European Urology

1. Historical background

Radical nephrectomy (RN), which includes nephrectomy with the perinephric fat and ipsilateral adrenalectomy, had been considered the standard of care of renal tumors. The concept was challenged in the 1980 s by favorable results with partial nephrectomy (PN) in imperative situations [1]. Nephron-sparing surgery (NSS) is considered imperative when the contralateral kidney is anatomically or functionally absent or when there is overall impairment of renal function such that an RN will drive the patient immediately or in the short term to end-stage renal disease.

In the 1990 s, when the widespread use of routine body imaging led to a greater number of small renal masses being diagnosed, elective PN became the preferred treatment for such masses. It had been demonstrated extensively that PN provides excellent survival and recurrence rates comparable to those achieved with RN for tumors <4 cm. Follow-up for larger NSS series showed better survival for those patients undergoing PN for tumors ≤4 cm compared with those >4 cm. Consequently, 4 cm became the accepted cut-off for electively treating renal masses with NSS and the threshold for splitting stage 1 into T1a and T1b.

The concept of a cut-off for size has been challenged subsequently, following proof that the risk of dying from stage T1b cancer is increased for both RN and PN patients [2]. Mortality would be inherent to tumor histology rather than to the surgical approach, suggesting that the indication for NSS be expanded to renal masses 4–7 cm in size. Once it was proved that cancer-specific survival (CSS) in selected cases was not worse, several reports indicated that, due to better preservation of renal function, NSS resulted in improved overall survival (OS) when compared with RN [3], and [4].

NSS is recommended in the European Association of Urology (EAU) guidelines [5] for solitary renal tumors up to a diameter of 7 cm. This ambitious concept of treating most T1b tumors by NSS is challenged by real practice. It is of concern that use of PN has yet to become widespread, since available data show that most T1a disease is currently treated with RN [6]. Additionally, in selected cases, patients could be better treated with RN than PN.

2. Oncologic outcome

From an oncologic point of view, it is important to consider both the type of surgical indication and the tumor size. For T1a tumors with an elective indication, NSS provides recurrence-free and long-term CSS rates equivalent to those obtained after RN [7]. Although a higher rate of complications is expected, the advantages of preserving renal function overcome this inconvenience. Whether NSS should be performed open or laparoscopically is, in my opinion, a matter of the surgeon's skills. It has been proven that laparoscopic NSS, with slightly more minor complications than open surgery, provides equivalent oncologic outcome with better postoperative patient recovery due to its lower morbidity. However, the latter data come from centers with extensive experience; NSS is one of the most demanding procedures to perform laparoscopically. Adequate training of urologists in the procedure or referral of patients to appropriate centers is mandatory. Regardless, laparoscopic PN seems to be the appropriate technique because most tumor specimens can be retrieved through minimal enlargement of the trocar incision.

For T1b tumors, PN has demonstrated feasibility and oncologic safety in selected patients, especially those with an elective NSS indication. There are probably patients who should be excluded up front from an NSS procedure, including those with suspicion of locally advanced tumor growth (ie, patients in whom a preoperative biopsy can help identify undifferentiated tumor). A second indication for RN will be avoiding complications and ensuring good postoperative recovery, as in the case of a technically unfavorable tumor location for resection or, even more important, in patients with significant deterioration of their general status but otherwise with good renal function.

Finally, we should consider that NSS performed due to imperative indications has poorer outcomes in the rates of surgical complications and locally recurrent disease. This is especially true in T1b or more advanced tumors.

3. Renal function and survival

Chronic renal insufficiency is associated with significant cardiovascular morbidity and mortality. Huang et al [3] suggested that RN may affect long-term survival compared with PN for T1a tumors. More recently, this concept has been proven in a different cohort of patients [4], specifically in those who were <65 yr old, in whom OS was reduced for those receiving a RN compared to those undergoing PN. This fact would represent a strong argument to perform PN instead of RN when feasible. However, it has been proven already in living donor nephrectomy (LDN) patients that reducing the nephron mass by a half has no impact on triggering chronic renal insufficiency or reducing OS. The explanation for this apparent contradiction is that we are considering two different patient populations. LDN is performed on a selected, healthy, younger population (50% of the potential donors are discarded during the study for health reasons) that recovers an average of 50% of the lost renal function in the 6 mo following nephrectomy [8], whereas renal tumor patients are older and usually have more associated comorbidities. It is important to remember that the reduced OS applies to the study population only, namely renal tumor patients that undergo RN and not PN.

