Seth P. Lerner

Lymphovascular Invasion Is Independently Associated With Overall Survival, Cause-Specific Survival, and Local and Distant Recurrence in Patients With Negative Lymph Nodes at Radical Cystectomy

Purpose We hypothesized that bladder cancer patients with associated lymphovascular invasion (LVI) are at increased risk of occult metastases. Methods A multi-institutional group (University of Texas Southwestern [Dallas, TX], Baylor College of Medicine [Houston, TX], Johns Hopkins University [Baltimore, MD]) carried out a retrospective study of 958 patients who underwent cystectomy for bladder cancer between 1984 and 2003. Of patients with transitional-cell carcinoma (n = 776), LVI status was available for 750. LVI was defined as the presence of tumor cells within an endothelium-lined space. Results LVI was present in 36.4% (273 of 750) overall, involving 26% (151 of 581) and 72% (122 of 169) of node-negative and node-positive patients, respectively. Prevalence of LVI increased with higher pathologic stage (9.0%, 23%, 60%, and 78%, for T1, T2, T3, and T4, respectively; P < .001). Using multivariate Cox regression analyses including age, stage, grade, and number of pelvic lymph nodes removed, LVI was an i...

Residual Pathological Stage at Radical Cystectomy Significantly Impacts Outcomes for Initial T2N0 Bladder Cancer

PURPOSE We hypothesized that in patients with T2N0 stage disease at transurethral bladder tumor resection a lower residual cancer stage (P1N0 or less) at radical cystectomy may correlate with improved outcomes relative to those with residual P2N0 disease. MATERIALS AND METHODS We analyzed 208 patients with T2N0 stage disease at transurethral bladder tumor resection whose tumors were organ confined at radical cystectomy (P2 or lower, pN0). None received perioperative chemotherapy. Kaplan-Meier as well as univariable and multivariable Cox regression models addressed the effect of residual pT stage at radical cystectomy on recurrence and cancer specific mortality rates. Covariates consisted of age, gender, grade, lymphovascular invasion, carcinoma in situ, number of lymph nodes removed and year of surgery. RESULTS Residual pT stage at radical cystectomy was P0 in 24 (11.5%) patients, Pa in 9 (4.3%), PCIS in 22 (10.6%), P1 in 35 (16.8%) and P2 in 118 (56.7%). Median followup of censored patients was 55.7 months for recurrence and 52.1 months for cancer specific mortality analyses. The 5-year recurrence-free survival rates of patients with P0/Pa/PCIS, P1 and P2 stage disease were 100%, 85% and 75%, respectively. The 5-year cancer specific survival rates for the same cohorts were 100%, 93% and 81%, respectively. On multivariable analysis the effect of residual stage P1 or lower at radical cystectomy achieved independent predictor status for recurrence (adjusted HR 0.20, p = 0.002) and cancer specific mortality (adjusted HR 0.24, p = 0.02). CONCLUSIONS Down staging from initial T2N0 bladder cancer at transurethral bladder tumor resection to lower stage at radical cystectomy significantly reduces recurrence and cancer specific mortality. Further validation of this finding is warranted.

Editorial Concerning “Impact of the Level of Urothelial Carcinoma Involvement of the Prostate on Survival after Radical Cystectomy”

