Purpose: To evaluate the clinical management and outcomes of renal cell carcinoma recurrence at a single academic institution.

Materials and Methods: A prospectively maintained, Institutional Review Board-approved database of patients treated for renal cell carcinoma (n=781) was reviewed to identify patients with confirmed local or metastatic recurrence between 2013-2023.

Results: A total of 12 patients were identified with renal cell carcinoma recurrence. Initial management of renal cell carcinoma was partial nephrectomy (50%), radical nephrectomy (41.7%), and percutaneous ablation (8.3%). Median follow up was 37.4 (5 – 143) months. Median time to recurrence was shortest amongst patients initially treated by radical nephrectomy (6.0 months). Five patients recurred with distant, multiple metastases and were referred to medical oncology without surgical reintervention. A single patient recurred with localized, well-defined nodal metastasis which was successfully managed by robotic retroperitoneal lymph node dissection. Five patients underwent repeat robotic partial nephrectomy or completion nephrectomy. All cases were technically successful without major complications. Average length of hospitalization was one day. Median creatinine preoperatively was 1.21 mg/dl (0.75-1.79), and post-reintervention the median creatinine was 1.42 mg/dl (1-2.7).

Conclusions: An algorithm for management of local recurrence includes review of initial pathology report, increased frequency of imaging in the context of positive margin, diligent compliance with surveillance, percutaneous biopsy to confirm histological evidence of recurrence and counseling patient as to risks of chronic renal failure, conversion to completion radical nephrectomy, and a multidisciplinary approach with medical oncology.

• Renal cell carcinoma

• Local or metastatic recurrence

• Clinical management

• Outcomes

• Algorithm for local recurrence

Deal C, Morrill CC, Suppanuntaroek S, Garcia K, Paster I, et al. (2024) Recurrence Following Primary Treatment of Localized Renal Cell Carcinoma: Management and Outcomes. J Urol Res 11(3): 1157.

RCC: Renal Cell Carcinoma; RAPN: Robotic-Assisted Partial Nephrectomy; IRB: Institutional Review Board; pNx: Partial nephrectomy; BMI: Body mass index; eGFR: Estimated Glomerular Filtration Rate; CKD: Chronic Kidney Disease; VHL: Von Hippel-Lindau syndrome

Accounting for up to 3% of all adult neoplasms, Renal Cell Carcinoma (RCC) is among the most lethal urologic cancers with an unsettling rising incidence in the United States [1]. For localized and locally advanced RCC, surgical resection represents the mainstay management option with demonstrated 5-year survival of 70 – 90% [2]. Nephron-sparing surgery, including robotic-assisted partial nephrectomy (RAPN), is an established standard of care for localized renal cell carcinoma, and has expanded indications from T1a to T1b with favorable anatomy.

Local RCC recurrence following primary partial or radical nephrectomy is a rare event and challenging management dilemma. Localized recurrence may present as new soft tissue masses in the ipsilateral renal fossa, adrenal gland, or retroperitoneal lymph nodes and occurs in up to 3% of radical nephrectomies [3-5]. Reoccurrence for partial nephrectomies is more variable and has been reported in up to 17% of cases [6]. The role of repeat RAPN in the setting of local recurrence of renal cancer is a challenging management dilemma and represents a more complicated surgical issue due to potential adhesions with a previously dissected renal artery and vein. While technically feasible, data regarding outcomes of RAPN in this setting are limited with conflicting results [7].

In this study, we evaluate the clinical management and outcomes of renal cell carcinoma recurrence in patients following primary surgical resection of localized RCC at a single academic institution.

A prospectively maintained, University of Arizona IRBapproved (IRB00000291), institutional database of patients treated for renal cell carcinoma (n=781) was reviewed to identify patients with local or metastatic recurrence between 2013-2023. A recurrent renal mass was defined as a new contrast enhancing mass in the ipsilateral renal fossa, or ipsilateral kidney (context of partial nephrectomy-pNx), adrenal gland, or retroperitoneal lymph nodes. All patients had a history of thermal ablation, partial nephrectomy, or radical nephrectomy.

