Occult Metastases in Pelvic Lymphadenectomy Specimens From Patients With Urothelial Carcinoma of the Bladder

doi:10.1016/j.urology.2016.03.058

Urology

Volume 94, August 2016, Pages 161-166

https://doi.org/10.1016/j.urology.2016.03.058 Get rights and content

Objective

To identify occult metastases within lymph nodes (LNs) reported as negative by routine histologic evaluation. In patients with high-grade, muscle-invasive urothelial carcinoma (UC) of the bladder, pelvic lymphadenectomy during radical cystectomy demonstrates a survival advantage, increasing with the number of LNs removed, even if negative for metastatic disease. This finding may potentially be explained by the presence of occult metastases.

Materials and Methods

Radical cystectomy specimens with high-grade UC invading the perivesical tissue and negative LNs (pT3N0) between 2000 and 2014 were reviewed. Five levels were cut for each LN block. Two sections were cut per level: 1 stained for hematoxylin and eosin and 1 for AE1/AE3. Micrometastases were defined as tumor deposits >0.2 mm but <2 mm. Isolated tumor cells were defined as ≤0.2 mm. Medical records and survival data were reviewed.

Results

We identified 21 cases, consisting of 370 lymph nodes. Six of 21 patients (29%) had occult metastases, including 5 occult metastatic UC and 1 occult metastatic prostate adenocarcinoma. There were 10 positive LNs; 2 macrometastases, 2 micrometastases, and 6 with ITCs. Two of 6 patients (33%) had lymphovascular invasion identified in the primary tumor. Kaplan-Meier analysis showed no significant difference in overall survival between the group of patients who remained N0 versus those upstaged due to discovery of occult metastases (P-value = .42).

Conclusion

In patients with pT3 UC undergoing cystectomy, we demonstrated the presence of occult metastases in 29% of patients. The high percentage of occult metastases present in these cases possibly explains the proven survival advantage of removing “negative” LNs. This finding might also have implications in the histologic evaluation of LNs.

Section snippets

Materials and Methods

We retrospectively reviewed the University of Alabama at Birmingham archives from 2000 to 2014 for radical cystectomy cases performed for invasive high-grade urothelial carcinoma that had negative lymph nodes by routine sectioning and hematoxylin and eosin (H&E) staining. For our institution, routine processing of lymph nodes includes gross palpation and identification of lymph nodes in pelvic lymphadenectomy specimens. Smaller lymph nodes are embedded whole, whereas larger lymph nodes (1 cm or

Results

We identified 21 radical cystectomy or cystoprostatectomy cases, including 15 males and 6 females, with final pathology demonstrating high-grade urothelial carcinoma invading the perivesical fat, containing a total of 370 negative lymph nodes by routine sectioning and H&E staining. Nine of 21 tumors (43%) were conventional high-grade urothelial carcinoma, 5 of 21 (24%) had papillary morphology, 5 of 21 (24%) showed squamous differentiation, 1 of 21 (5%) had glandular differentiation, and 1 of

Discussion

Accurate staging is important for patients with urothelial carcinoma of the bladder both in terms of prognosis and therapeutic options. The presence of lymph node metastases is a well-established predictor of disease recurrence and cancer-specific survival in patients with bladder cancer.4, 8, 9, 10, 11 In the tumor node metastasis staging system, lymph node (N) staging is based both on the number of metastases as well as location, with metastases outside of the true pelvis having a higher

Conclusion

We demonstrated the presence of occult metastases in lymph nodes considered negative by routine histology in 29% of patients with pT3 urothelial carcinoma undergoing radical cystectomy. The relatively high percentage of occult metastases possibly explains the survival advantage of lymphadenectomy even in “negative” lymph nodes as assessed by routine histology. Given that patients with nodal metastases can be offered adjuvant therapy, this finding might have implications in the standard

