Laparoscopic versus open nephroureterectomy for the treatment of upper urinary tract urothelial carcinoma: a systematic review and cumulative analysis of comparative studies

Context

Laparoscopic nephroureterectomy (LNU) has increasingly been used as a minimally invasive alternative to open nephroureterectomy (ONU), but studies comparing the efficacy and safety of the two surgical procedures are still limited.

Objective

Evaluate the oncologic and perioperative outcomes of LNU versus ONU in the treatment of upper urinary tract urothelial carcinoma.

Evidence acquisition

A systematic review and cumulative analysis of comparative studies reporting both oncologic and perioperative outcomes of LNU and ONU was performed through a comprehensive search of the Medline, Embase, and the Cochrane Library electronic databases. All analyses were performed using the Review Manager (RevMan) v.5 (Nordic Cochrane Centre, Copenhagen, Denmark) and Meta-analysis In eXcel (MIX) 2.0 Pro (BiostatXL) software packages.

Evidence synthesis

Twenty-one eligible studies (1235 cases and 3093 controls) were identified. A significantly higher proportion of pTa/Tis was observed in LNU compared to ONU (27.52% vs 22.59%; p = 0.047), but there were no significant differences in other stages and pathologic grades (all p > 0.05). For patients who underwent LNU, the 5-yr cancer-specific survival (CSS) rate was significantly higher, at 9% (p = 0.03), compared to those who underwent ONU, while the overall recurrence rate and bladder recurrence rate were notably lower, at 15% (p = 0.01) and 17% (p = 0.02), respectively. However, there were no statistically significant differences in 2-yr CSS, 5-yr recurrence-free survival (RFS), 5-yr overall survival (OS), 2-yr OS, and metastasis rates between LNU and ONU (all p > 0.05). Moreover, there were no significant differences between LNU and ONU in terms of intraoperative complications, postoperative complications, and perioperative mortality (all p > 0.05). The results of our study were mainly limited by the retrospective design of most of the individual studies included as well as selection biases based on different management of regional lymph nodes and pathologic characteristics.

Conclusions

Our data suggest that LNU offers reliable perioperative safety and comparable oncologic efficacy when compared to ONU. Given that some limitations cannot be overcome, well-designed prospective trials are needed to confirm our findings.     

Comparison of Oncologic Outcomes for Open and Laparoscopic Nephroureterectomy: A Multi-Institutional Analysis of 1249 Cases

Background

Data regarding the oncologic efficacy of laparoscopic nephroureterectomy (LNU) compared to open nephroureterectomy (ONU) are scarce.

Objective

We compared recurrence and cause-specific mortality rates of ONU and LNU.

Design, setting, and participants

Thirteen centers from three continents contributed data on 1249 patients with nonmetastatic upper tract urothelial carcinoma (UTUC).

Measurements

Univariable and multivariable survival models tested the effect of procedure type (ONU [n = 979] vs LNU [n = 270]) on cancer recurrence and cancer-specific mortality. Covariables consisted of institution, age, Eastern Cooperative Oncology Group (ECOG) performance status score, pT stage, pN stage, tumor grade, lymphovascular invasion, tumor location, concomitant carcinoma in situ, ureteral cuff management, previous urothelial bladder cancer, and previous endoscopic treatment.

Results and limitations

Median follow-up for censored cases was 49 mo (mean: 62). Relative to ONU, LNU patients had more favorable pathologic stages (pT0/Ta/Tis: 38.1% vs 20.8%, p < 0.001) and less lymphovascular invasion (14.8% vs 21.3%, p = 0.02) and less frequently had tumors located in the ureter (64.5 vs 71.1%, p = 0.04). In univariable recurrence and cancer-specific mortality models, ONU was associated with higher cancer recurrence and mortality rates compared to LNU (hazard ratio [HR]: 2.1 [p < 0.001] and 2.0 [p = 0.008], respectively). After adjustment for all covariates, ONU and LNU had no residual effect on cancer recurrence and mortality (p = 0.1 for both).

Conclusions

Short-term oncologic data on LNU are comparable to ONU. Since LNU was selectively performed in favorable-risk patients, we cannot state with certainty that ONU and LNU have the same oncologic efficacy in poor-risk patients. Long-term follow-up data and morbidity data are necessary before LNU can be considered as the standard of care in patients with muscle-invasive or high-grade UTUC.     

Laparoscopic versus Open Nephroureterectomy: Perioperative and Oncologic Outcomes from a Randomised Prospective Study

Background

Laparoscopic nephroureterectomy (LNU) is increasingly being used instead of open nephroureterectomy (ONU) for the treatment of urothelial carcinoma (UC) of the upper urinary tract (UUT), but the evidence of equal oncologic effectiveness is still lacking.

Objective

To present perioperative and oncologic results from a prospective randomised study comparing ONU and LNU.

Design, setting, and participants

Eighty patients with nonmetastatic UUT UC and without previous history of UC were enrolled. Of those, 40 patients (group A) randomly received ONU and 40 patients (group B) randomly received LNU.

Interventions

ONU was performed through a flank incision with a lower quadrant incision to allow excision of a bladder cuff. Transperitoneal LNU was performed with a four-trocar technique, and bladder cuff was detached with a 10-mm LigaSure device.

Measurements

Perioperative data were compared with the student t test. Bladder tumour–free survival (BTFS), metastasis-free survival (MFS), and cancer-specific survival (CSS) curves for both groups were compared with the log-rank test before and after stratifying patients for pT category and tumour grade.

