Clinical outcome of neobladder or augmentation after cystectomy in locally advanced colorectal cancer involving the urinary tract: Case series

doi:10.21203/rs.3.rs-4870050/v1

Background: In most cases of colorectal cancer (CRC) with bladder invasion, ileal conduit diversion is commonly performed. However, with increasing survival rates, quality of life becomes a significant concern, making this approach less favorable. Thus, this study aims to investigate the clinical outcomes of patients with CRC who underwent neobladder or augmentation surgeries.

Methods: We retrospectively reviewed the records of nine patients who underwent neobladder or augmentation surgeries combined with surgical management of locally advanced CRC involving the urinary tract between 2011 and 2018 at Asan Medical Center.

Result: Nine patients underwent neobladder or augmentation procedures following extensive cystectomy due to rectal or sigmoid colon cancer. The median age of these patients was 58, ranging from 45 to 71 years. Most of the patients were diagnosed with sigmoid colon cancer, and the bladder was the most commonly affected genitourinary tract organ. Of nine patients, two underwent total cystectomy with neobladder procedures, while seven had partial cystectomy and augmentation due to insufficient residual bladder. Four patients needed ureterectomy because of ureter invasion. Two female patients experienced vesico-vaginal fistula complications. Three out of the nine patients (33%) showed no bladder invasion at the pathological stage. Of the patients, seven achieved full continence while two did not.

Conclusion: Quality of life is crucial for CRC patients with improved survival rates. In our study, postoperative mortality or morbidity was not significant among patients who underwent total cystectomy. Neobladder or augmentation surgeries are feasible options for CRC patients with urinary tract invasion.

Colorectal cancer

Cystectomy

Neobladder

Quality of life

urinary tract invasion

More than 1.9 million new colorectal cancer (CRC) cases and 935,000 deaths were estimated to occur worldwide in 2020, representing about one in 10 cancer cases and deaths.[1] Locally advanced CRC accounts for approximately 10–20% of all CRC cases.[2] In patients with CRC, invasion into the bladder and prostate is relatively rare. Generally, it is reported that the genitourinary tract, which includes the bladder, prostate, ureters, or vagina, is infiltrated in about 3-10% of CRC cases.[3, 4] The most common location for CRC involvement of the urinary bladder is the distal sigmoid colon, followed by the rectum.[3]

Patients with bladder invasion by CRC may present with symptoms, such as hematuria (blood in the urine), increased urinary frequency, urgency, or urinary tract infection. In some cases, a fistula (an abnormal connection) may develop between the bladder and colon or rectum, leading to pneumaturia (passage of air during urination) and fecaluria (passage of fecal matter in the urine). Imaging studies, such as CT scan or MRI, can help identify the extent of the tumor and invasion into the bladder. Cystoscopy, a procedure that visualizes the interior of the bladder, can also be used to confirm the diagnosis. The treatment approach for CRC with bladder invasion is complex and often requires a multidisciplinary team.[5]

For patients with bladder invasion from rectal cancer, surgery typically serves as the initial treatment, involving the excision of the affected segment of the colon or rectum along with partial or complete removal of the bladder. Urologist and colorectal surgeon often collaborate to provide the best treatment for patients. After partial or complete removal of the bladder, reconstructive surgery might be necessary to create a new way for the body to store and pass urine. This can include procedures, such as ileal conduit (urostomy), augmentation, and creation of a neobladder. The choice of the surgical approach depends on various factors, including the location, size, and stage of the cancer, as well as the patient's overall health. However, in cases of partial or total cystectomy, urologists often opt for the ileal conduit procedure, as patients who underwent total cystectomy experienced significantly higher morbidity rates compared to those who underwent partial cystectomy.[6]

Currently, it has been observed that neoplasms located in the sigmoid colon and rectum may necessitate a lower propensity for permanent colostomy.[7-9] Furthermore, contemporary advancements in medical science and refinements in surgical methodologies have facilitated surgical procedures that either employ a temporary colostomy or obviate the need for a colostomy altogether. In such a situation, the patient may feel embarrassed to see an ileal conduit without a stoma after CRC surgery. Additionally, as the survival rate of CRC improves, patients may seek a better quality of life (QoL).[10-12] As a result, patients might harbor resentment towards the urologists who performed the ileal conduit. The most unfavorable situation arises when bladder invasion is indicated in clinical staging; however, subsequent histological evaluation post-surgery reveals absence of such invasion. In such a situation, the urologist is unable to provide an adequate explanation to the patient who underwent an ileal conduit.

