Japanese Journal of Clinical Oncology 31:399-402 (2001)
© 2001 Foundation for Promotion of Cancer Research
Prognostic Variables in Patients Who Have Undergone Radical Cystectomy for Transitional Cell Carcinoma of the Bladder
Department of Urology, Kobe University School of Medicine, Kobe, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Objective: To evaluate whether several clinicopathological factors could be used as prognostic predictors in patients who have undergone radical cystectomy for transitional cell carcinoma (TCC) of the bladder.
Methods: Between January 1985 and June 2000, 154 patients underwent radical cystectomy and pelvic lymphadenectomy for TCC of the bladder at a single institution. Their clinicopathological findings were analyzed based on the criteria of the Japanese Urological Association.
Results: Histopathological examination revealed that the tumor grade was 1 or 2 in 22 patients and 3 in 132 patients; the pathological stage was pT1 or less in 30 patients, pT2 in 51 patients, pT3 in 53 patients and pT4 in 20 patients. Vascular involvement and lymph node metastasis were found in 85 and 33 patients, respectively. The cause-specific 5-year survival rate was 64.2% for all patients, 74.4% for patients with grade 1 or 2 tumors, 62.9% for those with grade 3 tumors; 90.9% for those with stage pT1 or less, 77.9% for those with stage pT2, 45.0% for those with stage pT3 and 29.2% for those with stage pT4 (p < 0.001); 83.2% for patients without vascular involvement and 42.0% for those with vascular invasion (p < 0.001); and 76.5% for patients without lymph node metastasis and 22.7% for those with lymph node metastasis (p < 0.001). Multivariate analysis revealed a strong independent correlation of the pathological stage and lymph node metastasis with poor prognosis and, furthermore, the incidence of lymph node metastasis was significantly related to the increase in pathological stage.
Conclusions: In this series, the pathological stage, lymph node metastasis and vascular involvement, but not tumor grade, were significantly useful prognostic factors in patients who have undergone radical cystectomy for TCC and among them only pathological stage and lymph node metastasis could be used as independent predictors for poor prognosis.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Radical cystectomy has evolved into the most common therapeutic modality for muscle-invasive transitional cell carcinoma (TCC) of the bladder, with an overall 5-year disease-free survival rate of 50–70% (1–3). However, muscle-invasive TCC is an aggressive malignancy that is widely believed to have a high propensity for distant metastasis (4). In fact, recurrence develops in ~50% of patients who have no evidence of disease after surgery (3,4). Owing to the variability in the clinical behavior of TCC of the bladder after radical cystectomy, factors predicting the biological potential of this malignancy are required to select candidates who should receive adjuvant therapies. Surprisingly, little information on the predictors of outcome after radical cystectomy for bladder cancer are available in the literature (1,5–8). Furthermore, most studies of large series have focused on limited aspects and only a few reports have evaluated a wide range of variables in a non-homogeneous series to determine strong predictors of survival after radical cystectomy (5–8).
In this retrospective analysis, we identified the independent prognostic variables for survival in a large series of patients with adequate follow-up after radical cystectomy for TCC of the bladder.
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SUBJECTS AND METHODS |
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We performed a retrospective analysis of 154 evaluable patients who had undergone radical cystectomy, pelvic lymphadenectomy (bilateral iliac and obturator node dissection) and urinary diversion for TCC of the bladder by the same staff at Kobe University Hospital between January 1985 and June 2000. Bladder cancer was diagnosed by transurethral resection. Physical examination, laboratory studies, chest radiography and intravenous pyelogram (IVP) were performed in all patients. Computed tomography (CT), magnetic resonance imaging and/or abdominal ultrasonography were used for clinical staging. The tumor stage and grade were examined according to the criteria of the General Rules for Clinical and Pathological Studies on Bladder Cancer of the Japanese Urological Association and Japanese Society of Pathology (9). All pathological examinations were performed by a single pathologist.
Indications for surgery included muscle-invasive bladder cancer and diffuse carcinoma in situ before the availability of intravesical Bacillus Calmette–Guerin therapy. Concomitant urethrectomy was performed in patients with preoperative histologically proved TCC of the urethra and/or prostate. The patients were initially seen 2 months after surgery and then every 3 months for 2 years and every 6 months until disease progression or death. Laboratory studies and urinary cytology were performed every 3 months and chest radiography, abdominal and/or pelvic CT and IVP were carried out every 6 months. For the patients who had undergone neobladder replacement, neocystoscopy was performed every 12 months. All survival data were analyzed as the cause-specific survival by the Kaplan–Meier technique using a log-rank test. The prognostic value for some parameters was determined by multivariate Cox regression models. The level of significance was set at p < 0.05.
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RESULTS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The mean patient age was 66 years (range: 42–84 years) and there were 131 men and 23 women. The duration of follow-up ranged from 1 to 183 months with a mean of 23 months. Initial surgical management consisted of radical cystectomy, bilateral iliac and obturator node dissection and urinary diversion including neobladder replacement in 60 patients, continent urinary reserver in 19 patients, ileal conduit in 46 patients and ureterocutaneostomy in 42 patients. Non-surgical supportive treatment before and/or after surgery included 36 and 17 patients receiving neoadjuvant cisplatin-based combination chemotherapy by intravenous and intraarterial injection, respectively, nine patients receiving neoadjuvant radiation therapy, 41 patients receiving adjuvant cisplatin-based combination chemotherapy and two patients receiving adjuvant radiation therapy.
