Hangcheng Fu, Ruben Blachman-Braun, Lauren Loebach, Jeunice Owens-Walton, Braden Millan, Patrick Michael, Milan Patel, Cathy D Vocke, Christopher J Ricketts, Laura S Schmidt, Rabindra Gautam, Maria J Merino, Sandeep Gurram, W Marston Linehan, Mark W Ball
BACKGROUND AND OBJECTIVE: Bilateral or multifocal (BMF) papillary renal cell carcinoma (pRCC) arising without a confirmed pathogenic germline variant represents a clinically distinct entity with a poorly defined natural history. We aimed to establish clinical benchmarks for tumor growth kinetics, oncologic outcomes, and renal functional impact in this entity.
PATIENTS AND METHODS: We identified 89 patients with histopathologically confirmed clinically sporadic BMF pRCC from a prospectively maintained, institutional review board-approved database at the National Cancer Institute (1999-2025). Tumor growth rate was calculated with a linear mixed-effects model. Active surveillance was assessed in 105 tumors from 44 patients with ≥6 mo of serial cross-sectional imaging.
KEY FINDINGS AND LIMITATIONS: Over a median follow-up of 50 months, metastatic disease developed in six patients (6.7%), exclusively among patients whose largest tumor exceeded 3 cm at the time of assessment. A total of 156 renal procedures were performed, with partial nephrectomy predominating (81%). Variant pathology was identified in 18 of the 649 tumors (2.8%; 95% confidence interval 1.8%-4.3%). Among the 105 radiographically surveilled tumors, 64% demonstrated interval growth. The median tumor growth rate was 1.55 mm/yr (interquartile range 1.24-1.81). Repeat ipsilateral partial nephrectomy was associated with a significant decline in renal function (median estimated glomerular filtration rate 80.9-63.5 ml/min/1.73 m2; p = 0.002).
CONCLUSIONS AND CLINICAL IMPLICATIONS: Sporadic BMF pRCC demonstrates predominantly indolent growth and low metastatic potential, with no metastatic events observed in patients presenting with a largest tumor <3 cm. These findings provide growth-rate benchmarks consistent with active surveillance for small renal masses and nephron-sparing surgery when intervention is warranted.