Lymph node-positive bladder cancer treated with radical cystectomy and lymphadenectomy: effect of the level of node positivity

Background

The extent of lymphadenectomy needed to optimize oncologic outcomes after radical cystectomy (RC) for patients with regionally advanced bladder cancer (BCa) is unclear.

Objective

Evaluate the effect of the location of lymph node metastasis on recurrence-free survival (RFS) and cancer-specific survival (CSS) for patients undergoing RC with a mapping pelvic lymph node dissection (PLND).

Design, setting, and participants

A study of 591 patients undergoing RC with mapping PLND was completed between 2000 and 2010. Median follow-up was 30 mo.

Intervention

RC with mapping PLND.

Measurements

We evaluated the impact of lymph node involvement by location on disease outcomes using the 2010 TNM staging system. Survival estimates were described using Kaplan-Meier methods. Gender, age, pathologic stage, histology, number of positive nodes, location of positive nodes, node density, use of perioperative chemotherapy, and grade were evaluated as predictors of RFS and CSS using multivariate Cox proportional hazard regression.

Results and limitations

Overall, 114 patients (19%) had lymph node involvement, and 42 patients (7%) had pN3 disease. On multivariate analysis, the number of positive lymph nodes (one or two or more) was significantly associated with increased risk of cancer-specific death (hazard ratio [HR]: 1.9 [95% confidence interval (CI), 1.04–3.46], p = 0.036; versus HR: 4.3 [95% CI, 2.25–8.34], p < 0.0005). Positive lymph node location was not an independent predictor of RFS or CSS. Five-year RFS for pN3 patients undergoing RC with PLND was 25% (95% CI, 10–42). This finding was not statistically different from our pN1 and pN2 patients (38% [95% CI, 22–54] and 35% [95% CI, 11–60], respectively). This study is limited by the lack of prospective randomization and a control group.

Conclusions

The outcome for patients with involved common iliac lymph nodes was similar to the outcome for patients with primary nodal basin disease. These data support inclusion of the common iliac lymph nodes (pN3) in the nodal staging system for BCa. Lymph node location was not an independent predictor of outcome, whereas the number of positive lymph nodes was an independent predictor of worse oncologic outcome (pN1, pN2). Further refinements of the TNM system to provide improved prognostication are warranted.     

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.     

Robotic and Laparoscopic Radical Cystectomy for Bladder Cancer: Long-term Oncologic Outcomes

Background

Extended oncologic outcomes after minimally invasive cystectomy have not been previously reported.

Objective

To report outcomes of robot-assisted radical cystectomy (RARC) and laparoscopic radical cystectomy (LRC) for bladder cancer (BCa) at up to 12-yr follow-up.

Design, setting, and participants

All 121 patients undergoing RARC or LRC for BCa between December 1999 and September 2008 at a tertiary referral center were retrospectively evaluated from a prospectively maintained database.

Intervention

RARC or LRC.

Outcome measurements and statistical analysis

Primary end points were overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) calculated using Kaplan-Meier curves. Secondary end points were survival analysis by number of lymph nodes (LNs) and type of procedure. Surgical outcomes, including complications, were analyzed.

Results and limitations

Most tumors were muscle invasive (≥pT2; n = 81; 67%) urothelial carcinomas (n = 102; 84%). Extended LN dissection was performed in 98 patients (81%), with a median of 14 nodes removed (interquartile range [IQR]: 8–18). Twenty-four patients (20%) had node-positive disease (N1: 10 [8%]; N2: 14 [12%]). Eight patients (6.6%) had positive soft tissue margins. Median follow-up was 5.5 yr (mean: 5.9; IQR: 4.2–8.2; range: 0.13–12.1). At last follow-up, 58 patients (48%) had no evidence of disease, 3 (2%) were alive with recurrence, 59 (49%) had died, and status was unknown in 1. Twenty-eight patients (23%) died from cancer-specific causes, 20 (17%) from unrelated causes, and 11 (9%) from unknown causes. The 10-yr actuarial OS, CSS, and RFS rates were 35%, 63%, and 54%, respectively. At last follow-up, OS for pT0, pTis/a, pT1, pT2, and pT3 versus pT4 was 67%, 73%, 53%, 50%, and 16% versus 0%, respectively (p = 0.02). At last follow-up, CSS for pT0, pTis/a, pT1, pT2, and pT3 versus pT4 was 100%, 91%, 74%, 77%, and 56% versus 0%, respectively (p = 0.03).

