Prospective mapping of lymph node metastasis in Japanese patients undergoing radical cystectomy for bladder cancer: characteristics of micrometastasis

Abstract

Objective: To investigate node-disease prevalence including micrometastases and its survival impact on bladder cancer patients. Methods: A total of 60 patients participated in this study, in which extended lymph node dissection was carried out according to the prospective rule (below aortic bifurcation). Radical cystectomy and extended lymph node dissection were performed by open surgery (n = 23) or laparoscopically (n = 37). Perioperative, pathological and follow-up data were collected. Micrometastasis in lymph nodes was investigated by pan-cytokeratin immunohistochemistry. Recurrence-free survival was estimated with the Kaplan-Meier method. Results: The median number of lymph nodes removed was 29 (range: 10-103) and there was no significant difference between the two groups (open group: median 30, laparoscopic group: median 29). Routine pathological examination revealed that 10 patients had lymph node metastases. Immunohistochemistry revealed micrometastases in four additional patients (pNmicro+), who had been diagnosed with pN0 on routine pathological examination. After excluding the three patients with pure nonurothelial carcinoma on the final pathology (small cell carcinoma: n = 2, adenocarcinoma: n = 1), 10 out of the 57 urothelial carcinoma patients (17.5%) had node metastasis, and an additional 4 out of the 47 pN0 patients (4/47, 8.5%) had micrometastasis. The 2-year recurrence-free survival rates divided by pN stage were 82.4% for pN0, 66.7% for pNmicro+ and 12.5% for pN+ (three-sample log-rank test, P < 0.0001). Three out of the four patients with pNmicro+ were disease free at the last follow-up. Conclusions: We confirmed under extended lymph node dissection that a substantial proportion of the patients had node metastasis ( pN+: n = 10 and pNmicro+: n = 4), and the pN stage influenced patient survival. Our observations of micrometastasis yielded additional evidence for the potential survival benefit of extended lymphadenectomy by eliminating microdisease.

Is the pN category in radical cystectomy dependent on the pathologist dissection?

“…This issue has also been discussed for other neoplasia. Although in some studies, micrometastases were detected in 1%-3% of LN when the remaining fat tissue was embedded after palpation [12,13], these findings have a low prognostic impact [14]. Moreover, even if more LN are found when a complete embedding of the remaining tissue is performed, most of them are negative or were already positive at palpation [15][16][17].…”

Increased NUSAP1 expression is associated with lymph node metastasis and survival prognosis in bladder urothelial carcinoma

“…Unfortunately, the failure of several preoperative examinations in detecting micro-metastases is the main reason for the early recurrence of BUC after surgery. The occurrence of micro-metastases is closely related to the clinicopathological characteristics of the tumor (including pathological stage and pathological grade); the more advanced the pathological stage and higher the pathological grade, the more likely is the micro-metastases and recurrence after surgery 28 . In this study, we found that high NUSAP1 expression was significantly correlated with tumor pathological stage, lymph node metastasis, and pathological grade; NUSAP1 expression was significantly higher in patients with T3-T4 TNM stage, higher pathological grades, and positive lymph nodes ( p < 0.05).…”

Lymph node yield in node-negative patients predicts cancer specific survival following radical cystectomy for transitional cell carcinoma

“…Removal of lymph nodes with micrometastatic deposit may improve survival by reducing overall tumour burden and allowing the immune system and chemotherapeutics to target a smaller number of cancer cells [ 24 ]. New techniques employing immunohistochemical analysis and reverse transcription real-time polymerase chain reaction can aid in detection of micrometastases [ 25 26 ]. It has been demonstrated that patients with micrometastases who are otherwise node-negative on routine analysis have a trend toward worse cancer specific survival and recurrence free survival than truly node-negative patients [ 25 ].…”