Cancer‐specific survival after radical cystectomy and standardized extended lymphadenectomy for node‐positive bladder cancer: prediction by lymph node positivity and density

OBJECTIVE

To investigate the associations between different overall or topographically restricted lymph node (LN) variables and cancer‐specific survival (CSS) after radical cystectomy (RC) and extended LN dissection (LND) with curative intent in patients with LN‐positive bladder cancer.

PATIENTS AND METHODS

Between 2001 and 2006, 152 patients had RC with standardized extended LND for bladder cancer with curative intent. Patients with positive LNs were stratified according to the median of the LN variables (LNs removed, number of positive LNs, LN density). CSS was related to overall and topographically restricted LN variables, e.g. different levels of LND, and relationships were tested by univariate and multivariate analyses. Level 1 LND comprised the regions of the external and internal iliac LNs and of the obturator LNs, level 2 the templates of common iliac and presacral LNs, and level 3 the para‐aortic and paracaval LNs up to the inferior mesenteric artery. The mean (range) follow‐up was 22 (1–84) months.

RESULTS

LN metastases were diagnosed in 46 of the 152 patients (30%) with extended LND. In these 46 patients, the median number of removed LNs was 33 (level 1, 15.5; level 2, 9.0; level 3, 7.0), the median number of positive LNs was 3 (1.5, 0.5 and 0.0, respectively) and the median LN density was 0.11 (0.10, 0.02 and 0.0, respectively). The CSS was 76% at 1 year and 23% at 3 years. There were significant correlations between the 3‐year CSS and the overall LN density (≤0.11 vs >0.11; 34% vs 8%, P = 0.008), and the total number of positive LNs (≤3 vs >3; 33% vs 8%; P = 0.05). Overall LN density (hazard ratio 0.33, 95% confidence interval 0.15–0.72; P = 0.006) was an independent predictor for CSS in multivariate analysis.

CONCLUSIONS

Overall LN density is an independent predictor of survival after RC and extended LND with curative intent. Evaluation of topographically restricted LN positivity and density for different regions and levels of LND does not improve the prediction of CSS compared with overall LN positivity and density. A low incidence of level 3 LN positivity questions the clinical relevance of removing para‐aortic and paracaval LNs. However, our data need to be confirmed by a prospective randomized trial.     

Outcome of patients with grossly node positive bladder cancer after pelvic lymph node dissection and radical cystectomy

PURPOSE: Should the surgeon proceed with surgery when grossly positive nodes are found at cystectomy? To answer this question, we determine the outcome of patients after radical surgery alone for grossly node positive bladder cancer. MATERIALS AND METHODS: A total of 84 patients with grossly node positive (N2-3) bladder cancer found at cystectomy underwent extended pelvic lymph node dissection and have been followed for up to 10 years. The end point of study was disease specific survival. RESULTS: Of the 84 patients 20 (24%) survived and 64 (76%) died of disease. Median survival time was 19 months for all patients and 10 years for surviving patients. Of 53 patients with clinical stage T2 (organ confined) tumors 17 (32%) survived versus 3 of 31 (9.7%) with stage T3 (extravesical) tumors. CONCLUSIONS: A proportion of patients with grossly node positive bladder cancer can be cured with radical cystectomy and thorough pelvic lymph node dissection.     

Nodal involvement in bladder cancer cases treated with radical cystectomy: incidence and prognosis

