A systematic review and meta-analysis of lymphovascular invasion in patients treated with radical cystectomy for bladder cancer

Purpose

Lymphovascular invasion (LVI) is an important step in bladder cancer cell dissemination. We aimed to perform a systematic review and meta-analysis of the literature to assess the prognostic value of LVI in radical cystectomy (RC) specimens.

Pathologic Nodal Staging Score for Bladder Cancer: A Decision Tool for Adjuvant Therapy After Radical Cystectomy

Background

Radical cystectomy (RC) with pelvic lymph node dissection (PLND) is the standard of care for high-risk non–muscle-invasive and muscle-invasive bladder cancer (BCa).

Objective

To develop a model that allows quantification of the likelihood that a pathologically node-negative patient has, indeed, no positive nodes.

Design, setting, and participants

We analyzed data from 4335 patients treated with RC and PLND without neoadjuvant chemotherapy at 12 international academic centers.

Interventions

Patients underwent RC and PLND.

Outcome measurements and statistical analysis

We estimated the sensitivity of pathologic nodal staging using a beta-binomial model and developed a pathologic (postoperative) nodal staging score (pNSS) that represents the probability that a patient is correctly staged as node negative as a function of the number of examined nodes.

Results and limitations

Overall, the probability of missing a positive node decreases with the increasing number of nodes examined (52% if 3 nodes are examined, 40% if 5 are examined, and 26% if 10 are examined). The proportion of having a positive node increased proportionally with advancing pathologic T stage and lymphovascular invasion (LVI). Patients with LVI who had 25 examined nodes would have a pNSS of 80% (pT1), 88% (pT2), and 66% (pT3–T4), whereas 10 examined nodes were sufficient for pNSS exceeding 90% in patients without LVI and pT0–T2 tumors. This study is limited because of its retrospective design and multicenter nature.

Conclusions

We developed a tool that estimates the likelihood of lymph node (LN) metastasis in BCa patients treated with RC by evaluating the number of examined nodes, the pathologic T stage, and LVI. The pNSS indicates the adequacy of nodal staging in LN-negative patients. This tool could help to refine clinical decision making regarding adjuvant chemotherapy, follow-up scheduling, and inclusion in clinical trials.     

Gender-specific Differences in Clinicopathologic Outcomes Following Radical Cystectomy: An International Multi-institutional Study of More Than 8000 Patients

Background

The impact of gender on the staging and prognosis of urothelial carcinoma of the bladder (UCB) is insufficiently understood.

Objective

To assess gender-specific differences in pathologic factors and survival of UCB patients treated with radical cystectomy (RC).

Design, setting, and participants

Data from 8102 patients treated with RC (6497 men [80%] and 1605 women [20%]) for UCB between 1971 and 2012 were analyzed.

Outcome measurements and statistical analysis

Multivariable competing-risk regression analyses were performed to evaluate the relationship of gender on disease recurrence (DR) and cancer-specific mortality (CSM). We also tested the interaction of gender and tumor stage, nodal status, and lymphovascular invasion (LVI).

Results and limitations

Female patients were older at the time of RC (p = 0.033) and had higher rates of pathologic stage T3/T4 disease (p < 0.001). In univariable, but not in multivariable analysis, female gender was associated with a higher risk of DR (p = 0.022 and p = 0.11, respectively). Female gender was an independent predictor for CSM (p = 0.004). We did not find a significant interaction between gender and stage, nodal metastasis, or LVI (all p values >0.05).

Conclusions

We found female gender to be associated with a higher risk of CSM following RC. However, these findings do not appear to be explained by gender differences in pathologic stage, nodal status, or LVI. This gender disparity may be due to differences in care and/or the biology of UCB.     

Effect of pathological high-risk features on cancer-specific mortality in non-metastatic clear cell renal cell carcinoma: a tool for optimizing patient selection for adjuvant therapy

Purpose

Adjuvant therapies for non-metastatic renal cell carcinoma (nmRCC) are being tested to improve outcomes in patients with high-risk (hR) nmRCC. The objective of the current study is to test the ability of three hR features to identify patients who are at the highest risk of cancer-specific mortality (CSM) after partial or radical nephrectomy.

Methods

Within the Surveillance Epidemiology and End Results (SEER) database (1988–2013), we identified 23,632 nm “clear cell” RCC partial or radical nephrectomy patients with hR features: Fuhrman grade (FG) 3 or 4 or pathological classifications T3a or T3b or lymph node invasion (LNI), or combination of these. Kaplan–Meier analyses (KM) and multivariable Cox’s regression models (CRM) evaluated the effect of hR features on CSM.