Results and limitations

Operative times were comparable, while mean blood loss and mean time to discharge were significantly lower in group B (both p values <0.001). At a median follow-up of 44 mo, BTFS, CSS, and MFS were not significantly different between the two groups (log rank test; BTFS: p = 0.86; CSS: p = 0.2; MFS: p = 0.124). When matched for pT3 and high-grade tumours, CSS and MFS were significantly different between the two groups in favour of ONU (p = 0.039 and p = 0.004, respectively, for pT3 tumours; p = 0.078 and p = 0.014, respectively, for high-grade tumours).The limitations of our study include the small sample size, the single-centre experience, the personal choice of laparoscopic technique, and not performing lymphadenectomies.Perioperative data and preliminary oncologic results were presented at 22nd Congress of the European Association of Urology, Berlin, Germany.

Conclusions

In patients with organ-confined UUT UCs, LNU has the advantages of minimal invasiveness and oncologic outcomes comparable to those of ONU, while its effectiveness in patients with advanced stage diseases remains to be proven.     

Anatomic Bladder Neck Preservation During Robotic-Assisted Laparoscopic Radical Prostatectomy: Description of Technique and Outcomes

Background

Robotic-assisted laparoscopic radical prostatectomy (RALP) has been rapidly adopted despite a daunting learning curve with bladder neck dissection as a challenging step for newcomers.

Objective

To describe an anatomic, reproducible technique of bladder neck preservation (BNP) and associated perioperative and long-term outcomes.

Design, settings, and participants

From September 2005 to May 2009, data from 619 consecutive RALP were prospectively collected and compared on the basis of bladder neck dissection technique with 348 BNP and 271 standard technique (ST).

Surgical procedure

RALP with BNP.

Measurements

Tumor characteristics, perioperative complications, and post-operative urinary control were evaluated at 4, 12 and 24 months using (1) the Expanded Prostate Cancer Index (EPIC) urinary function scale scored from 0–100; and (2) continence defined as zero pads per day.

Results and limitations

Mean age for BNP versus ST was 57.1 ± 6.6 yr versus 58.9 ± 6.7 yr (p = 0.033), while complication rates did not vary significantly by technique. Estimated blood loss was 183.7 ± 95.8 ml versus 224.6 ± 108 ml (p = 0.938) in men who underwent BNP versus ST. The overall positive margin rate was 12.8%, which did not differ at the prostate base for BNP versus ST (1.4% vs. 2.2%, p = 0.547). Mean urinary function scores for BNP versus ST at 4, 12, and 24 mo were 64.6 versus 57.2 (p = 0.037), 80.6 versus 79.0 (p = 0.495), and 94.1 versus 86.8 (p < 0.001). Similarly, BNP versus ST continence rates at 4, 12, and 24 mo were 65.6% versus 26.5% (p < 0.001), 86.4% versus 81.4% (p = 0.303), and 100% versus 96.1% (p = 0.308).

Conclusions

BNP versus ST is associated with quicker recovery of urinary function and similar cancer control.     

Temporal national trends of minimally invasive and retropubic radical prostatectomy outcomes from 2003 to 2007: results from the 100% Medicare sample

Background

Although the use of minimally invasive radical prostatectomy (MIRP) has increased, there are few comprehensive population-based studies assessing temporal trends and outcomes relative to retropubic radical prostatectomy (RRP).

Objective

Assess temporal trends in the utilization and outcomes of MIRP and RRP among US Medicare beneficiaries from 2003 to 2007.

Design, setting, and participants

A population-based retrospective study of 19 594 MIRP and 58 638 RRP procedures was performed from 2003 to 2007 from the 100% Medicare sample, composed of almost all US men ≥65 yr of age.

Intervention

MIRP and RRP.

Measurements

We measured 30-d outcomes (cardiac, respiratory, vascular, genitourinary, miscellaneous medical, miscellaneous surgical, wound complications, blood transfusions, and death), cystography utilization within 6 wk of surgery, and late complications (anastomotic stricture, ureteral complications, rectourethral fistulae, lymphocele, and corrective incontinence surgery).

Results and limitations

From 2003 to 2007, MIRP increased from 4.9% to 44.5% of radical prostatectomies while RRP decreased from 89.4% to 52.9%. MIRP versus RRP subjects were younger (p < 0.001) and had fewer comorbidities (p < 0.001). Decreased MIRP genitourinary complications (6.2–4.1%; p = 0.002), miscellaneous surgical complications (4.7–3.7%; p = 0.030), transfusions (3.5–2.2%; p = 0.005), and postoperative cystography utilization (40.3–34.1%; p < 0.001) were observed over time. Conversely, overall RRP perioperative complications increased (27.4–32.0%; p < 0.001), including an increase in perioperative mortality (0.5–0.8%, p = 0.009). Late RRP complications increased, with the exception of fewer anastomotic strictures (10.2–8.8%; p = 0.002). In adjusted analyses, RRP versus MIRP was associated with increased 30-d mortality (odds ratio [OR]: 2.67; 95% confidence interval [CI], 1.55–4.59; p < 0.001) and more perioperative (OR: 1.60; 95% CI, 1.45–1.76; p < 0.001) and late complications (OR: 2.52; 95% CI, 2.20–2.89; p < 0.001). Limitations include the inability to distinguish MIRP with versus without robotic assistance and also the lack of pathologic information.

