Study results underscore alarming aggressiveness of early stage micropapillary bladder cancer

Radical cystectomy (RC) outcomes in patients with cT1 micropapillary bladder cancer (MP) were similar or worse compared with patients with cT2 conventional urothelial carcinoma (UC), underscoring the aggressiveness of this rare bladder cancer variant.¹

The findings come from a study from Fox Chase Cancer Center shared during the 2021 AUA Annual meeting. Using data from the National Cancer Database, the investigators determined that the likelihood of having pathologically node positive disease (pN+) was higher in patients with cT1 MP (odds ratio [OR], 1.74; P = .009) and lower in patients with cT1 UC (OR 0.76; P <.001) at RC, compared to patients with cT2 UC. Overall, 39% of patients with cT1 MP had pN+ disease versus 11% of patients with cT1 UC and 19% of patients with cT2 UC.

Similarly, 31% of patients with cT1 MP experienced an advanced pathologic stage (pT3/4) at RC, whereas a significantly lower percentage of patients with cT1 and cT2 UC (18% and 27%, respectively) were upstaged.

“Micropapillary bladder cancer is a rare and often aggressive variant of bladder cancer, which poses a very difficult treatment dilemma when diagnosed in the non-muscle invasive stage because it often presents at an advanced stage. When it’s caught at an early stage, it’s very difficult to know what to do with it because it is such an aggressive variant,” lead author Kevin Ginsburg, MD, second-year fellow in the Urologic Oncology Fellowship Program at Fox Chase Cancer Center, Philadelphia, Pennsylvania, stated in a news release.²

To assess the association of clinical stage and histology with oncological outcomes, multivariable models and Cox proportional hazards models tested for upgrades to pT3/4 disease and pN+, and the Kaplan-Meier method estimated overall survival (OS) at RC. Models were adjusted for use of systemic therapy, radiation therapy, comorbidity score, age, year of diagnosis, race, urban/rurality index, education status, income, sex, transfer status, distance from treating facility, and facility type.

Patients from the National Cancer Database who underwent RC for cT1/cT2 UC or cT1 MP bladder cancer between 2004 and 2016 were examined in this study, excluding patients who previously received neoadjuvant RT, patients with missing information, and any clinical evidence or suspicion for nodal disease or metastasis. Overall 27,404 patients were identified: 112 (0.45%) with cT1 MP, 305 (1.1%) with cT2 MP, 6889 (25%) with cT1 UC, and 20,088 (73%) with cT2 UC.

“The point was to find out whether someone who’s being treated with a cystectomy with cT1 micropapillary cancer behaves like someone who has a cystectomy for cT1 urothelial carcinoma or whether they have outcomes more like someone who has cT2 urothelial cell carcinoma,” Ginsburg explained.

Results showed similar OS between patients with cT2 UC and cT1 MP (HR 0.74; P = .059), whereas patients with cT1 UC had improved OS versus patients with cT2 UC (HR. 0.70; P <.001).

“[This] suggests [cT1 MP disease] is a very aggressive variant despite the fact that it’s at an earlier stage,” said Ginsburg.

Other results found that after adjustment in the multivariable model, patients with cT1 MP and patients with cT2 UC experienced similar odds of upstaging to pT3/4 at RC (OR, 0.96; P = 0.830), while upstaging was less common in patients with cT1 UC versus patients with cT2 UC (OR, 0.60; P <.001).

Commenting on the primary outcomes of the study, Ginsburg concluded, “This is just another piece of information that physicians can use when discussing the aggressiveness of early stage micropapillary bladder cancer with their patients. Physicians can also use it to explain to patients that an aggressive treatment, such as bladder removal, may be necessary because cT1 micropapillary bladder cancer may behave like cT2 urothelial cell bladder cancer.”

References

1. Ginsburg K, Chandra A, Murray N, et al. Oncological Outcomes of cT1 Micropapillary Bladder Cancer Compared with cT2 Conventional Urothelial Carcinoma Treated with Radical Cystectomy. Paper presented at 2021 American Urological Association Annual Meeting; September 10-13, 2021; virtual. Abstract PD63-11.

2. Researchers Find Early Stage Micropapillary Bladder Cancer Outcomes Similar to Late-Stage Conventional Urothelial Carcinoma. September 13, 2021. Accessed September 14, 2021. https://bit.ly/3kzaYgg.