upper urinary tract transitional cell carcinoma (UUT-TCC): a systematic review. BJU Int. 2012;110(10):1426–35.

    Article  PubMed  Google Scholar 

  41. Siefker-Radtke AO, Dinney CP, Shen Y, et al. A phase 2 clinical trial of sequential neoadjuvant chemotherapy with ifosfamide, doxorubicin, and gemcitabine followed by cisplatin, gemcitabine, and ifosfamide in locally advanced urothelial cancer: final results. Cancer. 2012 Aug 22.

  42. •• De Santis M, Bellmunt J, Mead G, et al. Randomized phase II/III trial assessing gemcitabine/ carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer "unfit" for cisplatin-based chemotherapy: phase II–results of EORTC study 3098. J Clin Oncol. 2009;27(33):5634–9. This article highlights the use of alternative therapeutic regimens in patients who can not tolerate cisplatin based regimens.

    Article  PubMed  Google Scholar 

  43. • Alva AS, Matin SF, Lerner SP, et al. Perioperative chemotherapy for upper tract urothelial cancer. Nat Rev Urol. 2012;9(5):266–73. A review of the role chemotherapy in treatment of UTUC.

    Article  PubMed  CAS  Google Scholar 

  44. Shariat SF, Godoy G, Lotan Y, et al. Advanced patient age is associated with inferior cancer-specific survival after radical nephroureterectomy. BJU Int [Multicenter Study Research Support, NIH, Extramural]. 2010;105(12):1672–7.

    Google Scholar 

  45. Fajkovic H, Cha EK, Jeldres C, et al. Prognostic value of extranodal extension and other lymph node parameters in patients with upper tract urothelial carcinoma. J Urol. 2012;187(3):845–51.

    Article  PubMed  Google Scholar 

  46. Fritsche HM, Novara G, Burger M, et al. Macroscopic sessile tumor architecture is a pathologic feature of biologically aggressive upper tract urothelial carcinoma. Urol Oncol. 2012;30(5):666–72.

    Article  PubMed  Google Scholar 

  47. Remzi M, Haitel A, Margulis V, et al. Tumour architecture is an independent predictor of outcomes after nephroureterectomy: a multi-institutional analysis of 1363 patients. BJU Int [Multicenter Study]. 2009;103(3):307–11.

    Article  Google Scholar 

  48. Chromecki TF, Cha EK, Fajkovic H, et al. The impact of tumor multifocality on outcomes in patients treated with radical nephroureterectomy. Eur Urol. 2012;61(2):245–53.

    Article  PubMed  Google Scholar 

  49. Seitz C, Gupta A, Shariat SF, et al. Association of tumor necrosis with pathological features and clinical outcome in 754 patients undergoing radical nephroureterectomy for upper tract urothelial carcinoma: an international validation study. J Urol. 2010;184(5):1895–900.

    Article  PubMed  Google Scholar 

  50. Raman JD, Ng CK, Scherr DS, et al. Impact of tumor location on prognosis for patients with upper tract urothelial carcinoma managed by radical nephroureterectomy. Eur Urol. 2010;57(6):1072–9.

    Article  PubMed  Google Scholar 

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Gayed, B.A., Thoreson, G.R. & Margulis, V. The Role of Systemic Chemotherapy in Management of Upper Tract Urothelial Cancer. Curr Urol Rep 14, 94–101 (2013). https://doi.org/10.1007/s11934-013-0307-z

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