Conclusions

The longest oncologic outcomes following RARC and LRC for BCa reported demonstrates results similar to those reported for open RC. Continued analysis and direct randomized comparison between techniques is necessary.     

Lymph node density affects cancer-specific survival in patients with lymph node-positive urothelial bladder cancer following radical cystectomy

Background

The prognosis for patients with lymph node (LN)–positive bladder cancer (BCa) is likely affected by the extent of lymphadenectomy in radical cystectomy (RC) cases. Specifically, the prognostic significance of the LN density (ratio of positive LNs to the total number removed) has been demonstrated.

Objective

To evaluate the prognostic signature of lymphadenectomy variables, including the LN density, for a large, multicentre cohort of RC patients with LN-positive BCa.

Design, setting, and participants

The clinical and histopathologic data from 477 patients with LN-positive urothelial BCa (pN1–2) were analysed. The median follow-up period for all living patients was 28 mo.

Measurements

Multivariable Cox regression analysis was used to test the effect of various pelvic lymph node dissection (PLND) variables on cancer-specific survival (CSS) based on colinearity in various models.

Results and limitations

The median number of LNs removed was 12 (range: 1–66), and the median number of positive LNs was 2 (range: 1–25). Two hundred ninety (60.8%) of the patients presented with stage pN2 disease. The median and mean LN density was 17.6% and 29% (range: 2.3–100), respectively, where 268 (56.2%) and 209 (43.8%) patients exhibited am LN density of ≤20% and >20%, respectively. In separate multivariable Cox regression models adjusted for age, sex, pTN stage, grade, associated Tis, and adjuvant chemotherapy, the interval-scaled LN density (hazard ratio [HR]: 1.01; p = 0.002) and the LN density, ordinal-scaled by 20% (HR: 1.65; p < 0.001) exhibit independent effects on CSS. In addition, an independent contribution appears from the pT but not the pN stage. Limitations include surgeon selection bias when determining the extent of lymphadenectomy.

Conclusions

Our results support the prognostic relevance of LN density in patients with LN-positive BCa, where a threshold value of 20% stratifies the population into two prognostically distinct groups. Before LN density is integrated into the clinical decision-making process, these results should be validated by prospective studies with defined LN templates and standardised histopathologic methods.     

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.     

Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the MGH experience

Background

Whether organ-conserving treatment by combined-modality therapy (CMT) achieves comparable long-term survival to radical cystectomy (RC) for muscle-invasive bladder cancer (BCa) is largely unknown.

Objective

Report long-term outcomes of patients with muscle-invasive BCa treated by CMT.

Design, setting, and participants

We conducted an analysis of successive prospective protocols at the Massachusetts General Hospital (MGH) treating 348 patients with cT2–4a disease between 1986 and 2006. Median follow-up for surviving patients was 7.7 yr.

Interventions

Patients underwent concurrent cisplatin-based chemotherapy and radiation therapy (RT) after maximal transurethral resection of bladder tumor (TURBT) plus neoadjuvant or adjuvant chemotherapy. Repeat biopsy was performed after 40 Gy, with initial tumor response guiding subsequent therapy. Those patients showing complete response (CR) received boost chemotherapy and RT. One hundred two patients (29%) underwent RC—60 for less than CR and 42 for recurrent invasive tumors.

Measurements

Disease-specific survival (DSS) and overall survival (OS) were evaluated using the Kaplan-Meier method.

