Impact of Positive Surgical Margins on Overall Survival After Partial Nephrectomy, a Matched Comparison Based on the National Cancer Database

En-bloc resection with negative surgical margins (NSM) has been a key fundamental in the surgical treatment of almost all localized tumors. Positive surgical margins (PSM) is often considered equivalent to failure for oncologic clearance, and results in additional adjuvant treatments, more frequent clinical visits and more anxiety among patients. Interestingly, many studies on partial nephrectomy (PN) seem to suggest that cancer-specific and overall survivals (OS) are not affected by PSM. Concurrently, owing to the increasing use of high-definition imaging modalities, most renal cancers (RCC) are diagnosed as small renal masses (SRMs). Over time, the ‘gold standard’ treatment of SRMs shifted from radical nephrectomy to PN, which results in better OS. Various adjuncts, such as pre-operative 3-dimensional CT reconstruction, renal arterial mapping, intra-operative frozen sections, on-table ultrasound and florescence imaging, have been used to reduce PSM in PN. Having the largest matched samples in the published literature and working from a well-known national database, we showed that PSM do impact on OS after PN.

Among the 21243 patients with T1 or T2N0M0 RCC treated with PN, 1279 of them had PSM while 19489 had negative surgical margins (NSM). We performed propensity score matching to select 1265 PSM and 1265 NSM patients, perfectly matched for age, comorbidity index, tumor size, histology and grade, and highly similar in sex and race. Cox multiple regression showed that PSM patients had a hazard ratio of 1.35 for all-cause mortality, compared to NSM patients. Matched Kaplan-Meier analysis showed significantly better OS among NSM patients throughout follow-up.

Our subgroup analysis showed some interesting findings. First, the impact of PSM on OS was most significant among patients 70-year-old and above, highlighting the importance to maintain NSM when elderly patients are treated with PN. This challenges the common belief that such elderly patients may die with RCC rather than from RCC despite residual tumors. It is possible that a higher percentage of these patients underwent enucleation instead of formal PN, and enucleation techniques are known to confound surgical margin status in histological examination. Unfortunately, the National Cancer Database does not code ‘enucleation’ as a separate category so we could not evaluate this further. Second, PSM worsens OS regardless of tumor grade, so even residual cancer cells from low grade RCC should not be taken lightly. The slow growth rate of low grade tumors can be interpreted in both ways: these residual tumors grow slowly and patients live for years before clinically affected by them, allowing time for surveillance after PN; or the patients live long enough that these residual tumors eventually catch up with them. Knowing the cancer-specific survivals among these patients will help in differentiating them.

To conclude, we advocate the continuous effort to reduce PSM because it translates into actual survival benefits among patients.

Written by: Cheuk Fan Shum, MD and Chandru P Sundaram, MD

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