Urologic malignancies (UM) represent a major threat to long-term survival in renal transplant (RT) recipients, yet comprehensive analyses of their risk profiles and subtype-specific impacts remain limited. This study aimed to: 1) Identify risk factors for post-transplant UM (PTUM), including renal (RCa), prostate (PCa), and bladder cancers (BCa); 2) Compare their effects on patient/graft survival; 3) Inform personalized surveillance strategies.

Using OPTN/UNOS data (2000-2019; n=268,606 recipients), we conducted a retrospective cohort study. Recipients were stratified into PTUM groups (RCa:2,079; PCa:1,983; BCa:846) versus cancer-free controls (n=263,698). Multivariable logistic regression identified risk factors, while Kaplan-Meier analysis evaluated survival outcomes (RStudio v1.1.456). Statistical significance was defined as p<0.05.

Incidence: Cumulative PTUM incidence increased linearly post-transplant (RCa:7.74%, PCa:7.38%, BCa:3.15%).
Risk stratification:
         Common risks: Older age (aOR:1.03–1.07 per year), male sex (RCa/BCa: aOR=1.66–2.15), Black ethnicity (RCa/PCa: aOR=1.78–1.94 vs. White), calcineurin inhibitors (cyclosporine: aOR=1.36–1.87; tacrolimus: aOR=1.56–1.74).
         Protective factors: Hypertension-related ESRD (aOR=0.76–0.84), T-cell depletion therapy (aOR=0.82–0.88).
Survival:
         Patient survival: BCa demonstrated the worst 5-year survival (81.0% [78.4–83.7%]) vs. PCa (93.3% [92.2–94.4%]; P<0.001). RCa (87.2% [85.8–88.7%]) matched cancer-free controls (87.2% [87.0–87.3%]; P=1.00).
         Graft survival: BCa had the highest failure rate (54.7% partial failure; P<0.001 vs. PCa).
         Mortality: UM caused 41.5% (RCa), 23.5% (PCa), and 50.4% (BCa) of deaths.

The diverging outcomes highlight UM heterogeneity:
      PCa: Favorable prognosis likely reflects slower progression and effective screening.
      BCa: Poor survival correlates with delayed diagnosis (median onset:5.7 years) and therapeutic limitations (e.g., cisplatin avoidance).
      RCa: Comparable survival to controls suggests manageable tumor biology (e.g., low-grade RCC).
Unexpectedly, mTOR inhibitors (presumed anti-neoplastic) increased PCa/BCa risk (aOR=1.60–1.62), warranting mechanistic investigation. Ethnic disparities (Black:↑RCa/PCa; White:↑BCa) mirror general population trends but are amplified by immunosuppression.

PTUM outcomes are malignancy-specific, necessitating tailored approaches:
High-priority screening: BCa in older White males, RCa in Black recipients with prolonged calcineurin inhibitor use.
De-escalated surveillance: PCa given favorable prognosis; RCa if graft-preserving surgery is feasible.
Immunosuppression modulation: Consider T-cell-sparing regimens in high-risk profiles.
These findings challenge uniform PTUM management and advocate risk-adapted protocols to optimize transplant longevity.