Risk Factors For Intravesical Recurrence Research Articles

Suppressed Recurrent Bladder Cancer after Androgen Suppression with Androgen Deprivation Therapy or 5α-Reductase Inhibitor

We determined whether intravesical recurrence is affected by inhibition of androgen signaling among men with nonmuscle invasive bladder cancer. We examined the intravesical recurrence rate among men treated with or without androgen suppression therapy by androgen deprivation therapy for prostate cancer or 5α-reductase inhibitor dutasteride for benign prostatic hyperplasia. We studied 228 men, including 32 with and 196 without androgen suppression therapy. During a median followup of 3.6 and 3.0 years intravesical recurrence developed in 4 (12.5%) and 59 men (30.1%) with and without androgen suppression therapy, respectively. On multivariate analysis multiple tumors (HR 1.82, p = 0.027), a large tumor (HR 2.13, p = 0.043) and ever smoking (HR 2.45, p = 0.020) as well as the presence of androgen suppression therapy (HR 0.36, p = 0.024) were independent risk factors for intravesical recurrence. Notably, tumor progressed to muscle invasive bladder cancer in 6 men (3.1%) without androgen suppression therapy. No man with androgen suppression therapy progressed to muscle invasive bladder cancer. Our study suggests the possibility of androgen suppression therapy as prophylaxis for intravesical recurrence of bladder cancer. Further explorations are warranted of the prophylactic effect of androgen suppression therapy on bladder cancer pathogenesis.

Bacillus Calmette-Guerin therapy after the second transurethral resection significantly decreases recurrence in patients with new onset high-grade T1 bladder cancer.

BackgroundThe purpose of this study was to assess the efficacy of Bacillus Calmette-Guerin (BCG) therapy after a second transurethral resection (TUR) in new onset high-grade T1 bladder cancer.MethodsFrom January 2008 to September 2013, 207 patients with new onset high-grade T1 bladder cancer after an initial TUR were treated at our university and at affiliated hospitals. Residual cancer rate, intravesical recurrence-free survival (RFS), and risk factors for intravesical recurrence were analyzed.ResultsAmong a total of 207 patients, 42 patients were treated with BCG therapy following a second TUR (group 1), 23 were treated with second TUR alone (group 2), 72 were treated with BCG alone (group 3), and 70 were treated without a second TUR or BCG. The median patients’ age was 72.0 years, and the median follow-up period was 33.5 months. The second TUR revealed that 34 patients (52 %) had residual cancer. Between groups 1 and 2 and groups 1 and 3, the differences in RFS were statistically significant (p = 0.002 and 0.045, respectively). In addition, BCG therapy was the most significant factor to predict RFS after the second TUR. Among the 31 patients whose pathology of the second TUR was pT0, only 1 of 12 patients (8 %) in group 1 and 11 of 19 patients (58 %) in group 2 had a recurrence.ConclusionsBCG instillation following a second TUR decreases intravesical recurrence, even if the pathology of the second TUR is pT0.

Tumour multifocality and grade predict intravesical recurrence after nephroureterectomy in patients with upper urinary tract urothelial carcinoma without a history of bladder cancer.

Patients with upper urinary tract urothelial carcinoma (UUT-UC) without a history of bladder cancer have a different natural history of intravesical recurrence after nephroureterectomy compared with those with a history of bladder cancer. The aim of this study was to identify predictive factors for post-operative intravesical recurrence in patients with non-metastatic upper urinary tract-localized urothelial carcinoma without a history of bladder cancer and who were not taking medication during the perioperative period. This retrospective study included 133 patients who were treated between 1995 and 2012. Univariate and multivariate analyses were used to evaluate the clinical and pathological factors associated with the cumulative incidence of bladder cancer. Of the 133 patients, 51 (38.3%) developed intravesical recurrence during a median follow-up of 71 months (range, 0.8-210.8). In the multivariate analysis, multifocality (P = 0.03) and high tumour grade (P = 0.007) were significantly associated with the cumulative incidence of bladder cancer. We constructed a prediction classification model on the basis of the total number of risk factors. The 2-year cumulative incidence rates were 5.6, 34.8 and 50.0% in individuals with no, one and two risk factors, respectively. There was a significant difference between patients with no risk factors and those with two risk factors (P = 0.01). Although this retrospective study had several limitations, tumour multifocality and tumour grade were found to be potential risk factors for intravesical recurrence in our cases.