Results and limitations

Seventy-two percent of patients (78% with stage T2) had CR to induction therapy. Five-, 10-, and 15-yr DSS rates were 64%, 59%, and 57% (T2 = 74%, 67%, and 63%; T3–4 = 53%, 49%, and 49%), respectively. Five-, 10-, and 15-yr OS rates were 52%, 35%, and 22% (T2: 61%, 43%, and 28%; T3–4 = 41%, 27%, and 16%), respectively. Among patients showing CR, 10-yr rates of noninvasive, invasive, pelvic, and distant recurrences were 29%, 16%, 11%, and 32%, respectively. Among patients undergoing visibly complete TURBT, only 22% required cystectomy (vs 42% with incomplete TURBT; log-rank p < 0.001). In multivariate analyses, clinical T-stage and CR were significantly associated with improved DSS and OS. Use of neoadjuvant chemotherapy did not improve outcomes. No patient required cystectomy for treatment-related toxicity.

Conclusions

CMT achieves a CR and preserves the native bladder in >70% of patients while offering long-term survival rates comparable to contemporary cystectomy series. These results support modern bladder-sparing therapy as a proven alternative for selected patients.     

Diagnostic efficacy of [11C]choline positron emission tomography/computed tomography compared with conventional computed tomography in lymph node staging of patients with bladder cancer prior to radical cystectomy

Background

Current imaging techniques are of limited value for lymph node (LN) staging in bladder cancer (BCa) patients scheduled for radical cystectomy (RC).

Objective

Evaluate the diagnostic efficacy of [11C]choline positron emission tomography in combination with computed tomography (PET/CT) for LN staging of patients with BCa scheduled for RC and compare that efficacy with the diagnostic efficacy of CT and the gold standard of histopathologic evaluation.

Design, setting, and participants

From June 2004 to May 2007, 44 patients with localized BCa were staged with [11C]choline PET with low-dose CT for attenuation correction and simultaneous intravenous and rectal contrast-enhanced diagnostic CT before RC and pelvic lymph node dissection (PLND). LNs were dissected from the internal and external iliac arteries up to the origin of the inferior mesentery artery according to a template with 14 predefined anatomic fields.

Intervention

Diagnostic [11C]choline PET/CT before RC and regional LN dissection.

Measurements

Histopathologic findings of resected LN were correlated with the results of [11C]choline PET/CT and CT alone in a patient- and field-based manner. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of [11C]choline PET/CT and CT were assessed.

Results and limitations

LN metastases were found in 12 of 44 patients (27%). On patient-based analysis, sensitivity, specificity, PPV, NPV, and accuracy for [11C]choline PET/CT were calculated as 58%, 66%, 39%, 81%, and 64%, respectively; and for CT the calculated percentages were 75%, 56%, 39%, 86%, and 61%, respectively. Twenty-five of 471 dissected LN fields (5%) showed metastases. On field-based analysis, sensitivity, specificity, PPV, NPV, and accuracy for [11C]choline PET/CT were 28%, 95%, 21%, 96%, and 91%, respectively; for CT, the calculated percentages were 39%, 92%, 20%, 96%, and 90%, respectively. Limitations of this study are small patient number and the fact that not all patients underwent extensive PLND.

Conclusions

In patients with BCa who were scheduled for RC, preoperative LN staging with [11C]choline PET/CT was not able to improve diagnostic efficacy compared with conventional CT alone.     

Early salvage radiation therapy does not compromise cancer control in patients with pT3N0 prostate cancer after radical prostatectomy: results of a match-controlled multi-institutional analysis

Background

Previous randomised trials demonstrated that adjuvant radiation therapy (aRT) improves cancer control in patients with pT3 prostate cancer (PCa). However, there is currently no evidence supporting early salvage radiation therapy (eSRT) as equivalent to aRT in improving freedom from biochemical recurrence (BCR) after radical prostatectomy (RP).

Objective

To evaluate BCR-free survival for aRT versus observation followed by eSRT in cases of relapse in patients undergoing RP for pT3pN0, R0–R1 PCa.

Design, setting, and participants

Using a European multi-institutional cohort, 890 men with pT3pN0, R0–R1 PCa were identified.

Intervention

All patients underwent RP. Subsequently, patients were stratified into two groups: aRT versus initial observation followed by eSRT in cases of relapse.

