Violation of onco-surgical principles is associated with survival outcomes in upper tract urothelial carcinomas after radical nephroureterectomy.

OBJECTIVE: Disease recurrence, particularly intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), is common. We investigated whether violations of onco-surgical principles before or during RNU, collectively referred to as surgical violation (SV), were associated with survival outcomes.  Material and methods: Data from a consecutive series of patients who underwent RNU for UTUC 2001-2012 at Skåne University Hospital Lund/Malmö were collected. Preoperative insertion of a nephrostomy tube, opening the urinary tract during surgery or refraining from excising the distal ureter were considered as SVs. Survival outcomes in patients with and without SV (IVR-free [IVRFS], disease-specific [DSS] and overall survival [OS]) were assessed using multivariate Cox regression analyses (adjusted for tumour stage group, prior or concomitant bladder cancer, comorbidity and preoperative urinary cytology). RESULTS: Of 150 patients, 47 (31%) were subjected to at least one SV. Overall, SV was not associated with IVRFS (HR 0.81, 95% CI 0.4-1.6) but with worse DSS (HR 1.9, 95% CI 1.03-3.7) and OS (HR 1.9, 95% CI 1.2-3) in multivariable analysis. Additional analyses with a broader definition of SV including also preoperative instrumentation of the upper urinary tract (ureteroscopy and/or double J stenting) showed similar outcomes for DSS (HR 2.1, 95% CI 1.1-4.3). CONCLUSION: Worse survival outcomes, despite no difference in IVR, for patients that were subjected to the violation of sound onco-surgical principles before or during RNU for UTUC strengthen the notion that adhering to such principles is a cornerstone in upper tract urothelial cancer surgery.

Location of Retroperitoneal Lymph Node Metastases in Upper Tract Urothelial Carcinoma: Results from a Prospective Lymph Node Mapping Study.

Background: There is limited information on the distribution of retroperitoneal lymph node metastases (LNMs) in upper tract urothelial carcinoma (UTUC). Objective: To investigate the location of LNMs in UTUC of the renal pelvis or proximal ureter and short-term complications after radical nephroureterectomy (RNU) with lymph node dissection (LND). Design setting and participants: This was a prospective Nordic multicenter study (four university hospitals, two county hospitals). Patients with clinically suspected locally advanced UTUC (stage >T1) and/or clinical lymph node-positive (cN+) disease were invited to participate. Participants underwent RNU and fractionated retroperitoneal LND using predefined side-specific templates. Outcome measurements and statistical analysis: The location of LNMs in the LND specimen and retroperitoneal lymph node recurrences during follow-up was recorded. Postoperative complications within 90 d of surgery were ascertained from patient charts. Descriptive statistics were used. Results and limitations: LNMs were present in the LND specimen in 23/100 patients, and nine of 100 patients experienced a retroperitoneal recurrence. Distribution per side revealed LNMs in the LND specimen in 11/38 (29%) patients with right-sided tumors, for whom the anatomically larger, right-sided template was used, in comparison to 12/62 (19%) patients with left-sided tumors, for whom a more limited template was used. High-grade complications (Clavien grade ≥3) within 90 d of surgery were registered for 13/100 patients. The study is limited in size and not powered to assess survival estimates. Conclusions: The suggested templates that we prospectively applied for right-sided and left-sided LND in patients with advanced UTUC included the majority of LNMs. High-grade complications directly related to the LND part of the surgery were limited. Patient summary: This study describes the location of lymph node metastases in patients with cancer in the upper urinary tract who underwent surgery to remove the affected kidney and ureter. The results show that most metastases occur within the template maps for lymph node surgery that we investigated, and that this surgery can be performed with few severe complications.

Urosymphyseal fistula after pelvic radiotherapy in a tertial referral centre - a rare entity with significant comorbidity requiring multidisciplinary management.