Results

Overall 11,568 (48.9%) patients harbored FG3-4, 5575 (23.6%) pT3a/b, 140 (0.6%) LNI, 5366 (22.7%) FG3-4 and pT3a/b, 183 (0.8%) LNI and pT3a/b, 203 (0.9%) LNI and FG3-4 and 597 (2.5%) LNI, FG3-4 and pT3a/b. Median CSM-free survival was 51, 58 and 22 months for LNI and pT3a/b, for LNI and FG3-4 and for LNI, FG3-4 and pT3a/b and was not reached for the other groups. These results remained unchanged in multivariable CRMs, where all hR features represented independent predictors.

Conclusions

Individuals with combination of LNI with FG3-4 or pT3a/b and patients with all three hR features are at highest risk of CSM. In consequence, these patients may represent ideal candidates for adjuvant therapy either in clinical practice or future prospective trials.

     

Features Associated with Recurrence Beyond 5 Years After Nephrectomy and Nephron-Sparing Surgery for Renal Cell Carcinoma: Development and Internal Validation of a Risk Model (PRELANE score) to Predict Late Recurrence Based on a Large Multicenter Database (CORONA/SATURN Project)

Background

Approximately 10–20% of recurrences in patients treated with nephrectomy for renal cell carcinoma (RCC) develop beyond 5 yr after surgery (late recurrence).

Objective

To determine features associated with late recurrence.

Design, setting, and participants

A total of 5009 patients from a multicenter database comprising 13 107 RCC patients treated surgically had a minimum recurrence-free survival of 60 mo (median follow-up [FU]: 105 mo [range: 78–135]); at last FU, 4699 were disease free (median FU: 103 mo [range: 78–134]), and 310 patients (6.2%) experienced disease recurrence (median FU: 120 mo [range: 93–149]).

Interventions

Patients underwent radical nephrectomy or nephron-sparing surgery.

Outcome measurements and statistical analysis

Multivariable regression analyses identified features associated with late recurrence. Cox regression analyses evaluated the association of features with cancer-specific mortality (CSM).

Results and limitations

Lymphovascular invasion (LVI) (odds ratio [OR]: 3.07; p < 0.001), Fuhrman grade 3–4 (OR: 1.60; p = 0.001), and pT stage >pT1 (OR: 2.28; p < 0.001) were significantly associated with late recurrence. Based on accordant regression coefficients, these parameters were weighted with point values (LVI: 2 points; Fuhrman grade 3–4: 1 point, pT stage >1: 2 points), and a risk score was developed for the prediction of late recurrences. The calculated values (0 points: late recurrence risk 3.1%; 1–3 points: 8.4%; 4–5 points: 22.1%) resulted in a good-, intermediate- and poor-prognosis group (area under the curve value for the model: 70%; 95% confidence interval, 67–73). Multivariable Cox regression analysis showed LVI (HR: 2.75; p < 0.001), pT stage (HR: 1.24; p < 0.001), Fuhrman grade (HR: 2.40; p < 0.001), age (HR: 1.01; p < 0.001), and gender (HR: 0.71; p = 0.027) to influence CSM significantly. Limitations are based on the multicenter and retrospective study design.

Conclusions

LVI, Fuhrman grade 3/4, and a tumor stage >pT1 are independent predictors of late recurrence after at least 5 yr from surgery in patients with RCC. We developed a risk score that allows for prognostic stratification and individualized aftercare of patients with regard to counseling, follow-up scheduling, and clinical trial design.     

Should Bladder Cuff Excision Remain the Standard of Care at Nephroureterectomy in Patients with Urothelial Carcinoma of the Renal Pelvis? A Population-based Study

Background

A large, multi-institutional, tertiary care center study suggested no benefit from bladder cuff excision (BCE) at nephroureterectomy in patients with upper tract urothelial carcinoma (UC).

Objective

We tested and quantified the prognostic impact of BCE at nephroureterectomy on cancer-specific mortality (CSM) in a large population-based cohort of patients with UC of the renal pelvis.

Design, setting, and participants

A cohort of 4210 patients with UC of the renal pelvis were treated with nephroureterectomy with (NUC) or without (NU) a BCE between 1988 and 2006 within 17 Surveillance, Epidemiology, and End Results registries.

Measurements

Cumulative incidence plots and competing risks regression models compared CSM after either NUC or NU. Covariates consisted of pathologic T and N stages, grade, age, year of surgery, gender, and race.

