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Examining the association between biopsy and clinical staging in upper tract urothelial cancer
Brendan M. Browne, MD, Kristian D. Stensland, MD, David Canes, MD.
Lahey Hospital and Medical Center, Burlington, MA, USA.

BACKGROUND: Ureteroscopic biopsy of upper tract urothelial carcinoma (UTUC) continues to be debated with advocates using it for additional diagnostic information and detractors wishing to minimize instrumentation of upper tract tumors. Nevertheless, trends have shown increasing use of ureteroscopy and biopsy over the past thirty years. Of note, biopsy is limited by small instruments and confined working space and small studies have shown modest accuracy for predicting tumor pathology. Here we used the National Cancer Database (NCDB) to investigate whether concordance between clinical and pathologic tumor stage differs based on whether a biopsy has been performed. The NCDB captures 70% of all cancer diagnoses in the US and allows large-scale analysis of pathologic outcomes for this rare disease.
METHODS: Using the NCDB, we identified all patients diagnosed with urothelial carcinoma of the renal pelvis or ureter who underwent nephroureterectomy or segmental ureterectomy between 2004-2013. Patients were included if they had both clinical and pathological T stage data. Exclusion criteria included positive lymph nodes or metastatic disease, one or more procedures (e.g. laser ablation) prior to definitive surgery, or administration of neoadjuvant chemotherapy.
RESULTS: Between 2004-2013, 12,652 patients met the inclusion criteria of whom 6,221 underwent biopsy and 6,431 did not have biopsy. Clinical T staging corresponded with pathological staging in 75.9% of patients who had a biopsy compared with 82.8% of patients who did not (p=0.0001). Upstaging occurred in 21.8% of patients after biopsy and 14.4% of patients without biopsy (p=0.0001). Stratified by clinical stage, cTa/cTis tumors were upstaged in 22.3% of patients after biopsy and 11.1% without biopsy (p<0.001). Clinical T1 tumors were most likely to be upstaged, occurring in 30.7% of biopsied patients and 21.9% without biopsy (p<0.001). Downstaging at final pathology occurred in 2% of each group. Biopsy caused a delay from diagnosis to definitive treatment, with an interval of 44 days for biopsied patients compared with 18 days for patients who did not undergo biopsy (p<0.001). However, multivariate logistic regression showed that when controlling for delay, biopsy still conferred an odds ratio for upstaging of 1.3.
CONCLUSIONS:
Biopsy in UTUC typically provides only grade, not stage, information and should not impact stage concordance. However, upstaging on final pathology occurs more frequently in patients for whom ureteroscopic biopsy has been performed. This is not fully explained simply by treatment delay, as controlling for delay does not diminish the effect of biopsy. This finding warrants exploration. Selection bias may exist, whereby biopsy may be done more often for patients in whom clinical staging by visual examination or axial imaging is less certain.


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