Two Cases of Revisional Urinary Diversion from Ureterocutaneostomy to Ileal Conduit: A Staged Urinary Diversion Strategy for Patients with Bladder Cancer in the Targeted and Immunotherapy Era

Introduction

Cutaneous ureterostomy (CU) is a typical urinary diversion procedure involving an ileal conduit (IC) and ileal neobladder. As CU does not involve intestinal manipulation, it is technically easier and faster to perform than other procedures, thus reducing the risk of postoperative intestinal complications and metabolic abnormalities [1–3]. These advantages have led urologists to choose this procedure for patients with a poor prognosis, such as those with advanced cancer, a single kidney, or older age. However, CU exhibits several drawbacks. Stoma stenosis frequently prevents the achievement of a catheter-free status, leading to an increased risk of catheter-related urinary tract infections (UTIs), and raises concerns about long-term kidney function. Additionally, the CU often necessitates frequent outpatient visits for regular catheter changes, substantially burdening patients and negatively affecting their quality of life (QOL) [1–3]. In contrast, IC is a more stable urinary diversion method than CU [1–3]. In most cases, IC eliminates the need for external catheters, thereby reducing the risk of infection and facilitating the better maintenance of renal function.

Advances in the treatment of advanced or metastatic urothelial carcinoma have been remarkable in recent years, and the advent of immune checkpoint inhibitors (ICIs) and antibody-drug conjugates has significantly improved the prognosis of patients with urothelial carcinoma [4–7]. Consequently, some patients who underwent CU and were previously thought to have a poor prognosis have achieved long-term remission. The next goal for these patients is to achieve stable urinary diversion while minimizing management time and effort, and reducing concerns about infection and renal dysfunction.

However, to date, urinary tract diversions have rarely been revised after their initial creation [8–11]. The reasons for this include the technical challenges associated with such surgeries, the previously poor prognosis of the patients, and the assumption that patients would unconditionally accept their urinary stoma as permanent. With the improved outcomes offered by modern ICI and targeted therapies, the clinical relevance of revisional urinary diversion is growing, as it provides a viable option for optimizing long-term QOL.

Herein, we share 2 cases of successful revisional urinary diversion from CU to IC in patients with locally advanced bladder cancer who initially underwent CU and achieved long-term remission with pembrolizumab.

Case Reports

CASE 1:

In April 2023, a 75-year-old man received a diagnosis of cT4aN0M0 bladder cancer (invasive urothelial carcinoma, grade 3, pathological T stage [pT] ≥2) at another hospital, after presenting with gross hematuria.

He started neoadjuvant chemotherapy with gemcitabine and cisplatin, but experienced acute renal failure due to a stricture of unknown cause at the vesicoureteral junction immediately after the first course of chemotherapy (Figure 1A, 1B). Emergency left CU was performed because a nephrostomy could not be created owing to technical difficulties. However, after the CU, the patient was unable to achieve a catheter-free status. In August 2023, imaging revealed that the disease progressively advanced and was unresectable. As second-line treatment, 2 courses of pembrolizumab were administered, and the disease was classified as stable (Figure 1C–1E). The patient declined further chemotherapy and requested cystectomy and revision of the urinary diversion to an IC to reduce his dependence on catheters. Subsequently, the patient was transferred to our hospital. In November 2023, we determined that the patient’s disease was technically resectable, and he underwent robot-assisted laparoscopic radical cystectomy with revisional urinary diversion from CU to IC. Extracorporeal urinary diversion was performed. During surgery, the adhesive left ureter was disconnected from the skin stoma, and the released distal ureter was trimmed (Figure 2A). An IC was prepared from the terminal ileum, and its proximal end was connected to the shortened left ureter using a Wallace anastomosis (Figure 2B). A new stoma was created in the right lower abdomen. Ligation was performed only on the right ureter because the cortex of the right kidney was very thin, and 99mTc-MAG3 scintigraphy revealed no residual renal function (Figure 3). The surgery lasted 7 h and 5 min, with a console time of 4 h and 33 min, and the estimated blood loss was 300 mL. Pathological examination revealed no residual cancer, confirming complete remission (CR). The patient achieved and maintained a catheter-free status for 1 year after surgery (Figure 1F, 1G), with significant improvements in QOL, and his renal function was preserved compared to that preoperatively.

CASE 2:

A 57-year-old woman received a diagnosis of cT3bN1M0 bladder cancer (urothelial carcinoma with glandular differentiation, grade 3, pT ≥1) (Figure 4A, 4B), in August 2020. She underwent 5 cycles of neoadjuvant chemotherapy with gemcitabine and carboplatin, followed by radical cystectomy with right nephroureterectomy and left CU, as the disease remained stable. CU was chosen because of the advanced stage of the disease and the presence of a single kidney. Pathological examination revealed pT4a (invaded the vaginal wall), the resected node was positive for cancer (1/20), lymphovascular invasion was positive, and resection margin was negative. The CU did not achieve catheter-free status. In April 2021, cancer recurred in the vaginal wall (Figure 4C–4E) and in the pelvic and inguinal lymph nodes. The patient underwent chemoradiotherapy with 50 Gy of radiation and cisplatin, followed by pembrolizumab in June 2021, which led to a confirmed CR in October 2021 (Figure 4F). After 30 courses of pembrolizumab, the patient wished to discontinue treatment in June 2023. During this period, she experienced recurrent fever and back pain due to frequent UTIs associated with CU, resulting in a decreased QOL. In February 2024, the patient requested a revisional urinary diversion to an IC to reduce her dependence on catheters and improve her QOL. The procedure was performed through a midline abdominal incision of 15 cm. During surgery, the adhesive left ureter was disconnected from the skin stoma, and the released distal ureter was trimmed (Figure 5A). After dissecting the IC from the terminal ileum, a small hole was made in the sigmoid mesocolon, and the IC was positioned on the left side of the pelvis (Figure 5B). The proximal end of the IC was connected to the shortened left ureter by using a Wallace anastomosis (Figure 5C). As the previous stoma was placed close to the midline of the abdomen, the new stoma was placed in the same position through the rectus abdominis muscle for patient convenience. The surgery required 3 h 55 min, with minimal blood loss. Postoperatively, the patient achieved a catheter-free status (Figure 4G, 4H), improved QOL, and stable renal function, with no signs of disease recurrence at 6 months.

