Skip to main content

Advertisement

SpringerLink
Log in

Concomitant CIS on TURBT does not impact oncological outcomes in patients treated with neoadjuvant or induction chemotherapy followed by radical cystectomy

  • Original Article
  • Published:
World Journal of Urology Aims and scope Submit manuscript

Abstract

Background

Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy.

Patients and methods

Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes.

Results

Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the ‘CIS’ versus ‘no-CIS’ groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63–1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01–1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23–2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34–0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82–1.35; p = 0.70).

Conclusion

In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, deVere White RW, Sarosdy MF, Wood DP Jr, Raghavan D, Crawford ED (2003) Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 349(9):859–866 PMID: 12944571

    Article  CAS  PubMed  Google Scholar 

  2. Zargar H, Espiritu PN, Fairey AS, Zargar H, Espiritu PN, Fairey AS, Mertens LS, Dinney CP, Mir MC, Krabbe LM, Cookson MS, Jacobsen NE, Gandhi NM, Griffin J, Montgomery JS, Vasdev N, Yu EY, Youssef D, Xylinas E, Campain NJ, Kassouf W, Dall’Era MA, Seah JA, Ercole CE, Horenblas S, Sridhar SS, McGrath JS, Aning J, Shariat SF, Wright JL, Thorpe AC, Morgan TM, Holzbeierlein JM, Bivalacqua TJ, North S, Barocas DA, Lotan Y, Garcia JA, Stephenson AJ, Shah JB, van Rhijn BW, Daneshmand S, Spiess PE, Black PC et al (2015) Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer. Eur Urol 67(2):241–249 PMID: 25257030

    Article  PubMed  Google Scholar 

  3. Zargar H, Zargar-Shoshtari K, Lotan Y, Shah JB, van Rhijn BW, Daneshmand S, Spiess PE, Black P, Collaborators (2016) Final Pathological Stage after Neoadjuvant Chemotherapy and Radical Cystectomy for Bladder Cancer-Does pT0 Predict Better Survival than pTa/Tis/T1?. J Urol 195(4 Pt 1):886–893 PMID: 26521718

    Article  CAS  PubMed  Google Scholar 

  4. Weight CJ, Garcia JA, Hansel DE, Fergany AF, Campbell SC, Gong MC, Jones JS, Klein EA, Dreicer R, Stephenson AJ (2009) Lack of pathologic down-staging with neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma of the bladder: a contemporary series. Cancer 115(4):792–799 PMID: 19127557

    Article  PubMed  Google Scholar 

  5. Van Allen EM, Mouw KW, Kim P, Iyer G, Wagle N, Al-Ahmadie H, Zhu C, Ostrovnaya I, Kryukov GV, O’Connor KW, Sfakianos J, Garcia-Grossman I, Kim J, Guancial EA, Bambury R, Bahl S, Gupta N, Farlow D, Qu A, Signoretti S, Barletta JA, Reuter V, Boehm J, Lawrence M, Getz G, Kantoff P, Bochner BH, Choueiri TK, Bajorin DF, Solit DB, Gabriel S, D’Andrea A, Garraway LA, Rosenberg JE (2014) Somatic ERCC2 mutations correlate with cisplatin sensitivity in muscle-invasive urothelial carcinoma. Cancer Discov 4:1140–1153 PMID: 25096233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Plimack ER, Dunbrack RL, Brennan TA, Andrake MD, Zhou Y, Serebriiskii IG, Slifker M, Alpaugh K, Dulaimi E, Palma N, Hoffman-Censits J, Bilusic M, Wong YN, Kutikov A, Viterbo R, Greenberg RE, Chen DY, Lallas CD, Trabulsi EJ, Yelensky R, McConkey DJ, Miller VA, Golemis EA, Ross EA et al (2015) Defects in DNA repair genes predict response to neoadjuvant cisplatin-based chemotherapy in muscle-invasive bladder cancer. Eur Urol 68:959–967 PMID: 26238431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Seiler Plimack ER, Dunbrack RL, Brennan TA, Andrake MD, Zhou Y, Serebriiskii IG, Slifker M, Alpaugh K, Dulaimi E, Palma N, Hoffman-Censits J, Bilusic M, Wong YN, Kutikov A, Viterbo R, Greenberg RE, Chen DY, Lallas CD, Trabulsi EJ, Yelensky R, McConkey DJ, Miller VA, Golemis EA, Ross EA (2015) Impact of molecular subtypes in muscle-invasive bladder cancer on predicting response and survival after neoadjuvant chemotherapy. Eur Urol 68(6):959–967 PMID: 26238431

