Longitudinal evaluation of the concordance and prognostic value of lymphovascular invasion in transurethral resection and radical cystectomy specimens.

OBJECTIVE: To evaluate the concordance transurethral resection of bladder tumour (TURBT) and radical cystectomy (RC) specimens with regard to the presence of lymphovascular invasion (LVI). Additionally, to evaluate the prognostic value of LVI in the prediction of lymph node metastases, overall survival, disease-specific survival and recurrence-free survival following RC. PATIENTS AND METHODS: The records of 487 patients who underwent RC at our institution between 1987 and 2008 were retrospectively reviewed and evaluated for the presence or absence of LVI as determined by pathological evaluation. The presence or absence of LVI was then evaluated on previous transrectal resection specimens of this cohort of patients undergoing RC. Cox regression and Kaplan-Meier analysis were undertaken to evaluate the contribution of LVI to various outcomes. RESULTS: Of 474 patients with complete LVI data, 60 (12.3%) were found to have LVI at TURBT compared to 161 (33.1%) at RC. Although the presence of LVI at TURBT was more significantly associated with the presence of LVI at RC, only 42.9% of patients in whom LVI was documented at TURBT were found to harbour LVI at RC. The risk of nodal disease was higher in those patients with LVI at TURBT than in those with no evidence of LVI at TURBT (48.3% vs 25.0%, P < 0.001). Additionally, LVI at TURBT was associated with an increasing risk of pathological upstaging and the receipt of adjuvant chemotherapy. Survival analysis showed a significant decrement in overall and recurrence-free survival among those with LVI at TURBT compared to those with no evidence of LVI. CONCLUSIONS: Lymphovascular invasion at TURBT provides useful prognostic information that should be incorporated into clinical decision-making, particularly with regard to cystectomy for nonmuscle-invasive carcinoma and the administration of neoadjuvant chemotherapy.

Comparison of radiographical imaging modalities for measuring the diameter of renal masses: is there a sizeable difference?

OBJECTIVE: •To determine which imaging modality (magnetic resonance imaging, MRI; computed tomography, CT; ultrasonography, US) best predicted pathological tumour size before radical or partial nephrectomy. PATIENTS AND METHODS: •The clinicopathological data of 776 patients who underwent radical or partial nephrectomy were retrospectively reviewed in the context of the radiological modality used for preoperative diagnosis. •The maximum reported diameter of the tumour was compared with the maximum diameter of the tumour after resection. Data were analyzed by a paired Student's t-test, correlation and logistic regression analysis. RESULTS: •In total, 717 patients had available data for analysis, including 414 CT scans, 121 ultrasonographs and 455 MRIs. When tumour size was compared with preoperative tumour size on ultrasonography, CT and MRI, there was no significant differences between the estimated preoperative tumour size and pathological tumour size (CT: P= 0.56, MRI: P= 0.62, ultrasonography: P= 0.55). Tumour size was also well correlated with all three modalities. CONCLUSIONS: •All three standard renal imaging modalities appear to accurately predict pathological tumour size. •These data are relevant to the interpretation and comparison of treatment strategies, such as active surveillance protocols and ablative therapy, where pathological size is not available. •Furthermore, lack of inferiority of ultrasonography in predicting pathological tumour size affords opportunities for the reduction of patient radiation exposure and for cost containment.

Defining pathological variables to predict biochemical failure in patients with positive surgical margins at radical prostatectomy: implications for adjuvant radiotherapy.