As already noted in the EAU guidelines [5], evidence shows that for small (T1a) tumors in patients with a normal contralateral kidney, renal function is better preserved with PN rather than with RN. Consequently, NSS results in improved OS, especially in patients aged <65.

4. Impact of warm ischemia time on renal function

It has already been established that long-term renal function depends on the duration of the intraoperative ischemia time [9]. In the present issue of European Urology, Thompson et al [10] prove and quantify the progressive impact of warm ischemia in short-term and, to some extent, long-term renal function. To achieve this goal, the authors analyze the larger series in the literature of a very unique population of tumors in a solitary kidney, pooling together the 18 yr of experience of the Mayo Clinic and the Cleveland Clinic. This population is extremely appropriate for evaluating renal function because there is no opposite kidney to compensate. However, this is an old population with already-impaired global renal function due to loss of the opposite kidney, among other reasons. Therefore, it is not clear whether these results could be extrapolated to patients with elective NSS surgery who have a healthy contralateral kidney.

As already mentioned, Thompson et al [10] demonstrated that progressive warm ischemia time (WIT) has an impact on the short-term renal function measured as the incidence of acute renal failure or an estimated glomerular filtration rate (GFR) <15 ml/min within 30 d after surgery. Long-term renal function was estimated after the acute postoperative period using the Kaplan-Meier method and was evaluated qualitatively using a cut-off of GFR <30 ml/min (stage IV chronic kidney disease). Seventeen percent of the patients developed stage IV chronic kidney disease. Notably, only 2% of the patients went into chronic dialysis. A quantitative analysis of the reduction of GFR, instead of using a cut-off (eg, <30 ml/min GFR), might be more appropriate to assess the impact of prolonged WIT on long-term renal function; ultimately, renal function is the factor that affects patient survival.

As expected, WIT was not the only prognostic factor for the impairment in the renal function. Other factors were tumor size, since these patients suffer a wider excision of renal tissue and the deleterious effect of extensive suturing the healthy parenchyma; the use of laparoscopy; and, of special relevance in my opinion, previous renal function.

The study [10] proves first that WIT has an impact on renal function and establishes a limit of 25 min that should not be exceeded to minimize the risk of postoperative dialysis or the development of long-term stage IV chronic kidney disease. This new cut-off challenges, by 5 min, the widely recommended limit of 30 min. Again, the reader should remember the special characteristics, particularly the overall impaired renal function, of the study population in which the 25-min cut-off has been developed. Second, and very important, is the progressive character of the warm ischemia lesion. Once the upper limit (25 min) has been established, it will be important to determine the lower limit at which there is no impact of ischemia time on renal function. Future studies including patients with no WIT will be necessary.

5. Conclusions

Patients with T1a asymptomatic tumors should be offered NSS. The underuse of the technique is no longer acceptable because oncologic outcomes and better OS support this NSS approach. Laparoscopic RN must not be substituted for PN.

Sufficient evidence supports PN in most tumors 4–7 cm. Patients with frail health but otherwise with good renal function and patients with tumors with difficult surgical excision locations might benefit more from a laparoscopic RN to favor a complication-free postoperative experience.

Finally, to preserve renal function as much as possible, the technique must be refined. The current trend is to perform more laparoscopic NSS. However, several reports in the literature [9] point to the importance of reducing WIT during surgery, which will affect long-term function and survival. Twenty-five minutes of warm ischemia is a very useful cut-off but should not be taken as dogma. A PN with a slightly longer WIT or use of parenchyma cooling is better for renal function than an RN.

Conflicts of interest

The author has nothing to disclose.