Impact of double J stenting or nephrostomy placement during transurethral resection of bladder tumour on the incidence of metachronous upper urinary tract urothelial cancer

The majority of urothelial cancers (UC) are located in the bladder (> 90%), while < 10% are upper urinary tract urothelial cancers (UUTUC) [1]. In 17% of UUTUC patients synchronous bladder cancer (BCa) can also be found [1, 2]. UC recurs in the bladder during follow-up in up to 50% of all UUTUC patients, i.e., as BCa [1, 3]. By contrast, only 1.8% of patients with non-muscle invasive BCa (NMIBC) show synchronous UUTUC [4], and post-cystectomy upper urinary tract recurrences occur in < 10% of BCa patients [5‐10]. Risk factors for post-cystectomy UUTUC development include history of carcinoma in situ (CIS) or recurrent BCa, cystectomy for NMIBC, and tumour involvement of the distal ureter or prostatic urethra [7, 8, 10]. In addition, risk factors for metachronous UUTUC following BCa diagnosis include high grade BCa and tumour localisation at the trigone/ureteral orifice [11, 12].

At time of initial diagnosis, 7.5 and 2.1% of all NMIBC patients present with unilateral and bilateral hydronephrosis, respectively. Among radical cystectomy patients unilateral and bilateral hydronephrosis is present in 19 and 4%, respectively [9]. Hydronephrosis is known to be associated with advanced BCa, unfavourable survival, as well as recurrence and progression [13‐15]. While a nephrostomy tube is placed only in cases of hydronephrosis for drainage, a DJ stent can be placed under the same scenario, but also to protect the ureteral orifice during transurethral resection of a bladder tumour (TURBT), preventing vesicoureteral obstruction.

Kiss et al. retrospectively analysed radical cystectomy patients and indicated a higher risk for metachronous UUTUC in patients who underwent DJ stenting prior to radical cystectomy, compared to a nephrostomy tube or no urinary drainage of the upper urinary tract. Consequently, the authors recommended nephrostomies as preoperative drainage [9].

There are two main hypotheses for an increased UUTUC rate subsequent to DJ stenting during TURBT, enabling tumour cell seeding in the upper urinary tract: (I) a reflux volume between bladder and upper urinary tract, and (II) retrograde manipulation during DJ placement [9]. This study evaluated the impact of placement of a DJ stent compared to a nephrostomy tube during TURBT for BCa on the incidence of metachronous UUTUC.

There is a debate as to whether DJ stenting during TURBT harms patients with regard to possible metachronous UUTUC development. Why is this? On the one hand, there is the aforementioned assumption of UUTUC caused by DJ implementation via retrograde tumour cell seeding. On the other hand, not every UUTUC results in synchronous or metachronous BCa although there is a constant tumour cell seeding from the upper to the lower urinary tract.

The main findings of our study were: (I) patients with DJ stenting during TURBT for BCa were at increased risk for UUTUC development during follow-up, compared to patients with nephrostomies or no urinary drainage of the upper urinary tract during TURBT; (II) an increased risk of mortality in cases of nephrostomy placement for urinary drainage; and (III) a notably low incidence of metachronous UUTUC in general (1.3%).

All patients with UUTUC and DJ stenting in our cohort developed UUTUC congruent with the stent location (Table 2). However, not every DJ stent at the time of TURBT resulted in a metachronous UUTUC. Despite the low UUTUC incidence, our results suggested that a nephrostomy tube should be placed in cases of hydronephrosis, rather than a DJ stent. The increased mortality rate in the nephrostomy group mirrored that of hydronephrosis as an unfavorable prognostic factor. However, due to the high mortality rate among nephrostomy patients, UUTUC development during longer follow-up might be anticipated. Kaplan-Meier curves showed that deaths in the nephrostomy group (Fig. 4c) and UUTUC in the DJ stenting group (Fig. 3a and b) occurred within a 5 year follow-up. Thus, it remained unclear whether the use of nephrostomy tubes during TURBT might cause UUTUC over a longer period (> 5 years).

There are other studies evaluating the need for, and harmful effects of, DJ stenting in BCa patients; however, the results are controversial. Notably, our study was the first to compare the potential harm caused by both DJ stents and nephrostomy tubes during TURBT for BCa with regard to metachronous UUTUC.

