Salvage surgery after energy ablation for renal masses

Salvage surgery after energy ablation for renal masses Jose A. Karam, Christopher G. Wood, Zachary R. Compton, Priya Rao*, Raghunandan Vikram, Kamran Ahrar and Surena F. Matin Departments of Urology, *Pathology, Diagnostic Radiology and Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Objectives To evaluate the feasibility, safety, pathological, radiological and functional outcomes of salvage surgery after previous renal mass ablation therapy. Patients and Methods After institutional review board approval, we reviewed our renal tumour database, and described the characteristics and outcomes of patients who experienced a local recurrence after energy ablation for renal masses and underwent salvage surgical therapy. Results A total of 14 patients fit the inclusion criteria. The median (interquartile range [IQR]) age was 65 (59 77) years, with a median (IQR) Charlson comorbidity index score of 2 (0.75 3.00). Three patients had a solitary kidney. Seven patients received their ablation therapies at an outside institution. Ten patients had undergone percutaneous radiofrequency ablation, three percutaneous cryoablation and one laparoscopic cryoablation. The median (IQR) R.E.N.A.L. nephrometry score at time of surgery was 7 (5 9), while the median (IQR) time from ablation to surgery was 26.5 (16.3 39.3) months. Of the 14 patients, 11 underwent partial nephrectomy and three underwent planned radical nephrectomy. The median (IQR) surgery time was 203 (177 265) min and the median length of stay was 5.5 days. There was one microscopic positive surgical margin. The median tumour size at final pathology was 3.1 cm. In all, 13 patients had renal cell carcinoma and one had no tumour present. Nine were pt1a, 1 pt1b, 2 pt3a, and 1 pt3b tumours. There were four Clavien grade III complications in four patients. The median preoperative estimated glomerular filtration rate (egfr) and the egfr at last follow-up were 66 and 66 ml/min/1.73 m 2.Therehadbeennodeathsbythe median (IQR) follow-up of 26.5 (10.5 49.5) months. Conclusions Patients who have undergone previous renal ablation therapy can be salvaged with partial or radical nephrectomy with good intermediate-term outcomes. These procedures may be associated with a high rate of adverse events. Longer follow-up is necessary. Keywords renal cell carcinoma, ablation, surgery, salvage Introduction In recent years, there has been an increase in the rate in the diagnosis of RCC [1], with a tendency towards both smaller tumour size and lower stage at diagnosis [2,3]. This can be partly attributed to increased use of abdominal imaging and detection of small renal masses [4]. Options for treating small renal masses include active surveillance, energy ablation using radiofrequency ablation (RFA) or cryoablation, or surgery using partial or radical nephrectomy [5 7]. Given that energy ablation is typically a percutaneous procedure, especially in the case of RFA, ablative techniques have seen an increase in popularity; they have a relatively low morbidity profile and favourable effectiveness, especially in older patients and in patients with multiple medical comorbidities [8]. As reviewed in the AUA guidelines [5] for treatment of small renal masses, the recurrence rate for energy ablation therapies may be less favourable compared with surgery, and recurrences may require additional therapies. Surgery is the most definitive treatment but is also potentially associated with more morbidity [9,10]. To date, to our knowledge, only two studies [9,10] have reported on the outcome of patients treated with surgery after energy ablation therapies for renal masses. We report our single-centre experience with surgical consolidation after ablation, and provide a detailed review of the pathological, surgical, radiological and functional outcomes. BJU Int 2015; 115: 74 80 wileyonlinelibrary.com BJU International 2014 BJU International doi:10.1111/bju.12743 Published by John Wiley & Sons Ltd. www.bjui.org