OBJECTIVE: To report population-based clinical presentation and outcomes in patients with urosymphyseal fistula (USF) after pelvic radiotherapy (RT). PATIENTS AND METHODS: A retrospective chart review was performed in 33 consecutive patients diagnosed with suspicion of USF in a tertial referral center from 2014-2022 to ascertain information about diagnostic delay, clinical presentation, precipitating causes, treatments received and outcomes during the median 22 months follow-up. Out of 33 consecutive patients with suspicion of USF, one female with vesicovaginal fistula, one patient developing RT-associated bladder angiosarcoma, four patients with short follow-up (<3 months), and three patients that during chart review not were considered to have a USF were excluded. RESULTS: In all, 24 males with a median age of 77 years were diagnosed with USF. Local pain was the predominating symptom in 17/24 (71%) patients. Endourologic manipulations preceded the diagnosis of USF in 16 patients. Five patients had a diagnostic delay of more than 3 months. At diagnosis, 20/24 patients had radiological signs of osteomyelitis, and five had a concomitant rectourethral fistula. Due to comorbidity, five patients were not amenable to any other interventions than urinary catheter or suprapubic tube in conjunction with long-term antibiotics, of which three died from infections related to the USF. Out of the remaining 19 patients receiving some form of urinary diversion, five had recurrent osteomyelitis, of which four did not undergo cystectomy in conjunction with surgery for the USF. CONCLUSIONS: Urethral endourologic interventions in patients previously subjected to pelvic RT should be performed cautiously.

Learning curve for robot-assisted laparoscopic radical prostatectomy in a large prospective multicentre study.

OBJECTIVE: Differences in outcome after radical prostatectomy for prostate cancer can partly be explained by intersurgeon differences, where degree of experience is one important aspect. This study aims to define the learning curve of robot-assisted laparoscopic prostatectomy (RALP) regarding oncological and functional outcomes. MATERIALS AND METHODS: Out of 4003 enrolled patients in the LAPPRO trial, 3583 met the inclusion criteria, of whom 885 were operated on by an open technique. In total, 2672 patients with clinically localized prostate cancer from seven Swedish centres were operated on by RALP and followed for 8 years (LAPPRO trial). Oncological outcomes were pathology-reported surgical margins and biochemical recurrence at 8 years. Functional outcomes included patient-reported urinary incontinence and erectile dysfunction at 3, 12 and 24 months. Experience was surgeon-reported experience before and during the study. The relationship between surgeon experience and functional outcomes and surgical margin status was analysed by mixed-effects logistic regression. Biochemical recurrence was analysed by Cox regression, with robust standard errors. RESULTS: The learning curve for positive surgical margins was relatively flat, with rates of 21% for surgeons who had performed 0-74 cases and 24% for surgeons with > 300 cases. Biochemical recurrence at 4 years was 11% (0-74 cases) and 13% (> 300 cases). Incontinence was stable over the learning curve, but erectile function improved at 2 years, from 38% (0-74 cases) to 53% (> 300 cases). CONCLUSIONS: Analysis of the learning curve for surgeons performing RALP showed that erectile function improved with increasing number of procedures, which was not the case for oncological outcomes.

Functional and Oncological Outcomes After Open Versus Robot-assisted Laparoscopic Radical Prostatectomy for Localised Prostate Cancer: 8-Year Follow-up.

BACKGROUND: Radical prostatectomy reduces mortality among patients with localised prostate cancer. Evidence on whether different surgical techniques can affect mortality rates is lacking. OBJECTIVE: To evaluate functional and oncological outcomes 8 yr after robot-assisted laparoscopic prostatectomy (RALP) and open retropubic radical prostatectomy (RRP). DESIGN, SETTING, AND PARTICIPANTS: We enrolled 4003 patients in a prospective, controlled, nonrandomised trial comparing RALP and RRP in 14 Swedish centres between 2008 and 2011. Data for functional outcomes were assessed via validated patient questionnaires administered preoperatively and at 12 and 24 mo and 8 yr after surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was urinary incontinence. Functional outcomes at 8 yr were analysed using the modified Poisson regression approach. RESULTS AND LIMITATIONS: Urinary incontinence was not significantly different at 8 yr after surgery between RALP and RRP (27% vs 29%; adjusted risk ratio [aRR] 1.05, 95% confidence interval [CI] 0.90-1.23). Erectile dysfunction was significantly lower in the RALP group (66% vs 70%; aRR 0.93, 95% CI 0.87-0.99). Prostate cancer-specific mortality (PCSM) was significantly lower in the RALP group at 8 yr after surgery (40/2699 vs 25/885; aRR 0.56, 95% CI 0.34-0.93). Differences in oncological outcomes were mainly seen in the group with high D'Amico risk, with a lower risk of positive surgical margins (21% vs 34%), biochemical recurrence (51% vs 69%), and PCSM (14/220 vs 11/77) for RALP versus RRP. The main limitation is the nonrandomised design. CONCLUSIONS: In this prospective multicentre controlled trial, PCSM at 8 yr after surgery was lower for RALP in comparison to RRP. A causal relationship between surgical technique and mortality cannot be inferred, but the result confirms that RALP is oncologically safe. Taken together with better short-term results reported elsewhere, our findings confirm that implementation of RALP may continue. PATIENT SUMMARY: Our study comparing two surgical techniques for removal of the prostate for localised prostate cancer shows that a robot-assisted minimally invasive technique is safe in the long term. Together with previous results showing some better short-term effects with this approach, our findings support continued use of robot-assisted surgery.