Prostatic involvement by urothelial carcinoma in patients with bladder cancer is a frequent finding and their prognostic significance and implication for the management of these patients has been the subject of study for many years. In one of the largest series of radical cystoprostatectomy with 995 patients with bladder cancer, Moschini M et al have shown that prostatic involvement by urothelial carcinoma was identified in 307 patients with an incidence of 30.9%. The authors provided further evidence to confirm that prostatic stromal invasion is associated with significantly worse outcome when compare to prostatic involvement by carcinoma in-situ (urethra or prostatic duct/acini) or subepithelial (lamina propria) invasion of prostatic urethra. Multifocality of bladder tumor and presence of CIS was found to be associated with a higher probability of prostatic involvement by urothelial carcinoma [1]. It has becomes clear that careful clinical and pathologic evaluation of the prostate before and post-surgery are helpful in the planning and management of male patients with bladder cancer. Over the last few decades, many studies have shown that the incidence of prostatic urothelial carcinoma is quite variable, ranging from 15% to 48% [2]. However, the more contemporary series with large number of cases and when the prostate is evaluated by whole mount section, demonstrate that the incidence is consistently around 30%–35% [3, 4]. It has also been long recognized that there are variable levels or patterns of involvement of prostate in patients with bladder cancer. The involvement of the prostate by urothelial carcinoma can be divided by the topographic distribution, presence or absence of invasion, extend or level of prostatic stromal invasion, contiguous (bladder origin) or non-contiguous (prostate origin). Many studies have addressed the prognostic significance of each type or levels of prostatic involvement by urothelial carcinoma and attempts have been made to best incorporate these findings into the anatomic staging of bladder cancer. These have resulted in revisions of staging scheme in the last two AJCC staging manuals in 2010 and 2017. It is the recognition that prostatic involvement by CIS or subepithelial invasion of prostatic urethra has a significantly more favorable outcome than that of prostatic stromal invasion, AJCC 2010 specified that for bladder tumor with only established prostatic stromal invasion regardless of contiguous (bladder origin) or non-contiguous (prostate origin), be considered pT4a disease. It has also been recognized that there are two distinct pathways of prostatic stromal invasion, i.e. invasion of prostate by primary invasive bladder tumor penetrating through the entire bladder wall into prostate or through the extraprostatic soft tissue, or invasion of prostate stroma by urothelial carcinoma arising from either prostatic urethra prostatic duct/acini without direct invasion of prostate from bladder cancer. Unfortunately, this issue was not addressed in the study of Moschini et al. due to lack of this pathologic information [1]. However, the results have been inconclusive with regard to the prognostic significance of these two pathways of stromal invasion. While some studies showed that contiguous invasion (bladder origin) of prostate is associated with a worse prognosis compared to prostatic stromal invasion arising from prostatic urethra,

Lymphovascular Invasion is Independently Associated With Overall Survival, Cause-Specific Survival, and Local and Distant Recurrence in Patients With Negative Lymph Nodes at Radical Cystectomy

PURPOSE We hypothesized that bladder cancer patients with associated lymphovascular invasion (LVI) are at increased risk of occult metastases. METHODS A multi-institutional group (University of Texas Southwestern [Dallas, TX], Baylor College of Medicine [Houston, TX], Johns Hopkins University [Baltimore, MD]) carried out a retrospective study of 958 patients who underwent cystectomy for bladder cancer between 1984 and 2003. Of patients with transitional-cell carcinoma (n = 776), LVI status was available for 750. LVI was defined as the presence of tumor cells within an endothelium-lined space. RESULTS LVI was present in 36.4% (273 of 750) overall, involving 26% (151 of 581) and 72% (122 of 169) of node-negative and node-positive patients, respectively. Prevalence of LVI increased with higher pathologic stage (9.0%, 23%, 60%, and 78%, for T1, T2, T3, and T4, respectively; P < .001). Using multivariate Cox regression analyses including age, stage, grade, and number of pelvic lymph nodes removed, LVI was an independent predictor of local (HR = 2.03, P = .049), distant (HR = 2.60, P = .0011), and overall (HR = 2.02, P = .0003) recurrence in node-negative patients. LVI was an independent predictor of overall (HR = 1.84, P = .0002) and cause-specific (HR = 2.07, P = .0012) survival in node-negative patients. LVI maintained its independent predictor status in competing risks regression models (P = .013), where other-cause mortality was considered as a competing risk. LVI was not a predictor of recurrence or survival in node-positive patients. CONCLUSION LVI is an independent predictor of recurrence and decreased cause-specific and overall survival in patients who undergo cystectomy for invasive bladder cancer and are node-negative. These patients represent a high risk group that may benefit from integrated therapy with cystectomy and perioperative systemic chemotherapy.