Results and limitations

Respectively, 2492 (59.2%) and 1718 (40.8%) patients underwent a nephroureterectomy with or without BCE. In univariable and multivariable analyses, BCE omission increased CSM rates in patients with pT3N0/x, pT4N0/x, and pT(any)N1-3 UC of the renal pelvis. For example, in patients with pT3N0/x disease, holding all other variables constant, BCE omission increased CSM in a 1.25-fold fashion (p = 0.04). Similarly, in patients with pT4N0/x disease, BCE omission resulted in a 1.45-fold increase (p = 0.02). The main limitation of our study is the lack of data on disease recurrence.

Conclusions

Nephroureterectomy with BCE remains the standard of care in the treatment of UC of the renal pelvis and should invariably be performed in patients with locally advanced disease. Conversely, patients with pT1 and pT2 disease could be considered for NU without compromising CSM. However, recurrence data are needed to fully confirm the validity of this option.     

The presence of carcinoma in situ at radical cystectomy increases the risk of urothelial recurrence: Implications for follow-up schemes

Introduction

To evaluate the incidence of carcinoma in situ (CIS) in patients treated with radical cystectomy (RC) due to bladder cancer and to assess its effect on recurrence and survival rates.

Predicting Survival of Patients with Node-positive Prostate Cancer Following Multimodal Treatment

Background

According to the TNM staging system, patients with prostate cancer (PCa) with lymph node invasion (LNI) are considered a single-risk group. However, not all LNI patients share the same cancer control outcomes.

Objective

To develop and internally validate novel nomograms predicting cancer-specific mortality (CSM)–free rate in pN1 patients.

Design, setting, and participants

We evaluated 1107 patients with pN1 PCa treated with radical prostatectomy, pelvic lymph node dissection, and adjuvant therapy at two tertiary care centers between 1988 and 2010.

Outcome measurements and statistical analysis

Univariable and multivariable Cox regression models tested the relationship between CSM and patient clinical and pathologic characteristics, which consisted of prostate-specific antigen (PSA) value, pathologic Gleason score, pathologic tumor stage, status of surgical margins, number of positive lymph nodes, and status of adjuvant therapy. A Cox regression coefficient-based nomogram was developed and internally validated.

Results and limitations

All 1107 patients received adjuvant hormonal therapy (aHT). Additionally, 35% of patients received adjuvant radiotherapy (aRT). The 10-yr CSM-free rate was 84% in the entire cohort and 87% in patients treated with aRT plus aHT versus 82% in patients treated with aHT alone (p = 0.08). At multivariable analyses, PSA value, pathologic Gleason score, pathologic tumor stage, surgical margin status, number of positive lymph nodes, and aRT status were statistically significant predictors of CSM (all p ≤ 0.04). Based on these predictors, nomograms were developed to predict the 10-yr CSM-free rate in the overall patient population and in men with biochemical recurrence. These models showed high discrimination accuracy (79.5–83.3%) and favorable calibration characteristics. These results are limited by their retrospective nature.

Conclusions

Some patients with pN1 PCa have favorable CSM-free rates at 10 yr. We developed and internally validated the first nomograms that allow an accurate prediction of the CSM-free rate in these patients at an individual level.     

Radical cystectomy for urothelial carcinoma of the bladder without neoadjuvant or adjuvant therapy: long-term results in 1100 patients

Background

The optimal treatment strategy for muscle-invasive bladder cancer (BCa) remains controversial.

Objective

Better define the long-term outcomes of radical cystectomy (RC) alone for BCa and determine the impact of pathologic downstaging after transurethral resection in a large and homogeneous single-center series.

Design, setting, and participants

A cohort of 1100 patients undergoing RC with pelvic lymph node dissection (PLND) without neoadjuvant therapy for urothelial carcinoma of the bladder between January 1, 1986, and December 2009 was evaluated. Patients with other than metastases to the pelvic lymph nodes were excluded. Median age was 65 yr. Clinical course, pathologic characteristics, and long-term outcomes were evaluated. Follow-up was obtained until December 2009 with a median of 38 mo and a completeness of 96.5%.

Intervention

RC with PLND; urinary diversion with ileal neobladder whenever possible.

Measurements

Primary end points were disease-specific survival (DSS), recurrence-free survival (RFS), and overall survival (OS) according to the tumor stage of the RC specimen versus the maximum tumor stage. The log-rank test was used to compare subgroups.

