Independent predictors of metachronous bladder transitional cell carcinoma (TCC) after nephroureterectomy for TCC of the upper urinary tract

OBJECTIVE

To identify the prognostic factors predictive of metachronous bladder transitional cell carcinoma (TCC) in a multi‐institutional dataset of patients who had undergone nephroureterectomy (NU) for nonmetastatic upper urinary tract (UUT) TCC.

PATIENTS AND METHODS

The clinical and pathological data of 231 patients who had had NU for UUT‐TCC from 1989 to 2005 in three European centres were collected retrospectively, and analysed for clinical and pathological variables.

RESULTS

The median follow‐up was 38 months; during the follow‐up, bladder TCC was detected in 109 patients (47.2%), and was significantly more common in patients who had UUT‐TCC after previous bladder TCC (P < 0.001), in those with ureteric cancer (P = 0.022), and in those with pT2 UUT‐TCC (P = 0.017). On multivariate analysis, a previous history of bladder TCC was the only independent predictor of metachronous bladder TCC (hazard ratio 2.825; P < 0.001). The 5‐year probability of being free from metachronous bladder TCC was 45.5%. A history of bladder TCC (P < 0.001) and UUT tumour site (P = 0.01) were significantly associated with the probability of bladder recurrence‐free survival. On multivariate analyses, a previous history of bladder TCC (hazard ratio 2.226; P < 0.001) and the presence of ureteric TCC (1.562; P = 0.036) were independent predictors of the probabilities of being free from metachronous bladder TCC.

CONCLUSION

In this multi‐institutional study of patients who had had NU for UUT‐TCC, a history of bladder TCC was the only independent predictor of metachronous bladder TCC, while both a history of bladder TCC and the presence of ureteric tumours were predictive of the probabilities of being free from metachronous bladder TCC.     

Clinical and epidemiological features of patients with genitourinary tract tumour in a blackfoot disease endemic area of Taiwan

OBJECTIVES

To evaluate the clinical and epidemiological characteristics of patients with genitourinary (GU) tract transitional cell carcinoma (TCC) in an endemic area of blackfoot disease (BFD), the arsenic‐exposed group, to compare them with characteristics among other non‐BFD endemic areas (unexposed group).

PATIENTS AND METHODS

In all, 474 patients with pathologically diagnosed GU‐TCC were enrolled in the study. All follow‐up data were prospectively collected and entered into a database throughout the study period. Statistical analysis was used to determine the association between clinical variables and prognosis, and multivariate regression models were used to assess the association between arseniasis and mortality from GU‐TCC.

RESULTS

There were no significant differences between the groups in age, sex, tumour stage and grade. However, the exposed group had a significantly higher proportion of females. The overall 5‐year survival rate of patients with upper urinary tract (UUT) TCC was 49%, and the two groups had similar 5‐year survival rates. The overall 5‐year survival rate of patients with urinary bladder (UB) TCC was 68.3%, and there was a statistically significant difference in survival between the groups, with a 5‐year survival rate of 58.7% for the exposed and 72.4% for the unexposed group. For patients with early‐stage (pTa and pT1) UB cancers, the death rate was five times higher in exposed patients with tumour progression and recurrence after transurethral resection of bladder tumour than in the unexposed group.

CONCLUSIONS

There was a significantly higher mortality rate for UB‐TCC among exposed patients in the area endemic for arseniasis than in those from other non‐endemic areas. The arsenic content of artesian‐well water might contribute to the increased ratio of female patients with GU‐TCC and the unusually high incidence of UUT‐TCC in the BFD endemic area in Taiwan.     

Pathological characteristics and clinical course of bladder tumour developing after nephroureterectomy

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVES

To determine the pathological features and clinical course of intravesical recurrence after nephroureterectomy (NU) for upper urinary tract (UUT) cancer.

PATIENTS AND METHODS

Among 325 patients undergoing NU with bladder cuff excision for UUT cancer, in this retrospective multi‐institutional study we evaluated 113 who developed bladder tumour after NU. Excluding patients with (i) perioperative systemic chemotherapy or radiotherapy for UUT cancer; (ii) a history of previous or synchronous bladder cancer at the time of NU; (iii) distant metastasis at the time of NU; (iv) a follow‐up of <1 year after the initial bladder cancer recurrence; or (v) missing data, 74 patients were included in this study. We compared the pathology between UUT cancer and the first bladder cancer recurrence, using Fisher’s exact test. Further intravesical recurrence and bladder cancer progression was analysed using the Kaplan‐Meier method, with the log‐rank test used to assess significance. A Cox proportional hazard model was used for multivariate analysis.