Discussion

We documented 2 cases of revisional urinary diversion from CU to IC. Similar cases have been reported previously, although they are rare [8–11]. The primary goal of cancer treatment is survival; however, once survival is achieved, improvement in QOL replaces that goal. Revisional urinary diversion is considered when persistent catheter dependence, recurrent UTIs, and progressive renal dysfunction significantly affect a patient’s QOL. Significant advances have been made in the treatment of advanced or metastatic urothelial carcinoma in recent years [5–7], and patients who have achieved long-term remission with ICI and targeted therapies, such as pembrolizumab and enfortumab vedotin, are particularly good candidates for such surgery. This staged urinary diversion strategy may be a therapeutic option to improve the QOL of cancer survivors in this new therapeutic era.

Monotherapy with pembrolizumab and enfortumab vedotin is widely recognized as an effective treatment for advanced or metastatic urothelial carcinoma. These treatments extend overall survival (OS) and increase CR rates [5,6]. In the KEYNOTE-045 trial, pembrolizumab extended the median OS by approximately 3 months, compared with conventional chemotherapy in the second-line setting (10.3 vs 7.4 months).

The CR rate improved from 11% to 21% [5]. In the EV-301 trial, enfortumab vedotin extended the median OS by approximately 4 months, compared with conventional chemotherapy in the third-line setting (12.9 vs 9.0 months). The CR rate improved from 4% to 12% [6]. The latest clinical trials evaluating the combination of these therapies in first-line settings have demonstrated significant improvements in OS and progression-free survival, compared with traditional chemotherapy, suggesting notable benefits over monotherapy. In the EV302 trial, the combination of enfortumab, vedotin, and pembrolizumab extended the median OS by approximately 15 months, compared with conventional chemotherapy in the first-line setting (31.5 vs 16.1 months). The CR rate improved from 12% to 28% [7]. Enfortumab vedotin and pembrolizumab combination therapy recently received approval for use in Japan and is a candidate for a new standard of care. It is expected that more patients with metastatic or progressive urothelial carcinoma will achieve CR, compared with the current situation.

Revision surgeries are technically challenging. As such surgeries constitute reoperation in previously operated adhesive areas, there is a possibility that intestinal perforation or blood vessel damage can occur due to adhesiolysis. There can also be risks of ureteroileal conduit suture failure and anastomotic restenosis. It is important to share the decision-making process before surgery, including the benefits and risks. In the 2 cases presented herein, there were strong adhesions between the left ureter and the left external iliac artery and vein, as well as between the intestinal tract and pelvic floor, making dissection difficult. The urologist in charge of this surgery should be familiar with the adhesiolysis techniques. Surgical robots can be beneficial in revisional urinary diversion surgery. Indocyanine green imaging using near-infrared light, which is standard equipment for surgical robots, can reduce the risk of postoperative ureteral strictures [12]. Unfortunately, in our country, the use of robots is not covered by medical insurance and remains virtually impossible. However, as the patient demand for minimally invasive revisional surgeries increases, the use of robots may be permitted in the future.

As the IC is considered the criterion standard for urinary diversion [13,14], it may be best to create an IC during the initial surgery. However, despite some drawbacks of CU in clinical practice, it is selected to avoid long surgical times or intestinal manipulation in patients with advanced cancer, a single kidney, or advanced age [1–3]. These drawbacks include a high likelihood of catheter dependence, UTI, and progressive renal dysfunction, which can impair QOL. For decades, techniques for creating catheter-free CU have been actively discussed, and catheter-free rates of 74% to 90% have been reported [2,15,16]. Kim et al described the usefulness of suturing the anterior and posterior sheaths to prevent abdominal wall tunnel misalignment [15]. However, these techniques are not generally accepted and have not become widespread in practice. A recent report from a center in Egypt showed a catheter-free rate of 56% [3], and general hospitals in Japan are likely to have similar rates. The 2-stage surgical concept proposed here alleviates the concern of not being able to achieve a catheter-free status during the initial surgery, allowing surgeons and patients to focus on cancer treatment with hope, even if a catheter-free status is not achieved initially.

Conclusions

We presented 2 cases of revisional urinary diversion from CU to IC in patients with locally advanced bladder cancer who initially underwent CU and achieved long-term remission with pembrolizumab.

The staged urinary diversion proposed in this paper aims to provide patients with advanced urothelial carcinoma with the courage and hope to undertake more challenging treatments in this modern era of rapidly evolving therapies. As urological surgeons, we should not rule out the possibility of performing revisional urinary diversion surgery and should be prepared to offer it if the patients desire it.