Real-world outcomes of patients with renal cell carcinoma, surgically treated at regional hospitals, based on a prospective long-term survey of the pre-robotic era

Since robotic partial nephrectomies (PN) became covered by Japanese insurance in 2016, the treatment of renal cancer has been increasingly performed in tertiary medical centers, such as university hospitals, in the United States and European countries. However, until recently, in Japan, surgery on several patients with renal cancer has been performed in regional hospitals with fewer than 500 beds. Owing to the centralization of surgery for renal cancer, the risk of surgical complications has been raised among patients treated in small and medium-sized hospitals [1]. In addition, it is economically challenging to introduce robotic surgical systems into these hospitals, and systemic treatment after recurrence has become complicated, making it difficult to manage renal cancer.

Although several studies have reported on the long-term prognosis of renal cancer surgery in Japan and overseas, most of them are retrospective investigations conducted in tertiary centers. Therefore, it is difficult to conclude that the long-term outcomes of renal cancer surgery reflect the real-world results obtained from various regional hospitals in our country.

In this study, data on renal cancer surgery cases were prospectively collected from 14 regional hospitals, including Tohoku University Hospital in the north-eastern region of Japan. The real-world outcomes and long-term prognoses obtained before robotic surgery were analyzed, especial for cT1 patients. We focused on cT1 patients who underwent radical nephrectomies (RN), recruited for this study, to examine their long-term renal function after undergoing bilateral renal loss. RN and partial nephrectomy (PN) comparisons were made by assessing postoperative renal function. The comparison in oncologic outcomes was considered less important in this study because of the large number of enrolled cT1a cases with a good prognosis and the small number of cT1b cases in which PN was performed. The extent of renal functional compensation (RFC) by the preserved kidneys after RN has not been adequately studied in this population. Hence, this study will provide baseline data for comparing the results of renal cancer surgery in the robotic era in Japan.

Several patients had undergone renal cancer surgery in regional hospitals just before robotic surgery became widely known in Japan. The oncological outcomes of this study were comparable to those of previous studies on renal cancer surgery [2]. Of the 14 registered hospitals, 11 had fewer than 10 renal cancer surgeries per year, but the survival rates of patients with cT1 to cT3 cases were not significantly different from those of the university hospital. This could be due to the fact that the urologists in the 14 registered hospitals exchanged posts and information, and the surgical techniques were standardized to a certain extent. Occasional meetings and exchanges of information during meetings may be good for urologists in regional hospitals. However, geographical factors were reported to cause poor prognoses [1]. Compared with academic hospitals, significant differences were observed in staging at diagnosis, and the mortality rate within 30 days after surgery was extremely high (odds ratio: 4.98) at low-volume facilities, like many regional hospitals [3]. In Australia, the pT stage of renal cancer patients living in rural areas tends to be higher, and the distance to a tertiary facility influences the outcomes [1].

In the real-world data of our study, RN was performed in 53.3% of cT1a patients at regional hospitals, which was significantly higher than that performed at the university hospital. For cT1a renal cancer, PN is recommended, and RN should be selected based on the American Urological Association guidelines [4]. RN is thought to worsen the prognosis due to the decline in postoperative renal function. However, our results indicated that patients with preoperative CKD stage 3 rarely developed end-stage renal failure (< 1%, data not shown) due to the decreased renal function caused by RN. Recent studies have reported long-term functional stability and favorable survival outcomes in patients with surgically induced CKD. PN does not contribute significantly to an improvement in prognosis, compared with RN [5]. Even the well-known randomized control study EORTC30904 showed no significant difference between RN and PN in terms of long-term survival benefit in patients with an eGFR of < 30 and an eGFR of < 15 [6]. More efforts should be made to reduce the complications during PN and RN procedures, whether open or endoscopic type, which increase the risk of perioperative death and cost [7].

In all cases in our study, the recurrence rate was significantly different between cT1a and cT1b patients, and v+ and G3 for cT1b were independent factors for recurrence. Based on the National Comprehensive Cancer Network guidelines, imaging studies and renal function tests should be performed in stage I patients (cT1 without high risks) within 3–12 months after surgery and then every year for at least three years. As can be seen from the KM curve, the 10-year RFS rates of patients with cT1a with v+ and cT1b with v+ were 73 and 64%, respectively. Therefore, a long-term follow-up of approximately 10 years is required for the early detection of cancer recurrence.

It was considered that RFC after RN should start early after surgery, and that renal function would eventually stabilize within a few months. We found, however, that RFC may occur late after surgery and continue slowly even in CKD stage 3 cases. As shown in Fig. 4, RN patients showed improved renal function over a long period. The RFC after RN was greater in patients with low preoperative eGFR and larger tumors [8]. Of course, some patients experienced inadequate compensation. In our study we found that HT and the magnitude of preoperative proteinuria indicated through urine quantitative testing were risk factors for poor RFC. Reportedly, female sex, BMI, HT, and eGFR could be factors influencing RFC early after RN. The factors contributing to the late occurrence of RFC include young age, BMI, and DM [9]. Although PN has less benefit for patients with non-pre-existing CKD [10], the management of postoperative comorbidities is important, regardless of the status of RN and PN (especially in patients with HT and proteinuria), contributing to survival benefits [11, 12]. Although AUA guidelines recommend PN for patients with cT1, the survival benefit of PN was not clear in our study, partly due to the small number of severe cases of DM and HT, and partly due to the inclusion of patients in good general condition. As shown in Fig. 4B, the decrease in eGFR seven years after surgery in PN patients might be due to the fact that many of those with good renal function were lost to follow-up.

This study has some limitations. First, many of the patients withdrew from the study. Second, the preoperative baseline data, urinary albumin measurements, and background data associated with certain comorbidities were insufficient. The difference in the backgrounds of cases from the regional hospitals and from the university hospital render accurate comparison difficult. Albuminuria is an important risk factor for the exacerbation of postoperative CKD [13]. The lack of baseline data is a further limitation of this study. Third, regional bias possibly exists. However, this study reflects the actual clinical practice of renal cancer surgery based on a long-term prospective investigation of the pre-robotic surgery era in Japan.

This prospective observational study of surgical cases in regional hospitals across north-eastern Japan indicated the long-term, real-world results of pre-robotic surgery for RCC. RN was performed in several cT1 patients in regional hospitals. This resulted in good prognoses, with the compensatory mechanisms maintained for a longer period to preserve renal function. These findings can be used as baseline data for determining the necessity for renal cancer surgery, which has been centralized in the robotic era.