    Article  CAS  Google Scholar 

  8. Liu D, Plimack ER, Hoffman-Censits J, Garraway LA, Bellmunt J, Van Allen E, Rosenberg JE (2016) Clinical validation of chemotherapy response biomarker ERCC2 in muscle-invasive urothelial bladder carcinoma. JAMA Oncol 2:1094–1096 PMID: 27310333

    Article  PubMed  PubMed Central  Google Scholar 

  9. Choi W, Porten S, Kim S, Willis D, Plimack ER, Hoffman-Censits J, Roth B, Cheng T, Tran M, Lee IL, Melquist J, Bondaruk J, Majewski T, Zhang S, Pretzsch S, Baggerly K, Siefker-Radtke A, Czerniak B, Dinney CP, McConkey DJ (2014) Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell 25(2):152–165 PMID: 24525232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Dinney CP, Hansel D, McConkey D, Shipley W, Hagan M, Dreicer R, Lerner S, Czerniak B, Waldman F, Groshen S, True LD, Petricoin E, Theodorescu D, Hruszkewycz A, Bajorin D (2014) Novel neoadjuvant therapy paradigms for bladder cancer: results from the national cancer center institute forum. Urol Oncol 32(8):1108–1115

    Article  PubMed  PubMed Central  Google Scholar 

  11. Masood S, Sriprasad S, Palmer JH, Mufti GR (2004) T1G3 bladder cancer—Indications for early cystectomy. Int Urol Nephrol 36(1):41–44 Int Urol Nephrol. 2004;36(1):41-4.PMID: 15338671

    Article  CAS  PubMed  Google Scholar 

  12. Hermans TJN, Voskuilen CS, van der Heijden MS, Schmitz-Dräger BJ, Kassouf W, Seiler R, Kamat AM, Grivas P, Kiltie AE, Black PC, van Rhijn BWG (2017) Neoadjuvant treatment for muscle-invasive bladder cancer: The past, the present, and the future. Urol Oncol. https://doi.org/10.1016/j.urolonc.2017.10.014

    Article  PubMed  Google Scholar 

  13. Chade DC, Chade DC, Shariat SF, Godoy G, Savage CJ, Cronin AM, Bochner BH, Donat SM, Herr HW, Dalbagni G (2010) Clinical outcomes of primary bladder carcinoma in situ in a contemporary series. J Urol 184(1):74–80 PMID: 20546806

    Article  PubMed  PubMed Central  Google Scholar 

  14. Thomas DE, Kaimakliotis HZ, Rice KR, Pereira JA, Johnston P, Moore ML, Reed A, Cregar DM, Franklin C, Loman RL, Koch MO, Bihrle R, Foster RS, Masterson TA, Gardner TA, Sundaram CP, Powell CR, Beck SDW, Grignon DJ, Cheng L, Albany C, Hahn NM (2017) Prognostic effect of carcinoma in situ in muscle-invasive urothelial carcinoma patients receiving neoadjuvant chemotherapy. Clin Genitourin Cancer 15(4):479–486 PMID: 28040424

    Article  PubMed  Google Scholar 

  15. Parker WP, Ho PL, Melquist JJ, Parker WP, Ho PL, Melquist JJ, Scott K, Holzbeierlein JM, Lopez-Corona E, Kamat AM, Lee EK et al (2015) The effect of concomitant carcinoma in situ on neoadjuvant chemotherapy for urothelial cell carcinoma of the bladder: inferior pathological outcomes but no effect on survival. J Urol 193:1494–1499 PMID: 25451834

    Article  PubMed  Google Scholar 

  16. Choi W, Ochoa A, McConkey DJ, Aine M, Höglund M, Kim WY, Real FX, Kiltie AE, Milsom I, Dyrskjøt L, Lerner SP, Choi W, Ochoa A, McConkey DJ, Aine M, Höglund M, Kim WY, Real FX, Kiltie AE, Milsom I, Dyrskjøt L, Lerner SP (2017) Genetic alterations in the molecular subtypes of bladder cancer: illustration in the cancer genome atlas dataset. Eur Urol. 72(3):354–365 PMID: 28365159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Knowles MA, Hurst CD (2015) Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity. Nat Rev Cancer 15(1):25–41. https://doi.org/10.1038/nrc3817 PMID: 25533674