Salvage surgery after renal mass ablation Patients and Methods We reviewed the medical records of all patients who underwent renal surgery at the University of Texas MD Anderson Cancer Center between 2006 and 2013 after energy ablation for renal masses. Patients were treated with energy ablation therapies, either in our own institution or elsewhere, and referred after local recurrence for further management. The University of Texas MD Anderson Cancer Center Institutional Review Board approved this study. Surgery was performed if a growing renal mass at the site of ablation was noted, if enhancement was seen at the previous ablation site or if the ablated lesion failed to shrink. Biopsies were not routinely performed before surgical therapy. Patients were evaluated with abdominal CT or abdominal MRI, chest X-ray or chest CT, baseline serum chemistries and blood count. The modification of diet in renal disease equation was used to calculate the estimated GFR (egfr) [11]. Charlson s comorbidity index and the R.E.N.A.L. nephrometry score were calculated [12 14]. Postoperative complications were scored using the Clavien Dindo system [15]. Our electronic medical records were used to collect information, including baseline patient demographics, details from operative reports and discharge summaries, including intraoperative and postoperative complications. A dedicated genitourinary pathologist reviewed all pathology slides from renal surgery. Data are reported in a descriptive fashion using medians and interquartile ranges (IQRs). Results Our retrospective study population included 14 patients who underwent partial or radical nephrectomy for local recurrence after energy ablation for renal masses. The patients median (IQR) age at surgery was 65 (59 77) years and six patients were male. The median (IQR) Charlson comorbidity index score was 2 (0.75 3.00). Three patients had a solitary kidney and six had right-sided tumours. Of the 14 patients, 10 had previously undergone percutaneous RFA while three had undergone percutaneous cryoablation and one had undergone laparoscopic cryoablation. Seven patients had undergone biopsy before surgery with all of them having evidence of RCC of various histologies. The median (IQR) R.E.N.A.L. nephrometry score was 7 (5 9). Surgery was performed in two patients because of tumour progression with renal vein or inferior vena cava thrombus, in three patients because of failure of the tumour to shrink (with a positive preoperative biopsy) and in nine patients because of enhancement with contrast or tumour enlargement. Seven patients had percutaneous biopsy confirming recurrent disease, some of whom have been previously reported as part Table 1 Baseline patient demographics and preoperative characteristics. Number of patients 14 Median (IQR) age at surgery, years 65 (59 77) Gender (male/female), n 6/8 Median (IQR) BMI, kg/m 2 30.2 (23.8 35.1) Median (IQR)ASA score 3 (3 3.25) Median (IQR) CCI score 2 (0.75 3.00) Solitary kidney, n 3 Tumour side (right/left), n 6/8 Ablation type, n Percutaneous RFA 10 Percutaneous cryoablation 3 Laparoscopic cryoablation 1 Biopsy prior to surgery 7 Clear-cell RCC 4 Papillary RCC 1 RCC, NOS 1 MTSCC 1 Median (IQR) RENAL nephrometry score 7 (5 9) Median (IQR) time from ablation to surgery, months 26.5 (16.3 39.3) IQR, interquartile range; CCI, Charlson comorbidity index; ASA, American Society of Anesthesiologists; RFA, radiofrequency ablation; NOS, not otherwise specified; MTSCC, mucinous tubular and spindle cell carcinoma. of our RFA experience [8]. Patients underwent surgery at the median (IQR) time of 26.5 (16.3 39.3) months after the ablation was performed. The rest of the baseline demographic data are listed in Table 1. In all, 11 patients underwent planned partial nephrectomy: 10 open (including one with renal vein thrombectomy; Fig. 1) and one robot-assisted laparoscopic partial nephrectomy. Three patients underwent planned radical nephrectomy: two open and one laparoscopic-assisted with inferior vena cava thrombectomy. Of the three patients who underwent radical nephrectomy, one patient had already been on dialysis preoperatively with end-stage renal disease, one patient had an associated inferior vena cava thrombus (this patient was the subject of a previous report [16]), and one patient had a hilar recurrence with a multilobulated mass measuring 4 cm, with a R.E.N.A.L. nephrometry score of 9 and a preoperative egfr of 125 ml/min/1.73 m 2.All four patients who had previously undergone cryoablation underwent open partial nephrectomy. Surgical and pathological characteristics are listed in Table 2. The median (IQR) surgery duration was 203 (177 265) min and estimated blood loss was 275 (175 675) ml. Two patients required intra-operative transfusions. Intense desmoplastic reaction was noted in the operative report in 11 of 14 patients, seven of whom had undergone RFA (7/10 patients), and four of whom had undergone cryoablation (4/4 patients). One patient required resection of a portion of the psoas muscle during open partial nephrectomy and another patient needed en bloc partial diaphragm resection and primary closure as a result of extensive adherence of the ablated zone to the diaphragm. The median (IQR) ischaemia BJU International 2014 BJU International 75