OBJECTIVE: To evaluate the utility of estimated tumour volume, number of positive surgical margins (PSMs), and margin location for predicting biochemical failure in patients with PSM, in an attempt to better risk-stratify the heterogeneous group of patients at high risk of biochemical failure after radical prostatectomy (RP) for prostate cancer. PATIENTS AND METHODS: We reviewed our database of 2410 patients who had RP, and isolated 423 with PSMs who had a prostate-specific antigen (PSA) nadir at undetectable levels. Kaplan-Meier curves were used for univariate survival analysis, with the log-rank test used to examine differences between survival curves. Multivariate Cox regression analysis was used to assess the independent main effect of estimated tumour volume, number of PSMs and margin location on biochemical-free survival. RESULTS: Increasing estimated tumour volume was directly associated with increasing risk of biochemical failure in patients with PSMs (P = 0.041). Patients with more than one PSM were at greater risk of biochemical failure than those with one PSM (P = 0.001). Margin location had no effect on biochemical-free survival in patients with PSMs. When incorporated into a multivariate Cox regression model including age, preoperative PSA level and pathological Gleason score, estimated tumour volume and number of PSMs remained independent predictors of biochemical recurrence. CONCLUSIONS: Coupled with other variables before and after RP, both estimated tumour volume and number of PSMs might serve to further discriminate those patients most likely to benefit from immediate adjuvant radiotherapy after RP.

Impact of adjuvant chemotherapy on patients with lymph node metastasis at the time of radical cystectomy.

INTRODUCTION: Radical cystectomy (RC) remains the gold standard treatment for patients with muscle-invasive bladder cancer. Unfortunately, a significant proportion of patients will have lymph node involvement at the time of RC. We set out to determine the impact of adjuvant cisplatin-based chemotherapy (AC) in a cohort of lymph node positive patients following RC. PATIENTS AND METHODS: We reviewed our RC database and isolated patients with lymph node positive disease at the time of RC. Univariate and multivariable analysis was performed to identify predictors of poor outcome in patients receiving AC. Overall survival (OS), disease specific survival (DSS) and recurrence free survival (RFS) were calculated for those patients who received AC compared to those who did not. RESULTS: Of the 316 patients, we identified 85 patients with metastatic lymph node involvement at the time of RC. Fifty-five (65%) of these patients received AC. Median follow up was 46 months. On multivariable analysis lymph node positive patients receiving AC had significantly improved OS, DSS and RFS compared to patients who did not receive AC (p = 0.031, p = 0.028, p = 0.004). The delivery of AC conferred the greatest recurrence-free, disease-specific, and overall survival advantages to those with lymph node densities (LND) of < 20% with (p = 0.016, p = 0.011, p = 0.007, respectively). CONCLUSION: AC administered to patients with known lymph node metastasis conferred a significant survival advantage compared to observation. Furthermore, a LND of < 20% predicts of a more favorable response to AC. Further studies in larger patient populations are warranted to reveal the exact impact of AC in this subset of patients.

The presence of lymphovascular invasion in radical cystectomy specimens from patients with urothelial carcinoma portends a poor clinical prognosis.

OBJECTIVES: To assess the prognostic significance of lymphovascular invasion (LVI) on clinical outcomes in patients with transitional cell carcinoma of the bladder treated with radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively evaluated a prospectively maintained and authorised cystectomy database; the presence or absence of LVI was determined by pathological examination of the RC specimen. Cox regression analysis and Kaplan-Meier tables were developed to evaluate the contribution of LVI to clinical outcomes. RESULTS: In all, we analysed 356 patients treated with RC and urinary diversion between 1988 and 2006, with a mean follow-up of 45.6 months. Of these patients, 242 (68%) had no evidence of LVI in the RC specimen, whereas 114 (32%) had LVI. Patients with LVI tended to present with higher pathological stage; 84 (74%) had pT3 or pT4 disease. On univariable analysis the presence of LVI conferred a significant risk for decreased overall, cancer-specific and recurrence-free survival (P < 0.001); the mean values for LVI-negative patients were 96.8, 157.4, and 135.0 months, respectively, vs LVI-positive patients, whose survival times were 52.3, 82.7 and 75.2 months, respectively. The multivariable analysis showed significant independent risk for cancer-specific and overall survival for patients who were LVI-positive and had no lymph-node metastases. The hazard ratios (95% confidence interval) were 1.63 (1.06-2.51, P < 0.026) and 1.81 (1.06-3.08, P < 0.03) for overall and disease-specific survival, respectively. CONCLUSIONS: The presence of LVI in the pathological RC specimen confers significant independent risk for reduced bladder cancer-specific and overall survival. This variable could be used to prospectively stratify patients who would benefit from adjuvant chemotherapy.