Outcome measurements and statistical analyses

Propensity-matched analysis was employed, and patients were stratified into two groups: aRT versus observation and eventual eSRT, defined as RT given at a postoperative serum prostate-specific antigen (PSA) ≤0.5 ng/ml at least 6 mo after RP. BCR, defined as PSA >0.20 ng/ml and rising after administration of RT, was compared between aRT and initial observation followed by eSRT in cases of relapse using Kaplan-Meier and Cox regression methods.

Results and limitations

Overall, 390 (43.8%) and 500 (56.2%) patients were treated with aRT and initial observation, respectively. Within the latter group, 225 (45.0%) patients experienced BCR and underwent eSRT. In the postpropensity-matched cohort, the 2- and 5-yr BCR-free survival rates were 91.4% and 78.4% in aRT versus 92.8% and 81.8% in patients who underwent initial observation and eSRT in cases of relapse, respectively (p = 0.9). No differences in the 2- and 5-yr BCR-free survival rates were found, even when patients were stratified according to pT3 substage and surgical margin status (all p ≥ 0.4). These findings were also confirmed in multivariable analyses (p = 0.6). Similar results were achieved when the cut-off to define eSRT was set at 0.3 ng/ml (all p ≥ 0.5).

Conclusions

The current study suggests that timely administration of eSRT is comparable to aRT in improving BCR-free survival in the majority of pT3pN0 PCa patients. Therefore, eSRT may not compromise cancer control but significantly reduces overtreatment associated with aRT.     

Decreasing rate and extent of lymph node staging in patients undergoing radical prostatectomy may undermine the rate of diagnosis of lymph node metastases in prostate cancer

Background

At radical prostatectomy (RP), pelvic lymph node dissection (PLND) represents the most accurate staging procedure for the presence of lymph node (LN) metastases.

Objective

We evaluated the rate of PLND use and its lymph node count (LNC) over the last two decades. We also tested the relationship between LNC and the rate of pN1 stage.

Design, setting, and participants

Between 1988 and 2006, 130 080 RPs were recorded in 17 Surveillance Epidemiology and End Results registries.

Measurements

The statistical significance of temporal trends was evaluated with the chi-square trend test. Separate univariable and multivariable regression analyses tested the relationship between predictors and two end points: (1) lack of LN staging (pNx) and (2) presence of LN metastases (pN1).

Results and limitations

Stage pNx was recorded in 25.9% of patients, and pNx rate was higher in more contemporary years (30.1% in 2000–2006 vs 20.8% in 1988–1993; multivariable p < 0.001). When PLND was performed, an average of 7.4 LNs (median: 6) were removed. The average LNC decreased from 12.0 nodes (median: 12) in 1988 to 6.0 nodes (median: 4) in 2006. Overall pN1 rate was 3.4% and decreased from 10.7% to 3.1% between 1988 and 2006 (p < 0.001). LNC was an independent predictor of pN1 stage (multivariable p < 0.001).

Conclusions

An increasingly larger proportion of prostate cancer patients remain without LN staging at RP. Fewer LNs were removed at PLND over time, resulting in fewer patients diagnosed with pN1 stage at RP. The impact of this phenomenon on cancer control outcomes is still to be verified.     

Clinical role of additional adjuvant chemotherapy in patients with locally advanced urothelial carcinoma following neoadjuvant chemotherapy and cystectomy

Purpose

Neoadjuvant chemotherapy (NAC) can downstage invasive bladder cancers prior to radical cystectomy (RC) and improve overall survival. However, the optimal management in patients with persistent non-organ confined disease (pT3–T4 and/or pN+) following RC has not been completely defined. The aim of this study was to describe outcomes associated with the use of adjuvant chemotherapy (AC) in patients with residual non-organ confined cancer at RC following NAC.

Materials and methods

Using data from a high-volume referral institution, pT3–T4 and/or pN+ patients who received NAC and then also RC were identified. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were assessed with Kaplan–Meier analysis.

Results

From 2001 to 2013, 161 patients received NAC and then RC. Eighty-eight pT3–T4 and/or pN+ patients were identified. Twenty-nine (33 %) received AC. Adjuvant chemotherapy in the majority of patients was carboplatin-based (16), followed by cisplatin (8) and other, mainly taxane-containing regimens (5). The median RFS was 17.5 months in the AC and 13.7 months in the non-AC group (p = 0.78). AC remained an insignificant predictor for RFS after adjusting for pT, pN and margin status (HR 0.89, 95 % CI 0.48–1.68]). CSS was 23 and 22 months (p = 0.65) and remained insignificant after adjusting for pathologic confounders.