RISK FACTORS FOR INTRAVESICAL RECURRENCE AFTER SURGICAL MANAGEMENT OF UROTHERIAL CARCINOMA OF THE UPPER URINARY TRACT

To identify risk factors for developing recurrent bladder cancer in patients who underwent surgical resection for urothelial carcinoma of the upper urinary tract. We retrospectively analyzed 322 patients who underwent surgical resection for urothelial carcinoma of the upper urinary tract at the Jikei University Hospital and our affiliated hospitals between January 2005 and July 2011. Univariate and multivariate analyses by using the Cox proportional hazards model were performed to determine the risk factors for intravesical recurrence after nephroureterectomy in these 322 patients. Of the 322 patients, 111 patients (34.5%) developed recurrent bladder cancer after a median interval of 8.0 months. On multivariate analysis, the presence of a superficial tumor and the presence of a ureteral tumor were independent predictors for intravesical recurrence. The risk factors for developing recurrent bladder cancer were the presence of a superficial tumor and the presence of a ureteral tumor. Further investigation is required to evaluate the efficacy of perioperative intravesical therapy for the prevention of intravesical recurrence.

Risk factors for intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma: A meta-analysis

PurposeAfter radical nephroureterectomy (RNU), approximately 22% to 47% of patients with upper tract urothelial carcinoma (UTUC) develop a subsequent intravesical recurrence (IVR). Considering this high incidence of occurrence, several risk factors were reported as predictive of IVR after RNU. Until recently, most of the risk factors were still under debate. The aim of study was to conduct a meta-analysis based on the recent literature to explore the risk factors for IVR after RNU for UTUC. Patients and methodsAn electronic search of the Medline, Embase, Cochrane Library, CancerLit, and ClinicalTrials.gov databases was performed to identify relevant studies published before May 2013. The studies were included if they reported risk factors related to bladder or IVR after RNU for UTUC. ResultsOverall, 40 studies, with 12,010 patients, were included in our meta-analysis. Our study indicated that a statistically significant difference in IVR after RNU was found in the male vs. female patients (odds ratio [OR] = 0.72, 95% CI: 0.59–0.85), ureteral vs. renal pelvis (OR = 1.18, 95% CI: 1.00–1.36), T2–4 vs. Tis, Ta, and T1 (OR = 0.53, 95% CI: 0.40–0.66), larger vs. smaller tumor size (OR = 1.02, 95% CI: 1.01–1.03), and previous/synchronous bladder cancer vs. the absence of bladder cancer (OR = 1.59, 95% CI: 1.26–1.9). No significant differences in IVR after RNU were found in the younger vs. older age groups, multifocal tumors vs. single tumor, G3 vs. G1 and G2, high vs. low grade, N0 vs. N+, concomitant carcinoma in situ vs. the absence of carcinoma in situ, positive vs. negative lymphovascular invasion, open vs. laparoscopic nephroureterectomy, and endoscopic vs. transvesical technique. ConclusionsOur study showed that female patient; ureteral tumor; larger tumor; Tis, Ta, and T1; and the history of bladder cancer were significant risk factors related to IVR after RNU.

Pathological risk factors in upper urinary tract cancer

To evaluate pathological factors for prognosis, intravesical recurrence and distant metastasis of upper urinary tract cancer. This clinical study included 105 patients with renal pelvic and ureteral cancer who were treated at the Kochi Medical School Hospital between 1982 and 2008. Of these patients, 90 who underwent nephroureterectomy were analyzed for pathological risk factors using uni- and multivariate analysis. The mean follow-up period of the 105 patients was 53 months. The disease-specific survival rates were 70% and 62% at 3 and 5 years. Twenty-three patients (23%) developed intravesical recurrence, and the mean and median times to recurrence were 18.8 and 9.2 months, respectively. Seventeen patients (19%) had distant metastasis, and the mean and median times to distant metastasis were 25.2 and 25.3 months, respectively. Multivariate analysis identified the pathological grade as an independent risk factor for prognosis (P = 0.031), age (≥67 years) and tumor diameter (≥3 cm) as independent risk factors for intravesical recurrence (P = 0.007 and 0.003, respectively), and the pathological grade (G1,2 vs G3) and lymphatic invasion as independent risk factors for distant metastasis (P = 0.006 and 0.003, respectively). Patients with higher-grade upper urinary tract cancer show a poor prognosis, and often develop distant metastasis, suggesting the need for careful postoperative follow-up. Those with lymphatic invasion or tumors of 3 cm or more in diameter frequently develop intravesical recurrence and distant metastasis, respectively, indicating the need for strict follow-up.