Kiss et al. also retrospectively assessed the risk of urinary drainage with either a DJ stent or nephrostomy tube for UC recurrence in the upper urinary tract [9]. Their study design is similar to ours, however there are two major differences. First, Kiss et al. analysed a radical cystectomy cohort (n = 1005; vs. TURBT cohort in our study). Second, they assessed the impact of preoperative urinary drainage (vs. intraoperative urinary drainage in our cohort, i.e. increased risk of tumour cell seeding due to cutting/resection of the tumour). In their cohort, preoperative hydronephrosis was present in 4% of the patients bilaterally and in 19% unilaterally. Half of the patients with hydronephrosis underwent preoperative urinary drainage with either a DJ stent (46%) or nephrostomy tube (54%). In total, there were 3% UUTUC recurrences, including 13% of patients with DJ stents, 0% from the nephrostomy group and 3% from the no urinary drainage group. As such, the authors identified preoperative DJ stenting, but not hydronephrosis, as an independent risk factor for metachronous UUTUC. Consistent with our results, UUTUC-free survival was shorter in the DJ stenting group, and OS was shorter in the nephrostomy group. Consequently, Kiss et al. proposed the use of nephrostomies for preoperative urinary drainage of the upper urinary tract, when necessary [9].

A study by Chou et al. revealed ureteral orifice localisation of BCa in 31 out of 572 (5.4%) patients who underwent TURBT [12], with metachronous UUTUC occurring in four (12.9%) of these patients. DJ stents were placed in six patients due to surgical damage of the ureteral orifice during the procedure; however, there were no metachronous UUTUCs or vesicoureteral obstruction during their follow-up. On the contrary, vesicoureteral obstruction developed in three (10%) patients without DJ stenting due to scar formation of the ureteral orifice [12].

Mano et al. also examined the outcome of ureteral orifice resection during TURBT (n = 84) [16]. Patients with preoperative hydronephrosis and DJ stenting during the procedure were excluded. Postoperative hydronephrosis was documented in 13% of patients, with it being due to vesicoureteral obstruction in only three patients (4%). Only one patient showed UUTUC recurrence [16].

Altok et al. also retrospectively investigated TURBTs for BCa including the ureteral orifice (n = 138) [17]. There was no DJ stenting in this cohort. Synchronous and metachronous UUTUC developed in 10.1 and 5.3% of these cases, respectively. Postoperative hydronephrosis occurred in 19.5% of the patients without preoperative hydronephrosis due to vesicoureteral reflux (47%), disease progression including the ureteral orifice (29%), urolithiasis (3%), and vesicoureteral obstruction (6%; n = 1). Therefore, the authors recommended against routine DJ stenting during TURBT of the ureteral orifice [17].

Taken together and based in the aforementioned studies [12, 16, 17], the rate of postoperative vesicoureteral obstruction rate due to a TURBT close to the ureteral orifice seems to be low and thus DJ stenting to protect the ureteral orifice eventually abdicable. However, these studies include only small cohorts. Larger cohorts are certainly needed to support this assumption.

Limitations of our study were its retrospective design, including the lack of information about the cause of death; therefore, cancer specific mortality was not determined. There was no information about prior manipulation of the upper urinary tract for those BCa patients who were diagnosed prior to 2008 and about the DJ stent dwell time. Furthermore, tumour localization, number of tumours in the bladder as well as subsequent therapies or upper urinary tract manipulations were not investigated. There was no standardized screening for an UUTUC at the time of BCa diagnosis. Notably, the low incidence of metachronous UUTUCs in our cohort as well as the short median follow-up need to be considered during interpretation of the results. Thus, further investigation on larger cohorts and randomised studies comparing DJ with nephrostomy tube drainage during TURBT are needed to confirm these results.

In conclusion, patients with DJ stenting during TURBT for BCa had an increased risk for UUTUC development during follow-up. The results indicated that a nephrostomy tube should be placed in cases of hydronephrosis, rather than DJ stent, if feasible. Previous reports demonstrated acceptably low rates of postoperative vesicoureteral obstruction during TURBT close to the ureteral orifice. Thus, DJ stenting to protect the ureteral orifice might be abdicable.