RESULTS

The grade of the first bladder cancer recurrence strongly correlated with that of the UUT tumour (P < 0.001) and the carcinoma in situ (CIS) lesion with the first bladder cancer recurrence correlated with high grade (grade 3) UUT tumour (P < 0.001). In all, 56 of the assessable 70 patients further developed intravesical recurrence at a median interval of 7 months after the first bladder cancer recurrence. There were no clinicopathological factors that predicted the second recurrence. Progression occurred in 14 patients, at a median interval of 25 months. A CIS lesion with the first bladder cancer recurrence was a risk factor for progression on multivariate analysis.

CONCLUSIONS

A large proportion of the patients who developed bladder tumour after NU had further intravesical recurrence, which indicated its refractory nature. Especially when a CIS lesion is detected in the initial intravesical recurrence, a careful follow‐up is mandatory to detect bladder cancer progression.     

Survival of patients with transitional cell carcinoma of the ureter and renal pelvis in Balkan endemic nephropathy and non-endemic areas of Serbia

OBJECTIVE: To evaluate the characteristics and survival of patients with upper urinary tract (UUT) transitional cell carcinoma (TCC) in Serbia, followed for >/=5 years or until death. PATIENTS AND METHODS: From 1998 to 2005 we analysed 114 cases of pathologically confirmed UUT TCC, divided into two groups according to topographical characteristics, and compared their demographic, clinical and pathological characteristics. The influence of various factors on overall 5-year survival of patients with UUT TCC was also tested. The prognostic value of different variables was assessed by univariate and multivariate Cox proportional-hazard models. RESULTS: The most important change in demographic characteristics of the patients with UUT TCC in Serbia was a similar proportion of patients residing in areas of Balkan endemic nephropathy (BEN) and non-endemic areas. The median (range) follow-up was 67 (46-88) months. The 5-year probability of survival was 51.2 +/- 5.8%. There was a significantly lower probability of 5-year survival for patients with a higher histological grade (P = 0.001), higher T stage (P < 0.001) and tumour size >3 cm (P = 0.001) at diagnosis. In this cohort of patients the independent predictors of a poorer outcome of the disease were being female (hazard ratio, HR, 2.2, P = 0.010), tumour size >3 cm (HR 2.8, P = 0.001) and T3 or T4 stages (HR 3.1, P = 0.001). CONCLUSION: Comparative analysis of the characteristics of UUT TCC between patients from BEN and non-endemic areas of Serbia showed similarities in demographic, clinical and pathological features. Factors that significantly influenced survival of patients with UUT TCC were being female, tumour size and tumour grade and stage.     

Clinical significance of lymphovascular invasion in upper urinary tract urothelial cancer

OBJECTIVES

To clarify the significance of lymphovascular invasion (LVI) in patients with pT3N0M0 upper urinary tract (UUT) urothelial carcinoma (UC) relative to prognosis in terms of disease‐specific survival, as LVI, which implies both blood vessel and lymph vessel involvement, is reportedly a poor prognostic factor in patients with UUT‐UC.

PATIENTS AND METHODS

The clinical records of 90 patients who had surgery for UUT‐UC were reviewed retrospectively. The median patient age was 71 years and the median follow‐up was 42 months. The prognostic significances of LVI (with vs without), T stage (<1 vs 2–4), grade (1–2 vs 3), N stage (0 vs 1–2), age (≤70 vs >70 years), gender and tumour location (renal pelvis vs ureter) for survival time were evaluated.

RESULTS

LVI of UUT‐UC was found in 34 patients (37.8%). There were significantly higher frequencies of LVI with advancing stage and lymph node metastasis. Kaplan‐Meier analysis showed that LVI was strongly associated with disease‐specific survival in all patients (P < 0.001) and in patients with pT3N0M0 disease (P < 0.001). Univariate analyses showed that LVI, T stage, N stage and tumour grade were significantly related to disease‐specific survival in all patients (P < 0.001, <0.001, 0.003 and 0.007, respectively). Multivariate analysis using Cox proportional hazards model showed that LVI was the only prognostic factor with independent significance for disease‐specific survival (P < 0.001).