Conclusions

From 2003 to 2007, there were fewer MIRP transfusions, genitourinary complications, and miscellaneous surgical complications, whereas most RRP perioperative and late complications increased. RRP versus MIRP was associated with more postoperative mortality and complications.     

Perioperative efficacy of laparoscopic partial nephrectomy for tumors larger than 4 cm

Background

Laparoscopic partial nephrectomy (LPN) is typically reserved for kidney tumors ≤4 cm in size. The use of LPN in patients with larger tumors (>4 cm) has not been systematically evaluated.

Objective

To examine technical feasibility and perioperative safety and efficacy of LPN for clinical stage pT1b–T2 tumors >4 cm.

Design, setting, and participants

This is a retrospective review of data from an Institutional Review Board–approved, prospectively maintained database of 425 LPN procedures over a 6-yr period (September 1999 through December 2005). Patients were grouped according to tumor size: control group1: <2 cm (n = 89; 21% of patients); control group 2: 2–4 cm (n = 278; 65% of patients); and study group 3: >4 cm (n = 58; 14% of patients).

Intervention

Retroperitoneal and transperitoneal LPN.

Measurements

Serum creatinine levels, estimated glomerular filtration rates.

Results and limitations

For groups 1, 2, and 3, mean tumor size was 1.5 cm, 2.9 cm, and 6 cm in diameter, respectively (p < 0.001). Study group 3 patients more often had an American Society of Anesthesiologists score ≥3 (p < 0.05), central tumors (p < 0.001), pelvicalyceal repair (p = 0.004), and heminephrectomy (p < 0.001). Total operative time, estimated blood loss, and duration of hospital stay were equivalent. Mean warm ischemia time was 30 min, 32 min, and 38 min in groups 1, 2, and 3, respectively (p = 0.007). Tumor size >4 cm did not increase significant risk for positive tumor margins, intraoperative complications, or postoperative genitourinary complications. In each group preoperative stage ≥3 chronic kidney disease (CKD) was present in 31%, 35%, and 44% of patients in groups 1, 2, and 3, respectively (p = 0.15); postoperatively, stage 3–5 CKD incidence increased to 52%, 52%, and 63% in groups 1, 2, and 3, respectively (p = 0.20). Patients with tumor size >4 cm and preoperative stage 3–5 CKD had an 8-fold increase in risk for CKD stage progression. Limitations of the study include retrospective analysis and a relatively low number of patients in group 3.

Conclusions

Given laparoscopic expertise and appropriate patient selection, LPN is feasible and efficacious for kidney tumors >4 cm. Indications for LPN should be expanded to include patients with amenable tumors >4 cm in order to maximally preserve kidney function in these patients.     

Radiofrequency ablation versus partial nephrectomy in patients with solitary clinical T1a renal cell carcinoma: comparable oncologic outcomes at a minimum of 5 years of follow-up

Background

Long-term comparative outcomes for radiofrequency ablation (RFA) versus partial nephrectomy (PN) for the primary treatment of clinical T1a renal cell carcinoma (RCC) have not previously been reported.

Objective

Report comparative 5-yr oncologic outcomes for RFA versus PN in patients with clinical T1a RCC.

Design, setting, and participants

Observational single-institution cohort study, involving consecutive patients with a solitary histologically confirmed T1a RCC treated by RFA or PN and followed for a minimum of 5 yr. Those presenting with synchronous multiple, metachronous, bilateral, and/or metastatic disease, a history of hereditary RCC syndromes, a family history of RCC, and with post-treatment follow-up <5 yr were excluded from analysis.

Measurements

The Kaplan-Meier method was used to determine 5-yr overall survival (OS), cancer-specific survival (CSS), local recurrence-free survival (local RFS), overall disease-free survival (DFS), and metastasis-free survival (MFS) for RFA versus PN. Survival curves were compared using the log-rank test. A p value ≤0.05 was considered statistically significant.

Results and limitations

A total of 37 patients in each group met the selection criteria. The RFA cohort was significantly older and had more advanced comorbidities, but other patient characteristics were similar. For RFA versus PN, median follow-up was 6.5 yr (interquartile range [IQR]: 5.8–7.1) versus 6.1 yr (IQR: 5.4–7.3) (p = 0.68), respectively. The 5-yr OS was 97.2% versus 100% (p = 0.31), CSS was 97.2% versus 100% (p = 0.31), DFS was 89.2% versus 89.2% (p = 0.78), local RFS was 91.7% versus 94.6% (p = 0.96), and MFS was 97.2% versus 91.8% (p = 0.35), respectively. Study limitations are retrospective data analysis, loss to follow-up, limited statistical power, and limited generalizability of our data.

Conclusions

In appropriately selected patients, RFA is an effective minimally invasive therapy for the treatment of cT1a RCC, yielding comparable long-term oncologic outcomes to nephron-sparing surgery.     

A prospective trial comparing consecutive series of open retropubic and robot-assisted laparoscopic radical prostatectomy in a centre with a limited caseload

Background

Robot-assisted radical prostatectomy (RALP) is performed worldwide, even in institutions with limited caseloads. However, although the results of large RALP series are available, oncologic and functional outcomes as well as complications from low-caseload centres are lacking.

Objective

To compare perioperative, oncologic, and functional outcomes from two consecutive series of patients with localised prostate cancer treated by retropubic radical prostatectomy (RRP) or recently established RALP in our hospital, which has a limited caseload.