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Artificial intelligence-based model for lymph node metastases detection on whole slide images in bladder cancer: a retrospective, multicentre, diagnostic study
2023, The Lancet Oncology
Accurate lymph node staging is important for the diagnosis and treatment of patients with bladder cancer. We aimed to develop a lymph node metastases diagnostic model (LNMDM) on whole slide images and to assess the clinical effect of an artificial intelligence-assisted (AI) workflow.
In this retrospective, multicentre, diagnostic study in China, we included consecutive patients with bladder cancer who had radical cystectomy and pelvic lymph node dissection, and from whom whole slide images of lymph node sections were available, for model development. We excluded patients with non-bladder cancer and concurrent surgery, or low-quality images. Patients from two hospitals (Sun Yat-sen Memorial Hospital of Sun Yat-sen University and Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China) were assigned before a cutoff date to a training set and after the date to internal validation sets for each hospital. Patients from three other hospitals (the Third Affiliated Hospital of Sun Yat-sen University, Nanfang Hospital of Southern Medical University, and the Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China) were included as external validation sets. A validation subset of challenging cases from the five validation sets was used to compare performance between the LNMDM and pathologists, and two other datasets (breast cancer from the CAMELYON16 dataset and prostate cancer from the Sun Yat-sen Memorial Hospital of Sun Yat-sen University) were collected for a multi-cancer test. The primary endpoint was diagnostic sensitivity in the four prespecified groups (ie, the five validation sets, a single-lymph-node test set, the multi-cancer test set, and the subset for a performance comparison between the LNMDM and pathologists).
Between Jan 1, 2013 and Dec 31, 2021, 1012 patients with bladder cancer had radical cystectomy and pelvic lymph node dissection and were included (8177 images and 20 954 lymph nodes). We excluded 14 patients (165 images) with concurrent non-bladder cancer and also excluded 21 low-quality images. We included 998 patients and 7991 images (881 [88%] men; 117 [12%] women; median age 64 years [IQR 56–72]; ethnicity data not available; 268 [27%] with lymph node metastases) to develop the LNMDM. The area under the curve (AUC) for accurate diagnosis of the LNMDM ranged from 0·978 (95% CI 0·960–0·996) to 0·998 (0·996–1·000) in the five validation sets. Performance comparisons between the LNMDM and pathologists showed that the diagnostic sensitivity of the model (0·983 [95% CI 0·941–0·998]) substantially exceeded that of both junior pathologists (0·906 [0·871–0·934]) and senior pathologists (0·947 [0·919–0·968]), and that AI assistance improved sensitivity for both junior (from 0·906 without AI to 0·953 with AI) and senior (from 0·947 to 0·986) pathologists. In the multi-cancer test, the LNMDM maintained an AUC of 0·943 (95% CI 0·918–0·969) in breast cancer images and 0·922 (0·884–0·960) in prostate cancer images. In 13 patients, the LNMDM detected tumour micrometastases that had been missed by pathologists who had previously classified these patients' results as negative. Receiver operating characteristic curves showed that the LNMDM would enable pathologists to exclude 80–92% of negative slides while maintaining 100% sensitivity in clinical application.
We developed an AI-based diagnostic model that did well in detecting lymph node metastases, particularly micrometastases. The LNMDM showed substantial potential for clinical applications in improving the accuracy and efficiency of pathologists' work.
National Natural Science Foundation of China, the Science and Technology Planning Project of Guangdong Province, the National Key Research and Development Programme of China, and the Guangdong Provincial Clinical Research Centre for Urological Diseases.
Squamous Cell Carcinoma of the Bladder Is Not Associated With High-risk HPV
2020, Urology
Citation Excerpt :
Other studies in bladder cancer have similarly identified the number of positive lymph nodes and the total lymph nodes removed as a predictor of survival.17 This consistently prognostic feature across studies highlights the importance of appropriate lymphadenectomy and pathologic processing/assessment in cystectomy cases.18,19 Interestingly, we found perineural invasion to be an independent prognostic marker of overall mortality, cancer-specific mortality, and recurrence-free survival.
To evaluate the clinical features, pathologic features, and prevalence of human papilloma virus (HPV) in squamous cell carcinoma (SCC) of the bladder. SCC of the bladder is known to be associated with conditions that cause chronic inflammation/irritation. The literature is inconsistent regarding the association of HPV with pure SCC of the bladder.
A multi-institutional study identified cases of SCC of the bladder. Pure squamous histology and the absence of urothelial carcinoma in situ were required for inclusion. Clinical and pathologic features were collected, and tissues were evaluated for high-risk HPV using p16 immunohistochemistry and in situ hybridization.
We identified 207 cases of SCC of the bladder. Risk factors for bladder cancer included smoking (133/207, 64%) and chronic bladder irritation (83/207, 40%). The majority (155/207, 75%) of patients had > pT2 disease. Mean tumor size was 5.6 ± 3.0 cm and 36/207 (17%) patients had lymph node positive disease. p16 immunohistochemistry was positive in 52/204 (25%) cases but high-risk HPV was identified with in situ hybridization in only 1 (0.5%) case. Tumor size, stage, number of lymph nodes removed, number of positive lymph nodes, lymphovascular invasion, perineural invasion, and positive margins each were associated with cancer-specific mortality when adjusted for demographic factors. A multivariate analysis of variable importance further revealed sex and race as important factors in predicting cancer-specific mortality.
SCC of the bladder is an aggressive histologic subtype. Although bladder SCC can express p16, it is not typically associated with high-risk HPV, although rare cases can occur.
Disseminated tumour cells in bladder cancer
2022, Urologie

: Financial Disclosure: The authors declare that they have no relevant financial interests.

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OncologyOccult Metastases in Pelvic Lymphadenectomy Specimens From Patients With Urothelial Carcinoma of the Bladder

Objective

Materials and Methods

Results

Conclusion

Section snippets

Materials and Methods

Results

Discussion

Conclusion

Urology

J Urol

Surgery

Eur Urol

Urol Oncol

Urology

Eur Urol

Mod Pathol

Eur Urol

Eur Urol

J Urol

Eur Urol

Clin Genitourin Cancer

Cancer Treat Rev

Oncology
Occult Metastases in Pelvic Lymphadenectomy Specimens From Patients With Urothelial Carcinoma of the Bladder