Updated Outcomes and Evolving Treatment Paradigms for Small Cell Carcinoma of the Bladder

Committee/Faculty

Presenting Author(s)

AS

Austin J. Sim, MD, JD

Department of Radiation Oncology
H. Lee Moffitt Cancer Center
Tampa, Florida, United States

Disclosure: ViewRay, Inc (Grant/Research Support) (Research Grant includes principal investigator, collaborator or consultant and pending grants as well as grants already received)

Co-Author(s)

JZ

Jingsong Zhang, MD, PhD

Department of Genitourinary Oncology
Moffitt Cancer Center
Tampa, Florida, United States

Disclosure: Disclosure information not submitted.
RJ

Rohit K. Jain, MD, MPH

Department of Genitourinary Oncology
Moffitt Cancer Center
Tampa, Florida, United States

Disclosure: Disclosure information not submitted.
SN

Shreyas Naidu

College of Arts and Sciences
University of South Florida
Tampa, Florida, United States

Disclosure: Disclosure information not submitted.
LZ

Logan W. Zemp, MD

Department of Genitourinary Oncology
Moffitt Cancer Center
Tampa, Florida, United States

Disclosure: Disclosure information not submitted.
AY

Alice Yu, MD

Department of Genitourinary Oncology
Moffitt Cancer Center
Tampa, Florida, United States

Disclosure: Disclosure information not submitted.
MC

Monica S. Chatwal, MD

Department of Genitourinary Oncology
Moffitt Cancer Center
Tampa, Florida, United States

Disclosure: Disclosure information not submitted.
WS

Wade J. Sexton, MD

Department of Genitourinary Oncology
Moffitt Cancer Center
Tampa, Florida, United States

Disclosure: Disclosure information not submitted.
PS

Philippe E. Spiess, MD

Department of Genitourinary Oncology
Moffitt Cancer Center
Tampa, Florida, United States

Disclosure: Disclosure information not submitted.
SG

Scott M. Gilbert, MD, MS

Department of Genitourinary Oncology
Moffitt Cancer Center
Tampa, Florida, United States

Disclosure: Disclosure information not submitted.
MP

Michael A. Poch, MD

Department of Genitourinary Oncology
Moffitt Cancer Center
Tampa, Florida, United States

Disclosure: Disclosure information not submitted.
JP

Julio Pow-Sang, MD

Department of Genitourinary Oncology
Moffitt Cancer Center
Tampa, Florida, United States

Disclosure: Disclosure information not submitted.
RL

Roger Li, MD

Department of Genitourinary Oncology
Moffitt Cancer Center
Tampa, Florida, United States

Disclosure: Disclosure information not submitted.
BM

Brandon J. Manley, MD

Department of Genitourinary Oncology
Moffitt Cancer Center
Tampa, Florida, United States

Disclosure: Disclosure information not submitted.
JT

Javier F. Torres-Roca, MD

Department of Radiation Oncology
Moffitt Cancer Center
Tampa, Florida, United States

Disclosure: Disclosure information not submitted.
PJ

Peter A. Johnstone, MD

Department of Radiation Oncology
Moffitt Cancer Center
Tampa, Florida, United States

Disclosure: Disclosure information not submitted.
KY

Kosj Yamoah, MD, PhD

Department of Radiation Oncology
Moffitt Cancer Center
Tampa, Florida, United States

Disclosure: Disclosure information not submitted.
GG

G. Daniel Grass, MD, PhD

Department of Radiation Oncology
Moffitt Cancer Center
Tampa, Florida, United States

Disclosure: Disclosure information not submitted.

Purpose: Small cell carcinoma of the bladder (SmCCB) is a rare histology with a poor prognosis and an unclear treatment paradigm. We aim to better define treatment paradigms and patient/tumor characteristics correlating with outcomes in patients with SmCCB and mixed urothelial/neuroendocrine carcinoma (NE).

Methodology: We retrospectively evaluated our single institution experience in patients with SmCCB/NE. Time to event analysis was performed with Kaplan-Meier estimates. Univariable (UVA), multivariable (MVA) analyses were performed to assess the impact of patient and tumor characteristics on outcomes.

Results: Between 2001-2021, 82 patients with SmCCB (70%, n=57)/NE (30%, n=25) were treated. Median age at diagnosis was 72.5 (range 47-85). 82% (n=67) were smokers with a median pack-year history of 27.5 (range 0.1-200). The proportions of clinical Stage I/II/III /IV patients at diagnosis were 6% (n=5)/60% (n=49)/24% (n=20) /10% (n=8); 19 patients were node positive (23%). A majority (74%) received neoadjuvant chemotherapy (NACT, median 4 cycles, range 1-12) and surgery (n=56, 68%; 51 radical cystectomy, 5 partial cystectomy, all with pelvic lymph node dissections), whereas 22% (n=18) underwent definitive radiation (XRT) (16 chemoradiation, 2 XRT alone) and 20% (n=16) underwent adjuvant chemotherapy (ACT). 73% (n=44) of NACT regimens consisted of a platinum/etoposide (P/E) doublet. Of the surgical patients, 25% (n=14) had any positive margin, 32% (n=18) had perineural invasion (PNI), 57% (n=32) had lymphovascular invasion (LVSI), and of the 21 patients with pN+ disease, 13 (62%) had extracapsular extension (ECE). Proportions of pathologic Stage 0/I/II/III/IV patients were 23% (n=13)/4% (n=2)/7% (n=4)/61% (n=34)/5% (n=3). Of the NACT+surgery patients (n=41), 32% had no invasive disease (ypT0/T0is). Of the 40 patients who experienced treatment failure, 25% were treated with salvage immunotherapy. With a median follow-up of 52 months (95% CI 47-56), the median locoregional control (LRC), progression free survival (PFS), and overall survival (OS) were NR, 16 months (95% CI 13-18), and 27 months (95% CI 9-44). On UVA, smokers (p=0.002), NACT (p=0.009), pathologic complete response (pCR; p=0.004), negative margins (p=0.014), and adjuvant chemotherapy (ACT; p=0.03) had improved LRC; smokers (p=0.042), pCR (p=0.004), and pathologic stage (p=0.006) had improved PFS; pCR (p=0.021), pathologic stage (p=0.002), no LVSI (p=0.004), ACT (p=0.02), and salvage immunotherapy (SIO, p=0.013) had improved OS. Gender, clinical stage, CT type, margins, PNI, and all other therapies (NACT, surgery, XRT) had no influence on OS. On MVA, ACT (p=0.006) and SIO (p=0.022) remained significantly associated with improved OS.

Conclusions: Even in a modern series of SmCCB/NE, prognoses remain poor. However, chemotherapy may improve survival by either inducing pCR or adjuvantly. Although prospective validation is needed, adverse surgical features, including LVSI should prompt consideration of adjuvant therapy. As with other small cell carcinomas, novel therapies, such as immunotherapy, may improve outcomes.

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