Clinical T1 Micropapillary Bladder Cancer: Assessing Management and Outcomes

Micropapillary carcinoma (MPC) of the bladder is a rare variant of urothelial carcinoma that has an aggressive course and that presents at an advanced stage in most cases (Fig. 1). MPC is often associated with conventional urothelial carcinoma and is sometimes found with other rare variants.(1),(2)

MPC limited to the lamina propria (≤cT1) at initial and restaging transurethral resection of the bladder tumor (TURBT) presents a clinical dilemma.

It is unclear whether micropapillary non-muscle-invasive bladder cancer (NMIBC) can be safely managed following current guidelines for conventional NMIBC, or if patients with MPC should undergo early radical cystectomy.(3),(4)

Current studies are inconclusive, with some showing relatively poor response of MPC to intravesical therapy, external beam radiotherapy, and chemotherapy. Therefore, employing these modalities as initial treatment may potentially delay definitive surgical therapy. (3),(5),(6),(7)

Retrospective Review

To better delineate treatment options, we retrospectively reviewed the clinical experience and analyzed the outcomes of patients with restaged cT1 micropapillary NMIBC treated at Memorial Sloan Kettering with early radical cystectomy or initially conservative management.(8)

In the review, we included 36 patients treated at our institution between September 2000 and February 2012. Available pathology slides were reevaluated by our genitourinary pathologists to:

  • confirm the diagnosis;
  • assess the presence and semi-quantitatively estimate the percentage of the micropapillary component on initial or restaging TURBT specimens; and
  • determine tumor multifocality, associated carcinoma in situ, lymphovascular invasion, lymph node involvement, and surgical margin status.

Management options included early radical cystectomy or conservative management (intravesical bacillus Calmette-Guérin, surveillance, or deferred radical cystectomy) offered at the discretion of the treating physician according to disease features at restaging TURBT (residual tumor volume, multifocality, presence of carcinoma in situ, and lymphovascular invasion), surgical risk assessment, and patient preference.

All patients underwent restaging TURBT. Fifteen underwent early radical cystectomy and 21 were managed conservatively.

Findings

Cumulative incidence of cancer-specific mortality (Fig. 2, Table 1) at five years after restaging TURBT was 17 percent in the early radical cystectomy group and 25 percent in the conservative management group (absolute difference: 7 percent). The log rank test did not show evidence of difference between the groups in cumulative incidence of cancer-specific mortality (p = 0.8).

Risk assessment is critical for proper treatment assignment in patients with cT1 NIMBC, which is a heterogeneous disease with significant potential for metastasis and systemic involvement. Carefully selected patients with micropapillary features could be treated conservatively with TURBT and intravesical bacillus Calmette-Guérin.

 

Figure 1. Micropapillary bladder cancer. Small, slender, and tight papillary clusters in lacunar spaces are characteristic of micropapillary carcinoma. Enlarge Image Figure 1. Micropapillary bladder cancer. Small, slender, and tight papillary clusters in lacunar spaces are characteristic of micropapillary carcinoma.

 

Figure 2. Kaplan-Meier estimate of cumulative incidence of cancer-specific mortality for patients treated with early cystectomy (dashed line) and conservative treatment (solid line). Figure 2. Kaplan-Meier estimate of cumulative incidence of cancer-specific mortality for patients treated with early cystectomy (dashed line) and conservative treatment (solid line).

Table 1. Cumulative incidence of cancer-specific mortality and metastasis by treatment modality.

Years from Landmark
(3 months after restaging TURBT)
Treatment Modality  
Early Cystectomy Conservative Management
  Cancer-Specific Mortality, % Difference, % (95% Confidence Interval)
1 0 0 0
2 to 4 17 14 -4 (-32.1, 25)
5 17 25 7 (-26, 41)

Abbreviations: TURBT = transurethral resection of bladder tumor; CI = confidence interval