Results and limitations

The 30-d (90-d) mortality rate was 3.2% (5.2%). The 10-yr OS, DSS, and RFS rates were 44.3%, 66.8%, and 65.5%, respectively. Based on the tumor stage of the RC specimen, the 10-yr DSS rate was pT0/a/is/1 pN0: 90.5%, pT2a/b pN0: 66.8%, pT3a/b pN0: 59.7%, pT4a/b pN0: 36.6%, and pTall pN+: 16.7%. Downstaging by transurethral resection of the prostate was observed in 382 patients. Patients with maximum tumor stage pT2a/b pN0 had distinctly better 10-yr DSS rates than those with pT2a/b pN0 in the RC specimen: pT2a pN0: 92.2% versus 73.8%; pT2b: 75.0% versus 62.0%. A total of 49% female and 80% male patients received an ileal neobladder.

Conclusions

This contemporary and homogeneous single-center series found acceptable OS, DFS, and RFS for patients undergoing RC. Pathologic downstaging had a significant impact on survival.     

Selecting the Optimal Candidate for Adjuvant Radiotherapy After Radical Prostatectomy for Prostate Cancer: A Long-term Survival Analysis

Background

The role of adjuvant radiotherapy (ART) after radical prostatectomy (RP) on survival of patients with prostate cancer (PCa) is still controversial.

Objective

We tested the impact of ART on cancer-specific mortality (CSM) and overall mortality (OM) in PCa patients according to pathologic PCa features.

Design, setting, and participants

We evaluated 1049 PCa patients treated with RP and extended pelvic lymph node dissection alone or in combination with adjuvant treatments between 1998 and 2008. All patients had positive surgical margins and/or pT3/pT4 disease with or without positive lymph nodes.

Outcome measurements and statistical analysis

Cox regression analyses tested the relationship between pathologic characteristics and CSM rates. Independent predictors of survival were used to develop a novel risk score based on the number of risk factors. Finally, Cox regression models tested the relationship between ART and survival according to the number of risk factors.

Results and limitations

On multivariable analyses, only pathologic Gleason score ≥8, pT3b/T4 stage, and presence of positive lymph nodes represented independent predictors of CSM (all p ≤ 0.02). The cumulative number of these pathologic findings was used to develop a risk score, which was 0, 1, 2, and 3 in 43.6%, 22.1%, 20.7%, and 13.6% of patients, respectively. In patients sharing more than two mentioned predictors of CSM (primarily having a risk score of 0 or 1), ART did not significantly improve survival (all p ≥ 0.4). Conversely, in patients with a risk score ≥2, ART was associated with lower CSM and OM rates (all p = 0.006). The observational nature of the cohort represents a limitation of the study.

Conclusions

ART significantly improved survival only in patients with at least two of the following pathologic features at RP: Gleason score ≥8, pT3/pT4 disease, and positive lymph nodes. These patients represent the ideal candidates for ART after RP.     

Retroperitoneal Lymph Node Dissection with No Adjuvant Chemotherapy in Clinical Stage I Nonseminomatous Germ Cell Tumours: Long-Term Outcome and Analysis of Risk Factors of Recurrence

Background

The best management for patients with clinical stage I (CS1) nonseminomatous germ cell tumours (NSGCT) is still under debate.

Objective

We evaluated the long-term oncologic outcome of retroperitoneal lymph node dissection (RPLND) in patients with CS1 NSGCTs and reevaluated the traditional predictors of recurrence in a set of patients not undergoing adjuvant treatment.

Design, setting, and participants

Between 1985 and 1995, 322 consecutive CS1 NSGCT patients underwent primary RPLND not followed by adjuvant chemotherapy in a single referral centre. Patients were followed until relapse for a median time of 17 yr.

Measurements

We estimated the crude cumulative incidence of any recurrence. Categories pN and pT, vascular invasion (VI), percentage of embryonal carcinoma, and presence of teratoma were evaluated as 2-yr recurrence predictors of event in a binary logistic model.

Results and limitations

Fifty patients had a recurrence (46 in ≤2 yr and only 4 [1.2%] in >2 yr). The 10-yr recurrence incidence was 15.2%. Significant predictors of recurrence at multivariable analysis were pN+, pT >1, and the presence of VI. However, the discriminative ability of the model was modest (Harrell C = 0.74); only 9% and 3% of patients had a predicted recurrence probability >30% and >50%, respectively.