Conclusions

In our current study population, adjuvant conventional cytotoxic chemotherapy was not associated with significant improvements in RFS or CSS. The choice of AC regimens, and incorporation of newer treatments, may be the key for improving outcomes in this high-risk patient group.

     

Pathologic Nodal Staging Scores in Patients Treated with Radical Prostatectomy: A Postoperative Decision Tool

Background

Nodal metastasis is the strongest risk factor of disease recurrence in patients with localized prostate cancer (PCa) treated with radical prostatectomy (RP).

Objective

To develop a model that allows quantification of the likelihood that a pathologically node-negative patient is indeed free of nodal metastasis.

Design, setting, and participants

Data from patients treated with RP and pelvic lymph node dissection (PLND; n = 7135) for PCa between 2000 and 2011 were analyzed. For external validation, we used data from patients (n = 4209) who underwent an anatomically defined extended PLND.

Intervention

RP and PLND.

Outcome measurements and statistical analysis

We developed a novel pathologic (postoperative) nodal staging score (pNSS) that represents the probability that a patient is correctly staged as node negative based on the number of examined nodes and the patient's characteristics.

Results and limitations

In the development and validation cohorts, the probability of missing a positive node decreases with an increasing number of nodes examined. Whereas in pT2 patients, a 90% pNSS was achieved with one single examined node in both the development and validation cohort, a similar level of nodal staging accuracy was achieved in pT3a patients by examining five and nine nodes, respectively. The pT3b/T4 patients achieved a pNSS of 80% and 70% when 17 and 20 nodes in the development and validation cohort were examined, respectively. This study is limited by its retrospective design and multicenter nature. The number of nodes removed was not directly correlated with the extent/template of PLND.

Conclusions

Every patient needs PLND for accurate nodal staging. However, a one-size-fits-all approach is too inaccurate. We developed a tool that indicates a node-negative patient is indeed free of lymph node metastasis by evaluating the number of examined nodes, pT stage, RP Gleason score, surgical margins, and prostate-specific antigen. This tool may help in postoperative decision making.     

A randomized prospective trial to assess the impact of transurethral resection in narrow band imaging modality on non-muscle-invasive bladder cancer recurrence

Background

Narrow band imaging (NBI) is an optical enhancement technology that filters white light into two bandwidths of illumination centered on 415 nm (blue) and 540 nm (green). NBI cystoscopy can increase bladder cancer (BCa) visualization and detection at the time of transurethral resection (TUR). NBI may therefore reduce subsequent relapse following TUR.

Objective

Assess the impact of NBI modality on 1-yr non–muscle-invasive BCa (NMIBC) recurrence risk.

Design, setting, and participants

Consecutive patients with overt or suspected BCa were included in a prospective study powered to test a 10% difference in 1-yr recurrence risk in favor of cases submitted to NBI TUR. Excluding patients with muscle-invasive BCa, negative pathologic examination, or without follow-up, the study population was composed of 148 subjects randomized from August 2009 to September 2010 to NBI TUR (76 cases) or white light (WL) TUR (72 cases).

Intervention

TUR was performed in NBI or standard WL modality.

Measurements

The 1-yr recurrence risks in NBI or WL TUR groups were compared using odds ratio (OR) point and interval estimates derived from logistic regression modeling.

Results and limitations

The 1-yr recurrence-risk was 25 of 76 patients (32.9%) in the NBI and 37 of 72 patients (51.4%) in the WL group (OR = 0.62; p = 0.0141). Simple and multiple logistic regression analyses provided similar OR points and interval estimates.

Conclusions

TUR performed in the NBI modality reduces the recurrence risk of NMIBC by at least 10% at 1 yr.     

Is There a Need to Further Subclassify pT2 Renal Cell Cancers as Implemented by the Revised 7th TNM Version?