CONCLUSIONS

LVI appears to be an important and independent prognostic factor for UUT‐UC in patients treated by nephroureterectomy. Our data suggest that the LVI status might be a predictive marker for disease‐specific survival in patients with T3N0M0 UTT‐UC.     

Risk factors for upper tract recurrence in patients undergoing long-term surveillance for stage ta bladder cancer

PURPOSE: While the evidence is clear that patients with carcinoma in situ or high grade T1 TCC of the bladder are at higher risk for developing UUT tumors, the role of imaging the UUT in patients with Ta tumors remains controversial. We hypothesized that the number and frequency of recurrences in patients with Ta disease would allow us to identify a population who should undergo routine UUT surveillance. MATERIALS AND METHODS: We reviewed our database of 375 patients who underwent resection of a stage Ta TCC between 1975 and 1995. Median followup was 6 years. Patients were stratified according to the presence of an UUT occurrence, rate and timing of superficial recurrences, and grade of the initial bladder tumor. RESULTS: Among the 375 patients 50% had no bladder recurrence, 25% had 1 tumor, 15% had 2 tumors, and 10% had 3 or more tumors. Average time between tumors was 17 months. UUT tumor developed in 13 patients (3.4%) at an average of 22 months after their initial bladder tumor. A high risk group consisting of patients who had 2 or more bladder recurrences recurring within 12 months of each other were at 4.5-fold the risk of UUT tumor. CONCLUSIONS: Stage Ta bladder cancer patients with 2 or more recurrences of bladder tumors with a median of less than 12 months between recurrences are at higher risk for developing an UUT tumor and should be considered for more frequent UUT surveillance.     

Long-term follow-up of T1 high-grade bladder cancer after intravesical bacille Calmette-Guérin treatment

Study Type – Therapy (cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? High‐grade non muscle invasive bladder cancer is a very aggressive disease, potentially lethal if not managed adequately, because of the ability of these tumours to invade surrounding tissues and become metastatic. Treatment with intravesical BCG has been shown to delay progression to muscle invasive or/and metastatic disease, preserve the bladder, and decrease the risk of death from bladder cancer. However, most studies have analyzed patients with short follow‐up, and long‐term data about the real efficacy of BCG to prevent tumour recurrence, progression and impact mortality are lacking. This study has analyzed a large series of patients with high‐grade non muscle invasive bladder cancer treated with intravesical BCG in two University Institutions (Toronto and Rotterdam), with a central pathology review by a very experienced uro‐pathologist. It provides further insight into the long‐term risks of progression of patients harbouring high‐grade T1 bladder cancer treated with BCG, demonstrating that about 30% of patients are at risk of progression and that late progressions even more than 3 years after the initial resection and BCG treatment are rare but not exceptional.

OBJECTIVE

To report the long‐term results of bacille Calmette‐Guérin (BCG) intravesical therapy in relation to disease progression and recurrence in primary T1 high‐grade (HG) bladder cancer (BC) confirmed by central pathological review.

PATIENTS AND METHODS

In all, 136 patients from two university centres (Rotterdam, n= 49; Toronto, n= 87) were diagnosed with primary T1HG BC. One experienced uro‐pathologist reviewed all slides, ensuring all cases were indeed HG and that muscle was present in all specimens. Patients were treated with BCG induction (six instillations) after transurethral resection (TUR) of the tumour and followed with cystoscopy and urinary cytology. Predictors for recurrence, progression and survival were assessed with multivariable Cox regression models.

RESULTS

Mean (range) follow‐up was 6.5 (0.3–21.6) years. There were no significant differences for recurrence (P= 0.52), progression (P= 0.35) and disease‐specific survival (DSS) (P= 0.69) between the two centres. Among the cohort, 47 patients (35%) recurred and 42 (30.9%) progressed with a median time to progression of 2.1 years; 16 (38%) of these progressions occurred ≥3 years after the initial BCG course; 22 (16%) patients who progressed died from BC. Overall, 96 (71%) patients had no evidence of disease at the last follow‐up. Carcinoma in situ was the only independent predictor for recurrence in multivariate analysis (P= 0.011). No independent predictors were found for progression.

CONCLUSIONS

Conservative treatment with BCG is a valid option in primary T1HG BC. Nevertheless, the aggressive nature of T1HG BC is evident in the fact that 30% progressed, with a high proportion of these progression events occurring ≥3 years after BCG. Caution should be exercised when relying on the long‐term effects of BCG, and close follow‐up of these patients should not be neglected.     