Neobladder or augmentation surgery assists the patients in leading a more comfortable daily life. But currently, there is no universally agreed-upon method for genitourinary reconstructive surgery when CRC spreads to the urinary tract. Thus, this study aims to investigate the clinical outcomes of patients with CRC who underwent neobladder or augmentation surgery.

We retrospectively reviewed the medical records of nine patients who underwent ileal bladder substitution combined with surgical management of locally advanced CRC involving the urinary tract between 2011 and 2018 at Asan Medical Center. The study was reviewed and approved by the Institutional Review Board of the Asan Medical Center (No. 2023-1356), and it was performed in accordance with the Declaration of Helsinki. The Institutional Review Board of the Asan Medical Center waived the requirement for obtaining informed consent due to the retrospective design of the study. The indications for ileal bladder substitution included the following: 1) direct involvement of the genito-urinary tract on radiography, 2) no evidence of distant metastasis (except patients underwent complete metastasectomy), 3) lack of preoperative radiation physical status that makes the patient incapable of withstanding the invasive surgical stress, and 4) absence of significant comorbid medical conditions that would make the operation unsafe. Clinical characteristics of enrolled patients are summarized in Table 1. All patients were diagnosed with CRC by endoscopic biopsy. The clinical staging work-up included chest radiography, CT of the abdomen and pelvis , and MRI.

The patients underwent total cystectomy followed by neobladder surgery using standard techniques. The patients received near-total cystectomy followed by augmentation. Pathologic staging was performed according to the American Joint Committee on Cancer (8th ed. 2017). After surgery, a urodynamic study was performed to evaluate the voiding function after surgery. In addition, continence after surgery and presence or absence of medications related to urination were evaluated. The oncological follow-up schedule included chest radiography and APCT every six months for two years, and annually thereafter. The diagnosis of disease recurrence was based on the radiological findings, and it was confirmed by a biopsy if required. We evaluated the surgical procedure, reconstruction of the urinary tract, complication, surgical histologic subtype, and pathologic stage.

Surgical Technique

According to the degree of invasion during surgery, en bloc resection was performed as much as possible. The method for reconstructing the damaged bladder was determined based on the extent of the defect at the time of surgery, as assessed by the urologist. (W shape, U shape, and I shape) Also, if the ureteral length was insufficient due to ureteral invasion, a chimney was made and a neobladder was created. The length of the resected small intestine was approximately 25 cm ~ 55 cm, and a chimney measuring approximately 5-7.5 cm was made. Table 2 and figure 1 present clear and concise descriptions of the surgical procedures undertaken for each individual patient, facilitating easy comprehension.

A total of nine patients underwent neobladder or augmentation surgery after total cystectomy and near-total cystectomy for rectal or sigmoid colon cancer. Table 1 provides the clinical characteristics of these nine patients diagnosed with sigmoid colon cancer or rectal cancer. Median age of the enrolled patients was 58 years (range, 45 to 71 years), and they included seven men and two women. Sigmoid colon cancer was the most common, followed by recto-sigmoid cancer and rectal cancer. Bladder was the most frequently involved organ in the genitourinary tract, followed by uterus and ovary. All of these nine patients were diagnosed with the cT4b clinical stage. Out of these nine patients, three patients had clinical lymph node metastases. Two patients had clinical metastatic lesions before surgery and they underwent complete metastasectomy.

Table 2 provides a comprehensive overview of the surgical procedure, urinary tract reconstruction, complication, and disease stage for each of these nine patients. Out of these nine patients, two patients underwent total cystectomy, prostate enucleation, and neobladder surgery. Seven patients underwent partial cystectomy, and augmentation cystoplasty was performed when there was insufficient residual bladder tissue for proper repair. Four patients underwent ureterectomy due to ureteral invasion. Two female patients (100%) experienced a complication, known as vesico-vaginal fistula. Out of these nine patients, three patients (33%) did not have bladder invasion according to the pathological stage.