Conclusions

RPLND alone could prevent recurrence in 85% of patients and minimise late relapses to 1.2%. Most patients could avoid the immediate and late toxicity of chemotherapy. Prognostic parameters combined into the multivariable model appeared of limited use in identifying a subset of patients at high risk of recurrence.     

Extranodal Extension Is a Powerful Prognostic Factor in Bladder Cancer Patients with Lymph Node Metastasis

Background

Lymph node metastasis (LNM) is the most powerful pathologic predictor of disease recurrence after radical cystectomy (RC). However, the outcomes of patients with LNM are highly variable.

Objective

To assess the prognostic value of extranodal extension (ENE) and other lymph node (LN) parameters.

Design, setting, and participants

A retrospective analysis of 748 patients with urothelial carcinoma of the bladder and LNM treated with RC and lymphadenectomy without neoadjuvant therapy at 10 European and North American centers (median follow-up: 27 mo).

Intervention

All subjects underwent RC and bilateral pelvic lymphadenectomy.

Outcome measurements and statistical analysis

Each LNM was microscopically evaluated for the presence of ENE. The number of LNs removed, number of positive LNs, and LN density were recorded and calculated. Univariable and multivariable analyses addressed time to disease recurrence and cancer-specific mortality after RC.

Results and limitations

A total of 375 patients (50.1%) had ENE. The median number of LNs removed, number of positive LNs, and LN density were 15, 2, and 15, respectively. The rate of ENE increased with advancing pT stage (p < 0.001). In multivariable Cox regression analyses that adjusted for the effects of established clinicopathologic features and LN parameters, ENE was associated with disease recurrence (hazard ratio [HR]: 1.89; 95% confidence interval [CI], 1.55–2.31; p < 0.001) and cancer-specific mortality (HR: 1.90; 95% CI, 1.52–2.37; p < 0.001). The addition of ENE to a multivariable model that included pT stage, tumor grade, age, gender, lymphovascular invasion, surgical margin status, LN density, number of LNs removed, number of positive LNs, and adjuvant chemotherapy improved predictive accuracy for disease recurrence and cancer-specific mortality from 70.3% to 77.8% (p < 0.001) and from 71.8% to 77.8% (p = 0.007), respectively. The main limitation of the study is its retrospective nature.

Conclusions

ENE is an independent predictor of both cancer recurrence and cancer-specific mortality in RC patients with LNM. Knowledge of ENE status could help with patient counseling, clinical decision making regarding inclusion in clinical trials of adjuvant therapy, and tailored follow-up scheduling after RC.     

Laparoscopic Radical Cystectomy with Orthotopic Ileal Neobladder for Bladder Cancer: Oncologic Results of 171 Cases With a Median 3-Year Follow-up

Background

Radical cystectomy (RC) with pelvic lymph node dissection (PLND) is the standard treatment for muscle-invasive and high-risk non–muscle-invasive bladder cancer (BCa). Large series with long-term oncologic data after laparoscopic RC (LRC) are rare.

Objective

To report oncologic outcomes of LRC for 171 cases with a median 3-yr follow-up.

Design, setting, and participants

From December 2002 to June 2009, 171 consecutive patients with BCa who underwent LRC with orthotopic ileal neobladder (OIN) at our institution were enrolled in this retrospective study.

Intervention

All patients underwent LRC OIN. Adjuvant chemotherapy was administered to patients with non–organ-confined disease or positive lymph nodes.

Measurements

The demographic, perioperative, complication, pathologic, and survival data were collected and analysed.

Results and limitations

Most tumours were transitional cell carcinoma (TCC; 160, 93.6%). Tumours were organ confined in 113 patients (pT1–T2; 66.1%) and non–organ confined in 58 patients (pT3–T4a; 33.9%). There was involvement of the lymph nodes in 38 patients (22.2%). Surgical margins were all tumour free. The mean number of removed lymph nodes was 16 (5–46). Follow-up ranged from 3 to 83 mo, and 54 (31.6%) patients completed 5-yr follow-up. Two patients (1.2%) had local recurrence and distant metastasis, 9 patients (5.3%) had local recurrence alone, and 23 patients (13.5%) had distant metastasis. One patient (0.6%) had port-site seeding. One hundred twenty-four patients (72.5%) were alive with no evidence of recurrence; 28 patients (16.4%) died, 20 from metastasis and 8 from tumour-unrelated causes. The estimated 5-yr overall survival, cancer-specific survival, and recurrence-free survival rates were 73.7%, 81.3%, and 72.6%, respectively. The relatively low percentage of patients reaching 5-yr follow-up is a limitation of this retrospective study.