Independent prognostic value of tumour diameter and tumour necrosis in upper urinary tract urothelial carcinoma

OBJECTIVE

To identify significant prognostic indicators of upper urinary tract (UUT) urothelial carcinoma (UC) and to assess a risk stratification of patients.

PATIENTS AND METHODS

We retrospectively analysed data from 162 patients with non‐metastatic UC primarily occurring in UUT treated with open nephroureterectomy. Variables assessed included age, gender, pT, tumour grade, tumour necrosis extension, pN, tumour location, multifocal location, tumour diameter, and subsequent development of a bladder tumour. Tumour necrosis was measured using commercial software (Eureka interface system, version 4.0.22, HESP technology, Menarini Diagnostics, Italy) and was classified as none, focal (<10% of tumour area) or extensive, ≥10% of tumour area). The prognostic significance of each variable on metastasis‐free survival (MFS) and disease‐free survival (DFS) was tested in univariable analysis with the log‐rank test. Variables with significance levels of P < 0.05 according to the univariable analyses were entered into a multivariable forward‐stepwise Cox regression model.

RESULTS

At a mean follow‐up of 66 months, 20 cancer‐related deaths (12.3%) were censored. In multivariable analysis, tumour diameter, pT stage and tumour necrosis were independent predictors of MFS and DFS. All events occurred in patients with extensive tumour necrosis and a tumour diameter of ≥3 cm. The median survival of patients with advanced‐stage tumours, extensive necrosis and a tumour diameter of ≥3 cm were significantly impaired by increasing pT stage(P < 0.001).

CONCLUSION

Tumour necrosis and tumour diameter are compelling prognostic factors that deserve further study in a prospective setting to determine if their use in combination with more traditional variables, such as pT stage, might better determine prognosis and guide the follow‐up and treatment of patients.     

Does photodynamic transurethral resection of bladder tumour improve the outcome of initial T1 high‐grade bladder cancer? A long‐term follow‐up of a randomized study

OBJECTIVE

To evaluate, in a long‐term follow‐up of T1 high‐grade bladder cancer treated in a prospective, randomized trial, whether fluorescence diagnosis (FD) increases recurrence‐free survival (RFS) or reduces progression to muscle‐invasive stages.

PATIENTS AND METHODS

In all, 191 patients with suspected superficial bladder cancer were treated with transurethral resection under white light (WL) or with FD; 46 presented with initial T1 high‐grade BC (WL, 25; FD, 21). There were no differences in multifocality of tumours, concomitant carcinoma in situ or tumour size in either group.

RESULTS

Patients were followed for a median of 7.3 (WL) and 7.5 (FD) years to evaluate RFS. In the WL group there were 11, and in the FD group three, recurrent tumours of the same stage and grade. The RFS at 4 and 8 years was 69% and 52% in the WL, and 91% and 80% in FD group, respectively. With FD, the RFS was significantly longer according to Kaplan‐Meier analysis (P = 0.025). In the WL group, three (12%), and in the FD group four (19%) patients progressed to muscle‐invasive stages (≥ T2).

CONCLUSION

In initial T1 high‐grade bladder cancer, FD is significantly better than conventional WL transurethral resection for RFS. However, the progression rate to muscle‐invasive disease was not reduced by FD. Thus the clinical course (progression) of T1 high‐grade bladder cancer remains unaffected by FD.     

Risk factors for positive findings in patients with high‐grade T1 bladder cancer treated with transurethral resection of bladder tumour (TUR) and bacille Calmette‐Guérin therapy and the decision for a repeat TUR

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

To determine factors predictive of positive findings at the 3‐month follow‐up evaluation (after transurethral resection of bladder tumour [TUR] and bacille Calmette‐Guérin [BCG] therapy) in patients with initial high‐grade (HG)T1 bladder cancer, and to assess the depth of lamina propria (LP) invasion and effectiveness of BCG therapy.

PATIENTS AND METHODS

In all, 138 patients with initial HGT1‐transitional cell carcinoma (TCC) were prospectively assigned, after TUR + BCG and according to depth of LP invasion, to a postBCG‐TUR (T1b) or cystoscopy/cytology (T1a) at 3 months. Any finding at 3 months was considered positive. The predictive value of 11 clinical and pathological variables was assessed by chi‐squared, Mann–Whitney U and multivariate logistic regression.