Baseline patient characteristics including age, gender, race, body mass index (BMI), and baseline estimated glomerular filtration rate (eGFR) were collected. Oncologic history factors including method of previous treatment, nephrometry score, history of high-grade disease, positive surgical margins, or aggressive histology were obtained. Time to recurrence, tumor size, and method of surgical management were evaluated for all patients. For patients undergoing repeat robotic partial nephrectomy, perioperative variables including warm ischemia time, transfusion rate, hospital length of stay, and complication rates were reviewed. Functional outcomes include renal function preservation which was evaluated by eGFR immediately post operative and at or beyond 3 months post operatively.

Patient Characteristics

A cohort consisting of 12 patients with a combination of previous thermal ablation (8.3%), partial nephrectomy (50%), and radical nephrectomy (42%) were identified from our single institutional RCC database. The patient cohort was predominantly male (92%), Caucasian (50%), and ranging in age from 45.4 to 81.2 years at time of RCC diagnosis [Table 1].

Table 1: Patient Cohort Demographics, Oncologic Characteristics, Recurrence, and Functional Outcomes

Abbreviations: BMI: Body Mass Index; eGFR: estimated Glomerular Filtration Rate; ISUP Grade: International Society of Urological Pathology Grade; SCreat: Creatinine

Average BMI was 26.5 with 33% cohort obese (>30). Baseline chronic kidney disease (CKD) was observed in 8.3% (1/12) of cohort. Median nephrometry scores for RAPN (n=6) was 8.25 with one hilar mass. Clear cell RCC was the predominant histology with 64% highgrade; one patient’s histology exhibited sarcomatoid features and another patient with papillary type 1 histology. Overall positive margin rate for robotic Partial nephrectomy was 6.6%.

Recurrence

Patient cohort were followed for a median of 37.4 months (5 – 143 months). Median time to recurrence was 8.4 months with shortest time to recurrence amongst those initially treated with radical nephrectomy (6 months), advanced staging (6.1 months), high-grade histology (8.2 months), and positive margins (9.7 months). Five patients developed multiple, distant metastases and were referred to medical oncology without surgical reintervention [Table 2].

Table 2: Recurrent RCC Patient Cohort Oncologic Characteristics

A single patient recurred with localized, well defined nodal metastasis which was successfully managed by robotic retroperitoneal lymph node dissection. Five patients were managed with repeat robotic partial nephrectomy or completion nephrectomy. All cases were technically successful without major complications or post operative blood transfusion. Transperitoneal access was obtained for all robotic, laparoscopic cases.

No Clavien complications ≥3 were observed. Total complication rate was 17% (1/12). Average length of hospitalization following re-operation was 1 day (1-6 days). Median serum creatinine preoperatively was 1.21 mg/dl (0.75- 1.79). Three months or greater post reintervention median creatinine was 1.42 mg/dl (1-2.7).

Several surgical options are available for management of localized and locally advanced renal cell carcinoma and can be tailored based on patient characteristics, comorbidities, clinical staging, and patient preference. Risk of recurrence following primary surgical resection is a consideration to be made when evaluating management strategies as initial therapies may limit access to and further complicate future surgical interventions. Reported incidence rates of local RCC recurrence range widely between 0 – 17% [4, 6, 8]. In this study, we report the clinical recurrence of RCC in 12 patients following surgical resection or ablation of localized RCC. Though this study represents a small cohort, it is comparable to published literature on this relatively rare surgical problem [7].

In many cases of recurrence, there is debate of actual recurrence of previously resected tumor vs de novo mass and/or multifocal disease process [6]. Notably, our study had a median follow up period of 37.4 months with median time to recurrence at 8.4 months (range: 3.5 to 123.2 months). With increased postoperative follow up, we anticipate higher risks of de novo masses. In a study by Shuch and colleagues, median time to redo RAPN for recurrent renal masses was 23.2 months in cohort of predominately cT1a masses (59.2%) [6]. In studies reviewing retroperitoneal recurrence following nephrectomy, median time to retroperitoneal mass diagnosis ranged from 19 to 25 months [3,4]. A single patient in our cohort recurred in a similar matter at 5.5 months following nephrectomy.

