Optical Coherence Tomography as an Adjunct to White Light Cystoscopy for Intravesical Real-Time Imaging and Staging of Bladder Cancer

doi:10.1016/j.urology.2008.02.002

Urology

Volume 72, Issue 1, July 2008, Pages 133-137

https://doi.org/10.1016/j.urology.2008.02.002 Get rights and content

Objectives

Optical coherence tomography (OCT) is a novel, real-time endoscopic imaging modality that permits delineation of microarchitectural features of bladder lesions. It may provide an extension of conventional cystoscopy by allowing noninvasive examination of bladder tissue at microscopic resolution (10 to 20 μm). The purpose of this study was to examine the application of OCT in augmenting the diagnosis and staging of bladder lesions.

Methods

We conducted a retrospective institutional review board–approved, single-institution, single-user review on the use of OCT as an adjunct to conventional cystoscopy in 32 patients with a history of bladder cancer (24), primary tumor (6), prostate cancer (1), or hematuria (1). We obtained OCT images of suspicious areas before biopsy or resection, interpreted them in real time, and subsequently compared them with pathology results.

Results

We obtained 94 images in 32 patients undergoing bladder biopsy or transurethral resection of bladder tumor. Age of the patients ranged from 49 to 84 years (mean, 59 years), with 25 men (78%) and 7 women (22%). We correlated 38 suspicious areas with biopsy findings. OCT imaging correctly identified tumors confined to the mucosa with a sensitivity and specificity of 90% and 89%, respectively. Muscle-invasive tumors were detected in 7 of 7 lesions with 100% sensitivity, 90% specificity, and 92% accuracy.

Conclusions

Optical coherence tomography is a rapid, easy-to-use tool that can help differentiate Ta and T1 tumors and identify muscle-invasive bladder tumors. It provides real-time microarchitectural information that can aid in the evaluation of bladder tumors and adjacent and remote urothelium.

Section snippets

Material and Methods

We performed a retrospective institutional review board–approved review of one surgeon's (SPL's) experience with the use of OCT in providing additional diagnostic information in 32 patients undergoing conventional cystoscopy from December 2005 to April 2007. Indications for cystoscopy under anesthesia included history of bladder cancer (24) with a new visible lesion, initial occurrence of bladder cancer seen on flexible cystoscopy (6), prostate cancer (1), or hematuria without visible lesion

Results

The cohort included 25 men (78%) and 7 women (22%) and ages ranged from 49 to 84 years (mean, 59 years). Most (30 of 32) of these patients had a preoperative diagnosis of bladder cancer or initial occurrence of bladder tumor. OCT delineated all three layers of the bladder wall including mucosa, lamina propria, and muscularis propria. The mucosa generally appeared as a dark, thin, clearly defined layer. The lamina propria gave a bright, distinct signal, whereas muscularis showed a darker,

Discussion

The dichotomy of non–muscle-invasive versus muscle-invasive bladder tumors has significant implications for oncologic management as well as patient outcome. In contrast to tumors involving the lamina propria, muscle-invasive tumors are more highly associated with locally advanced disease and distant spread.⁷ The distinctive behavior of muscle-invasive lesions emphasizes the critical importance of early, accurate identification and necessity for aggressive intervention.

Transurethral resection

Conclusion

We explored OCT in this study as a tool to enhance clinical staging of bladder tumors. The real-time, high-resolution images captured by OCT provide a glimpse of tissue microstructure in vivo. The advantage of such an image modality is that tissue can be studied without being altered or destroyed as in conventional biopsy. The potential is that areas of suspicion can be inspected with OCT before resection to maximize the information gained from biopsy and minimize unnecessary removal of tissue.

