Locally recurrent kidney cancer is an uncommon but complicated problem. Due to the recognition of the importance of renal preservation and an increase in the use of nephron-sparing approaches via surgery or ablation, locally recurrent disease is being encountered with greater frequency. Treatments for locally recurrent kidney cancer include radical nephrectomy, repeat or salvage partial nephrectomy, de novo or repeat ablation, observation, or experimental systemic therapy. Each of these options has its own constellation of risks and benefits. When local recurrence is detected, the majority of renal units may be saved, but this often comes at the expense of higher perioperative complication rates, which rise with the number of previous interventions on the ipsilateral kidney. Extensive preoperative patient counseling is required to properly individualize therapy. Referral to a center of excellence should be considered before attempting repeat or salvage renal surgery.
KeywordsKidney cancer Recurrent kidney cancer Multifocal kidney cancer Partial nephrectomy Repeat renal surgery Salvage partial nephrectomy Ablation
Comparison of perioperative partial nephrectomy outcomes by procedure type
Herring et al. 
Johnson et al. 
Bratslavsky et al. 
Kowalczyk et al. 
Partial nephrectomy type
Partial nephrectomy, n
Median tumors removed (range)
Median EBL, mL (range)
Transfusion requirement (%)
Median units transfused (range)
Visceral or vascular injury (%)
Ureteral injury (%)
Pleural injury (%)
Prolonged urine leak (%)
Permanent hemodialysis (%)
Renal unit loss (%)
Cardiovascular events (%)
Outcomes of surgical interventions on a solitary kidney
Median blood loss, mL (range)
Operative time, h (range)
Overall complication rate, %
Urine leak, %
Permanent dialysis, %
Ghavamian et al. 
NSS in surgically naïve kidney
Early complication, 23.8; late complication, 27
Saranchuk et al. 
NSS in surgically naïve kidney
Fergany et al. 
NSS in surgically naïve kidney
Jacobsohn et al. 
RFA (including previously operated kidney)
Lane et al. 
LPN vs OPN in surgically naïve kidney
OPN, 169; LPN, 30
OPN, 300 (200–450); LPN, 200 (100–300)
OPN, 4.4 (3.8–5.1); LPN, 3.4 (2.9–4.5)
OPN, 24; LPN, 43
OPN, 4.7; LPN, 10
OPN, 0.6; LPN, 6.6
Liu et al. 
NSS on previously operated kidney
25 (all repeat NSS)
The incidence of locally recurrent renal cell carcinoma (RCC) will likely rise with the increased utilization of nephron-sparing procedures. Disease recurrence at the site of previous treatment, or elsewhere within the ipsilateral kidney, has been described after NSS and ablative therapy [22, 23, 24•]. In a recent meta-analysis examining 99 reported series from 87 institutions describing 6,471 renal tumors, Kunkle et al. [24•] found the local recurrence rate after primary therapy to be 2.6% for NSS, 4.6% for cryoablation, and 11.7% for radiofrequency ablation (RFA). The development of optimal strategies for the management of local recurrences is paramount, but the desire for maximal renal preservation must be balanced with the need for oncologic efficacy. Despite significant improvements in molecular therapeutics, present systemic therapies are limited in their ability to provide a complete and durable response for patients with metastatic disease [25•], which further underscores the importance of timely and effective management of a local recurrence.
Definition of Local Recurrence
It is often difficult to determine whether a local recurrence represents a failure of the surgical therapy, detection of a new “satellite” lesion that may have been present at the time of initial therapy and was simply missed due to limitations in pre- or intraoperative imaging, or development of a de novo tumor in the same kidney. Thus, it is not always clear if local recurrence after surgical therapy is the result of inadequate resection or the multifocal nature of RCC, which has been observed in as many as 25% of patients . Recognizing the presence of multifocality prior to an intervention, searching for syndromes associated with multifocal renal carcinoma, and understanding the multifocal nature of RCC in nonhereditary patients may allow treating physicians to tailor their treatment and recommended follow-up.