Karam et al. Fig. 1 CT scans of a patient with failed cryoablation carried out elsewhere, who presented with an estimated GFR of 42 ml/min/1.73m 2 and a right renal mass with concomitant renal vein tumour thrombus. (A) Preoperative coronal view of the right renal mass. (B) Preoperative coronal view of the right renal mass and renal vein thrombus (white arrow). (C) Preoperative axial view of the right renal mass and renal vein thrombus (white arrow). (D) Postoperative coronal view of the right kidney with no evidence of recurrence 27 months after right open partial nephrectomy and renal vein thrombectomy. A B C D time for patients who underwent partial nephrectomy was 20 (16 25) min. In all, 13 patients had confirmed RCC on final pathology and one patient was found to be free of tumour. Pathological grade was 2 in seven patients and 3 in six patients. Pathological stage was pt1 in 10 patients, pt3a in two patients and pt3b in one patient. One patient with von Hippel-Lindau disease had a focally positive margin in a pt3a lesion with invasion to renal sinus fat. Representative images from a partial nephrectomy specimen after ablation are shown in Figs 2 and 3. Intra-operative and postoperative complications are listed in Table 3. Intra-operative complications included a pleurotomy in one patient that was primarily repaired. Postoperative complications were noted in nine of the 14 patients; six of those patients had previously undergone RFA (6/10 of the patients who had undergone RFA) and three had undergone cryoablation (3/4 patients who had undergone cryoablation). Transfusions were given more frequently after salvage treatment after cryoablation than after RFA (3/4 vs 2/10, respectively). Grade III complications included one 76 BJU International 2014 BJU International

Salvage surgery after renal mass ablation Table 2 Surgical and pathological characteristics. Salvage nephrectomy type, n Open partial 10 Robot-assisted partial 1 Open radical 2 Laparoscopic-assisted radical 1 Median (IQR) length of stay, days 5.5 (4.0 8.3) Median (IQR) size on pathology, cm 3.1 (2.5 3.9) Final histology, n Clear-cell RCC 12 Papillary RCC 1 No cancer 1 Final pathological Fuhrman grade, n 2 7 3 6 Final pathological stage*, n pt1a 9 pt1b 1 pt3a 2 pt3b 1 Focal positive margin, n 1 Median (IQR) surgery duration, min 203 (177 265) Median (IQR) estimated blood loss, ml 275 (175 675) Patients transfused intraoperatively, n 2 Median (IQR) ischaemia time, min 20 (16 25) Cold ischaemia, n 1 Fig. 2 Surgical specimen from partial nephrectomy after previous radiofrequency ablation showing central necrosis and grossly negative margins. *American Joint Committee on Cancer 2010. pseudoaneurysm that was selectively embolized, one pleural effusion that required temporary percutaneous drainage, one intolerance to oral intake that required a percutaneous endoscopic gastrostomy tube placement, and one urine leak that required readmission, temporary ureteric stent and percutaneous drain placement. Grade III complications occurred in three of the 10 patients who had undergone RFA and in one of the four who had undergone cryoablation. Renal functional outcomes are shown in Table 4. One patient had end-stage renal disease on haemodialysis before surgery and was not included in the end-stage renal disease calculations. The median (IQR) preoperative egfr was 66 (55 88) ml/min/1.73 m 2, the median (IQR) egfr at first follow-up was 59 (44 78) ml/min/1.73 m 2 andatlast follow-up was 66 (40 85) ml/min/1.73 m 2.Themedian (IQR) follow-up was 26.5 (10.5 49.5) months after salvage surgery. The patient with von Hippel-Lindau disease had a local recurrence that was being observed after last follow-up. The other 13 patients were free of disease at last follow-up. All 14 patients were alive at last follow-up. Discussion Our data show that surgical salvage of post-ablation recurrences can be performed effectively, including successful partial nephrectomy, in the majority of patients who had prior percutaneous ablation. Options for treating patients with a local recurrence after ablation include active surveillance, repeat energy ablation or surgical salvage therapy. The most commonly used option after failed ablation therapy is repeat ablation therapy but, in more recent years, surgical salvage has increasingly been performed [9,10]. To our knowledge, two