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Bladder Cancer Treatment (PDQ®)

Recurrent Bladder Cancer Treatment

The prognosis for any patient with progressive or recurrent invasive bladder cancer is generally poor. Management of recurrence depends on previous therapy, sites of recurrence, and individual patient considerations.

Treatment Options for Recurrent Bladder Cancer

Treatment options for patients with recurrent bladder cancer include the following:

  1. Combination chemotherapy.
  2. Surgery for new superficial or localized tumors.
  3. Palliative therapy.
  4. Clinical trials.

Combination chemotherapy

Patients who have not received previous chemotherapy for urothelial carcinoma should be considered for chemotherapy as described above for stage IV disease.

In patients with recurrent transitional cell carcinoma, combination chemotherapy has produced high response rates, with occasional complete responses seen.[1,2]

Evidence (combination chemotherapy):

  1. Results from a randomized trial that compared methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with single-agent cisplatin in patients with advanced bladder cancer show a significant advantage with MVAC in both response rate and median survival.[3] The overall response rate with MVAC in this cooperative group trial was 39%.
  2. Results from a randomized trial that compared MVAC with cisplatin, cyclophosphamide, and doxorubicin in 110 patients reported longer overall survival (OS) with MVAC (median survival 48.3 weeks vs. 36.1 weeks; P = .0003).[4]
  3. Results from a randomized trial that compared cisplatin, methotrexate, and vinblastine (CMV) with methotrexate plus vinblastine reported longer OS with CMV (median survival 7 months vs. 4.5 months; hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.41–0.73; P = .0001).[5]
  4. In a multicenter, randomized, phase III trial that compared the combination of gemcitabine plus cisplatin (GC) with the MVAC regimen in 405 patients with advanced or metastatic bladder cancer, GC yielded response rates, time-to-progression, and OS (HR, 1.04; 95% CI, 0.82–1.32; P = .75) similar to MVAC, but GC had a better safety profile and was better tolerated than MVAC. Although this study was not designed to show the equivalence of the two regimens, the similar efficacy and reduced toxic effects of GC make it a reasonable alternative in patients who may not tolerate the MVAC regimen.[6][Level of evidence: 1iiA]
  5. Other chemotherapy regimens that have shown activity in metastatic bladder cancer include single-agent paclitaxel, single-agent gemcitabine, single-agent pemetrexed, carboplatin combined with either gemcitabine or paclitaxel, and gemcitabine combined with paclitaxel. There are no phase III trials demonstrating a survival or quality-of-life benefit from second-line chemotherapy.[7-14]

Surgery for new superficial or localized tumors

Treatment of new superficial or locally invasive tumors that develop in the setting of previous conservative therapy for superficial bladder neoplasia has been discussed earlier in stage I in this summary.

Palliative therapy

Palliative radiation therapy should be considered for patients with symptomatic tumors.

Clinical trials

Recurrent or progressive disease in distant sites or after definitive local therapy has an extremely poor prognosis, and clinical trials should be considered whenever possible.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent bladder cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.


  1. Sternberg CN, Yagoda A, Scher HI, et al.: Methotrexate, vinblastine, doxorubicin, and cisplatin for advanced transitional cell carcinoma of the urothelium. Efficacy and patterns of response and relapse. Cancer 64 (12): 2448-58, 1989. [PUBMED Abstract]
  2. Harker WG, Meyers FJ, Freiha FS, et al.: Cisplatin, methotrexate, and vinblastine (CMV): an effective chemotherapy regimen for metastatic transitional cell carcinoma of the urinary tract. A Northern California Oncology Group study. J Clin Oncol 3 (11): 1463-70, 1985. [PUBMED Abstract]
  3. Loehrer PJ Sr, Einhorn LH, Elson PJ, et al.: A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol 10 (7): 1066-73, 1992. [PUBMED Abstract]
  4. Logothetis CJ, Dexeus FH, Finn L, et al.: A prospective randomized trial comparing MVAC and CISCA chemotherapy for patients with metastatic urothelial tumors. J Clin Oncol 8 (6): 1050-5, 1990. [PUBMED Abstract]
  5. Mead GM, Russell M, Clark P, et al.: A randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced transitional cell carcinoma: results and a report on prognostic factors in a Medical Research Council study. MRC Advanced Bladder Cancer Working Party. Br J Cancer 78 (8): 1067-75, 1998. [PUBMED Abstract]
  6. 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 18 (17): 3068-77, 2000. [PUBMED Abstract]
  7. Roth BJ: Preliminary experience with paclitaxel in advanced bladder cancer. Semin Oncol 22 (3 Suppl 6): 1-5, 1995. [PUBMED Abstract]
  8. Witte RS, Elson P, Bono B, et al.: Eastern Cooperative Oncology Group phase II trial of ifosfamide in the treatment of previously treated advanced urothelial carcinoma. J Clin Oncol 15 (2): 589-93, 1997. [PUBMED Abstract]
  9. Einhorn LH, Roth BJ, Ansari R, et al.: Phase II trial of vinblastine, ifosfamide, and gallium combination chemotherapy in metastatic urothelial carcinoma. J Clin Oncol 12 (11): 2271-6, 1994. [PUBMED Abstract]
  10. Pollera CF, Ceribelli A, Crecco M, et al.: Weekly gemcitabine in advanced bladder cancer: a preliminary report from a phase I study. Ann Oncol 5 (2): 182-4, 1994. [PUBMED Abstract]
  11. Seidman AD, Scher HI, Heinemann MH, et al.: Continuous infusion gallium nitrate for patients with advanced refractory urothelial tract tumors. Cancer 68 (12): 2561-5, 1991. [PUBMED Abstract]
  12. Roth BJ: Ifosfamide in the treatment of bladder cancer. Semin Oncol 23 (3 Suppl 6): 50-5, 1996. [PUBMED Abstract]
  13. Bajorin DF: Paclitaxel in the treatment of advanced urothelial cancer. Oncology (Huntingt) 14 (1): 43-52, 57; discussion 58, 61-2, 2000. [PUBMED Abstract]
  14. Sweeney CJ, Roth BJ, Kabbinavar FF, et al.: Phase II study of pemetrexed for second-line treatment of transitional cell cancer of the urothelium. J Clin Oncol 24 (21): 3451-7, 2006. [PUBMED Abstract]
  • Updated: April 24, 2015