The National Cancer Institute (NCI) experience managing local recurrences comes from the ongoing evaluation and treatment of patients with hereditary forms of renal cancer, such as von Hippel-Lindau (VHL), hereditary papillary renal carcinoma (HPRC), and Birt-Hogg-Dubé (BHD). These patients tend to present at a younger age than the sporadic kidney cancer population and have a greater incidence of multifocal and bilateral tumors [27•], which makes these syndromes an informative model, especially when looking at local tumor recurrence and its management.
Management of Recurrence After Partial Nephrectomy
Planning a repeat partial nephrectomy (RPN) requires a careful balance between renal preservation and oncologic efficacy. Given the added operative challenges and potential postoperative morbidity, few reports are available to guide patients and practitioners alike [28, 29, 30]. A recent review of 51 planned RPNs in 47 patients with locally recurrent disease by Johnson et al.  constitutes the largest cohort reported in the literature to date and is illustrative of the complexity of subsequent surgery on the same renal unit (Table 1).
When performing reoperative surgery, a more challenging dissection is often encountered due to the alteration of normal tissue planes and perinephric scarring. Not surprisingly, in this study of 51 RPNs, there were 40 perioperative complications. Although the majority did not result in long-term sequelae, one patient suffered an intraoperative myocardial infarction and died postoperatively, and three patients had the loss of a renal unit. Urine leak, the most common postoperative complication, resolved in all patients. The overall major perioperative complication rate was 19.6%, which is higher than rates reported by Pasticier et al.  (12.6%) and Ray et al.  (11%) in their partial nephrectomy series of surgically naïve patients. Compared with results reported by Magera et al. , who evaluated perioperative outcomes of RPN, the complication rates were higher in Johnson’s series . This could potentially be explained by a larger number of tumors removed (median, 7; range, 1–55) in the NCI RPN series.
Although there was a statistically significant increase in postoperative serum creatinine (1.35 vs 1.16 mg/dL; P < 0.05) and a significant decrease in creatinine clearance (84.6 mL/min vs 95.3 mL/min; P = 0.05) and renogram split function (52.3% vs 54.8%; P < 0.05), only three patients (5.8%) in Johnson’s series  required renal replacement therapy. Because a third of all cases were performed on a solitary kidney, this number would certainly have been higher had completion nephrectomy been performed instead of RPN. Three patients developed metastatic disease, all were treated with aggressive metastasectomy without systemic therapy, and all were alive at the time of analysis at 28 months, 37 months, and 47 months without evidence of disease. Of greatest importance, 46 of 47 patients were alive at the time of analysis with median follow-up of 56 months. The more than 95% survival rate seen in this cohort after aggressive surgical intervention is significantly higher than the survival rates of patients who are on hemodialysis or have received a renal transplant .
To examine the outcomes and challenges of reoperative renal surgery further, Liu et al.  identified 25 VHL patients with solitary kidneys who underwent RPN. They recorded a median operative time of 8.5 h, median blood loss of 2,400 mL (although half of the procedures were completed without clamping the renal artery), and 54% of patients experienced major perioperative complications, including renovascular or caval injury. A statistically significant increase in serum creatinine and decline in glomerular filtration rate were seen, three patients lost their solitary renal unit, and 12% of patients required long-term hemodialysis. The outcomes of this highly complex series are compared with other published reports in Table 2. Of note, the majority of other series examined NSS in the surgically naïve kidney. Although associated with high perioperative morbidity, RPN in a solitary kidney is a feasible alternative that allows most patients to avoid the need for renal replacement therapy.