Histopathological examination revealed that the tumor grade at diagnosis was 1, 2 and 3 in one patient (0.7%), 21 patients (13.6%) and 132 patients (85.7%), respectively, and that the pathological stage at diagnosis was pT1 or less, pT2, pT3 and pT4 in 30 patients (19.5%), 51 patients (33.1%), 53 patients (34.4%) and 20 patients (13.0%), respectively. Vascular involvement, as defined by the presence of cancer cells in blood and/or lymph vessels, was demonstrated in 77 patients (50%). After bilateral pelvic lymph node dissection, lymph node metastases were detected in 31 patients (20.1%). The clinical stage in 62 patients who had undergone neoadjuvant therapy was T1 or less, T2, T3 and T4 in 4 patients (6.5%), 22 patients (35.5%), 26 patients (41.9%) and 10 patients (16.1%), respectively, and the pathological stage in those after neoadjuvant therapy was pT1 or less, pT2, pT3 and pT4 in 19 patients (30.6%), 14 patients (22.6%), 24 patients (38.7%) and five patients (8.1%), respectively.
The 5-year survival rates for the patients with stage pT1 or less, pT2, pT3 and pT4 tumors were 90.9, 77.9, 45.0 and 29.2%, respectively. Survival was directly associated with the final pathological stage, that is, as the tumor stage progressed from superficial disease through muscle invasive disease, the survival rates decreased significantly (p < 0.0001) (Fig. 1A). The 5-year survival rate was 83.2% for 77 patients without vascular involvement and 42% for 77 patients with vascular involvement (p < 0.0001) (Fig. 1B). The 5-year survival rates were 76.5% for 123 patients without lymph node metastasis and 22.7% for 31 patients with lymph node metastasis (p < 0.0001) (Fig. 1C). In contrast, there were no significant differences in survival according to gender (male versus female), age (<70 versus 
70 years old) or tumor grade (grade 1 or 2 versus grade 3) (data not shown).
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A Cox multivariate regression analysis was also performed to identify independent predictors and the results of multivariate analysis are summarized in Table 1. Only pathological stage and nodal involvement were predictive of survival in patients undergoing radical cystectomy for TCC of the bladder (p < 0.05 and p < 0.005, respectively), irrespective of gender, age, tumor grade and vascular involvement. Furthermore, as shown in Table 2, the incidence of lymph node metastasis was closely related to the increase in pathological stage.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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An accurate prediction of clinical outcome is particularly important for tailoring the optimal therapeutic strategy for patients with malignant disease. However, for patients who have undergone radical cystectomy for invasive TCC of the bladder, little information on the prognostic predictors is available in the literature (1,5–8). This lack of knowledge of cystectomy for bladder cancer was emphasized by the Consensus Conference on Bladder Cancer (8). Furthermore, based on experimental studies at cellular and molecular levels, novel possible prognostic factors for bladder cancer have been reported, such as serum levels of various growth factors (10,11), activity of matrix metalloproteases (12) and expression of angiogenic factors (13,14); therefore, there is increasing interest in introducing these new factors into routine clinical practice and so a comparison between classical and emerging prognostic factors is required. Identification of prognostic predictors after radical cystectomy also allows the identification of patients at higher risk of tumor recurrence and subsequently the selection of adjuvant therapy. These findings prompted us to evaluate retrospectively a large series of patients with adequate follow-up after radical cystectomy for TCC of the urinary bladder.
The 5-year survival rate after radical cystectomy and pelvic lymphadenectomy for TCC of the bladder was similar to that reported in larger series published previously (15), confirming the proper selection criteria of the present series. In the present retrospective series at a single institution, tumor stage and nodal involvement were the independent predictors of survival, whereas other variables, including gender, age, the tumor grade and vascular involvement, were unable to predict prognosis. To our knowledge, there has been only one report on the classical predictive variables of outcome in a large series of a homogeneous cohort of patients treated with radical cystectomy as monotherapy for bladder cancer (8), demonstrating that tumor stage and lymph node metastasis were independent prognostic predictors. Although some patients in the present series received not only radical cystectomy and pelvic lymphadenectomy but also perioperative chemotherapy or radiation therapy, the multivariate analyses in these two studies identified the same variables as independent prognostic predictors. In fact, our previous studies have demonstrated that such kinds of perioperative therapies did not have a significant impact on the survival in patients with TCC of the bladder (16,17). Moreover, the incidence of nodular involvement was closely related to the increase in pathological stage. These findings suggest that the predictive values of pathological stage and nodal involvement for survival are powerful enough to overcome the differences in the patients’ characteristics, including the treatment schedule.
McDonald and Thompson first reported vascular involvement as more frequently associated with the increasing incidence of muscle invasion, resulting in an unfavorable prognostic significance (18). Heney et al. reported a relationship between vascular involvement and lymph node metastasis (19). However, these findings were not evaluated in a large series of patients and with multivariate analysis. In the present series, despite a significant difference in survival between patients with and without vascular involvement, this variable could not be an independent prognostic predictor. These findings may suggest that vascular involvement is closely associated with more powerful prognostic predictors; therefore, vascular involvement is relevant in univariate but not multivariate analysis.
In conclusion, despite retrospective analysis with a comparatively short duration of follow-up, the present study revealed that pathological stage and lymph node metastasis are the only independent predictors for survival in patients who have undergone radical cystectomy for TCC of the bladder. Therefore, careful follow-up and aggressive adjuvant therapy in patients with these factors should be considered.
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FOOTNOTES |
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+ For reprints and all correspondence: Isao Hara, Department of Urology, Kobe University School of Medicine, 7–5–1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. E-mail: hara@med.kobe-u.ac.jp
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Received January 26, 2001; accepted May 7, 2001.
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