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Ex-vivo evaluation of miniaturized probes for endoscopic optical coherence tomography in urothelial cancer diagnostics
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The gold standard for detecting bladder cancer is white light cystoscopy (WLC) and resection of suspicious lesions. In this study, we evaluate two miniaturized Optical Coherence Tomography (OCT) probes for endoscopic use, regarding their applicability in diagnosing urothelial cancer.
In total, 33 patients who underwent a radical cystectomy were included. Preoperative oncological staging and determining the indication for the surgical intervention were done following the latest European Association of Urology (EAU) guidelines. Samples were taken from bladder tissue after bladder removal and prepared for OCT measurement. Additionally, porcine bladder samples were used as reference tissue. We took measurements using two miniaturized probes: a bimodal probe and a single modality OCT probe. A non-miniaturized standard OCT scanner was used as a reference.
Histopathological examination revealed urothelial cancer in all but three patients. Measurements on porcine tissue revealed a clear distinction between the urothelial layers for all probes. Furthermore, we detected improved image quality thanks to the stretching of the tissue. We took 271 measurements in human samples. While the urothelial layers were well delineated in healthy tissue, all the probes revealed a loss of these structures in cancerous regions. While the single-modality probe delivered an image quality equaling the reference images, it was possible to detect cancerous areas with the bimodal probe.
We demonstrate that endoscopic probes for OCT imaging are technologically feasible and deliver acceptable image quality. A distinction between healthy and abnormal tissue is possible. We propose combining different endoscopic imaging modalities as a promising approach for urothelial cancer diagnostics.
Phase II multi-center trial of optical coherence tomography as an adjunct to white light cystoscopy for intravesical real time imaging and staging of bladder cancer
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Optical coherence tomography (OCT) is a novel imaging modality that provides microstructural information of different tissue layers using near-infrared light. This prospective, multicenter phase II trial aimed to assess the accuracy of OCT-assisted cystoscopy for bladder tumor staging.
Patients with primary or recurrent bladder tumors (Ta,T1) identified by outpatient cystoscopy were included. The primary objective was to assess the accuracy and positive predictive value of for determining tumor stage ≥T1 correlated by histopathology. 72 suspicious lesions from 63 patients were eligible to analyze in the study. All suspected lesions were evaluated with conventional cystoscopy, interpreted in real-time using OCT, and then resected. All results were compared to pathology. A total of 363 OCT images of tumor and normal mucosa in 25 patients were obtained to evaluate diagnostic efficacy of the computer-aided texture analysis algorithm.
Sensitivity and specificity for predicting invasive tumors (≥ T1, n = 17) were 58.8% and 92.7% for cystoscopy, 64.7% and 100% for OCT-assisted cystoscopy, respectively. Accuracy of cystoscopy and OCT-assisted cystoscopy for predicting invasive tumor was 84.7% and 91.7% (P = 0.063), respectively. Cystoscopy and OCT-assisted cystoscopy correctly predicted T stage in 52/72 and 59/72 cases, respectively (P = 0.016). Cystoscopy missed 2 more invasive tumors than OCT-assisted cystoscopy. Cystoscopy (14.3%, 1/7) and OCT-assisted cystoscopy (28.6%, 2/7) showed relatively low sensitivity in detecting muscle invasion. Computer aided texture analysis demonstrated 75.1% sensitivity, 64.0% specificity, and 74.4% accuracy for differentiating tumor and normal urothelium.
OCT-assisted cystoscopy is a real time noninvasive and simple procedure that enhanced the accuracy of staging bladder tumors and prediction of any tumor invasion. Though the study did not meet the prespecified primary endpoint, OCT imaging is a promising adjunct to cystoscopy that may supplement intraoperative decision-making during transurethral resection of bladder tumors and additional prospective studies are warranted.
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Citation Excerpt :
No threshold effect was suggested, with a Spearman coefficient of 0.06 (P = 0.87). Seven studies [17,20,21,23–26], including a total of 1437 lesions, reported the diagnostic accuracy of optical coherence tomography, used alone, for bladder cancer. Pooled sensitivity and specificity were 87.3% (95% confidence interval: 82.7%–91.1%, I2 = 77.5%) and 73.9% (95% confidence interval: 71.3%–76.4%, I2 = 84.2%), respectively (Table 2).