Endorectal T2-weighted MRI does not differentiate between favorable and adverse pathologic features in men with prostate cancer who would qualify for active surveillance.

OBJECTIVE: With the increased diagnosis of low grade, low volume, potentially non-lethal disease, active surveillance (AS) has become an increasingly popular alternative for select men with low-risk prostate cancer. The absence of precise clinical staging modalities currently makes it difficult to predict which patients are most appropriate for AS. The goal of our study was to evaluate the ability of endorectal MRI (eMRI) to predict adverse pathologic features in patients who would otherwise qualify for an AS program. MATERIALS AND METHODS: We retrospectively reviewed our institution's radical prostatectomy (RP) database from 1991 to 2007 and identified 172 patients who would have qualified for AS and underwent preoperative staging eMRI with T2-weighted (T2W) sequences. MRI findings were correlated to final pathology in order to assess the ability of staging eMRI to predict adverse pathologic features in patients suitable for AS. RESULTS: The mean age of our cohort was 59.8 ± 6.2 years. The mean PSA at the time of diagnosis was 5.2 ± 2.2 ng/ml. In 51% of patients, no discrete tumor was visualized on eMRI and in 49% of patients a discrete tumor was detected. At the time of RP, Gleason score upgrading, extracapsular extension, and a positive surgical margin occurred in 17%, 6%, and 5% of cases, respectively. Patients with documented tumor on eMRI did not have an increased incidence of adverse pathologic findings with regard to tumor volume (P = 0.31), extra-capsular extension (P = 0.82), Gleason upgrading (P = 0.92), seminal vesicle invasion (P = 0.97), or positive surgical margin rate (P = 0.95) compared with those in whom no tumor was seen. CONCLUSION: Discrete tumor identification on eMRI is not predictive of adverse pathologic features in patients who would otherwise qualify for AS. eMRI likely does not provide additional information when prospectively evaluating patients for AS protocols.

Repeat prostate biopsy and the incremental risk of clinically insignificant prostate cancer.

OBJECTIVES: To determine the incremental risk of diagnosis of clinically insignificant prostate cancer with serial prostate biopsies. METHODS: We reviewed our institutional radical prostatectomy (RP) database comprising 2411 consecutive patients undergoing RP. We then stratified patients by the prostate biopsy on which their cancer was diagnosed and correlated biopsy number with the risk of clinically insignificant disease and adverse pathology at radical prostatectomy. RESULTS: A total of 1867 (77.4%), 281 (11.9%), and 175 (7.3%) patients underwent 1, 2, and 3 or more prostate biopsies, respectively, before RP. Increasing number of prostate biopsies was associated with increasing prostate volume (P <.01), prostate-specific antigen (P <.01), associated prostate intraepithelial neoplasia (P <.01), and increased likelihood of clinical Gleason 6 or less disease (P <.01). On pathologic analysis, increasing number of prostate biopsies was associated with increased risk of low-volume (P <.01), organ-confined (P <.01) disease. The risk of clinically insignificant disease was found to be 31.1%, 43.8%, and 46.8% in those undergoing 1, 2, and 3+ prostate biopsies, respectively. Conversely, the risk of adverse pathology was found to be 64.6%, 53.0%, and 52.0% in those undergoing 1, 2, and 3+ prostate biopsies, respectively. CONCLUSIONS: Patients undergoing multiple prostate biopsies before RP are more likely to harbor clinically insignificant prostate cancer than those who only undergo 1 biopsy before resection. Nonetheless, the risk of adverse pathology in patients undergoing serial biopsies remains significant. The increased risk of prostate cancer overdiagnosis and overtreatment must be balanced with the continued risk of clinically significant disease when counseling patients regarding serial biopsies.