Background

The recently modified TNM classification of renal cell carcinoma (RCC) (7th edition) has implemented a subdivision of pT2 tumours into stage pT2a (>7 or ≤10 cm) versus pT2b disease (>10 cm).

Objective

Our aim was to evaluate whether this subdivision of pT2 RCC is justified due to a clinical prognosis divergence between the two groups (pT2a vs pT2b)

Design, setting, and participants

In total, 5122 patients were subjected to either radical nephrectomy or nephron-sparing surgery at three centres in Germany (University Hospitals of Hannover, Homburg/Saar, and Marburg). Patients were reclassified into stage pT2a and pT2b according to the maximum tumour diameter as suggested by the 7th revised version of the TNM classification system.

Measurements

The t test and Fisher exact test were applied to evaluate the comparability of the two groups (pT2a vs pT2b) regarding several additional patients’ and tumour-specific characteristics of known prognostic relevance for RCC. Univariable (Kaplan-Meier analysis) and multivariable statistical analyses (Cox proportional hazards regression model) were applied to identify a possible difference between the two groups (pT2a vs pT2b) regarding cancer-specific survival (CSS).

Results and limitations

Applying the new TNM classification, 579 previously pT2-staged patients were divided into 445 (76.9%) with pT2a and 134 (23.1%) with pT2b tumours. Kaplan-Meier curves revealed no significant difference in CSS between pT2a and pT2b patients; 5-yr CSS was 79.0% and 74.1%, respectively (p = 0.38). When applying multivariable analysis, unlike tumour grade and N/M status, pT2 subclassification failed to independently predict survival in RCC patients.

Conclusions

The new subclassification of pT2 RCC into two different subgroups as suggested by the latest modification of the TNM system does not yield additional/prognostic information.     

A systematic review and meta-analysis on the oncological long-term outcomes after trimodality therapy and radical cystectomy with or without neoadjuvant chemotherapy for muscle-invasive bladder cancer

Objective

This study aimed to comprehensively analyze the oncological long-term outcomes of trimodal therapy (TMT) and radical cystectomy (RC) for the treatment of muscle-invasive bladder cancer (BC) with or without neoadjuvant chemotherapy (NAC).

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.     

Neoadjuvant Chemotherapy in Small Cell Urothelial Cancer Improves Pathologic Downstaging and Long-term Outcomes: Results from a Retrospective Study at the MD Anderson Cancer Center

Background

Small cell urothelial carcinoma (SCUC) is a rare, aggressive malignancy with a propensity for early microscopic metastases. Data suggest that neoadjuvant chemotherapy may lead to improved survival compared with initial surgery.

Objective

To determine the influence of neoadjuvant chemotherapy on survival of SCUC patients in a large single-institution cohort.

Design, setting, and participants

Between 1985 and 2010, 172 patients were treated for SCUC at MD Anderson Cancer Center (MDACC). Clinical, pathologic, and surgical data were collected and analyzed.

Outcome measurements and statistical analysis

Overall survival (OS) and disease-specific survival (DSS) were calculated using the Kaplan-Meier method. Multivariable Cox proportional hazards models were used to evaluate the effects of neoadjuvant chemotherapy on survival.

Results and limitations

Of 125 patients with resectable disease (≤cT4aN0M0), 95 were surgical candidates. Forty-eight received neoadjuvant chemotherapy, and 47 underwent initial surgery. Neoadjuvant treatment was associated with improved OS and DSS compared with initial cystectomy (median OS: 159.5 mo vs 18.3 mo, p < 0.001; 5-yr DSS: 79% vs 20%, p < 0.001). Neoadjuvant chemotherapy resulted in pathologic downstaging to ≤pT1N0 in 62% of tumors compared with only 9% treated with initial surgery (odds ratio: 44.55; 95% confidence interval, 10.39–191). Eight patients with clinically node-positive disease had surgical consolidation with cystectomy and extended lymph node dissection after clinical complete response to chemotherapy. Median OS and DSS in this group of patients were 23.3 mo and 21.8 mo, respectively, with 5-yr OS and DSS of 38%.