RESULTS

Of the 138 patients (14 women, mean age 69 years), 42% had T1a and 58% T1b TCC. Tumour size and carcinoma in situ (CIS) were significantly associated with positive findings and present in 26% (36/138) of the patients. The postBCG‐TUR (T1b cases), was positive in 31% (25/80), including seven infiltrating tumours. On multivariate analysis, again a tumour size of >3 cm (odds ratio, OR, 7.02) and associated CIS (OR 5.4) were significantly related to a positive postBCG‐TUR. A secondary finding was that at 20.3 months; patients with T1a TCC, who did not undergo a repeat TUR, did not have increased progression; only 3% (two of 58) had progressed compared with 21% (17/80) of those with T1b/c TCC (P < 0.002).

CONCLUSIONS

In initial HGT1‐TCC, tumour size and CIS were predictive factors of positive findings at 3 months after the initial TUR + BCG therapy. Patients with HGT1‐TCC invading the LP (T1b TCC) had a seven times higher risk of a positive repeat TUR if the initial tumour was >3 cm and a five‐fold increased risk if associated with CIS. The repeat TUR after BCG therapy allowed confirmation of complete resection and pathological evaluation of the BCG response. Although data are still preliminary, the strategy of performing a repeat TUR only in cases with LP involvement, i.e. T1b TCC, did not increase the risk of progression in cases with T1a TCC.     

Upper urinary tract transitional cell carcinoma: location is not correlated with prognosis

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Tumour location has been shown to be of prognostic importance in UUT‐TCC, with tumours of renal pelvis having a better prognosis than ureteral tumours. Patients from Balkan Endemic Nephropathy (BEN) areas had a higher frequency of pelvis tumours. Also, we found that belonging to a BEN area is an independent predictor of disease recurrence.

OBJECTIVE

• ? To identify the impact of tumour location on the disease recurrence and survival of patients who were treated surgically for upper urinary tract transitional cell carcinoma (UUT‐TCC).

PATIENTS AND METHODS

• ? A single‐centre series of 189 consecutive patients who were treated surgically for UUT‐TCC between January 1999 and December 2009 was evaluated.
• ? Patients who had previously undergone radical cystectomy, preoperative chemotherapy or contralateral UUT‐TCC were excluded.
• ? In all, 133 patients were available for evaluation. Tumour location was categorized as renal pelvis or ureter based on the location of the dominant tumour.
• ? Recurrence‐free probabilities and cancer‐specific survival were estimated using the Kaplan–Meier method and Cox regression analyses.

RESULTS

• ? The 5‐year recurrence‐free and cancer‐specific survival estimates for the cohort in the present study were 66% and 62%, respectively.
• ? The 5‐year bladder‐only recurrence‐free probability was 76%. Using multivariate analysis, only pT classification (hazard ratio, HR, 2.46; P= 0.04) and demographic characteristics (HR, 2.86 for areas of Balkan endemic nephropathy, vs non‐Balkan endemic nephropathy areas; 95% confidence interval, 1.37–5.98; P= 0.005) were associated with disease recurrence
• ? Tumour location was not associated with disease recurrence in any of the analyses.
• ? There was no difference in cancer‐specific survival between renal pelvis and ureteral tumours (P= 0.476).
• ? Using multivariate analysis, pT classification (HR, 8.04; P= 0.001) and lymph node status (HR, 4.73; P= 0.01) were the only independent predictors associated with a worse cancer‐specific survival.

CONCLUSION

• ? Tumour location is unable to predict outcomes in a single‐centre series of consecutive patients who were treated with radical nephroureterectomy for UUT‐TCC.

     

The oncological results of laparoscopic nephroureterectomy for upper urinary tract transitional cell cancer are equal to those of open nephroureterectomy

OBJECTIVE

To compare the overall, tumour‐specific, recurrence‐free, and progression‐ free survival of patients with upper urinary tract transitional cell carcinoma (UUT‐TCC) treated with laparoscopic nephroureterectomy (LNU) or standard open NU (ONU).

PATIENTS AND METHODS

Clinical, pathological and follow‐up data were analysed for 43 LNUs and 59 ONUs performed at our institution from 1999 to 2006. In LNU the kidney was removed laparoscopically as in radical nephrectomy, but without transecting the ureter. The specimen was then removed intact with the entire ureter and a bladder cuff through a nonmuscle‐splitting supra‐inguinal incision. ONU was performed through separate intercostal and supra‐inguinal incisions with the entire specimen being removed intact with a bladder cuff through the latter.