Conclusions

Surgical technique of LRC with OIN can achieve the established oncologic criteria of open surgery, and our oncologic outcome is encouraging. Long-term follow-up is needed for further confirmation.     

Lymphovascular invasion is an independent predictor of oncological outcomes in patients with lymph node‐negative urothelial bladder cancer treated by radical cystectomy: a multicentre validation trial

Study Type – Prognosis (inception cohort)
Level of Evidence 1b

OBJECTIVES

To validate the association of lymphovascular invasion (LVI) with disease recurrence and cancer‐specific survival (CSS) in a multicentre cohort of patients treated with radical cystectomy (RC) for urothelial bladder cancer (UBC).

PATIENTS AND METHODS

We collected pathological and clinical data on 1099 lymph node‐negative patients treated with RC at six German institutions. LVI was defined as the presence of tumour cells within an unequivocal endothelium‐lined space in haematoxylin and eosin‐stained sections.

RESULTS

LVI was present in 295 (26.8%) patients; the presence of LVI correlated significantly with increasing tumour stage, i.e. pT1, 65 (29.4%); pT2, 88 (31.5%); pT3 110 (31.8%); and pT4 32 (38.1%) (P= 0.002) and grade (P < 0.001). In univariable analysis the presence of LVI was significantly associated with reduced recurrence‐free survival (P= 0.008) and reduced CSS (P= 0.039). On multivariable Cox regression analysis tumour stage (P < 0.001), age (>75 vs ≥75 years; P= 0.018) and LVI (P < 0.001) were identified as independent predictors of CSS.

CONCLUSIONS

Our large multicentre study confirms the independent prognostic value of LVI in patients with node‐negative UBC. LVI can be regarded as a surrogate variable for lymphatic micrometastasis in node‐negative UBC. Assessment of LVI might improve the selection of patients who are likely to benefit from adjuvant therapy after RC. The identification of factors involved in the process of LVI could reveal new therapeutic targets for UBC.     

Accuracy and prognostic value of variant histology and lymphovascular invasion at transurethral resection of bladder

Objectives

To evaluate the concordance rate of lymphovascular invasion (LVI) and variant histology (VH) of transurethral resection (TUR) with radical cystectomy (RC) specimens. Furthermore, to evaluate the value of LVI and VH at TUR for predicting non-organ confined (NOC) disease, lymph node metastasis, and survival outcomes.

Patients and methods

Two hundred and sixty-eight patients who underwent TUR and subsequent RC were reviewed. Logistic regression analyses were performed to evaluate the association of LVI and VH with NOC and lymph node metastasis at RC. Cox regression analyses were used to estimate recurrence-free survival (RFS) and cancer-specific survival (CSS).

Results

LVI and VH were detected in 13.8 and 11.2% of TUR specimens, and in 30.2 and 25.4% of RC specimens, respectively. The concordance rate between LVI and VH at TUR and subsequent RC was 69.8 and 83.6%, respectively. They were both associated with adverse pathological features such as lymph node metastasis and advanced stage. TUR LVI and VH were both independently associated with lymph node metastasis and TUR VH was independently associated with NOC. On univariable Cox regression analyses, TUR LVI was associated with RFS and CSS while TUR VH was only associated with RFS. Only TUR LVI was independently associated with RFS.

Conclusion

Detection of LVI is missed in a third of TUR specimens while VH seems more accurately identified. TUR LVI and VH are associated with more advanced disease and LVI predicts disease recurrence. Assessment and reporting of LVI and VH on TUR specimen are important for risk stratification and decision-making.

     

Comorbidity and performance indices as predictors of cancer-independent mortality but not of cancer-specific mortality after radical cystectomy for urothelial carcinoma of the bladder

Background

Comorbidity and performance indices allow assessment of preoperative health status. However, the optimal tool for use in patients with urothelial carcinoma of the bladder (UCB) who are undergoing radical cystectomy (RC) has not yet been established.

Objective

To evaluate correlation of Adult Comorbidity Evaluation-27 (ACE27), Charlson Comorbidity Index, Age-Adjusted Charlson Comorbidity Index, Eastern Cooperative Oncology Group performance status, and American Society of Anesthesiologists (ASA) score with survival.

Design, setting, and participants

A retrospective multicenter study was carried out on 555 unselected consecutive patients who underwent RC for UCB from 2000 to 2010.

Intervention

RC with pelvic lymph node dissection in patients with UCB without neoadjuvant chemotherapy.