Conclusions

Neoadjuvant chemotherapy is associated with a high rate of pathologic downstaging and correlates with significantly higher survival compared with historical expectations. Although limited by a small sample size and retrospective analysis, in the context of a rare disease, this experience suggests neoadjuvant chemotherapy as a standard approach in treating SCUC.     

Oncologic Outcome after Extraperitoneal Laparoscopic Radical Prostatectomy: Midterm Follow-up of 1115 Procedures

Background

Although the first laparoscopic radical prostatectomy was performed in 1997, few midterm oncologic data have been published for the extraperitoneal procedure.

Objective

To determine the oncologic outcome of extraperitoneal laparoscopic radical prostatectomy (ELRP).

Design, setting, and participants

From 2000 to 2007, 1115 consecutive patients underwent ELRP for a localized prostate cancer at our department. Follow-up was scheduled and standardized for all patients and recorded into a prospective database. Median postoperative follow-up was 35.6 mo.

Intervention

All ELRP were performed by three surgeons at the Department of Urology, Hospital Henri Mondor, Créteil, France.

Measurements

Biochemical recurrence was defined by prostate-specific antigen level ≥0.2 ng/ml.

Results and limitations

In pN0/pNx cancers, postoperative stage was pT2 in 664 patients (59.5%), pT3 in 350 patients (31.4%), and pT4 in 77 patients (6.9%). Positive lymph nodes were reported in 24 patients (2.2%). Margins were positive in 16.1% and 34.6% of pT2 and pT3 cancers, respectively. Final Gleason score was <7 in 288 men (25.8%), =7 in 701 men (62.9%), and >7 in 126 men (11.3%). Overall prostate-specific antigen (PSA) recurrence-free survival was 83% at 5 yr. The 5-yr progression-free survival rates were 93.4% for pT2, 74.5% for pT3a, and 55.0% for pT3b tumors, respectively. Multivariate Cox model showed that PSA, Gleason score, pT category, nodal status, and surgical margins were significant independent predictors of biochemical recurrence-free survival.

Conclusions

This assessment of oncologic results demonstrates that ELRP is a safe and effective procedure. On the basis of midterm follow-up data, the prognostic factors of PSA after ELRP failure are the same as those described previously in transperitoneal or open retropubic approaches. The oncologic results of ELRP also are in line with those reported with the use of the retropubic or the transperitoneal laparoscopic approaches.     

Natural history of pT3-4 or node positive bladder cancer treated with radical cystectomy and no neoadjuvant chemotherapy in a contemporary North-American multi-institutional cohort

Background:

The present study documents the natural history and outcomes of high-risk bladder cancer after radical cystectomy (RC) in patients who did not receive neoadjuvant chemotherapy during a contemporary time period.

Methods:

We analyzed 1180 patients from 1993 to 2008 with >pT3N0 or pT0-4N+ bladder cancer who underwent RC ± standard (sLND) or extended (eLND) lymph node dissection from 8 Canadian centres.

Results:

Of the 1180 patients, 55% (n = 643) underwent sLND, 34% (n = 402) underwent ePLND and 11% did not undergo a formal LND. Of the total number of patients, 321 (27%) received adjuvant chemotherapy. The median follow-up was 2.1 years (range: 0.6 to 12.9). Overall 30-day mortality was 3.2%. Clinical and pathological stages T3-4 were present in 6.1% and 86.7% of the patients, respectively; this demonstrates a dramatic understaging. Overall survival (OS) at 2 and 5 years was 60% and 43%, respectively. Patients who received adjuvant chemotherapy had a 2- and 5-year disease-specific survival (DSS) of 72% and 57% versus 64% and 51% for those who did not (log-rank p = 0.0039). The 2- and 5-year OS for high-risk node-negative disease was 67% and 52%, respectively, whereas for node-positive patients, the OS was 52% and 32%, respectively (p < 0.001). The OS, DSS and RFS for patients with pN0 were significantly improved compared to those who did not undergo a LND (log-rank p = 0.0035, 0.0241 and 0.0383, respectively).

Interpretation:

This series suggests that bladder cancer outcomes in advanced disease have improved in the modern era. The need for improved staging investigations, use of neoadjuvant chemotherapy and performance of complete LND is emphasized.