Every year there are an estimated 338 000 new diagnoses of renal cell carcinoma (RCC) and over 140 000 deaths from it in North America, Europe, and Australia [1]. With this high incidence rate of newly diagnosed RCC and consequent descending stage migration, the use of nephron‐sparing surgery (NSS), whenever technically feasible, has significantly increased in comparison to radical nephrectomy during the last decade [2, 3].

A generally suggested indication for NSS is a small renal mass, usually 4 cm or less, located peripherally and easily amenable to resection [4]. However, emerging data suggest that NSS can be performed in patients with anatomically amenable tumors larger than 4 cm, provided that an adequate surgical margin can be safely obtained [5]. As for radical nephrectomy specimens, positive surgical margins (PSMs) are not common, with reported rates of up to 6% [6]. If encountered, the recommendation is to mark with ink the doubtful area of the specimen. If the margins are positive, their anatomic location and whether there is extension into adjacent structures should be described. If there is renal vein invasion, the status of the cut edge of the renal vein or the vena cava should be indicated as well. However, high‐powered, prospective, randomized studies to identify the predictors of PSMs after radical nephrectomies are still lacking.

Although oncologic outcomes have been demonstrated to be comparable between procedures (radical nephrectomy vs. NSS), a common concern is the violation of tumor during resection, leaving residual disease in the resection bed [7]. One of the fundamental rules of nephron‐sparing oncologic renal surgery is that the largest amount of healthy renal tissue possible should be preserved without compromising the oncological outcomes. Conventionally, concerns about local recurrence due to inadequate tumor excision and the risk of pseudocapsule invasion on the parenchymal side has led most surgeons to remove normal‐appearing parenchyma around the tumor. More recently, large series have reported the results of simple enucleation of renal masses versus traditional partial nephrectomies, showing functional and oncological results equivalent to standard partial nephrectomy [8–10].

It has been suggested that a tumor‐free margin in the pathologic specimen, regardless of its size, can be sufficient to achieve complete local excision after NSS [11]. However, in some cases, NSS can result in incomplete cancer removal and consequent PSMs. Although NSS has been suggested not to be associated with an increased risk of local recurrence or metastatic disease [12–16], a recent multi‐institutional study, which retrospectively evaluated 1240 patients undergoing NSS and analyzed the relationship between positive margins and risk of relapse, concluded that a PSM in NSS increases risk of disease recurrence, primarily in patients with adverse pathologic features (e.g. pT2–pT3a or Fuhrman grade III–IV) [17].

In a recent large prospective multi‐institutional study, Schiavina et al. aimed to evaluate predictors of PSM after NSS for renal cell carcinoma. Eight hundred consecutive patients were evaluated and 761 and 39 patients achieved negative and positive margins, respectively. Patients with PSMs were significantly older compared with those with negative margins. A higher incidence of PSMs was observed when NSS was performed for renal masses located in the upper pole. A lower rate of PSMs was found in patients treated with simple enucleation rather than standard partial nephrectomy. A greater incidence of PSMs was found in Fuhrman 3/4 tumors [18].

In another recent study, Khalifeh et al. [19] looked at 943 robotically assisted NSS cases. PSM cases showed statistically significant higher local recurrence and metastasis rates when compared to the negative margin counterparts.

During NSS, intraoperative frozen section of the nephrectomy bed is commonly performed to confirm the presence of a negative surgical margin [20]. In 2007 a multi‐institutional survey in the United States and Europe showed that intraoperative frozen sections in NSS were performed at 15 of 17 (88.2%) of the institutions and random biopsies of the tumor bed were routinely performed at 5 (29.4%). A more recent survey showed that 69% of urologists reported only sometimes obtaining a frozen section during NSS [21].

Despite being highly specific, the sensitivity of tumor bed frozen section in NSS in predicting the presence of a PSM in the resected tumor has been shown to be only 30% [22]. This low sensitivity is secondary to discrepancies between intraoperative frozen section pathology and final pathology and could be explained by numerous factors, including technical reasons, such as missing the remaining tumor during random biopsy, limited availability of special stains, freezing and drying artifacts, and/or pathologist error. Contributing to the controversy is the question whether a positive surgical margin is actually reflective of residual tumor in the patient. Some evidence suggests that even with a positive surgical margin, the remaining tumor burden can be destroyed by use of cautery on the resection bed [23].

Alternatives to intraoperative frozen section have also been developed and studied. Intraoperative imprint cytology examinations have been successfully used in other tumor entities to assess surgical margins. One of the main advantages of imprint cytology is its ability to assess the entire tumor surface rather than a specific area and it has been proven time‐ and cost‐effective [24]. A study by Palermo et al. analyzed 82 patients who underwent either open or minimally invasive NSS with imprint cytology and frozen section evaluation. The results were compared with permanent histology as the gold standard. They found that imprint cytology revealed a PSM in 10 tumors (12%). The sensitivity of the cytologic examination was 87.5%, positive predictive value (PPV) 70%, specificity 95.9%, and negative predictive value (NPV) 98.6% [24]. In another comparative study, imprint cytology showed a specificity of 98%, sensitivity of 100%, a PPV of 90%, and NPV of 100%, while frozen section showed a specificity of 99% and sensitivity of 98% in assessing surgical margins with a PPV of 95% and NPV 98%. They concluded that imprint cytology examinations exhibit equivalent diagnostic value compared with frozen section analysis, while being low‐cost and quicker [24, 25].

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