Design, setting, and participants

One hundred fifty consecutive patients were enrolled. Their data and outcomes were collected and extensively evaluated.

Intervention

Seventy-five consecutive patients underwent RRP, and 75 consecutive patients underwent RALP, including all patients of the learning curve.

Measurements

Patient baseline characteristics, perioperative and postoperative outcomes, and complications were evaluated. End points were oncologic data (positive margins, prostate-specific antigen [PSA]), perioperative complications, urinary continence, and erectile function at 3- and 12-mo follow-up.

Results and limitations

The preoperative parameters from the two groups were comparable. The positive surgical margin (PSM) rates were 32% for RRP and 16% for RALP (p = 0.002). For RRP and RALP, the PSA value was <0.2 ng/ml in 91% and 88% of patients 3 mo postoperatively (p = 0.708) and in 87% and 89% of patients 12 mo postoperatively (p = 0.36), respectively. Continence rates for RRP and RALP were 83% and 95% at 3-mo follow-up (p = 0.003) and 80% and 89% after 12-mo follow-up (p = 0.092), respectively. Among patients who were potent without phosphodiesterase type 5 inhibitors (PDE5-I) before RRP and RALP, recovery of erectile function with and without PDE5-Is was achieved in 25% (12 of 49 patients) and 68% (25 of 37 patients) 3 mo postoperatively (p = 0.009) and in 26% (12 of 47 patients) and 55% (12 of 22 patients) 12 mo postoperatively (p = 0.009), respectively. Minimal follow-up for RRP was 12 mo; median follow-up for the RALP group was 12 mo (range: 3–12). According to the modified Clavien system, major complication rates for RRP and RALP were 28% and 7% (p = 0.025), respectively; minor complication rates were 24% and 35% (p = 0.744), respectively.

Conclusions

Despite a limited caseload and including the learning curve, RALP offers slightly better results than RRP in terms of PSM, major complications, urinary continence, and erectile function.     

Robotic partial nephrectomy versus laparoscopic cryoablation for the small renal mass

Background

Open partial nephrectomy (OPN) remains the gold standard for treatment of small renal masses (SRMs). Laparoscopic cryoablation (LCA) has provided encouraging outcomes. Robotic partial nephrectomy (RPN) represents a new promising option but is still under evaluation.

Objective

Compare the outcomes of RPN and LCA in the treatment of patients with SRMs.

Design, setting, and participants

We retrospectively analyzed the medical charts of patients with SRMs (≤4 cm) who underwent minimally invasive nephron-sparing surgery (RPN or LCA) in our institution from January 1998 to December 2010.

Intervention

RPN and LCA.

Measurements

Perioperative complications and functional and oncologic outcomes were analyzed.

Results and limitations

A total of 446 SRMs were identified in 436 patients (RPN, n = 210; LCA, n = 226). Patients undergoing RPN were younger (p < 0.0001), had a lower American Society of Anesthesiologists score (p < 0.001), and higher baseline preoperative estimated glomerular filtration rate (eGFR) (p < 0.0001). Mean tumor size was smaller in the LCA group (2.2 vs 2.4 cm; p = 0.004). RPN was associated with longer operative time (180 vs 165 min; p = 0.01), increased estimated blood loss (200 vs 75 ml; p < 0.0001), longer hospital stay (72 vs 48 h; p < 0.0001), and higher morbidity rate (20% vs 12%, p = 0.015). Mean follow-ups for RPN and LCA were 4.8 mo and 44.5 mo, respectively (p < 0.0001). Local recurrence rates for RPN and LCA were 0% and 11%, respectively (p < 0.0001). Mean eGFR decrease after RPN and LCA was insignificant at 1 mo, at 6 mo after surgery, and during last follow-up. Limitations include retrospective study design, length of follow-up, and selection bias.

Conclusions

Both techniques remain viable treatment options in the management of SRMs. A higher incidence of perioperative complications was found in patients undergoing RPN. However, the technique was not predictive of the occurrence of postoperative complications. Early oncologic outcomes are promising for RPN, which also seems to be associated with better preservation of renal function. Long-term follow-up and well-designed prospective comparative studies are awaited to corroborate these findings.     

The Extent of Lymphadenectomy Seems to Be Associated with Better Survival in Patients with Nonmetastatic Upper-Tract Urothelial Carcinoma: How Many Lymph Nodes Should Be Removed?

Background

The role and extent of lymphadenectomy in patients with upper-tract urothelial carcinoma (UTUC) is debated.

Objective

To establish whether the number of lymph nodes (LNs) removed might be associated with better cause-specific survival in patients with UTUC.

Design, setting, and participants

The study included 552 consecutive patients who underwent radical nephroureterectomy (RNU) and lymphadenectomy between 1992 and 2006.

Intervention

Patients were treated with RNU and lymphadenectomy.

Measurements

Univariable and multivariable Cox proportional hazards regression models addressed the association between the number of LNs removed and cause-specific mortality (CSM). The number of LNs removed was coded as a cubic spline to allow for nonlinear effects. Finally, the most informative cut-off for the number of removed LNs was identified.