RESULTS

The mean (sd ) follow‐up was 41 (20) months for LNU and 41 (29) for ONU. Pathological staging was: pTa 26% vs 20%, pT1 21% vs 27%, pT2 12% vs 17%, pT3 42% vs 34% for LNU and ONU, respectively. In all, seven vs six patients had positive nodes on final histology. Recurrent tumours in the bladder were detected in 26% of patients after LNU and in 27% after ONU after the mean follow‐up. There were no local recurrences after LNU but there was local recurrence in six patients after ONU. There were no port‐site metastases during the follow‐up. Five LNU patients and seven ONU patients developed distant or lymph node metastasis. The actuarial 5‐year tumour free‐survival rate was 79% in the LNU group vs 76% in the ONU group (P = 0.82). The actuarial disease‐specific survival at 5‐years was 85% for LNU and 80% for ONU patients (P = 0.62). The surgical approach did not influence recurrence or survival.

CONCLUSION

Oncological results of LNU and ONU are comparable. The lower morbidity of LNU offers advantages for the patient.     

Glucose‐regulated protein 78 expression in urothelial carcinoma of the upper urinary tract

OBJECTIVE

To examine glucose‐regulated protein 78 (GRP78; a major molecular chaperone at the endoplasmic reticulum, strongly expressed in several tumours) expression in urothelial carcinoma (UC) of the upper urinary tract (UUT) and to evaluate the diagnostic and progressive importance of GRP78 expression in UC‐UUT.

PATIENTS AND METHODS

We investigated GRP78 expression (using immunohistochemistry) in 126 UC‐UUTs to assess its relevance to progression. GRP78 overexpression was recognised in 23 (18.3%) of tumour samples.

RESULTS

There was no association between GRP78 overexpression and clinicopathological findings, except for an association with low grade in invasive tumours. GRP78 overexpression significantly improved the disease‐free survival rate in all patients (according to univariate and multivariate analyses), but did not alter the overall survival rate.

CONCLUSION

The detection of GRP78 overexpression would appear to provide valuable information for the prognosis of UC‐UUT.     

In the cystoscopic follow-up of non-muscle-invasive transitional cell carcinoma, NMP-22 works for high grades, but unreliable in low grades and upper urinary tract tumors

Introduction and objectives

Two percent of the bladder non-muscle-invasive (NMI) transitional cell carcinomas (TCC) are associated with upper urinary tract (UUT) TCC. We evaluated the role of nuclear matrix protein-22 (NMP-22) (BladderChek^?) test in the diagnosis of lower urinary tract and UUT-TCC.

Methods

From March 2009 to June 2011, 122 patients with bladder NMI-TCC underwent 205 control cystoscopy. A total of 95 (78 men and 17 women, mean age 60.7?years, range, 27?C88) patients who were followed regularly with NMP-22 test and with follow-up cystoscopies (145 episodes; min. 1?Cmax. 5) were included in this study. For routine monitoring of the UUT, IVU or CT urography was used once a year for high grades (HG), and once in every other year for low grades (LG). The sensitivity and specificity of NMP-22 were evaluated by ROC curves, and sensitivity, specificity, and positive and negative predictive values were calculated. Chi-square test was used for the differences between the subgroups.

Results

Cystoscopy and NMP-22 results of the patients included in the study revealed the sensitivity (44.4%) of the test was very low and the specificity (98.4%) was quite high (p?Conclusions Nuclear matrix protein-22 cannot detect LG TCC. However, it detects overwhelming majority of HG TCC. For this reason, positive NMP-22 test largely indicates HG TCC. NMP-22 is also not reliable in UUT-TCC, even in HG tumors.     

How successful is the conservative management of pelvi‐ureteric junction obstruction in adults?

OBJECTIVE

To assess the conservative management of pelvi‐ureteric junction obstruction (PUJO), according to severity, accepted in paediatric urology but rarely reported in adults.

PATIENTS AND METHODS

A series of 23 patients (median age 58 years, 17 men and six women) with asymptomatic or minimally symptomatic PUJO were managed conservatively. The patients’ age, preference and comorbidities were considered. The diagnosis of PUJO was based on intravenous urography and isotopic renography. After stringently reviewing the renograms based on relative renal function (RRF) and output efficiency (OE), 15 patients had an OE consistent with definitive PUJO. One patient had no further imaging due to associated comorbidities. Ten patients had right PUJO, three left and one with bilateral PUJO, with unilateral conservative management. The follow‐up included annual renography and clinical consultation. Laparoscopic pyeloplasty was considered for patients with a >10% loss of RRF and/or <40% RRF during the follow‐up.