Lastly, Bratslavsky et al.  examined a small cohort of VHL patients who underwent salvage partial nephrectomy (SPN), which they defined as a third or fourth partial nephrectomy on the same renal unit (Table 1). Severe fibrosis, scarring, and obliteration of normal anatomical planes were encountered and greatly complicated those surgeries. Major perioperative complications occurred in 46% of cases and included bowel injury, vascular injury (renal vessels, vena cava, aorta), liver injury, rhabdomyolysis, and acute respiratory distress syndrome requiring reintubation. Despite these challenges, more than three fourths of the operated kidneys were saved, and postoperative changes in renal function (as measured by serum creatinine, creatinine clearance, and differential renal function) were minimal. SPN is a potential therapy for patients with continually recurrent, local kidney cancer, although its application outside the hereditary kidney cancer population and tertiary referral centers may be limited.
Management of Recurrence After Thermal Ablation
Cryoablation and RFA were first used in the treatment of small renal masses in the late 1990s, and both have been deployed via open, laparoscopic,and percutaneous techniques . Although ablative therapy offers less morbidity than even minimally invasive surgery, long-term outcomes data are lacking. Published series reporting intermediate-length results are difficult to compare with one another because of important differences in patient selection, tumor characteristics, treatment approach, follow-up design, and even the definition used to describe treatment success or failure [24•]. Despite these challenges, it appears that patients who undergo ablative therapies are more likely to experience tumor recurrence that those who undergo NSS . Many thermal ablation failures or recurrences can be salvaged with repeat ablation. However, when tumor location or size is not amenable to repeat treatment and NSS is required, the urologist and patient must be aware of the challenges awaiting them.
Nguyen et al. , reporting on the Cleveland Clinic experience with surgical salvage of RCC recurrence after thermal ablative therapy, found recurrence rates of 7.4% after cryoablation and 25% after RFA. The majority of these patients underwent repeat ablation, but those who failed a second ablation or were not candidates because of tumor size or location underwent attempted surgical excision. No patient in this series underwent laparoscopic partial nephrectomy, and open partial nephrectomy was successfully completed in two patients. Seven patients received total nephrectomy, and one procedure was aborted because of the patient’s strong desire to avoid renal replacement therapy.
The above series illustrates the difficulty of managing the postablation retroperitoneum . Although it is appropriate to counsel all patients about the potential for conversion from minimally invasive to open surgery and the possibility of renal unit loss during an intervention regardless of whether it is percutaneous, laparoscopic, or robot-assisted, postablation surgical salvage for disease recurrence is especially difficult. All patients should be informed of these potential scenarios prior to the initiation of any thermal ablation, and it underscores the need for the continued involvement of urologists in the evaluation and selection of patients for this type of therapy [1••].
Echoing these challenges, Kowalczyk et al.  described their experience performing a total of 16 partial nephrectomies on 13 patients following 18 previous RFA treatments (Table 1). Of these cases, 75% were complicated by extensive scarring at the site of previous ablation. Serious complications included intraoperative pleural injury, ureteral injury, postoperative urine leak, and hemorrhage requiring surgical re-exploration. Additionally, rhabdomyolysis, atrial fibrillation, and deep venous thrombosis were each seen in one patient. Despite these challenges, no renal units were lost and all patients avoided renal replacement therapy, although renal function (as measured by serum creatinine, creatinine clearance, and split function) declined postoperatively.
Although post-RFA NSS is feasible, the complexity and complications associated with postablative intervention warrant careful preoperative planning. Care must be taken to identify the lesion or lesions of interest and to understand their relationship to critical adjacent structures (eg, hilar vessels, bowel mesentery, ureter). Being facile with intraoperative ultrasound is a prerequisite for this type of surgery, and ensuring the availability of adequate supporting services, such as interventional radiology and a surgical intensive care unit, is advised. Additional consideration should be given prior to performing thermal ablation on a patient with multifocal renal lesions, as this subpopulation is at a higher risk to recur and outcomes data are far more limited than that for the treatment of a solitary renal mass.
