113Investigational Technologies in the Surgical Management of Renal Cell Carcinoma
HIGH INTENSITY FOCUSED ULTRASOUND
Just as there have been a multitude of advances in immunotherapy and targeted therapy for advanced renal cell carcinoma (RCC), new developments exist in the treatment of localized disease. Cryoablation and radiofrequency ablation (RFA) are well-established therapies for the treatment of small tumors less than 4 cm in patients who are considered poor surgical candidates (1). High-intensity focused ultrasound (HIFU) is another thermo-ablative technique for extracorporeal ablation of small renal masses. High-intensity ultrasound waves increase tissue temperatures to greater than 65°C and damage targeted tissue by thermal and acoustic cavitation (2). Compared to cryoablation and RFA, extracorporeal HIFU is entirely noninvasive, and the purely externally focused ablation eliminates the risk of tumor spillage or hemorrhage due to needle placement. Additionally, heat generation is extremely rapid; hence, potential heat sinks such as large blood vessels have less of an impact compared to slower ablative techniques.
The oncological efficacy of HIFU is not fully determined. In the first phase 2 study of 18 tumors treated with HIFU and evaluated by subsequent nephrectomy, areas of coagulative necrosis comprised only 15% to 35% of the targeted tumor, indicating incomplete ablation (3). Illing et al treated eight renal tumors with another HIFU device (HAIFU). Four of six kidneys had radiographic evidence of successful ablation 12 days after the procedure, but histologic examination of four kidneys showed clear thermal damage in only one of the six kidneys (4).
114The largest long-term study of HIFU involved a 3-year follow up of 17 patients treated with HIFU for renal masses with a mean size of 2.5 cm. There were no major complications related to HIFU and stable lesions were achieved in two-thirds of the patients (5). The difficulty in administering HIFU remains in energy attenuation by intervening tissue. While a laparoscopic approach is feasible, it detracts from the noninvasive advantage intrinsic to the extracorporeal approach. While limited data suggests HIFU to be inferior to existing ablative techniques, further studies are needed to determine patients that may benefit from this technology. Other minimally invasive technologies such as microwave thermotherapy and laser interstitial thermal therapy exist, but further long-term studies are needed to ascertain their role in the treatment of localized RCC.
NEAR-INFRARED FLUORESCENCE IMAGING
Near-infrared fluorescence (NIRF) imaging using intraoperative administration of indocyanine green (ICG) is another technology with emerging applications in urologic surgery. Due to preferential transport of ICG into proximal renal tubule cells, NIRF using intravenously injected ICG displays differential fluorescence in normal renal parenchyma compared to tumors and cysts. Theoretically, this imaging adjunct may assist in nephron-sparing surgery (NSS) where the desire is to preserve healthy tissue. The angiographic properties of ICG may also aid in the identification of renal vasculature and facilitate selective arterial clamping (6).
The two largest studies investigating the use of NIRF to aid in tumor localization have yielded inconsistent results. Manny et al described the ICG fluorescence pattern in 100 robot-assisted partial nephrectomies at a single institution (7). Hypofluoresence had both a high sensitivity and positive predictive value in determining malignant versus benign lesions. The authors concluded that ICG fluorescence patterns are associated with some histologic findings but are unable to reliably predict benign versus malignant lesions.
115A standardized ICG dosing regimen was developed by Angel et al and achieved differential fluorescence in 82% of 79 tumors. Overall, 65 of 79 tumors behaved appropriately for an 86% agreement between histology and infrared fluorescence behavior (8). The greatest utility of NIRF may be in its ability to facilitate selective arterial clamping and aid in rapid identification of local perfusion deficits. Several recent studies have shown the decrease in global ischemia with selective arterial clamping using NIRF to minimize resultant loss of renal function (9–11).