# Primary Versus Secondary Non-Urothelial Tumors Involving the Bladder: A 10-Year Analysis of Clinicopathologic Profiles and Adverse Feature Burden

## TL;DR

This study compares primary and secondary non-urothelial bladder tumors, finding that secondary tumors, especially from the prostate, are more aggressive and require tailored surgical approaches.

## Contribution

The study identifies origin-specific risk gradients in secondary bladder tumors and proposes a practical surgical strategy based on tumor origin and adverse features.

## Key findings

- Secondary bladder tumors showed significantly higher rates of adverse pathology compared to primary tumors.
- Prostate-origin secondary tumors had the highest burden of aggressive features like advanced pT and positive margins.
- Adverse feature count correlated strongly with advanced tumor stage (pT).

## Abstract

Non-urothelial tumors can involve the bladder either as primary cancers (squamous, adenocarcinoma, neuroendocrine, and sarcomatoid) or as “secondary” spread from nearby organs (colon, prostate, and cervix). In a 10-year single-center cohort of 235 patients, secondary involvement was much more likely to show aggressive pathology than primary non-urothelial tumors, including deeper local invasion, tumors in vessels or nerves, and lymph-node metastases. Among secondaries, prostate origin had the highest burden of adverse features, followed by colorectal and cervical sources. These patterns support a practical approach: confirm tumor origin with modern immunohistochemistry, map the extent of disease carefully before surgery, and tailor the operation to obtain negative margins—favoring organ-sparing when anatomically feasible and escalating when margin risk is high (e.g., suspected prostate-to-trigone spread).

Background and Objectives: Non-urothelial bladder tumors and secondary bladder involvement from extravesical primaries are uncommon but clinically challenging. We compared clinicopathologic patterns between primary non-urothelial tumors and secondaries, and explored correlates of adverse pathologic features to inform diagnostic triage and surgical planning. Methods: We performed a single-center retrospective cohort (2014–2024) of consecutive bladder lesions meeting WHO 2022 criteria and AJCC 8th staging. Eligible cases were primary non-urothelial malignancies (squamous cell carcinoma (SCC), adenocarcinoma (ADK), small-cell/neuroendocrine (NEC), sarcomatoid) or secondary bladder involvement (colorectal, prostate, cervix, ovary, uterus, breast). Outcomes included advanced pT (≥pT3), lympho–vascular invasion (LVI), perineural invasion (PNI), nodal metastasis, margin status, and composite adverse events. Results: Of 235 analyzable cases, 59 were primary and 176 were secondary. Age and sex distributions were similar. Secondaries had a higher adverse burden: advanced pT 56.8% vs. 23.7%, LVI 47.2% vs. 27.1%, PNI 40.3% vs. 22.0%, node-positive 11.9% vs. 0%, and any adverse 65.3% vs. 33.9% (all significant). Histology composition differed (p < 10−6): secondaries were ADK-dominant (59.1%), whereas primaries were enriched for SCC (38.5%), sarcomatoid (28.8%), and NEC (21.2%). Among secondaries, prostate origin showed the most ominous profile (advanced pT 97.5%, PNI 77.5%, positive margins 64.7%); colorectal cases combined high advanced pT (70.2%) with lower margin positivity (27.6%). Adverse-feature count correlated with pT (ρ = 0.586). Conclusions: Secondary bladder involvement carries substantially higher adverse-pathology rates than primary non-urothelial tumors, with origin-specific risk gradients (prostate > colorectal ≳ cervix). Rigorous origin adjudication and a margin-focused, anatomy-adapted surgical strategy may improve outcomes; prospective outcome-linked validation is warranted.