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2018 Friends of Israel Urological Symposium

FOIU 2018: Bladder Cancer – Oncologist’s View

Tel-Aviv, Israel (UroToday.com) Raya Leibowitz-Amit, MD discussed the topic of whether we should treat the primary tumor in patients with metastatic bladder cancer. First, Dr. Leibowitz presented the potential harm in treating the primary tumor. Detrimental oncologic sequalae (discovered in mice models) include:

  • ‘awakening'; of metastatic dormancy
  • Dissemination of disease during surgery
  • Complications of treatment
  • Delays in systemic therapy
Other negative palliative sequelae include:

  • Loss/compromise of the bladder
  • Lower urinary tract symptoms and treatment-induced cystitis
  • Pain
Therefore, it is prudent to treat the primary tumor only if symptoms occur and not prophylactically, according to Leibowitz. 

Next, Leibowitz discussed the potential benefits of treating the primary tumor. The oncologic benefits include:

  • Prevention of further dissemination of metastases, and thus improve outcomes
Palliative benefits include:

  • Palliation of symptoms derived from the primary tumor, including pain and irritative symptoms
  • Treat obstruction and stop bleeding
A study from the national cancer database (NCDB) examined the role of high-intensity local treatment for metastatic urothelial carcinoma of the bladder, demonstrating a benefit to local treatment.1 However, a commentary by Cristopher M. Booth et al. proposed that these observational findings are subject to such fundamental methodologic shortcomings that the purported findings of benefit to aggressive therapy are likely false and potentially dangerous to patients.2 The significant limitations eluded in this commentary include:

  • Staging issues – patients not deemed metastatic at presentation, very low/unequivocal tumor burden, and misclassifications
  • ‘immortal time’ bias – patients could not be included in the high-intensity local treatment group unless they survived long enough to undergo radical cystectomy (RC) or radiotherapy (RT). Patients in this group had a zero risk of dying during the period between diagnosis and treatment. Conversely, patients who did not undergo RC or RT were automatically included in the conservative local treatment group and were exposed to the risk of death from the date of diagnosis.
  • No correction for performance status or visceral metastatses.

Therefore, the difference in survival between the high-intensity local treatment and conservative local treatment groups in this observational NCDB study is almost certainly the result of residual confounding.2

A meta-analysis on the role of surgery in metastatic bladder cancer was published in the European Urology in 20183. This demonstrated that the beneficial role of consolidation surgery in metastatic bladder cancer is still unproven. In patients with clinically evident lymph node metastasis, data suggest a survival advantage for patients undergoing postchemotherapy radical cystectomy with lymphadenectomy, especially in those with measurable response to chemotherapy. There are anecdotal reports of resection of pulmonary metastasis as part of the multimodal approach, suggesting possible improved survival in well-selected patients.

The potential palliative local treatments for bladder tumor include RC, RT, transurethral resection of bladder tumor (TURBT), and bladder irrigation.

Leibowitz moved on to discuss the role of RT in this setting. According to her, almost half of the cases with muscle-invasive tumors are already systematically spread. To date, no standard regimen exists for the delivery of palliative pelvic RT. Various RT schedules manage successful and long-term palliation of pelvic symptoms in most patients and result in acceptable toxicity. For bladder cancer, the most common dose and fractionation range from 20 Gy in 5 fractions to 40 Gy in 20 fractions. Some retrospective studies reviewed 6 weekly fractions of 6 Gy to a total dose of 36 Gy.

Furthermore, radiotherapy has a hemostatic effect, proven for many tumor entities and usually begins after only a few fractions. This early effect can be explained by increased adherence of platelets to vascular endothelial cells.  In the long term, finally, the reduction of the risk of bleeding is due to a fibrosis of the blood vessels, possibly in conjunction with a tumor regression. Hypofractionated irradiation schemes are recommended in these setups.

Leibowitz concluded her talk by stating there is no good evidence to date, of any oncological benefit for treating the primary tumor in metastatic bladder cancer. Conversely, there is a palliative benefit in patients with symptoms. However, there is some evidence from mice models, on possible oncological harm. Currently, there is little evidence to support surgery as a primary palliative modality or as a means to improve outcome. Surgery may be considered in lymph node the only disease after reaching a response to chemotherapy. Finally, hypofractionated RT has an important role in preventing bladder local symptoms

References:
1. Seisen T et al. JCO 2016
2. Booth C. et al. JCO 2016
3. Abufaraj M. et al. Eur Urol 2018

Presented by: Raya Leibowitz-Amit, MD, Sheba Medical Center, Israel

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan  at the 2018 FOIU 4th Friends of Israel Urological Symposium, July 3-5. 2018, Tel-Aviv, Israel