Independent prognostic factors for initial intravesical recurrence after laparoscopic nephroureterectomy for upper urinary tract urothelial carcinoma

ObjectiveTo elucidate clinicopathologic independent prognostic factors for intravesical recurrence after laparoscopic nephroureterectomy for primary upper urinary tract urothelial carcinoma (UUT-UC). Methods and materialsThis study included 212 consecutive patients clinically diagnosed as localized UUT-UC and treated by retroperitoneal laparoscopic nephroureterectomy between January 2002 and October 2010, after exclusion of those with a previous or concurrent history of bladder cancer. The clinicopathologic features, risk factors, and intravesical recurrence–free survival were analyzed using the Kaplan-Meier method. Univariate and multivariate analyses by Cox proportional hazards regression model was used to identify independent risk factors for intravesical tumor recurrence. ResultsOf the patients, 64/212 (30.2%) developed subsequent intravesical recurrence during a median follow-up period of 39 months (range 7–78 months). Among them, 56/64 (87.5%) developed recurrent bladder cancer within 2 years after the surgery for UUT-UC, and the median interval between surgery and intravesical recurrence was 14 months (range 7–51 months). Multifocal tumors, renal insufficiency, and immunosuppression were determined as risk factors for intravesical recurrence by univariate analysis. However, by multivariate analyses, multifocality (hazard ratio = 2.060, P = 0.006) and immunosuppression (hazard ratio = 1.915, P = 0.037) were identified as independent predictors for the development of recurrent bladder cancer. ConclusionsThe incidence of intravesical recurrence after laparoscopic nephroureterectomy for UUT-UC is high, and most subsequent bladder cancers recur within 2 years after surgery. Tumor multifocality and immunosuppression are significant independent risk factors in developing initial intravesical recurrence after laparoscopic surgery for primary UUT-UC.

Risk Factors for Intravesical Recurrence in Patients with High-grade T1 Bladder Cancer in the Second TUR Era

We aimed to elucidate risk factors for intravesical recurrence of high-grade T1 bladder cancer in the second transurethral resection era. The analysis included 73 patients with high-grade T1 bladder cancer on initial transurethral resection. The median follow-up period was 49.2 months. Recurrence-free survival, progression-free survival and risk factors related to the presence of residual tumors or recurrence-free survival were statistically analyzed. The pathological findings for second transurethral resection were pT0 36 (49%), pTis/a 21 (29%), pT1 13 (18%) and pT2 3 (4%), respectively. The risk factor for residual tumors at second transurethral resection was the presence of concomitant carcinoma in situ at the initial transurethral resection (P < 0.01). The bladder was preserved in all 57 patients with pT0/is/a tumors on second transurethral resection, and 43 patients (75%) received intravesical BCG therapy. Of these patients, 3-year recurrence-free survival and 3-year progression-free survival rates were 81 and 96%, respectively. In addition, the presence of pTis/a residual tumors on second transurethral resection had a significant impact on the recurrence. Five of the 13 patients with pT1 on second transurethral resection were immediately treated by radical cystectomy or radiation therapy combined with chemotherapy, and two (25%) of the eight who were treated by intravesical BCG therapy had progression including distant metastasis. High recurrence-free survival and progression-free survival were achieved by a second transurethral resection and intravesical BCG therapy in the patients with pT0/is/a on the second transurethral resection. In this group, the residual tumors at second transurethral resection are risk factors for intravesical recurrence.