PURPOSE: We studied the factors that promote the incidence of nodal metastasis and characterized survival predictions in cases treated with radical cystectomy. MATERIALS AND METHODS: We retrospectively studied 418 bladder cancer cases treated with radical cystectomy and bilateral endopelvic lymphadenectomy. The incidence of nodal involvement was correlated with several patient and tumor characteristics. The number of involved nodes was also correlated with the number of retrieved nodes. Finally, survival in node positive cases was correlated with some select pathological features. RESULTS: Of the 418 cases nodal involvement was reported in 110 (26.3%). The mean number of harvested nodes per patient +/- SE was 17.9 +/- 6.7. The mean number of positive nodes per involved case was 4.1 +/- 5.4. A weak correlation between the number of retrieved nodes and number of positive nodes was noted (r = 0.4). Tumor pT stage and grade, and lymphovascular invasion were independent factors promoting the incidence of nodal involvement. Three-year disease-free survival in node positive cases was 37.8% +/- 4.8%. Two factors had an independent impact on survival in node positive cases, namely pT stage and the number of positive nodes. CONCLUSIONS: Tumor pT stage and grade, and lymphovascular invasion independently influence the incidence of lymph node involvement. There was a weak correlation between the number of retrieved nodes and number of positive nodes. The survival probability in pT N+ cases depended on pT stage and the number of involved nodes. A prospective study with anatomical mapping of retrieved nodes is necessary to define the optimal extent of lymphadenectomy with cystectomy.     

Stage specific lymph node metastasis mapping in radical cystectomy specimens

PURPOSE: We provide an accurate map of lymph node (LN) metastasis in patients with bladder cancer undergoing radical cystectomy and pelvic lymph node dissection. MATERIALS AND METHODS: We analyzed data on 176 consecutive patients operated on by the same surgeon. The extent of node dissection included presacral, bilateral common iliac and pelvic, and perivesical. The number of LNs removed from each site and the number of metastases bearing nodes were recorded separately. Stage specific maps were constructed. RESULTS: The median number of LNs removed was 25 (range 2 to 80). Metastases were found in the lymph nodes of 43 patients (24.4%) and the median number of positive nodes was 3 (range 1 to 63). Of these patients 22 (51%) had lymph node involvement at more than 1 site. The mean number of positive/total LNs sampled +/- SD in LN positive cases was 26% +/- 28% and the median was 13% (range 1.9 to 100%). Only 1 of the patients with pT1 (3.6%) had LN metastases, which was in the pelvic region. Only 2 of the patients with pT2 (3%) had LN metastases outside of the true pelvis and perivesical sites. Of patients with pT3 or pT4 16% had LN metastases outside the common boundaries for standard LN dissection, namely the common iliac artery and at or above aortic bifurcation. CONCLUSIONS: We present a detailed map of regional LN involvement in patients treated with radical cystectomy and lymph node dissection for transitional cell cancer of the bladder. Extensive LN dissection is essential for the complete removal of disease and accurate staging.     

根治性膀胱切除术中扩大淋巴结清扫术不可滥用

根治性膀胱全切+尿流改道术是目前肌层浸润性膀胱肿瘤的首选治疗,盆腔淋巴结清扫术是其中的必要步骤,其对进行肿瘤准确分期、判断患者预后、提高患者的生存率至关重要,而是否所有膀胱癌患者都应该行扩大淋巴结清扫术学界尚无定论。在此,作者结合文献报道和临床诊治体会,就根治性膀胱切除术中扩大淋巴结清扫术的意义与适应征作一简要探讨。     

Role of lymphadenectomy in the management of urothelial carcinoma of the bladder and the upper urinary tract

The role of lymphadenectomy has been controversial in urological malignancies. Urothelial carcinoma of the bladder and upper urinary tract has a high potential to spread through the lymphatic network compared with other malignancies, including renal cell carcinoma or prostate cancer. In urothelial carcinoma of the bladder, lymphadenectomy of pelvic nodes had been considered as the standard procedure when radical cystectomy was carried out. Recently, many investigators have examined the influence of its extent, and the majority of the studies have supported the beneficial role of extended lymphadenectomy in accurate staging or in improving patient survival. Although randomized controlled trials are required to establish a greater level of evidence, more urological surgeons have already noticed the necessity for extended lymphadenectomy in bladder cancer. In contrast to bladder cancer, there have been far fewer studies on urothelial carcinoma of the upper urinary tract. This might be because of the smaller number of the patients with urothelial carcinoma of the upper urinary tract and the lack of understanding of regional nodes. However, studies of lymph node mapping and the retrospective analyses with respect to the benefit of lymphadenectomy have been carried out in urothelial carcinoma of the upper urinary tract by some investigators, although the results are still controversial. However, the results from multi‐institutional studies by high volume centers have supported the beneficial role of lymphadenectomy in urothelial carcinoma of the upper urinary tract, as it has been proposed in bladder cancer. Thus, lymphadenectomy for urothelial carcinoma of the bladder and the upper urinary tract might have a potential role in staging and improving the oncological outcomes.     