RESULTS

Overall, 14 of 15 patients had renograms during the follow‐up. The mean RRF of the affected kidney at diagnosis was 48.6% which marginally decreased to 46.7% after a median (range) follow‐up of 44 (23–75) months. The RRF of 11 patients remained stable and in three decreased significantly (median 11% RRF), requiring pyeloplasty. None of the patients became symptomatic throughout the follow‐up.

CONCLUSION

In asymptomatic adults the conservative management of PUJO appears to be safe during a short‐ to medium‐term follow‐up. We recommend that patients are regularly followed with renography and seen promptly should they become symptomatic. A longer follow‐up is needed in a larger group to confirm these findings.     

Trends in epidemiology and treatment of upper urinary tract tumours in the Netherlands 1995–2005: an analysis of PALGA,the Dutch national histopathology registry

Study Type – Therapy (prospective cohort)
Level of Evidence 2b

OBJECTIVE

To evaluate changes in incidence, distribution of stage and grade as well as surgical treatment of upper urinary tract (UUT) tumours in the Netherlands from 1995 to 2005.

PATIENTS AND METHODS

The PALGA registry, a nationwide network and registry of pathology encompassing all hospitals in the Netherlands, was used as primary data source. Pathology reports of all primary surgical procedures or biopsies without further surgical treatment within the next year, of cancer of the renal pelvis or ureter during the period 1995–2005, were included. The number of surgically treated UUT tumours per year, type of treatment and tumour characteristics were recorded.

RESULTS

The population consisted of 2321 (67%) men and 1145 (33%) women with a mean age of 68.6 years. The distribution according to side was similar (left 44.1%, right 41.5%), bilateral tumours were rare (0.6%) and most tumours were in the renal pelvis (51.3%). Both the incidence and the incidence rate per 100 000 person‐years increased during the study period (P < 0.001). Most urothelial cancers were grade 2 (40.9%) or 3 (41.2%) and stage Ta (30.6%), T1 (18.1%) or T3 (22.8%). There was an increase in grade 3 (P = 0.003) and muscle‐invasive (P = 0.003) tumours in men only. Nephroureterectomy was performed in 41.3% of the cases and there was an increasing trend to endoscopic surgery (P = 0.019), although the absolute number was low.

CONCLUSION

The incidence of surgically treated UUT tumours increased, with a significant trend towards more advanced disease in men. Most tumours were treated by nephroureterectomy or nephrectomy, although there was an increasing trend to endoscopic surgery.     

A single‐institution experience with induction and maintenance intravesical docetaxel in the management of non‐muscle‐invasive bladder cancer refractory to bacille Calmette‐Guérin therapy

OBJECTIVE

To analyse the durability of response for patients with non‐muscle‐invasive bladder cancer (NMIBC) refractory to bacille Calmette‐Guérin (BCG) therapy and treated with intravesical docetaxel in a combined induction and maintenance regimen.

PATIENTS AND METHODS

A previous phase I trial showed docetaxel to be safe for intravesical therapy, with no systemic absorption and minimal toxicity after six weekly instillations for patients with BCG‐refractory NMIBC. In that trial, docetaxel gave a 56% complete response (CR) rate at 12 weeks, but the durability was only 22%. Thus a second group of patients was treated with a 6‐week induction and then given monthly maintenance therapy with intravesical docetaxel. Thirteen patients with BCG‐refractory Ta, T1, or Tis transitional cell carcinoma were treated. Induction therapy was administered as six weekly intravesical instillations of 75 mg followed by single‐dose monthly maintenance therapy for nine additional instillations in patients who had a CR. The initial response at 12 weeks from the start of induction therapy was evaluated by cystoscopy with biopsy, and urine cytology. The follow‐up consisted of quarterly cystoscopy with biopsy and cytology, and periodic imaging.

RESULTS

The median follow‐up was 13 months; 10 of 13 patients had a CR after induction, and six have remained disease‐free during the follow‐up. Of those in who the treatment failed, six had transurethral resection of the tumour and one a cystectomy. All 10 initial responders completed at least three instillations of maintenance therapy to date (median nine instillations), of whom six have remained recurrence‐free.