Intravesical Recurrence after Surgical Management of Urothelial Carcinoma of the Upper Urinary Tract

Objectives: To elucidate clinicopathological risk factors for intravesical recurrence (IVR) in patients undergoing nephroureterectomy for upper urinary tract urothelial carcinoma (UUT-UC). Methods: We identified a study population of 151 consecutive patients without previous or concurrent bladder cancer who underwent nephroureterectomy for UUT-UC. IVR was assessed in relation to tumor location, size, and multifocality, operation modality and time, stage, grade, lymphovascular invasion, regional lymph node metastasis, preoperative urinary cytology, and perioperative chemotherapy. The median follow-up time was 24 months. Results: Of 151 patients, 51 (34%) developed IVR after nephroureterectomy, and 50 (98%) of the patients presented with IVR within 2 years. Tumor multifocality and site (located in ureter) were determined as risk factors for IVR by univariate analysis. In a multivariate analysis, only tumor multifocality (relative risk: 4.024, p = 0.001) was an independent predictor of IVR. Ten-year cancer-specific survival rates for the patients with and without IVR were 68 and 52%, respectively (p = 0.06). Conclusions: Tumor multifocality is a significant risk factor in developing IVR after surgery for UUT-UC. These results indicate that despite most IVR occurring within 2 years of treatment, it is necessary to follow such patients more closely using cystoscopy. However, IVR is unlikely to indicate a poorer prognosis.

Muscle-invasive bladder cancer developing after nephroureterectomy for upper urinary tract urothelial carcinoma

ObjectivesTo evaluate the risk factors and prognosis of muscle-invasive bladder cancer (MIBC) developing after nephroureterectomy for upper urinary tract urothelial cell carcinoma (UUT-UC). Materials and methodsWe reviewed the medical records of 422 patients who underwent nephroureterectomy for UUT-UC between 1990 and 2010, and identified 173 (40.9%) with intravesical recurrence and 28 (6.6%) with MIBC. We evaluated the clinicopathologic features, risk factors, and cancer-specific survival (CSS) using the Kaplan-Meier method and the Cox proportional hazards regression models. ResultsThe median intervals from nephroureterectomy to intravesical recurrence and the development of MIBC were 8 and 17 months, respectively. On multivariate analysis, the pathologic stage (≥pT3 vs. Ta/T1, HR 5.03, P = 0.001) and ureteral tumor location (HR 2.79, P = 0.011) were independent risk factors for the development of MIBC, whereas a history of previous or concomitant bladder tumor was the only significant risk factor for intravesical recurrence. The probability of developing MIBC 5 years after nephroureterectomy was 12.6% in patients with 1 risk factor and 20.6% in patients with both risk factors. Patients with MIBC had significantly worse CSS than those without MIBC (P = 0.004), whereas CSS rates were similar in patients with and without intravesical recurrence (P = 0.593). However, stratification analysis for matching pathology revealed that CSS rates were not significantly different in patients with pT2 or higher stage of UUT-UC. ConclusionsApproximately 5% of the patients developed MIBC after nephroureterectomy with a median interval of 17 months. Patients with advanced pathologic stage (≥pT3) and a ureteral tumor location are at increased risk of developing MIBC after nephroureterectomy.

RISK FACTORS FOR INTRAVESICAL RECURRENCE FOLLOWING SURGICAL MANAGEMENT OF TRANSITIONAL CELL CARCINOMA OF THE UPPER URINARY TRACT

To identify risk factors for developing subsequent bladder cancer in patients undergoing surgical management of transitional cell carcinoma (TCC) of the upper urinary tract.This study included 177 patients who were diagnosed as having clinically localized upper urinary tract TCC and thereafter underwent nephroureterectomy after exclusion of those with a previous and/or concurrent history of bladder cancer. Univariate and multivariate analyses using both the logistic regression model and the Cox proportional hazards model were carried out in these 177 patients to determine the risk factors for intravesical recurrence after nephroureterectomy.Of the 177 patients, 63 (35.6%) developed recurrent bladder cancer after a median interval of 7.5 months. Intravesical recurrence-free survival rates for these 177 patients at 1, 3, and 5 years were 75.7%, 63.7%, and 54.1%, respectively. Univariate analyses showed that patients with low-stage tumors and those with multifocal tumors were likely to undergo subsequent intravesical recurrence; however, there was no significant impact of other factors on subsequent intravesical recurrence, including age, tumor side, tumor location, surgical modality, operation time, management of the distal ureter, tumor grade, lymph node metastasis, microvascular invasion, lymphatic invasion, and margin status. Furthermore, pathologic stage and tumor multifocality were identified as independent predictors for the development of recurrent bladder cancer by multivariate analyses.The incidence of intravesical recurrence after nephroureterectomy for upper urinary tract TCC is comparatively high. It could be important to perform careful follow-up targeting intravesical recurrence for such patients after nephroureterectomy, particularly those with low-stage tumors and/or multifocal tumors.