Table 3 provides details on the continence status of these nine patients during 1 year postoperatively. Seven patients achieved day and night continence (indicated as +/+), and two patients did not achieve day and night continence (-/-). There were no cases of self-catheterization or upper urinary tract damage in this study. Patient 1 had the longest follow-up, which lasted for 86 months and the outcome was NED (No Evidence of Disease) In total, five patients achieved the NED outcome. Patient 9 had a follow-up period of 27 months with an outcome of AWD (Alive with Disease). This patient underwent various treatments, including palliative chemotherapy, stereotactic body radiation therapy (SBRT) for liver metastasis, and radical cystectomy with an ileal conduit for bladder cancer recurrence.

Historically, CRC has been more commonly diagnosed in older adults. However, recent studies have shown an increase in the number of younger adults being diagnosed with this type of cancer. The general 5-year relative survival rate for regional stage (T4bN0 or T4bN1) CRC has improved to 35-76%.[13-15] Based on the aforementioned considerations, it is important to include a neobladder or augmentation procedure during surgical treatment of CRC patients with bladder invasion. But, urologists often perform an ileal conduit procedure due to various factors. These factors include extended duration of urological and reconstructive surgeries, physician fatigue, scheduling conflicts between urology and surgery, and the overall condition of the patient. Additionally, to date, a universally accepted strategy for genitourinary reconstructive surgery for CRC infiltrating the urinary tract has not yet been defined.

Urologists might regret later if they decide to perform an ileal conduit procedure without thinking over it. Modern surgical techniques, including sphincter-preserving and minimally invasive procedures, have decreased the reliance on permanent stomas for recto-sigmoid colon cancer patients.[16] Neo-adjuvant therapies, which shrink the tumors before surgery, also play a role in reducing the need for stomas.[17] Patient preferences and improved postoperative care further drive this trend. Following CRC surgery, a patient might feel uneasy or self-conscious on seeing an ileal conduit without the presence of a stoma. In clinically invasive bladder-infiltrating CRC, the histological noninvasiveness of the bladder relies on factors such as preoperative imaging accuracy and the presence of inflammatory adhesions.[18] A definitive determination of invasion is made histologically, i.e., by examining the tissue under a microscope after surgical removal. According to Vuillermet et al., histological analysis revealed bladder adherence in 53% of the cases and bladder invasion in the remaining 47% of cases.[19] Winter et al. reported that, despite the clinical indications of bladder infiltration, histological staging ultimately revealed bladder invasion in 54% of the cases. In their study, four of the ten patients who underwent total cystectomy showed inflammation, perforation, and abscess, but no bladder infiltration.[18] In our research, six of nine patients (66%) showed bladder invasion on microscopic examination. If there is no bladder infiltration in the pathology report after ileal conduit surgery, the urologists may have difficulty in explaining and persuading the patients who have received an ileal conduit. As CRC survival rates improve, urologists will hear complaints from patients for a long time.

There is evidence suggesting that a better QoL can lead to better survival outcomes in patients with colorectal cancer.[20, 21] Patients with a higher QoL might be more physically and mentally resilient, better able to tolerate treatments, and more proactive in their care. They might also have a stronger immune response, which can play a role in cancer progression. Patients with a good QoL might be more likely to follow dietary and exercise recommendations, leading to better overall health. This can reduce the risk of complications during treatment.[22] A good QoL is often associated with strong social support, which can have positive effects on the mental health, reduce stress, and potentially influence disease outcomes.[23] For this reason, several studies have reported that QoL is related to the survival rate in CRC patients.[10] For some patients, especially those with advanced CRC, the focus of treatment might shift from aggressive interventions aimed at prolonging life to palliative care aimed at improving or maintaining their QoL. In urology, an ileal conduit is a representative surgical method that reduces the QoL.[24-27] Therefore, urologists should first actively consider neobladder or bladder preservation surgery in patients with CRC that has invaded the bladder.

There are several papers on reconstructive procedures following total cystectomy in patients with CRC that has invaded the bladder.[28, 29] Based on these papers, we know that bladder sparing surgery is preferable to total cystectomy. In addition, it is noted that even if we inevitably perform total cystectomy, a neobladder creation is better than or similar to an ileal conduit in all factors, including QoL and complications.[30] We have no reason to perform an ileal conduit based on this fact. However, we suspect that in many cases in which an ileal conduit is performed, it might be due to the urologist's personal preference or judgment.