Bladder cancer is the fourth most common malignancy in men and a considerable disease burden globally. Multiple studies have focused on the accuracy of optical coherence tomography for bladder cancer diagnosis; however, the findings are inconsistent. Here, we assessed the accuracy of optical coherence tomography for bladder cancer diagnosis.
Embase, PubMed, Medline, Web of Science, and the Cochrane Library database were searched for relevant studies from the earliest date available through March 11, 2019. Studies evaluating the accuracy of optical coherence tomography bladder cancer diagnosis were included. Pooled sensitivity, specificity, and area under the curve values of weighted symmetric summary receiver operating curves, were calculated at the per-lesion level.
Eleven studies, with a total of 1933 lesions, were included in the final analysis. The pooled results indicated that optical coherence tomography can differentiate bladder cancer from benign lesions: sensitivity, 94.9% (95% confidence interval: 92.7%–96.6%); specificity, 84.6% (95% confidence interval: 82.6%–86.4%); area under the curve, 0.97. Moreover, compared with optical coherence tomography alone, combined optical coherence tomography and fluorescence cystoscopy increased the diagnostic accuracy (sensitivity, 94.3% vs. 87.3%; specificity, 89.2% vs. 73.9%). Cross-polarization optical coherence tomography could also distinguish bladder cancer from normal tissue: sensitivity, 92.0% (95% confidence interval: 87.0%–95.6%); specificity, 84.4% (95% confidence interval: 81.7%–86.9%); area under the curve, 0.95.
Optical coherence tomography can accurately differentiate malignant from benign bladder lesions, particularly when combined with fluorescence cystoscopy.
Recent advances in optical imaging technologies for the detection of bladder cancer
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White-light cystoscopy (WLC) is the diagnostic standard for the detection of bladder cancer (BC). However, the detection of small papillary and subtle flat carcinoma in situ lesions is not always possible with WLC. Several adjunctive optical imaging technologies have been developed to improve BC detection and resection. Photodynamic diagnosis, which requires the administering of a photoactive substance, has a higher detection rate than WLC for the detection of BC. Narrow-band imaging provides better visualization of tumors by contrast enhancement between normal mucosa and well-vascularized lesions. A technology called confocal laser endomicroscopy can be used to obtain detailed images of tissue structure. Optical coherence tomography is a high-resolution imaging process that enables noninvasive, real-time, and high-quality tissue images. Several other optical imaging technologies are also being developed to assist with the detection of BC. In this review, we provide an overview of the strengths and weaknesses of these imaging technologies for the detection of BC.
Recent Technological Advances in Cystoscopy for the Detection of Bladder Cancer
2018, Bladder Cancer
Cystoscopic examination has remained as the initial and key tool to diagnosis and observe bladder cancer for many decades. However, there is a crucial limitation of the conventional white light cystoscopy, particularly the high missing rate of small, flat tumors or ill-defined lesions of carcinoma in situ. Recently, new imaging modalities have been developed offering an opportunity to overcome the pitfalls of white light cystoscopy. These include narrow band imaging, fluorescence cystoscopy, and optical coherence. In this chapter, recent advances in endoscopic visualization of bladder cancers alongside scientific evidence of its use are detailed.

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: Nancy Tresser is affiliated with Imalux Corporation.

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OncologyOptical Coherence Tomography as an Adjunct to White Light Cystoscopy for Intravesical Real-Time Imaging and Staging of Bladder Cancer

Objectives

Methods

Results

Conclusions

Section snippets

Material and Methods

Results

Discussion

Conclusion

J Urol

Hum Pathol

Neoplasia

J Urol

Gastrointest Endosc

Infiltrating carcinoma of the bladder: relation of early diagnosis to five-year survival rate after complete extirpation

J Am Med Assoc

Discrepancy between clinical and pathologic stage: impact on prognosis after radical cystectomy

Eur Urol

Oncology
Optical Coherence Tomography as an Adjunct to White Light Cystoscopy for Intravesical Real-Time Imaging and Staging of Bladder Cancer