Risk Factors for Intravesical Recurrence After Surgical Management of Transitional Cell Carcinoma of the Upper Urinary Tract

To identify risk factors for developing subsequent bladder cancer in patients undergoing surgical management of transitional cell carcinoma (TCC) of the upper urinary tract. This study included 177 patients who were diagnosed as having clinically localized upper urinary tract TCC and thereafter underwent nephroureterectomy after exclusion of those with a previous and/or concurrent history of bladder cancer. Univariate and multivariate analyses using both the logistic regression model and the Cox proportional hazards model were carried out in these 177 patients to determine the risk factors for intravesical recurrence after nephroureterectomy. Of the 177 patients, 63 (35.6%) developed recurrent bladder cancer after a median interval of 7.5 months. Intravesical recurrence-free survival rates for these 177 patients at 1, 3, and 5 years were 75.7%, 63.7%, and 54.1%, respectively. Univariate analyses showed that patients with low-stage tumors and those with multifocal tumors were likely to undergo subsequent intravesical recurrence; however, there was no significant impact of other factors on subsequent intravesical recurrence, including age, tumor side, tumor location, surgical modality, operation time, management of the distal ureter, tumor grade, lymph node metastasis, microvascular invasion, lymphatic invasion, and margin status. Furthermore, pathologic stage and tumor multifocality were identified as independent predictors for the development of recurrent bladder cancer by multivariate analyses. The incidence of intravesical recurrence after nephroureterectomy for upper urinary tract TCC is comparatively high. It could be important to perform careful follow-up targeting intravesical recurrence for such patients after nephroureterectomy, particularly those with low-stage tumors and/or multifocal tumors.

Risk Factors for Intravesical Recurrence Following Urothelial Carcinoma of the Upper Urinary Tract: No Relationship to the Mode of Surgery

The aim of this study was to clarify whether intravesical recurrence of upper urinary tract cancer after treatment is related to the mode of surgery or other oncological factors. We evaluated 106 patients (mean age 70.4 years; mean follow-up 24.0 months) who underwent surgery for the upper urinary tract cancer at Hiroshima University and its affiliated hospitals between January 1995 and August 2005. Seventy-nine of the patients underwent retroperitoneoscopy-assisted radical nephroureterectomy (RN) and 27 underwent nephroureterectomy by open surgery (OS). Fifty-two patients had renal pelvic tumors, 48 had ureteral tumors, and six had both renal pelvic and ureteral tumors. Twenty-eight (26%) of the 106 patients had a pre-operative history of bladder cancer. We identified the risk factors predicting intravesical recurrence of upper urinary tract cancer according to the type of previous surgery using the Kaplan-Meier method, log-rank test, and univariate and multivariate analysis using the Cox proportional hazards model. Thirty-one (29%) of the 106 patients developed bladder tumors post-operatively. The 2-year intravesical recurrence-free rate was 55% in the RN group and 60% in the OS group. There was no significant difference (P = 0.51, log-rank test) in the rate of intravesical recurrence between the two groups. Multivariate analysis identified only a history of pre-operative bladder tumor (HR = 3.25, P = 0.003) as a predictor of post-operative intravesical recurrence. Intravesical recurrence after surgery for upper urinary tract cancer is not related to the mode of surgery (i.e. laparoscopy-assisted or open surgery) employed. The only risk factor for intravesical recurrence is a history of bladder cancer.