Based on the previous results, we should preferentially consider bladder conserving surgery or neobladder surgery in CRC patients with bladder invasion. However, this study has several limitations. The first limitation was that the study design was retrospective in nature, with a small sample size. The second limitation was that, without a control group for comparison, it was difficult to determine the causality or effectiveness of interventions. The third limitation was that the interpretation and presentation of patient cases could have been influenced by the author's beliefs, training, or biases. This could have resulted in subjective portrayal of the case. The fourth limitation was that the insights from patient cases were often qualitative. Although this offers depth, it can be challenging to perform quantification and statistical analysis. Nevertheless, summaries of this study allow for more flexibility in data collection and interpretation, making it easier to adapt to unexpected findings or conditions, unlike structured experimental studies. This study has an immediate clinical relevance, offering guidance or insights to the clinicians who might encounter similar cases.

As more patients with CRC involving the urinary tract survive longer, their QoL post-treatment has become a central concern. Neobladder or augmentation surgery not only enhances the patient's QoL but also contributes to improving survival rates. Our study found no issues concerning postoperative mortality or morbidity among patients who underwent total cystectomy. This study emphasizes the need to actively consider either bladder preservation or neobladder reconstruction during bladder surgery, with a focus on the patient's postoperative QoL.

Acknowledgements

Not applicable.

Author Contributions

C. Lee contributed to conceptualization, methodology, formal analysis, investigation, data curation, and writing the original draft. W. Nam was involved in conceptualization, formal analysis, investigation, and data curation. C. W. Kim and Y. S. Yoon focused on methodology and validation. D. You contributed to conceptualization, methodology, writing - review & editing, and supervision. All authors read and approved the final manuscript.

Funding

No funding was received for conducting this study.

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Review Board of the Asan Medical Center (Date. October 24, 2023/ No. 2023-1356). Informed consent was obtained from all individual participants included in the study.”

Consent to publish

Not applicable.

Competing interests

The authors have no relevant financial or non-financial interests to disclose.The authors have no conflicts of interest to declare that are relevant to the content of this article.

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Table 1 Clinical characteristics of patients

Patient No.	Age/Sex	Underlying disease	Involvement of the genito-urinary tract on radiography	Biopsy-based histologic subtype	Clinical stage
1	53/M	Sigmoid colon cancer	Urinary bladder	Adenocarcinoma, WD	cT4bN2M0
2	58/M	Rectal cancer	Urinary bladder	Adenocarcinoma, MD	cT4bN0M0
3	45/F	Recto-sigmoid colon cancer	Urinary bladder and uterus	Adenocarcinoma, MD	cT4bN0M0
4	71/M	Recto-sigmoid colon cancer	Urinary bladder	Adenocarcinoma, MD	cT4bN3M0/1
5	56/F	Sigmoid colon cancer	Right ovary	Adenocarcinoma, MD	cT4bN0M0
6	58/M	Sigmoid colon cancer	Urinary bladder	Adenocarcinoma, MD	cT4bN0M0
7	55/M	Rectal cancer	Urinary bladder	Adenocarcinoma, MD	cT4bN0M1
8	59/M	Recto-sigmoid colon cancer	Urinary bladder	Adenocarcinoma, MD	cT4bN2M0
9	71/M	Sigmoid colon cancer	Urinary bladder	Adenocarcinoma, WD	cT4bN0M0