Outcome measurements and statistical analysis

Cox regression models were calculated with established variables to assess predictive capacity for cancer-specific mortality (CSM) and cancer-independent mortality (CIM).

Results and limitations

All indices were independent predictors for CIM but not for CSM. The ASA score was the only index that significantly increased the predictive accuracy of the predefined CIM model (+2.3%; p = 0.045). To create a clinically valuable tool, we devised a weighted prognostic model including age and the best prognosticators within the performance and comorbidity scores (ASA/ACE27 0–1/2–3). A 3-yr CIM rate of 8%, 26%, and 47% was calculated for the low-, intermediate-, and high-risk groups, respectively. Patients >75 yr of age with ASA 3/4 and ACE27 >1 exhibited a CIM risk seven times greater than patients ≤75 yr with ASA 1/2 and ACE27 0/1. This study is limited by the short follow-up and its retrospective nature.

Conclusions

Comorbidity and performance assessment is mandatory in the preoperative prediction of CIM for patients undergoing RC for UCB. The present results indicate that the ASA score is the tool of choice. External and prospective validation is warranted.     

Performance characteristics of computed tomography in detecting lymph node metastases in contemporary patients with prostate cancer treated with extended pelvic lymph node dissection

Background

Computed tomography (CT) is a commonly used noninvasive procedure for prostate cancer (PCa) staging. All previous studies addressing the ability of CT scan to predict lymph node invasion (LNI) were based on historical patients treated with limited pelvic lymph node dissection (PLND).

Objective

Assess the value of CT in predicting LNI in contemporary PCa patients treated with extended PLND (ePLND).

Design, setting, and participants

We evaluated 1541 patients undergoing radical prostatectomy and ePLND between 2003 and 2010 at a single center. All patients were preoperatively staged using abdominopelvic CT scan. All lymph nodes with a short axis diameter ≥10 mm were considered suspicious for metastatic involvement.

Intervention

All patients underwent preoperative CT scan, radical retropubic prostatectomy, and ePLND, regardless of PCa features at diagnosis.

Measurements

The performance characteristics of CT scan were tested in the overall patient population, as well as according to the National Comprehensive Cancer Network (NCCN) classification and according to the risk of LNI derived from a nomogram developed on an ePLND series. Logistic regression models tested the relationship between CT scan findings and LNI. Discrimination accuracy was quantified with the area under the curve.

Results and limitations

Overall, a CT scan that suggested LNI was found in 73 patients (4.7%). Of them, only 24 patients (32.8%) had histologically proven LNI at ePLND. Overall, sensitivity, specificity, and accuracy of CT scan were 13%, 96.0%, and 54.6%, respectively. In patients with low-, intermediate-, or high-risk PCa according to NCCN classification, sensitivity was 8.3%, 96.3%, and 52.3%, respectively; specificity was 3.6%, 97.3%, and 50.5%, respectively; and accuracy was 17.9%, 94.3%, and 56.1%, respectively. Similarly, in patients with a nomogram-derived LNI risk ≥50%, sensitivity, specificity, and accuracy were only 23.9%, 94.7%, and 59.3%, respectively. At multivariable analyses, inclusion of CT scan findings did not improve the accuracy of LNI prediction (81.4% compared with 81.3%; p = 0.8). Lack of a central scan review represents the main limitation of our study.

Conclusions

In contemporary patients with PCa, the accuracy of CT scan as a preoperative nodal-staging procedure is poor, even in patients with high LNI risk. Therefore, the need for and the extent of PLND should not be based on the results obtained by CT scan.     

Validation of the AJCC TNM Substaging of pT2 Bladder Cancer: Deep Muscle Invasion Is Associated with Significantly Worse Outcome

Background

The current TNM bladder cancer staging system stratifies bladder muscle invasion into superficial (pT2a) and deep (pT2b). Controversy exists regarding the significance of the extent of muscle invasion on clinical outcome.

Objective

Our aim was to compare the cancer-specific outcomes of patients with pT2 urothelial carcinoma of the bladder (UCB) at radical cystectomy (RC) in a large international cohort of patients.

Design, setting, and participants

The records of patients treated with RC for UCB at six centers were reviewed. Of the 2605 reviewed patients, 565 (21.7%) had pT2 disease. None of the patients received preoperative systemic chemotherapy or radiotherapy.

Measurements

Patients’ characteristics and outcome were evaluated.