    Article  CAS  PubMed  Google Scholar 

  18. Dinney CP, McConkey DJ, Millikan RE, Wu X, Bar-Eli M, Adam L, Kamat AM, Siefker-Radtke AO, Tuziak T, Sabichi AL, Grossman HB, Benedict WF, Czerniak B (2004) Focus on bladder cancer. Cancer Cell 6:111–116 PMID: 15324694

    Article  CAS  PubMed  Google Scholar 

  19. Takayanagi A, Masumori N, Takahashi A, Takagi Y, Tsukamoto T (2012) Upper urinary tract recurrence after radical cystectomy for bladder cancer: incidence and risk factors. Int J Urol 19(3):229–233. https://doi.org/10.1111/j.1442-2042.2011.02916.x Epub 2011 Nov 28 PMID: 22121922

    Article  PubMed  Google Scholar 

  20. Volkmer BG, Schnoeller T, Kuefer R, Gust K, Finter F, Hautmann RE (2009) Upper urinary tract recurrence after radical cystectomy for bladder cancer—who is at risk? J Urol 182(6):2632–2637 PMID: 19836794

    Article  PubMed  Google Scholar 

  21. Kukreja JB, Porten S, Golla V, Ho PL, Noguera-Gonzalez G, Navai N, Kamat AM, Dinney CPN, Shah JB (2017) Absence of tumor on repeat transurethral resection of bladder tumor does not predict final Pathologic T0 stage in bladder cancer treated with radical cystectomy. Eur Urol Focus. https://doi.org/10.1016/j.euf.2016.12.005

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, Hertfordshire and Bedfordshire Urological Cancer Centre, Lister Hospital, Stevenage, SG1 4AB, UK

    N. Vasdev & J. P. Noël

  2. School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK

    N. Vasdev & J. P. Noël

  3. Department of Urology, Freeman Hospital, Newcastle Upon Tyne, UK

    N. Vasdev, R. Veeratterapillay, J. Aning & A. Thorpe

  4. Department of Urology, Royal Melbourne Hospital, Melbourne, VIC, Australia

    H. Zargar, M. C. Mir, C. E. Ercole & A. J. Stephenson

  5. Department of Surgery, University of Melbourne, Melbourne, VIC, Australia

    H. Zargar, M. C. Mir, C. E. Ercole & A. J. Stephenson

  6. Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada

    H. Zargar & P. C. Black

  7. Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    P. E. Spiess

  8. USC/Norris Comprehensive Cancer Center, Institute of Urology, University of Southern California, Los Angeles, CA, USA

    A. S. Fairey & S. Daneshmand

  9. Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands

    L. S. Mertens, S. Horenblas & B. W. van Rhijn

  10. Department of Urology, MD Anderson Cancer Center, Houston, TX, USA

    C. P. Dinney & J. B. Shah

  11. Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    L. M. Krabbe & Y. Lotan

  12. Department of Urology, University of Oklahoma College of Medicine, Oklahoma City, OK, USA

    M. S. Cookson

  13. University of Alberta, Edmonton, AB, Canada

    A. S. Fairey & N. E. Jacobsen

  14. Department of Urology, The Johns Hopkins School of Medicine, The James Buchanan Brady Urological Institute, Baltimore, MD, USA

    N. M. Gandhi & T. J. Bivalacqua

  15. Department of Urology, Medical Center, University of Kansas, Kansas City, KS, USA

    J. Griffin & J. M. Holzbeierlein

  16. Department of Urology, University of Michigan Health System, Ann Arbor, MI, USA

    J. S. Montgomery & T. M. Morgan

  17. Division of Oncology, Department of Medicine, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    E. Y. Yu, J. L. Wright & P. Grivas

  18. Department of Urology, Weill Cornell Medical College, Presbyterian Hospital, New York, NY, USA

    E. Xylinas & S. F. Shariat

  19. Department of Urology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria

    S. F. Shariat

  20. Department of Surgery, Exeter Surgical Health Services Research Unit, Royal Devon and Exeter NHS Trust, Exeter, UK

    N. J. Campain, J. S. McGrath & J. Aning

  21. (Division of Urology) Department of Surgery, McGill University Health Center, Montreal, QC, Canada