Repeat surgical intervention for local recurrence must be evaluated on a case-by-case basis. For patients with prior partial nephrectomy and/or ablative therapies, a completion nephrectomy +/- retroperitoneal lymph node dissection offers the most oncologic benefit at the cost of surgical morbidity and loss of renal function. Nephron-sparing surgery via either ablative techniques or repeat partial nephrectomy seek to minimize renal loss while achieving optimal oncologic control. Ablative therapy is a minimally invasive technique that may be used in poor surgical candidates and may repeat ablative therapies as needed. Partial nephrectomy offers the benefit of oncologic control if negative margins are achieved while preserving renal function.

Redo partial nephrectomy is not without its challenges including increased surgical complexity due to presence of adhesions, redissection of renal hilum, and a higher potential complication rate. While select studies have demonstrated ability to safely repeat robotic partial nephrectomy for local recurrence of RCC, several individual patient factors should be considered [5-12]. Recent data suggests up to 80% of initial renal function could be preserved in cases of successful re-operative renal surgery [6]. In a study by Bratslavsky et al., re-operative partial nephrectomy in patients with Von Hippel-Lindau syndrome (VHL) were able to undergo at least 3 partial nephrectomies on the same renal unit prior to progression to salvage nephrectomy [13].

Repeat surgical intervention following ablative, partial or complete nephrectomy increased the anticipated risk of major surgical complications. The literature suggests the rate of major complications in patients undergoing open repeat partial nephrectomy may be as high as 1 in 5 patients [10]. In a study of redo robotic partial nephrectomies in a VHL patient cohort, a major complication rate of 46% and 50% loss of renal units in those with more than 3 partial nephrectomy operations [13]. The implementation of robotic surgery in repeat partial nephrectomy is associated with decreased morbidity with major complications in up to 12% of patient cohorts [9,12].

Technical points include meticulous lysis of adhesions, dissection of previously dissected hilum may prove challenging, Gerota’s fascia may result in adherence of the kidney to the abdominal wall, and subcapsular dissection should be avoided to optimize reconstruction.

Algorithm for local recurrence

Given the findings of this study and review of relevant literature, we offer a limited decision tree for clinical management of recurrence in patients primarily treated for localized RCC (Figure 1).

Figure 1: This figure is a limited decision tree for clinical management of recurrence in patients primarily treated for localized RCC

Higher suspicion of local recurrence or disease progression should be held for patients with pT3 or higher staging, high grade histology, sarcomatoid pathology, or positive tumor margins. We strongly recommend biopsy confirmation of suspected local recurrence, nodal disease, or distant metastases prior to planned surgical or systemic intervention. Biopsy confirmed distant metastasis should immediately be referred to medical oncology for evaluation of systemic therapy.

Management of recurrent nodal disease should first be evaluated by number and locality of disease. If nodal disease is well defined and localized to the soft tissues of the retroperitoneum and/or adrenal gland, repeat surgical intervention may be considered in conjunction with medical oncology evaluation.

A singular mass (< 3cm) isolated to the prior surgical resection bed, renal parenchyma, or renal fossa should be strongly considered for surgical intervention via nephron sparing approaches. Exception to this approach includes patients with a history of Von Hippel-Lindau syndrome in which active surveillance is preferable until renal mass increases in size or multiple masses develop [14]. Patients with baseline chronic kidney disease, solitary kidneys, or high risk of new onset CKD must carefully weigh the risks and benefits of oncologic control vs preservation of renal function. Additionally, surgeon experience should be weighed when considering redo-robotic partial nephrectomy in patients with, or at high-risk for, CKD.

The findings of this study are subject to limitations that should be addressed. While our institutional database is prospectively maintained, many datapoints required retrospective review of patient charts and are limited in their ability to draw associations or perform relevant statistical analysis. Further, data availability within our database is limited prior to 2013 and incorporation of electronic medical records. Chronic kidney disease and renal function was approximated through use of serum creatinine which is limited in approximating acute renal changes such as those observed immediately post operatively. Renal scans and/ or urine studies were unavailable for our cohort.

An algorithm for management of local recurrence includes review of initial pathology report, increased frequency of imaging following in the setting of positive margin, diligent compliance with surveillance, percutaneous biopsy to confirm histological evidence of recurrence and counseling patient as to risks of chronic renal failure, conversion to completion radical nephrectomy, and a multidisciplinary approach with medical oncology.

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