Results and limitations

In the entire population, the number of LNs removed was not associated with CSM in univariable (hazard ratio [HR]: 0.99; p = 0.16) or in multivariable (HR: 0.97; p = 0.12) analyses. In contrast, in the subgroup of pN0 patients (n = 412), the number of LNs removed achieved the independent predictor status of CSM (HR: 0.93; p = 0.02). Eight LNs removed was the most informative cut-off in predicting CSM (HR: 0.42; p = 0.004). The inclusion of the variable defining dichotomously the number of removed LNs (<8 vs ≥8) in the base model (age, Eastern Cooperative Oncology Group performance status, pathologic stage, grade, architecture, and lymphovascular invasion) significantly increased the accuracy in predicting CSM (+1.7%; p < 0.001).

Conclusions

The extension of the lymphadenectomy in pN0 UTUC patients seems to be associated with CSM. Longer survival was observed in patients in whom at least eight LNs had been removed.     

Subclassification of pT3 urothelial carcinoma of the renal pelvicalyceal system is associated with recurrence-free and cancer-specific survival: proposal for a revision of the current TNM classification

Background

The clinical course of pT3 upper tract urothelial carcinoma (UTUC) is highly variable.

Objectives

The aim of the current study was to validate the clinical and prognostic importance of pT3 subclassification in the renal pelvicalyceal system in a large international cohort of patients.

Design, setting, and participants

From a multi-institutional international database, 858 renal pelvicalyceal tumors treated with radical nephroureterectomy (RNU) were systematically reevaluated by genitourinary pathologists. Category pT3 pelvic tumors were categorized as pT3a (infiltration of the renal parenchyma on a microscopic level only) versus pT3b (macroscopic infiltration of the renal parenchyma and/or infiltration of peripelvic adipose tissue).

Intervention

RNU.

Measurements

Associations of pT3 subclassifications with clinicopathologic features were assessed with the chi-square test. Prognostic impact was assessed with the log-rank test and multivariable Cox regression analyses.

Results and limitations

Of 858 patients with renal pelvicalyceal tumors, 266 (31%) had pT3 disease. Of these, 146 (54.9%) were classified as pT3a and 120 (45.1%) as pT3b. Compared with pT3a, pT3b cancers were associated with higher tumor grade, nodal disease, and tumor necrosis. Ten-year recurrence-free (pT3a 58% vs pT3b 38%; p < 0.001) and cancer-specific (pT3a 60% vs pT3b 39%; p = 0.002) survival rates were lower for patients with pT3b disease. In multivariable analyses, classification pT3b was an independent predictor of both disease recurrence (hazard ratio [HR]: 1.8, p = 0.003) and cancer-specific mortality (HR: 1.7; p = 0.02). The major limitation is the retrospective character of the study.

Conclusions

Subclassification of pT3 renal pelvicalyceal UTUC helps identify patients who are at increased risk of disease progression and cancer-related death. Further research may help assess the value of subclassification and its inclusion in future editions of the American Joint Committee on Cancer–International Union Against Cancer TNM classification system.     

Non-risk-adapted surveillance in clinical stage I nonseminomatous germ cell tumors: the Princess Margaret Hospital's experience

Background

Since 1981 Princess Margaret Hospital has used initial active surveillance (AS) with delayed treatment at relapse as the preferred management for all patients with clinical stage I nonseminomatous germ cell tumors (NSGCT).

Objective

Our aim was to report our overall AS experience and compare outcomes over different periods using this non–risk-adapted approach.

Design, setting, and participants

Three hundred and seventy-one patients with stage I NSGCT were managed by AS from 1981 to 2005. For analysis by time period, patients were divided into two cohorts by diagnosis date: initial cohort, 1981–1992 (n = 157), and recent cohort, 1993–2005 (n = 214).

Intervention

Patients were followed at regular intervals, and treatment was only given for relapse.

Measurements

Recurrence rates, time to relapse, risk factors for recurrence, disease-specific survival, and overall survival were determined.

Results and limitations

With a median follow-up of 6.3 yr, 104 patients (28%) relapsed: 53 of 157 (33.8%) in the initial group and 51 of 214 (23.8%) in the recent group. Median time to relapse was 7 mo. Lymphovascular invasion (p < 0.0001) and pure embryonal carcinoma (p = 0.02) were independent predictors of recurrence; 125 patients (33.7%) were designated as high risk based on the presence of one or both factors. In the initial cohort, 66 of 157 patients (42.0%) were high risk and 36 of 66 patients (54.5%) relapsed versus 17 of 91 low-risk patients (18.7%) (p < 0.0001). In the recent cohort, 59 of 214 patients (27.6%) were high risk and 29 of 59 had a recurrence (49.2%) versus 22 of 155 low-risk patients (14.2%) (p < 0.0001). Three patients (0.8%) died from testis cancer. The estimated 5-yr disease-specific survival was 99.3% in the initial group and 98.9% in the recent one.

Conclusions

Non–risk-adapted surveillance is an effective, simple strategy for the management of all stage I NSGCT.     

A prospective, randomised EORTC intergroup phase 3 study comparing the oncologic outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma

Background

Nephron-sparing surgery (NSS) can safely be performed with slightly higher complication rates than radical nephrectomy (RN), but proof of oncologic effectiveness is lacking.

Objective

To compare overall survival (OS) and time to progression.

Design, setting, and participants

From March 1992 to January 2003, when the study was prematurely closed because of poor accrual, 541 patients with small (≤5 cm), solitary, T1–T2 N0 M0 (Union Internationale Contre le Cancer [UICC] 1978) tumours suspicious for renal cell carcinoma (RCC) and a normal contralateral kidney were randomised to NSS or RN in European Organisation for Research and Treatment of Cancer Genito-Urinary Group (EORTC-GU) noninferiority phase 3 trial 30904.