surgical series have described the experience of renal surgery after ablation [9,10]. The first study, published in 2008, described renal surgery in 10 patients after ablation therapy, of whom four had previously undergone RFA and six cryoablation [9]. Seven patients (77%) underwent radical nephrectomy (including three open and four laparoscopic radical nephrectomies), two underwent partial nephrectomy and one had aborted surgery as per the patient s wish of not being anephric if the tumour was unresectable by partial nephrectomy. The authors did not note extensive scarring in the surgical field in their four patients who had previously undergone RFA, performed percutaneously. In addition, none of these four patients required a blood transfusion or had a complicated postoperative course. Conversely, all six patients treated previously with cryoablation, mostly laparoscopically, were noted to have extensive scarring at time of surgery. The BJU International 2014 BJU International 77

Karam et al. Fig. 3 Surgical specimen from partial nephrectomy after radiofrequency ablation showing RCC. (A) Low power. (B) High power. A B Table 3 Complications related to surgery. Total n Grade RFA n RFA % Grade Cryoablation n Cryoablation % Grade Intra-operative complications Pleurotomy 1 n/a 1 10 n/a 0 0 Postoperative complications Transfusion 5 2 2 20 2 3 75 2 Pseudoaneurysm 1 3a 1 10 3a 0 0 Pleural effusion 2 2,3a 1 10 3a 1 25 2 Pneumonia 1 2 1 10 2 0 0 Intolerance to oral intake (PEG tube placed) 1 3a 1 10 3a 0 0 Ileus 2 1 2 20 1 0 0 Pancreatitis 1 2 0 0 1 25 2 Hypertension 1 2 0 0 1 25 2 Urine leak 1 3b 0 0 1 25 3b Volume overload 1 2 1 10 2 0 0 RFA, radiofrequency ablation; PEG, percutaneous endoscopic gastrostomy. Table 4 Renal function outcomes. Median (IQR) preoperative creatinine, mg/dl 0.95 (0.77 1.21) Median (IQR) preoperative egfr, ml/min/1.73m 2 66 (55 88) Median (IQR) creatinine at first follow-up, mg/dl 1.00 (0.83 1.62) Median (IQR) egfr at first follow-up, ml/min/1.73m 2 59 (44 78) Median (IQR) creatinine at last follow-up, mg/dl 1.00 (0.83 1.36) Median (IQR) egfr at last follow-up, ml/min/1.73m 2 66 (40 85) egfr, estimated GFR. authors surmised in their study that this extensive tissue reaction, although partially resulting from laparoscopic mobilization, was more likely attributable to cryoablation per se, as such reaction had not normally been seen in their previous experience with salvage surgery after failed laparoscopic partial nephrectomy. In that study, all intra-operative and postoperative complications occurred in patients who had previously undergone cryoablation and included one renal artery injury, one diaphragmatic injury, one pleurotomy, one urine leak and one anephric patient. The second study published in 2009 reported on 16 partial nephrectomies (one laparoscopic and 15 open) in 13 patients with 18 previous RFAs (13 percutaneous and five laparoscopic) in the setting of bilateral multifocal disease [10]. All these patients underwent successful partial nephrectomy defined as tumour excision with grossly negative margins. A median of 7 tumours per surgery were removed, with a median operating time of almost 8 h and median estimated blood loss of 1500 ml. The authors noted difficulty in dissection around the ablated zone in 12 patients. Intra-operatively, one patient experienced a ureteric injury that was repaired by primary ureteroureterostomy. Postoperatively, three patients experienced a urine leak, one of which required ureteric stenting. In addition, one patient experienced rhabdomyolysis, one had refractory bleeding that required a re-exploration for bleeding control, one had deep vein thrombosis and one had atrial fibrillation. Interestingly, pathological evaluation revealed RCC in only seven of the 16 surgeries. The median egfr declined slightly from 78 BJU International 2014 BJU International