p53 nuclear accumulation is not associated with decreased disease-free survival in patients with node positive transitional cell carcinoma of the bladder

PURPOSE: Although the majority of patients with node positive transitional cell carcinoma of the bladder have disease progression, a definitive subset is cured by surgery only. Nuclear accumulation of p53 has been associated with disease progression in patients with superficial transitional cell carcinoma and decreased survival in those with muscle invasive disease. We determined whether p53 status would predict survival in a cohort with nodal metastasis. MATERIALS AND METHODS: We explored the comprehensive database of all 199 radical cystectomies performed at our institution between July 1988 and September 1999. The 59 patients in this database with node positive pathology comprise our study. We performed immunohistochemical analysis of specimens using the MAB1801 antibody with greater than 20% lymph node and primary tumor nucleus staining deemed positive. Additional covariates measured included patient age, sex, pathological disease stage, adjuvant chemotherapy and nodal stage. Disease-free survival curves were generated for the various covariates and compared using the log rank test. The Cox proportional hazards technique was used to determine covariate adjusted p53 survival. RESULTS: In the cohort overall median disease-free survival was only 21 months, although 18% of patients were disease-free at 5 years. There was evidence of p53 nuclear accumulation in 54% of cases and complete agreement of nodal with bladder p53 nuclear accumulation. No significant baseline differences were noted in the covariates with respect to p53 nuclear accumulation. For stratum specific disease-free survival univariate and multivariate analyses revealed that only pathological stages p0-p2b versus p3-p4 (hazards ratio 2.86, p = 0.03), and nodal stages N2 versus N1 and N3 versus N1 (hazards ratio 3.84, p = 0.01 and hazards ratio 13.3, p = 0.0002, respectively) were significantly associated with prolonged disease-free survival, while p53 nuclear accumulation was not. CONCLUSIONS: Despite credible evidence for p53 nuclear accumulation prognostication in patients with in situ and invasive transitional cell carcinoma, this marker is not predictive of disease-free survival in node positive disease.     

Superiority of ratio based lymph node staging for bladder cancer

PURPOSE: The current study evaluated lymph node staging and the outcome in patients with lymph node positive bladder cancer after radical cystectomy. MATERIALS AND METHODS: A total of 162 patients with lymph node positive bladder cancer were followed a median of 7.5 years after radical cystectomy and pelvic lymph node dissection for survival and local recurrence. Lymph node disease was stratified by pN stage, the number of positive lymph nodes and the number of positive lymph nodes in relation to the number removed (ratio based pN stage). RESULTS: A median of 13 lymph nodes (range 2 to 32) was examined, showing an average of 3.3 positive lymph nodes per specimen. An increased number of lymph nodes correlated with the identification of lymph node positive cases. The ratio of the number of positive-to-total number of lymph nodes removed better defined surgical outcome than conventional lymph node staging. CONCLUSIONS: Ratio based lymph node staging, which reflects the number of lymph nodes examined and the quality of lymph node dissection, was a significant prognostic variable for survival and local control in patients with lymph node positive bladder cancer after radical cystectomy.     