Intervention

Patients were randomised to NSS (n = 268) or RN (n = 273) together with limited lymph node dissection (LND).

Measurements

Time to event end points was compared with log-rank test results.

Results and limitations

Median follow-up was 9.3 yr. The intention-to-treat (ITT) analysis showed 10-yr OS rates of 81.1% for RN and 75.7% for NSS. With a hazard ratio (HR) of 1.50 (95% confidence interval [CI], 1.03–2.16), the test for noninferiority is not significant (p = 0.77), and test for superiority is significant (p = 0.03). In RCC patients and clinically and pathologically eligible patients, the difference is less pronounced (HR = 1.43 and HR = 1.34, respectively), and the superiority test is no longer significant (p = 0.07 and p = 0.17, respectively). Only 12 of 117 deaths were the result of renal cancer (four RN and eight NSS). Twenty-one patients progressed (9 after RN and 12 after NSS). Quality of life and renal function outcomes have not been addressed.

Conclusions

Both methods provide excellent oncologic results. In the ITT population, NSS seems to be significantly less effective than RN in terms of OS. However, in the targeted population of RCC patients, the trend in favour of RN is no longer significant. The small number of progressions and deaths from renal cancer cannot explain any possible OS differences between treatment types.     

Comparative analysis of outcomes and costs following open radical cystectomy versus robot-assisted laparoscopic radical cystectomy: results from the US Nationwide Inpatient Sample

Background

Although robot-assisted laparoscopic radical cystectomy (RARC) was first reported in 2003 and has gained popularity, comparisons with open radical cystectomy (ORC) are limited to reports from high-volume referral centers.

Objective

To compare population-based perioperative outcomes and costs of ORC and RARC.

Design, setting, and participants

A retrospective observational cohort study using the US Nationwide Inpatient Sample to characterize 2009 RARC compared with ORC use and outcomes.

Outcome measurements and statistical analysis

Propensity score methods were used to compare inpatient morbidity and mortality, lengths of stay, and costs.

Results and limitations

We identified 1444 ORCs and 224 RARCs. Women were less likely to undergo RARC than ORC (9.8% compared with 15.5%, p = 0.048), and 95.7% of RARCs and 73.9% of ORCs were performed at teaching hospitals (p < 0.001). In adjusted analyses, subjects undergoing RARC compared with ORC experienced fewer inpatient complications (49.1% and 63.8%, p = 0.035) and fewer deaths (0% and 2.5%, p < 0.001). RARC compared with ORC was associated with lower parenteral nutrition use (6.4% and 13.3%, p = 0.046); however, there was no difference in length of stay. RARC compared with ORC was $3797 more costly (p = 0.023). Limitations include retrospective design, absence of tumor characteristics, and lack of outcomes beyond hospital discharge.

Conclusions

RARC is associated with lower parenteral nutrition use and fewer inpatient complications and deaths. However, lengths of stay are similar, and the robotic approach is significantly more costly.     

A prospective randomised trial comparing the modified HM3 with the MODULITH® SLX-F2 lithotripter

Background

The relative efficacy of first- versus last-generation lithotripters is unknown.

Objectives

To compare the clinical effectiveness and complications of the modified Dornier HM3 lithotripter (Dornier MedTech, Wessling, Germany) to the MODULITH^® SLX-F2 lithotripter (Storz Medical AG, Tägerwilen, Switzerland) for extracorporeal shock wave lithotripsy (ESWL).

Design, setting and participants

We conducted a prospective, randomised, single-institution trial that included elective and emergency patients.

Interventions

Shock wave treatments were performed under anaesthesia.

Measurements

Stone disintegration, residual fragments, collecting system dilatation, colic pain, and possible kidney haematoma were evaluated 1 d and 3 mo after ESWL. Complications, ESWL retreatments, and adjuvant procedures were documented.

Results and limitations

Patients treated with the HM3 lithotripter (n = 405) required fewer shock waves and shorter fluoroscopy times than patients treated with the MODULITH^® SLX-F2 lithotripter (n = 415). For solitary kidney stones, the HM3 lithotripter produced a slightly higher stone-free rate (p = 0.06) on day 1; stone-free rates were not significantly different at 3 mo (HM3: 74% vs MODULITH^® SLX-F2: 67%; p = 0.36). For solitary ureteral stones, the stone-free rate was higher at 3 mo with the HM3 lithotripter (HM3: 90% vs MODULITH^® SLX-F2: 81%; p = 0.05). For solitary lower calyx stones, stone-free rates were equal at 3 mo (63%). In patients with multiple stones, the HM3 lithotripter's stone-free rate was higher at 3 mo (HM3: 64% vs MODULITH^® SLX-F2: 44%; p = 0.003). Overall, HM3 lithotripter led to fewer secondary treatments (HM3: 11% vs MODULITH^® SLX-F2: 19%; p = 0.001) and fewer kidney haematomas (HM3: 1% vs. MODULITH^® SLX-F2: 3%; p = 0.02).

Conclusions

The modified HM3 lithotripter required fewer shock waves and shorter fluoroscopy times, showed higher stone-free rates for solitary ureteral stones and multiple stones, and led to fewer kidney haematomas and fewer secondary treatments than the MODULITH^® SLX-F2 lithotripter. In patients with a solitary kidney and solitary lower calyx stones, results were comparable for both lithotripters.     