CONCLUSION

Monthly maintenance therapy with intravesical docetaxel appears to extend the durability of response to induction treatment for a selected group of patients with BCG‐refractory NMIBC, and might decrease the overall risk of recurrence in high‐risk NMIBC.     

A 1‐year maintenance after early adjuvant intravesical chemotherapy has a limited efficacy in preventing recurrence of intermediate risk non‐muscle‐invasive bladder cancer

Study Type – Therapy (RCT)
Level of Evidence 1b

OBJECTIVE

To evaluate the efficacy of 1‐year maintenance after a 6‐week cycle of early intravesical chemotherapy, as the role of maintenance in intravesical chemotherapy is debated.

PATIENTS AND METHODS

Between May 2002 and August 2003, 577 patients with non‐muscle‐invasive bladder cancer (NMI‐BC) underwent transurethral resection (TUR) and early intravesical chemotherapy (epirubicin, 80 mg/50 mL). They were randomized between a 6‐week induction cycle and the induction cycle plus maintenance with 10 monthly instillations. In all, 95 patients with T1G3, Tis or single and primary Ta–T1 G1–G2 tumours were excluded; 482 patients at intermediate risk of recurrence continued the study. All patients had cytology and cystoscopy at 3‐monthly intervals for the first 2‐years and 6‐monthly thereafter.

RESULTS

The tumours’ characteristics were equally distributed between the two arms. Treatment interruption for toxicity was required in 39 patients. One death due to toxicity of early instillation occurred. The median follow‐up was 48 months. Ten patients (2.5%) progressed and 117 patients (29.6%) recurred. No statistically significant difference in the recurrence‐free rate (RFS) was detected between the two arms (P = 0.43). An advantage in favour of the maintenance arm was evident only at 18 months after TUR (P = 0.03). A trend for a higher benefit from maintenance in primary and multiple tumours was detected.

CONCLUSIONS

In patients with intermediate risk NMI‐BC treated by TUR and early adjuvant chemotherapy, adding a maintenance regimen with monthly instillations for 1 year is of limited efficacy in preventing recurrence.     

Antegrade perfusion with bacillus Calmette-Guérin in patients with non-muscle-invasive urothelial carcinoma of the upper urinary tract: who may benefit?

Background

There is paucity of data on bacillus Calmette-Guérin (BCG) perfusion in patients with non-muscle-invasive urothelial carcinoma (NMIUC) of the upper urinary tract (UUT).

Objective

To assess the long-term results of BCG perfusion in patients with UUT NMIUC in terms of efficacy and tolerability.

Design, setting, and participants

Retrospective analysis of 55 consecutive patients (64 renal units [RUs]) with UUT NMIUC prospectively followed according to a standardised protocol for a median of 42 mo (range: 2-237 mo). Our series includes negatively selected patients, most of whom were not eligible for radical surgery, with additional invasive urothelial carcinoma of the urinary tract in roughly one-third of the cases.

Intervention

Antegrade BCG perfusion of the UUT was performed either with curative intent for carcinoma in situ (Tis; 42 RUs) or with adjuvant intent after ablation of Ta/T1 tumours (22 RUs).

Measurements

Primary outcome measures were recurrence-free, progression-free, and nephroureterectomy-free survival. The secondary outcome measure was treatment tolerability.

Results and limitations

Recurrence occurred in 30 of 64 RUs (47%), 17 of 42 (40%) with Tis and 13 of 22 (59%) with Ta/T1 tumours. Progression occurred in 11 of 64 RUs (17%), 2 of 42 (5%) with Tis and 9 of 22 (41%) with Ta/T1 tumours. Nephroureterectomy was eventually performed in 7 of 64 RUs (11%), 2 of 42 (5%) with Tis and 5 of 22 (23%) with Ta/T1 tumours. Patients treated with curative intent for Tis tended to have better recurrence-free survival (p = 0.42) and significantly better progression-free survival (p < 0.01) and nephroureterectomy-free survival (p = 0.05) compared with those treated with adjuvant intent after ablation of Ta/T1 tumours. Adverse events, mostly minor, occurred in a total of 11 patients (20%), with one case of fatal Escherichia coli septicaemia.

Conclusions

In our patients with UUT NMIUC, antegrade BCG perfusion resulted in a high kidney-preservation rate. Patients treated with curative intent for Tis apparently benefited in terms of local disease control more than those treated with adjuvant intent after ablation of Ta/T1 tumours. Treatment tolerability was good.