Results and limitations

The median patient age in the entire group was 66.2 yr. Of the 565 patients with pT2 UCB, 249 patients (44.1%) had substage pT2a; 316 patients (55.9%) had pT2b. One hundred and eleven patients (19.6%) had metastases to regional lymph nodes. Median follow-up was 50.5 mo. Recurrence-free survival (73.2% vs 58.7%) and cancer-specific survival (78.0% vs 65.1%) estimates were significantly better for pT2a patients compared with those with pT2b (p = 0.002 and p = 0.001, respectively). Pathologic T2 substaging was associated with worse recurrence-free and cancer-specific survival after adjusting for the effects of standard pathologic features (p = 0.011 and p = 0.006, respectively). The statistical significance of these associations was reconfirmed in subgroup analysis limited to those patients with pathologically negative lymph nodes.

Conclusions

In this large international cohort, pathologic substaging helped to stratify patients with lymph node–negative pT2 UCB into statistically significantly different risk groups. These data support the value of the current American Joint Committee on Cancer TNM staging.     

External validation of postoperative nomograms for prediction of all-cause mortality, cancer-specific mortality, and recurrence in patients with urothelial carcinoma of the bladder

Background

The Bladder Cancer Research Consortium (BCRC) created nomograms to predict all-cause mortality (ACM), cancer-specific mortality (CSM), and recurrence after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB).

Objective

To perform a formal validation of the BCRC nomograms in a large multi-institutional patient cohort from Europe.

Design, setting, and participants

Records of 2501 patients who underwent RC for UCB at eight European centers were reviewed. Complete information for external validation was available in 2404 patients for the ACM and CSM nomograms and in 2243 patients for the recurrence nomogram.

Measurements

For the purpose of external validation, model discrimination was measured using the receiver operating characteristics derived area under the curve. Calibration plots examined the relationship between predicted and observed probabilities at 2 yr, 5 yr, and 8 yr. Decision curve analyses were applied to assess the net benefit derived from the three models.

Results and limitations

The discrimination accuracies of the BCRC nomograms for ACM and CSM at 2 yr, 5 yr, and 8 yr after RC were 71.0%, 69.1%, and 68.2%, and 74.9%, 73.1%, and 72.4%, respectively. The accuracy of discrimination for the recurrence nomogram at the same time points was 76.5%, 75.3%, and 74.9%, respectively. Calibration plots revealed slight underestimations from ideal predictions. Decision curve analyses showed an increased net benefit for the use of the BCRC nomograms in this cohort. Limitations include the retrospective study design, potential surgeon bias, and lack of a central pathologic review.

Conclusions

The ACM, CSM, and recurrence nomograms showed acceptable predictive accuracies and could thus be adopted into clinical practice in UCB patients treated in Europe.     

Prognostic Role of Lymphovascular Invasion in Patients with Urothelial Carcinoma of the Upper Urinary Tract: An International Validation Study

Background

Lymphovascular invasion (LVI) identified following pathologic slide review has been shown to be an independent predictor of recurrence-free survival (RFS) and cancer-specific survival (CSS) in a multicenter series of patients undergoing radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC). However, the validity of LVI in everyday practice, where pathologic re-review of all slides is uncommon, has not been assessed.

Objective

Our aim was to evaluate the prognostic role of LVI in an international cohort of patients treated with RNU for UTUC without pathologic slide review.

Design, setting, and participants

Data from 762 patients treated with RNU for UTUC without neoadjuvant chemotherapy were collected at nine centers located in Europe, Asia, and Canada.

Measurements

We evaluated patients’ characteristics, RFS, and CSS.

Results and limitations

LVI was present in 148 patients (19.4%). At a median follow-up of 34 mo, 23.5% of the patients developed disease recurrence and 19.8% died of UTUC. The 5-yr RFS and CSS rates were 79.3% and 82.1%, respectively, in the absence of LVI compared with 45.1% and 45.8%, respectively, in the presence of LVI (p values <0.0001). On multivariable Cox regression analyses, LVI was an independent predictor of RFS (hazard ratio [HR]: 3.3; p = 0.005) and CSS (HR: 5.9; p < 0.0001). Similarly, among patients with pN0/Nx disease, LVI was an independent predictor of RFS (HR: 2.1; p = 0.001) and CSS (HR: 2.3; p < 0.0001).

Conclusions

In a large multicenter series of patients treated with RNU for UTUC and for which no pathologic slide review was performed, LVI was present in approximately 20% and was an independent predictor of both RFS and CSS. LVI status should always be included in the pathologic report of RNU specimens, and patients with LVI should be considered for adjuvant therapy studies.