Analysis of factors predicting intravesical recurrence of superficial transitional cell carcinoma of the bladder without concomitant carcinoma in situ

The objective of this study was to investigate risk factors for intravesical recurrence in patients with superficial bladder cancer without concomitant carcinoma in situ (CIS). In this series, we analyzed data from patients with newly diagnosed superficial Ta or T1 transitional cell carcinoma (TCC) of the bladder without concomitant CIS who underwent complete transurethral resection (TUR) without any adjuvant intravesical instillation therapies. Multivariate analysis was used to determine significant risk factors affecting intravesical recurrence after TUR. Differences in clinicopathological features between primary and recurrent tumors were also characterized. Among 341 patients undergoing TUR of Ta or T1 bladder cancer, 187 diagnosed as having concomitant CIS and/or treated with adjuvant intravesical therapy were excluded, and the remaining 154 were evaluated. Intravesical recurrence was detected in 64 of the 154 patients, showing a 5-year recurrence-free survival rate of 58.3%. Among several factors examined, only tumor size was significantly associated with intravesical recurrence. Multivariate analysis identified tumor size as an independent predictor for intravesical recurrence irrespective of other parameters including age, gender, multiplicity, growth pattern, grade and stage. Recurrent tumors were significantly smaller and of a lower grade and lower stage than primary tumors, despite the absence of differences in growth pattern and the multiplicity between them. These findings suggest that primary tumor size could be used as a potential risk factor for predicting intravesical recurrence following TUR of superficial TCC of the bladder without concomitant CIS, and that the pathological characteristics of recurrent tumors are more favorable than those of primary tumors.

The expression of thymidine phosphorylase is a prognostic predictor for the intravesical recurrence of superficial bladder cancer

Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor, has been implicated in the angiogenesis of bladder cancer. The aim of this study is to investigate the association between TP expression and the clinicopathologic findings, and the prognostic value. TP immunohistochemical staining was performed in specimens from 71 patients (50 men and 21 women) with superficial bladder cancer (pTa or pT1). Thirty-nine patients had received intravesical instillation of tetrahydropyranyladriamycin (THP) after transurethral resection (TUR) and the other 32 had not. For immunohistochemistry, paraffin-embedded specimens were stained with mouse monoclonal antibody against TP. When more than 10% of tumor cells were positively stained, staining was defined as positive. The correlations between TP immunostaining and clinicopathological features were analyzed. Multivariate analysis, using the Cox proportional hazard model, was performed to determine the risk factors for intravesical recurrence. Specimens from 29 of the 71 patients (19 men and 10 women) were positive for TP. The expression of TP was not correlated with age, sex, histological grade, multiplicity, or morphology. Also, TP expression was not associated with whether the cases were primary or recurrent. Multivariate analysis demonstrated that the decreased expression of TP and the use of THP instillation could be independent predictors of a higher rate of intravesical recurrence-free bladder cancer. The present study suggests that immunohistochemical TP staining is useful for predicting the intravesical recurrence of superficial bladder cancer after Transurethral resection of bladder tumor (TUR-Bt).

Risk factors for the development of bladder cancer after upper tract urothelial cancer

Objectives. To determine the clinical and pathologic risk factors for initial intravesical recurrence in patients with primary renal pelvic and/or ureteral cancer and to examine the progression in the bladder in patients having high risk factors for intravesical recurrence. Methods. This study included 69 patients with renal pelvic and/or ureteral cancer. We excluded patients with distant metastases, those with a short period of follow-up, and those having a previous history or concomitance of bladder cancer. The exclusion criteria were chosen to avoid contamination by patients with a poor prognosis who might die of the primary cancer before bladder cancer development. Multivariate analysis by Cox’s proportional hazards model was used to determine what clinical and pathologic variables significantly affected the initial intravesical recurrence of cancer. We also studied the stage progression of cancer that recurred in the bladder. Results. Initial intravesical recurrence of the cancer was found in 22 patients during a median follow-up period of 53 months (range 12 to 225). The intravesical disease-free rate after upper tract urothelial cancer was 65% (rate of disease recurrence in bladder 35%) at 5 years by the Kaplan-Meier method. The extent (multifocality) of the upper urinary cancer ( P = 0.0038) and pathologic stage ( P = 0.0409) independently influenced intravesical recurrence. Age, sex, adjuvant chemotherapy, configuration of the primary tumor, primary cancer size, and pathologic grade did not affect recurrence. The rate of stage progression also was not influenced by the extent of the disease in the upper urinary tract. Conclusions. The extent and pathologic stage of cancer in the upper urinary tract were significant and independent factors for initial intravesical recurrence of cancer. However, no difference was found in clinical outcome in terms of stage progression between patients having high risk factors for intravesical recurrence and those without them.