Retroperitoneal lymph node dissection in patients with interaortocaval lymph node metastases of transitional cell carcinoma of the urinary tract

Three patients suffered from renal pelvic, ureteral and bladder cancers that were treated with both standard surgical treatments and two adjuvant cycles of cisplatin-based combination chemotherapy. Metastases of interaortocaval lymph nodes were detected in all patients between 9 and 33 months from the surgery for primary lesions. All patients received three cycles of cisplatin-based combination chemotherapy and retroperitoneal lymph node dissection (RPLND). The chemotherapy achieved partial response (62-98%). Two patients with viable cancer cells died with hepatic metastases; the first 15 months and the second 25 months from the date of diagnosis of distant lymph node metastasis. The third patient, who had no viable cancer cells, remains alive and disease-free 36 months later. Therefore, RPLND after chemotherapy provides prognostic information that helps to define patients who might benefit from additional systemic chemotherapy.     

Stage-specific impact of pelvic lymph node dissection on survival in patients with non-metastatic bladder cancer treated with radical cystectomy

Study Type – Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? In patients treated with radical cystectomy, pelvic lymph node dissection may have a beneficial effect on cancer control outcomes. We examined the effect of pelvic lymph node dissection on stage‐specific cancer control outcomes.

OBJECTIVE

• ? To examine the effect of stage‐specific pelvic lymph node dissection (PLND) on cancer‐specific (CSM) and overall mortality (OM) rates at radical cystectomy (RC) for bladder cancer.

METHODS

• ? Overall, 11 183 patients were treated with RC within the Surveillance, Epidemiology, and End Results database.
• ? Univariable and multivariable Cox regression analyses tested the effect of PLND on CSM and OM rates, after stratifying according to pathological tumour stage.

RESULTS

• ? Overall, PLND was omitted in 25% of patients, and in 50, 35, 27, 16 and 23% of patients with respectively pTa/is, pT1, pT2, pT3 and pT4 disease (P < 0.001).
• ? For the same stages, the 10‐year CSM‐free rates for patients undergoing PLND compared with those with no PLND were, respectively, 80 vs 71.9% (P = 0.02), 81.7 vs 70.0% (P < 0.001), 71.5 vs 56.1% (P = 0.001), 43.7 vs 38.8% (P = 0.006), and 35.1 vs 32.0% (P = 0.1).
• ? In multivariable analyses, PLND omission was associated with a higher CSM in patients with pTa/is, pT1 and pT2 disease (all P ≤ 0.01), but failed to achieve independent predictor status in patients with pT3 and pT4 disease (both P ≥ 0.05).
• ? Omitting PLND predisposed to a higher OM across all tumour stages (all P ≤ 0.03).

CONCLUSIONS

• ? Our results indicate that PLND was more frequently omitted in patients with organ‐confined disease.
• ? The beneficial effect of PLND on cancer control outcomes was more evident in these patients than in those with pT3 or pT4 disease.
• ? PLND at RC should always be considered, regardless of tumour stage.

     

Value of frozen sections of lymph nodes in pelvic lymphadenectomy in patients with invasive bladder tumor

AIM: We examined the reliability of classical lymph node evaluation methods. We compared the results of preoperative computed tomography (CT) and perioperative frozen section examination of lymph nodes in patients on whom radical cystectomy was performed because of invasive bladder tumors. METHODS: A total of 142 patients, in whom radical cystectomy was performed because of invasive bladder tumors between the years 1994 and 2005 in our clinic, and 284 pelvic lymph node regions were evaluated retrospectively. For each of the pelvic lymph node region, the conditions of the lymph nodes according to CT and in frozen sections were compared with the final pathology reports of the surgical specimens. RESULTS: Lymph node involvement was found in 36 pelvic regions out of 284 in the final pathology. It had been possible to show only two of the 36 positive lymph nodes in preoperative CT. Frozen section results of the 29 pelvic lymph node regions out of 36 that were involved according to the final pathology were positive also according to frozen section results. On the other hand, in all the 29 lymph node regions those that were positive according to frozen section had lymph node involvement in the final pathology. CONCLUSIONS: We recommend the performance of frozen section examination on obturator plus internal iliac lymph nodes when deciding extended lymph node dissection, and the performance of extended lymph node dissection only if the result is positive.