Salvage surgery after renal mass ablation 91 ml/min/1.73m 2 preoperatively to 81 ml/min/1.73m 2 postoperatively. We were able to carry out a partial nephrectomy in all 11 patients where such a procedure was planned, including the four patients with cryoablation. The three patients who underwent radical nephrectomy did so in a planned fashion. We experienced an intra-operative complication in one patient, and postoperative complications in nine patients (64%), with four complications being Clavien grade III. The patients eventually recovered from all these complications. None of the patients had a new-onset need for renal replacement therapy and all 13 patients who were not on dialysis before surgery maintained a stable egfr on intermediate-term follow-up. The only recurrence so far has occurred in a patient with von Hippel-Lindau disease, with no patients dying from their disease or from other causes during the study follow-up. In our experience, desmoplastic reaction was more frequent and was noted to be denser in patients treated with cryoablation. For this reason, we normally perform open partial nephrectomy in patients who have undergone cryoablation, while patients who have previously undergone RFA, particularly if performed percutaneously, can be potentially considered for minimally invasive partial nephrectomy, depending on the tumour location and amount of desmoplastic reaction predicted on preoperative imaging. We do not routinely perform preoperative percutaneous renal biopsies after ablation, but reserve them for those patients with clearly enlarging, enhancing masses or masses with lack of shrinkage >6 months after ablation, as previously described [8]. Our pathologists routinely assess microscopic surgical margins in patients treated with partial nephrectomy, which in the present study, led to the discovery of one focal microscopic positive margin (but grossly negative) in a patient with von Hippel-Lindau disease. This practice, however, is not routinely performed at other centre when dealing with patients with von Hippel-Lindau disease [10]. Patients treated with ablation need long-term diligent follow-up as they may be at higher risk of local recurrence than patients treated with surgery [17]. We performed surgery on two patients with renal vein and inferior vena cava tumour thrombus who could have potentially avoided such major surgery if more careful follow-up had been performed after ablation undergone elsewhere. When recurrences are detected early, it is usually still possible to perform repeat ablation or salvage partial nephrectomy in appropriate candidates. In addition, ablation should be very cautiously considered in patients with an inability to take i.v. contrast, as non-contrast imaging does not have good sensitivity to detect local recurrences after ablation. The present study was limited by the small number of patients, its single-institutional and retrospective nature and the lack of a control arm; however, finding a control arm for a study of this nature is neither likely nor feasible. In addition, patients were treated over a long period of time, which leads to inherent selection and practice biases. The renal function assessments need to be interpreted with care as patients included were treated with radical or partial nephrectomy without standardized protocol, and differential renal function was not measured. In conclusion, planned partial nephrectomy is feasible after energy ablation for small renal masses, particularly after percutaneous procedures, and radical nephrectomy should be reserved for patients otherwise not amenable to nephron-sparing surgery. These procedures may be associated with higher rates of adverse events, but renal salvage is not precluded as a result of previous ablation. Conflict of Interest None declared. References 1 Chow WH, Devesa SS, Warren JL, Fraumeni JF Jr. Rising incidence of renalcellcancerintheunitedstates.jama 1999; 281: 1628 31 2 Cooperberg MR, Mallin K, Ritchey J, Villalta JD, Carroll PR, Kane CJ. Decreasing size at diagnosis of stage 1 renal cell carcinoma: analysis from the National Cancer Data Base, 1993 to 2004. J Urol 2008; 179: 2131 5 3 Kane CJ, Mallin K, Ritchey J, Cooperberg MR, Carroll PR. Renal cell cancer stage migration: analysis of the National Cancer Data Base. Cancer 2008; 113: 78 83 4 Lightfoot N, Conlon M, Kreiger N et al. 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Karam et al. 15 Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240: 205 13 16 Hoang AN, Vaporcyian AA, Matin SF. Laparoscopy-assisted radical nephrectomy with inferior vena caval thrombectomy for level II to III tumor thrombus: a single-institution experience and review of the literature. J Endourol 2010; 24: 1005 12 17 Matin SF, Ahrar K, Cadeddu JA et al. Residual and recurrent disease following renal energy ablative therapy: a multi-institutional study. J Urol 2006; 176: 1973 7 Correspondence: Jose A. Karam, The University of Texas MD Anderson Cancer Center, Department of Urology, 1515 Holcombe Blvd, Unit 1373, Houston, TX 77030, USA. e-mail: JAKaram@mdanderson.org Abbreviations: RFA, radiofrequency ablation; IQR, interquartile range; egfr, estimated GFR. 80 BJU International 2014 BJU International