WD, well-differentiated; MD, moderately differentiated

Table 2 Operative results of patients

Patient No.		Surgical procedure for underlying disease	Reconstruction of urinary tract	Complication related to surgical procedure of urinary tract	Surgical histologic subtype	Pathological stage
1	Low anterior resection		Total cystectomy, prostate enucleation, orthotopic bladder substitute (two chimney W type, 7.5 + 40 + 7.5)	None	Adenocarcinoma, MD	pT4bN0M0 (urinary bladder)
2	Low anterior resection		Partial cystectomy, both distal ureterectomy, augmentation cystoplasty (one chimney I type, 7 + 13)	None	Adenocarcinoma, PD	pT3N0M0
3	Low anterior resection, total hysterectomy, left salphingo-ophorectomy		Partial cystectomy, both distal ureterectomy, augmentation cystoplasty (two chimney U type, 5 + 15 + 5)	VVF (IIIb)	Adenocarcinoma, MD	pT4bN0M0 (urinary bladder, uterus)
4	Anterior resection, left liver lobectomy		Partial cystectomy, augmentation cystoplasty (no chimney U type, 20)	Wound dehiscence (IIIa)	Adenocarcinoma, PD	pT4aN0M0 CCC, pT1N1M0
5	Anterior resection, right salphingo-ophorectomy, vaginal stump resection		Partial cystectomy, both distal ureterectomy, augmentation cystoplasty (one chimney U type, 5 + 15)	VVF	Adenocarcinoma, MD	pT4bN0M0 (vagina)
6	Anterior resection		Partial cystectomy, left distal ureterectomy, augmentation cystoplasty (one chimney I type, 5 + 15)	None	Adenocarcinoma, MD	pT4bN0M0 (urinary bladder)
7	Low anterior resection, liver segmentectomy		Partial cystectomy, both distal ureterectomy, augmentation cystoplasty (two chimney I type, 5 + 10 + 5)	None	Adenocarcinoma, MD	pT4bN0M1 (urinary bladder, liver)
8	Anterior resection		Total cystectomy, prostate enucleation, orthotopic bladder substitute (two chimney W type, 5 + 30 + 5)	None	Mucinous adenocarcinoma	pT4bN2aM0 (urinary bladder) Adenocarcinoma, MD, pT1
9	Ileostomy + neoadjuvant CTx -> Anterior resection		Partial cystectomy, left distal ureterectomy, augmentation cystoplasty (one chimney U type, 5 + 35)	None	Adenocarcinoma, MD	ypT4bN0M0 (urinary bladder)

WD, well-differentiated; MD, moderately differentiated; PD, poorly differentiated; VVF, vesico-vaginal fistula; ypTNM, neoadjuvant pathologic staging

Table 3 Long-term outcomes of patients

Patient No.	Urodynamic study (MCC-Qmax at Pdet/PVR)	Continence, postop 1 year	Management for voiding	Additional Tx for underlying	Follow-up, months/Outcome
1	Refused	Day & night continence(+/+), enuresis(+)	None	Adjuvant CTx	146/NED
2	144 – 10 at 25 / 400 cc	Day & night continence(+/+), enuresis(-)	Alpha-blocker, cholinergics, 5ARI	Adjuvant CTx	113/NED
3	233 – 9 at 0 / 0 cc	Day & night continence(-/-), 3~4 pads/day	Anticholinergics -> VVF repair	Adjuvant CTx -> Palliative CTx for peritoneal seeding	109/AWD
4	47 – 4 at 28 / 420 cc	Day & night continence(+/+), enuresis(-)	Alpha-blocker	Adjuvant CTx	56/NED
5	232 – 11 at 14 / 50 cc	Day & night continence(-/-), 1 pad/day	None	Adjuvant CTx -> stopped d/t refusal	44/NED
6	166 – 13 at 27 / 350 cc	Day & night continence(+/+), enuresis(-), decreased filling sensation	Alpha-blocker	Adjuvant CTx	51/NED
7	287 – 20 at 31 / 250 cc	Day & night continence(+/+), enuresis(-)	None	Adjuvant CTx -> Palliative CTx for liver & LN metastasis	38/DOD
8	0 – 0 at 0 / 1200 cc	Day & night continence(+/+), enuresis(-)	Timed voiding, alpha-blocker, cholinergics	Adjuvant CTx -> Palliative CTx for peritoneal seeding	29/AWD
9	Refused	Day & night continence(+/+), enuresis(-)	alpha-blocker, cholinergics	Adjuvant CTx -> Palliative CTx, SBRT for liver metastasis -> Radical cystectomy with ileal conduit, palliative CTx for bladder recurrence	69/AWD

MCC, maximum cystometric capacity; Qmax, maximum flow rate; Pdet, detrusor pressure; PVR, postvoid residual volume; VVF, vesico-vaginal fistula; NED, no evidence of disease; AWD, alive with disease

No competing interests reported.

Clinical outcome of neobladder or augmentation after cystectomy in locally advanced colorectal cancer involving the urinary tract: Case series

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