A non-cancer-related survival benefit is associated with partial nephrectomy

Background

Partial nephrectomy (PN) may better protect against other-cause mortality (OCM) when compared with radical nephrectomy (RN) in patients with localized renal cell carcinoma (RCC).

Objective

Test the effect of treatment type on OCM.

Design, setting, and participants

Using the Surveillance Epidemiology and End Results–Medicare-linked database, 4956 RN patients (82%) and 1068 PN patients (18%) with T1a RCC were identified (1988–2005).

Measurements

To adjust for inherent differences between treatment types, we relied on propensity-matched analyses. One-to-one matching was performed according to age, sex, race, baseline Charlson comorbidity index (CCI), baseline diagnosis of hypercalcemia and hyperlipidemia, socioeconomic status (SES), population density, tumor size, and year of surgery. The 2- and 5-yr OCM rates were computed using cumulative incidence. Univariable and multivariable competing-risks regression analyses for prediction of OCM were performed according to treatment type. Adjustment was made for cancer-specific mortality (CSM), patient age, CCI, sex, race, SES, tumor grade, and year of surgery.

Results and limitations

Following propensity-based matching, 1068 RN patients were matched with 1068 PN patients. The 2- and 5-yr OCM rates after nephrectomy were 5.0% and 16.0% for PN versus 6.9% and 18.1% for RN, respectively. In the postpropensity multivariable analyses, patients who underwent PN were significantly less likely to die of OCM compared with their RN-treated counterparts (hazard ratio [HR]: 0.83; 95% confidence interval, 0.69–0.98; p = 0.04). Increasing age (HR: 1.08, p < 0.001), higher CCI (HR: 1.14, p < 0.001), female gender (HR: 0.79, p = 0.02), baseline hypercalcemia (HR: 2.05, p = 0.03), baseline hyperlipidemia (HR: 0.73, p = 0.003), and year of surgery (HR: 0.95, p = 0.003) were independent predictors of OCM.

Conclusions

Compared with PN-treated patients, RN-treated patients are more likely to die of OCM after surgery, even after adjusting for CSM, as well as baseline CCI. Consequently, PN should be offered whenever technically feasible.     

Monotherapy with tadalafil or tamsulosin similarly improved lower urinary tract symptoms suggestive of benign prostatic hyperplasia in an international, randomised, parallel, placebo-controlled clinical trial

Background

Tadalafil improved lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH; LUTS/BPH) in clinical studies but has not been evaluated together with an active control in an international clinical study.

Objective

Assess tadalafil or tamsulosin versus placebo for LUTS/BPH.

Design, setting, and participants

A randomised, double-blind, international, placebo-controlled, parallel-group study assessed men ≥45 yr of age with LUTS/BPH, International Prostate Symptom Score (IPSS) ≥13, and maximum urinary flow rate (Q_max) ≥4 to ≤15 ml/s. Following screening and washout, if needed, subjects completed a 4-wk placebo run-in before randomisation to placebo (n = 172), tadalafil 5 mg (n = 171), or tamsulosin 0.4 mg (n = 168) once daily for 12 wk.

Measurements

Outcomes were assessed using analysis of covariance (ANCOVA) or ranked analysis of variance (ANOVA) (continuous variables) and Cochran-Mantel-Haenszel test or Fisher exact test (categorical variables).

Results and limitations

IPSS significantly improved versus placebo through 12 wk with tadalafil (−2.1; p = 0.001; primary efficacy outcome) and tamsulosin (−1.5; p = 0.023) and as early as 1 wk (tadalafil and tamsulosin both −1.5; p < 0.01). BPH Impact Index significantly improved versus placebo at first assessment (week 4) with tadalafil (−0.8; p < 0.001) and tamsulosin (−0.9; p < 0.001) and through 12 wk (tadalafil −0.8, p = 0.003; tamsulosin −0.6, p = 0.026). The IPSS Quality-of-Life Index and the Treatment Satisfaction Scale–BPH improved significantly versus placebo with tadalafil (both p < 0.05) but not with tamsulosin (both p > 0.1). The International Index of Erectile Function–Erectile Function domain improved versus placebo with tadalafil (4.0; p < 0.001) but not tamsulosin (−0.4; p = 0.699). Q_max increased significantly versus placebo with both tadalafil (2.4 ml/s; p = 0.009) and tamsulosin (2.2 ml/s; p = 0.014). Adverse event profiles were consistent with previous reports. This study was limited in not being powered to directly compare tadalafil versus tamsulosin.

Conclusions

Monotherapy with tadalafil or tamsulosin resulted in significant and numerically similar improvements versus placebo in LUTS/BPH and Q_max. However, only tadalafil improved erectile dysfunction.

Trial registration

Clinicaltrials.gov ID NCT00970632     

Laparoendoscopic single-site and conventional laparoscopic radical nephrectomy result in equivalent surgical trauma: preliminary results of a single-centre retrospective controlled study

Background

Laparoendoscopic single-site surgery (LESS) has been developed in an attempt to further reduce the morbidity and scarring associated with surgical intervention, and it has been proposed to result in less induced surgical trauma than conventional laparoscopy.

Objective

Investigate the surgical trauma after LESS radical nephrectomy (LESS-RN) and laparoscopic radical nephrectomy (LRN).

