NEOADJUVANT CHEMOTHERAPY IN MUSCLE-INVASIVE UROTHELIAL BLADDER CANCER: CORRELATION OF RESPONSE WITH PATIENTS SURVIVAL
Authors:
Michal Staník 1; Alexander Poprach 2; Daniel Macík 1; Ivo Čapák 1; Jiří Jarkovský 3; Denisa Malúšková 3; Natália Marečková 1; Radek Lakomý 2; Jan Doležel 1
Authors‘ workplace:
Oddělení onkourologie, Masarykův onkologický ústav, Brno
1; Klinika komplexní onkologické péče, Masarykův onkologický ústav, Brno
2; Institut biostatistiky a analýz, Masarykova univerzita, Brno
3
Published in:
Ces Urol 2016; 20(3): 221-228
Category:
Original Articles
Overview
Major statement:
Response rates to neoadjuvant chemotherapy were high in our cohort of 41 patients with muscle-invasive bladder cancer. Patients with a complete response had significantly improved 2-year progression-free survival compared with the patients with residual disease.
Aims:
Neoadjuvant chemotherapy (NAC) was shown to improve the overall survival in randomized trials. The aim of the study was to evaluate the frequency of response to NAC and the impact on prognosis of the disease.
Methods:
From January 2010 to October 2015 124 patients with bladder cancer underwent radical cystectomy and 41 of them (33 %) received NAC. Chemotherapy was indicated in cT3–4 or cN+ tumours, cT2N0 disease only in presence of risk factors like hydronephrosis or lymphovascular invasion.
Glomerular filtration rate >50 ml/min and ECOG performance status ≤1 were used as chemotherapy eligibility criteria. Gemcitabine and cisplatin was the most frequently used regimen (85 %). Response to chemotherapy was defined as complete (ypT0N0) or partial (≤ypT1N0). The median follow-up was 14 months (1–71). The Kaplan-Meier methods were used to calculate two-year progression-free survival (PFS) and subgroup survival comparison using log-rank test.
Results:
Two-year PFS rates were 69 % (95 % CI 52–86) for the whole cohort and 81 % in patients with clinically negative lymph nodes (cT2–4N0). Complete or partial responses to NAC were seen in 41 % and 59 %, respectively. The probability of attaining at least partial response to NAC (≤ ypT1N0) was significantly higher in cT2 tumours (76 %) than in cT3–4 (40 %). Two-year PFS was significantly higher in case of response to chemotherapy: 93 % in ypT0, 83 % in ypT1, 50 % in ypT2 and 31 % in ypT3–4 (p=0.003).
Conclusion:
Patients with a response to NAC had significantly improved 2-year PFS compared with the patients without the response. In the future, the development of new molecular biomarkers is warranted, that would allow better selection of patients to NAC.
KEY WORDS:
Chemotherapy, neoadjuvant therapy, urinary bladder neoplasms.
Sources
1. Stein JP, Lieskovsky G, Cote R, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol 2001; 19(3): 666–675.
2. Sternberg CN, Bellmunt J, Sonpavde G, et al. ICUD-EAU International consultation on bladder cancer 2012: chemotherapy for urothelial carcinoma – neoadjuvant and adjuvant settings. Eur Urol 2013; 63(1): 58–66.
3. Meeks JJ, Bellmunt J, Bochner BH, et al. A systematic review of neoadjuvant and adjuvant chemotherapy for muscle-invasive bladder cancer. Eur Urol 2012; 62: 523–533.
4. Advanced Bladder Cancer (ABC) Meta-Analysis Collaboration: 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; 48: 202–205.
5. Lavery HJ, Stensland KD, Niegisch G, Albers P, Droller MJ. Pathological T0 following radical cystectomy with or without neoadjuvant chemotherapy: a useful surrogate. J Urol. 2014; 191(4): 898–906.
6. Culp SH, Dickstein RJ, Grossman HB, et al. Refining patient selection for neoadjuvant chemotherapy before radical cystectomy. J Urol. 2014; 191(1): 40–47.
7. Lotan Y, Gupta A, Shariat SF, et al. Lymphovascular invasion is independently associated with overall survival, cause-specific survival, and local and distant recurrence in patients with negative lymph nodes at radical cystectomy. J Clin Oncol 2005; 23(27): 6533–6539.
8. Stimson CJ, Cookson MS, Barocas DA, et al. Preoperative hydronephrosis predicts extravesical and node positive disease in patients undergoing cystectomy for bladder cancer. J Urol. 2010; 183(5): 1732–1737.
9. Petrelli F, Coinu A, Cabiddu M, et al. Correlation of pathologic complete response with survival after neoadjuvant chemotherapy in bladder cancer treated with cystectomy: a meta-analysis. Eur Urol 2014; 65(2): 350–357.
10. Gandhi NM, Baras A, Munari E, et al. Gemcitabine and cisplatin neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma: Predicting response and assessing outcomes. Urol Oncol 2015; 33(5): 204e1–7.
11. 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: 859–866.
12. Sherif A, Holmberg L, Rintala E, et al. Neoadjuvant cisplatinum based combination chemotherapy in patients with invasive bladder cancer: a combined analysis of two Nordic studies. Eur Urol 2004; 45: 297–303.
13. Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK. 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 2011; 29(16): 2171–2177.
14. Zarger H, Espiritu PN, Fairey AS, et al. Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer. Eur Urol 2015; 67(2): 241–249.
15. Von der Maase H, Sengelov L, Roberts JT, et al. 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 2005; 23: 4602–4608.
16. Herr HW, Faulkner JR, Grossman HB, et al. Surgical factors influence bladder cancer outcomes: a cooperative group report. J Clin Oncol 2004; 22(14): 2781–2789.
17. Nuhn P, May M, Fritsche H-M, et al. External validation of disease-free survival at 2 or 3 years as a surrogate and new primary endpoint for patients undergoing radical cystectomy for urothelial carcinoma of the bladder. Eur J Surg Oncol 2012; 38: 637–642.
18. Plimack ER, Dunbrack RL, Brennan TA, et al. Defects in DNA repair genes predict response to neoadjuvant cisplatin-based chemotherapy in muscle-invasive bladder cancer. Eur Urol 2015; 68(6): 959–967.
19. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014; 507: 315–322.
Labels
Paediatric urologist Nephrology UrologyArticle was published in
Czech Urology
2016 Issue 3
Most read in this issue
- CYSTIC TUMORS OF THE KIDNEY
- A KNOWN (AND UNKOWN) HIV-POSITIVE PATIENT IN CLINICAL UROLOGICAL PRACTICE
- CABAZITAXEL FOR THE TREATMENT OF METASTATIC CASTRATION-RESISTANT PROSTATE CANCER
- LAPAROSCOPIC NEPHROPEXY