Placing Nephron-sparing Surgery Complications in Context
When comparing primary versus repeat versus salvage versus postablation NSS outcomes, the rates of perioperative complications increase with the complexity and number of repeat interventions on the same renal unit  (Table 1). The risks associated with prolonged surgery, higher blood loss, and an increased incidence of postoperative complications must be weighed against the potential benefits of NSS. In some patients, their comorbidities or aversion to the possibility of renal replacement therapy may make observation the most reasonable alternative [1••]. Walther et al.  recommended active surveillance for small renal masses in VHL patients until the largest mass has reached 3 cm. No patients have developed metastatic disease using this strategy . Presently, this approach is employed at the NCI for the management of not only VHL, but also HPRC and BHD. Once the threshold for intervention is reached, NSS still remains advantageous over completion nephrectomy. Preoperative counseling and informed consent should reflect the complexity of the proposed intervention and help patients weigh the risks, benefits, and alternatives of each therapeutic option.
Areas of Future Research
Although the NCI experience of surgical management for locally recurrent kidney cancer is illustrative, its retrospective nature, unique patient population, and relatively small numbers make it difficult to extrapolate the lessons learned to many tertiary referral centers, let alone community practice. Additional research into all forms of kidney cancer therapy, including that for recurrent disease, is clearly needed, as increases in detection and treatment have failed to improve mortality rates . To start with, a uniform method of describing the complexity of renal masses will certainly enhance the quality of case series reporting on NSS and facilitate the performance of meta-analyses in order to improve patient counseling and treatment recommendations [42•].
Robotic surgery continues to be used in NSS, is being applied to increasingly complex renal masses, and will likely continue to grow in popularity given its advantages in performing fine dissection and complex renorrhaphy . Outcomes data must be given time to mature, but the guiding principle in NSS treatment selection should continue to be based on patient need and surgeon experience. The optimal therapeutic intervention should be determined for a specific patient and then performed in the manner most likely to succeed given the surgeon’s expertise and the hospital resources available, regardless of whether it is via an open, laparoscopic, robotic, or ablative approach. Preservation of a renal unit should be held as a paramount goal. Complex cases, including reoperative and postablative NSS, may benefit from referral to tertiary centers of excellence for a second opinion or definitive treatment.
Targeted systemic therapies for RCC have grown rapidly and play a crucial role in the management of locally advanced and metastatic disease [25•]. Several investigational studies (eg, National Clinical Trials NCT00184015, NCT00459875, NCT00566995) are examining the use of angiogenesis inhibitors to treat recurrent kidney cancer that is not amenable to surgical excision . Although these are only phase 2 trials, they offer the potential to spare select patients repeated surgery, prolong the time interval for repeat intervention, and allow some patients to avoid renal replacement therapy by preserving their renal remnants. Although targeted therapies are often well tolerated when compared with traditional systemic chemotherapy regimens or immunotherapy, they still pose unique side effects and risks, making a multidisciplinary approach that combines the expertise of urologic oncologists and medical oncologists preferred.
NSS should be considered the treatment of choice for localized kidney cancer whenever feasible. However, despite the advantages of preserved renal function, some patients will experience local disease recurrence. This seems more likely when ablative therapy has been used as the primary treatment. Preoperative identification of patients with multifocal RCC may help the treating physician to tailor the type of intervention and follow-up needed. Once detected, recurrence can be managed with observation, ablation, NSS, or total nephrectomy. The risks, benefits, and burdens of each of these modalities must be placed into context with the patient’s history, comorbidities, and treatment preferences.
The NCI experience of repeat, salvage, and post-RFA NSS has shown that the majority of renal units can be preserved, and that although there is a modest decline in postoperative renal function, renal replacement therapy can be avoided in the majority of patients. Although associated with longer surgery, greater blood loss, and a greater number of perioperative complications, surgical management of local recurrences allows for excellent oncologic outcomes and overall survival at intermediate follow-up. Active investigation into the use of systemic therapy is ongoing and offers great potential for appropriately selected patients. All practitioners should familiarize themselves with the clinical trials available at the local, regional, and national levels and make a concerted effort to refer patients to them so that the treatments available for locally recurrent kidney cancer may continue to evolve.
This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.
No potential conflicts of interest relevant to this article were reported.
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