    W. Kassouf

  22. Department of Urology, Davis Medical Center, University of California at Davis, Sacramento, CA, USA

    M. A. Dall’Era

  23. Princess Margaret Cancer Center, Toronto, ON, Canada

    J. A. Seah & S. S. Sridhar

  24. Cross Cancer Institute, Edmonton, AB, Canada

    S. North

  25. Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

    D. A. Barocas

Authors
  1. N. Vasdev
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Zargar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. P. Noël
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. Veeratterapillay
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. S. Fairey
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. L. S. Mertens
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C. P. Dinney
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. C. Mir
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. L. M. Krabbe
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M. S. Cookson
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. N. E. Jacobsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. N. M. Gandhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. J. Griffin
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. J. S. Montgomery
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. E. Y. Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. E. Xylinas
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. N. J. Campain
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. W. Kassouf
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. M. A. Dall’Era
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. J. A. Seah
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. C. E. Ercole
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. S. Horenblas
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. S. S. Sridhar
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. J. S. McGrath
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. J. Aning
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. S. F. Shariat
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. J. L. Wright
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. T. M. Morgan
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. T. J. Bivalacqua
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. S. North
    View author publications

    You can also search for this author in PubMed Google Scholar

  31. D. A. Barocas
    View author publications

    You can also search for this author in PubMed Google Scholar

  32. Y. Lotan
    View author publications

    You can also search for this author in PubMed Google Scholar

  33. P. Grivas
    View author publications

    You can also search for this author in PubMed Google Scholar

  34. A. J. Stephenson
    View author publications

    You can also search for this author in PubMed Google Scholar

  35. J. B. Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  36. B. W. van Rhijn
    View author publications

    You can also search for this author in PubMed Google Scholar

  37. S. Daneshmand
    View author publications

    You can also search for this author in PubMed Google Scholar

  38. P. E. Spiess
    View author publications

    You can also search for this author in PubMed Google Scholar

  39. J. M. Holzbeierlein
    View author publications

    You can also search for this author in PubMed Google Scholar

  40. A. Thorpe
    View author publications

    You can also search for this author in PubMed Google Scholar

  41. P. C. Black
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

NV: protocol/project development, data collection/management, manuscript writing/editing; HZ: data collection/management, data analysis, manuscript writing/editing; JPN: data collection, manuscript writing/editing; RV: data collection, manuscript review; ASF: data collection, manuscript review; LSM: data collection, manuscript review; CPD: data collection, manuscript review; MCM: data collection, manuscript review; LMK: data collection, manuscript review; MSC: data collection, manuscript review; NEJ: data collection, manuscript review; NMG: data collection, manuscript review; JG: data collection, manuscript review; JSM: data collection, manuscript review; EYY: data collection, manuscript review; EX: data collection, manuscript review; NJC: data collection, manuscript review; WK: data collection, manuscript review; MAD: data collection, manuscript review; JAS: data collection, manuscript review; CEE: data collection, manuscript review; SH: data collection, manuscript review; SSS: data collection, manuscript review; JSM: data collection, manuscript review; JA: data collection, manuscript review; SFS: data collection, manuscript review; JLW: data collection, manuscript review; TMM: data collection, manuscript review; TJB: data collection, manuscript review; SN: data collection, manuscript review; DAB: data collection, manuscript review; YL: data collection, manuscript review; PG: data collection, manuscript review; AJS: data collection, manuscript review; JBS: data collection, manuscript review; BWR: data collection, manuscript review; SD: data collection, manuscript review; PES: data collection, manuscript review; JMH: data collection, manuscript review; AT: manuscript writing/editing; PCB: manuscript writing/editing.

Corresponding author

Correspondence to N. Vasdev.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflict of interest.

Research involving human participants and animals

For this type of study formal consent is not required. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study where applicable.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vasdev, N., Zargar, H., Noël, J.P. et al. Concomitant CIS on TURBT does not impact oncological outcomes in patients treated with neoadjuvant or induction chemotherapy followed by radical cystectomy. World J Urol 37, 165–172 (2019). https://doi.org/10.1007/s00345-018-2361-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00345-018-2361-0

Keywords

Search

Navigation