Design, setting, and participants

This was a retrospective single-centre study including 66 patients: 31 patients underwent LESS-RN and 35 historical control patients who had undergone LRN. LRNs were performed between April 2008 and May 2009; LESS-RNs were performed between May 2009 and February 2011.

Intervention

LESS-RN and LRN were both performed via a transperitoneal access. Blood samples were collected pre- and intraoperatively at 6, 24, and 48 h, and at 5 d postoperatively.

Measurements

Serum concentrations of acute-phase markers, C-reactive protein (CRP), serum amyloid A (SAA) antibody, and interleukin 6 (IL-6) and interleukin 10 (IL-10) were measured at each time point by enzyme-linked immunosorbent assay. Clinical data were collected by reviewing the patient's records.

Results and limitations

There were no differences in serum CRP and SAA levels between the groups (CRP: p = 0.12; SAA: p = 0.09) at all time points. The changes in IL-6 levels in the LRN group were statistically significantly higher compared with the LESS-RN group at 6 h after surgery (p = 0.02), whereas the LESS-RN group showed statistically significantly higher IL-6 levels than the LRN group at 24 h after surgery (p = 0.02).Also, the serum levels of the anti-inflammatory cytokine IL-10 showed different kinetics in each group, being higher in the LESS-RN during the early postoperative phase (at 6 h: p = 0.01) and higher in the LRN group at 48 h after surgery (p = 0.01). The limitations of this study were its nonrandomized character and the small cohort of patients.

Conclusions

LESS-RN is as effective as LRN without compromising surgical and postoperative outcomes, but it does not add any significant advantage in comparison with traditional LRN in terms of systemic stress response and surgical trauma.     

A Pollen Extract (Cernilton) in Patients with Inflammatory Chronic Prostatitis–Chronic Pelvic Pain Syndrome: A Multicentre, Randomised, Prospective, Double-Blind, Placebo-Controlled Phase 3 Study

Background

National Institutes of Health (NIH) category III prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent condition for which no standardised treatment exists.

Objectives

To assess the safety and efficacy of a standardised pollen extract in men with inflammatory CP/CPPS.

Design, setting, and participants

We conducted a multicentre, prospective, randomised, double-blind, placebo-controlled phase 3 study comparing the pollen extract (Cernilton) to placebo in men with CP/CPPS (NIH IIIA) attending urologic centres.

Intervention

Participants were randomised to receive oral capsules of the pollen extract (two capsules q8 h) or placebo for 12 wk.

Measurements

The primary endpoint of the study was symptomatic improvement in the pain domain of the NIH Chronic Prostatitis Symptom Index (NIH-CPSI). Participants were evaluated using the NIH-CPSI individual domains and total score, the number of leukocytes in post–prostatic massage urine (VB3), the International Prostate Symptom Score (IPSS), and the sexuality domain of a life satisfaction questionnaire at baseline and after 6 and 12 wk.

Results and limitations

In the intention-to-treat analysis, 139 men were randomly allocated to the pollen extract (n = 70) or placebo (n = 69). The individual domains pain (p = 0.0086) and quality of life (QoL; p = 0.0250) as well as the total NIH-CPSI score (p = 0.0126) were significantly improved after 12 wk of treatment with pollen extract compared to placebo. Response, defined as a decrease of the NIH-CPSI total score by at least 25% or at least 6 points, was seen in the pollen extract versus placebo group in 70.6% and 50.0% (p = 0.0141), respectively. Adverse events were minor in all patients studied.

Conclusions

Compared to placebo, the pollen extract significantly improved total symptoms, pain, and QoL in patients with inflammatory CP/CPPS without severe side-effects.     

Age-adjusted incidence, mortality, and survival rates of stage-specific renal cell carcinoma in North America: a trend analysis

Background

The rising incidence of renal cell carcinoma (RCC) has been largely attributed to the increasing use of imaging procedures.

Objective

Our aim was to examine stage-specific incidence, mortality, and survival trends of RCC in North America.

Design, setting, and participants

We computed age-adjusted incidence, survival, and mortality rates using the Surveillance Epidemiology and End Results database. Between 1988 and 2006, 43 807 patients with histologically confirmed RCC were included.

Measurements

We calculated incidence, mortality, and 5-yr survival rates by year. Reported findings were stratified according to disease stage.

Results and limitations

Age-adjusted incidence rate of RCC rose from 7.6 per 100 000 person-years in 1988 to 11.7 in 2006 (estimated annual percentage change [EAPC]: +2.39%; p < 0.001). Stage-specific age-adjusted incidence rates increased for localized stage: 3.8 in 1988 to 8.2 in 2006 (EAPC: +4.29%; p < 0.001) and decreased during the same period for distant stage: 2.1 to 1.6 (EAPC: −0.57%; p = 0.01). Stage-specific survival rates improved over time for localized stage but remained stable for regional and distant stages. Mortality rates varied significantly over the study period among localized stage, 1.3 in 1988 to 2.4 in 2006 (EAPC: +3.16%; p < 0.001), and distant stage, 1.8 in 1988 to 1.6 in 2006 (EAPC: −0.53%; p = 0.045). Better detailed staging information represents a main limitation of the study.

Conclusions

The incidence rates of localized RCC increased rapidly, whereas those of distant RCC declined. Mortality rates significantly increased for localized stage and decreased for distant stage. Innovation in diagnosis and management of RCC remains necessary.