Surgeon heterogeneity significantly affects functional and oncological outcomes after radical prostatectomy in the Swedish LAPPRO trial.

OBJECTIVES: To evaluate how surgeon heterogeneity - the variation in outcomes between individual surgeons - influences functional and oncological outcomes after robot-assisted laparoscopic prostatectomy (RALP) and retropubic radical prostatectomy (RRP), and to assess whether surgeon heterogeneity affects the comparison between RALP and RRP. PATIENTS AND METHODS: Laparoscopic Prostatectomy Robot Open (LAPPRO) is a prospective, controlled, non-randomized trial performed at 14 Swedish centres with 68 operating surgeons. A total of 4003 men with localized prostate cancer were enrolled between 2008 and 2011. The endpoints were urinary incontinence, erectile dysfunction (ED) and recurrence at 24 months after surgery. Logistic regression models were built to evaluate surgeon heterogeneity and, secondarily, surgeon-specific factors were added to the models to investigate their influence on heterogeneity and the comparison between RALP and RRP. RESULTS: Among surgeons who performed at least 20 surgeries during the study period (n=25), we observed statistically significant heterogeneity for incontinence (P = 0.001), ED (P < 0.001) and rate of recurrent disease (P < 0.001). The significant heterogeneity remained when analysing only experienced surgeons with a stated experience of at least 250 radical prostatectomies (n=12). Among all participating surgeons (n=68), differences in surgeon volume explained 42% of the observed heterogeneity for incontinence (P = 0.003), 11% for ED (P = 0.03) and 19% for recurrence (P = 0.01). Taking surgeon volume into account when comparing RALP and RRP had a significant impact on the results. The effect was greatest for functional outcomes, and the additional adjustments for the surgeons' previous experience changed whether the difference between techniques was statistically significant or not. The surgeons' annual volume had the greatest effect on the recurrence rate. CONCLUSIONS: There was a large degree of heterogeneity among surgeons regarding both functional and oncological outcomes and this had a significant impact on the results when comparing RALP and RRP. Some of the observed heterogeneity was explained by differences in surgeon volume. Efforts to decrease heterogeneity are warranted and variation among surgeons must be accounted for when conducting comparative analyses between surgical techniques.

Risk of Recurrent Disease 6 Years After Open or Robotic-assisted Radical Prostatectomy in the Prospective Controlled Trial LAPPRO.

BACKGROUND: Conclusive evidence of superiority in oncological outcome for robot-assisted laparoscopic prostatectomy (RALP) over retropubic radical prostatectomy (RRP) is lacking. OBJECTIVE: To compare RALP and RRP regarding recurrent disease and to report the mortality rate 6 yr after surgery. DESIGN SETTING AND PARTICIPANTS: A total of 4003 men with localized prostate cancer were enrolled between 2008 and 2011 in Laparoscopic Prostatectomy Robot Open (LAPPRO)- a prospective, controlled, nonrandomized trial performed at 14 Swedish centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Data were collected at visits and by patient questionnaires at 3, 12, and 24 mo, and through a structured telephone interview at 6 yr. Cause of death was retrieved from the National Cause of Death Register in Sweden. The modified Poisson regression approach was used for analyses. RESULTS AND LIMITATIONS: After adjustment for patient-, tumor-, and surgeon-related confounders, no statistically significant difference was observed between RALP and RRP in biochemical recurrence rate (14 vs 16%, relative risk [RR] 0.77, 95% confidence interval [CI] 0.56-1.06) or in not cured endpoint (22% vs 23%, RR 0.82, 95% CI 0.6-1.11). Stratified by D'Amico risk group, a significant benefit for RALP existed for recurrent disease in high-risk patients (RR 0.47, 95% CI 0.26-0.86, p = 0.02). All-cause mortality was 3% (n = 96). Prostate cancer-specific mortality was 0.6% (n = 21) overall, 0.3% (n = 8) after RALP, and 1.5% (n = 13) after RRP. The nonrandomized design is a limitation. CONCLUSIONS: No significant difference was observed for cancer recurrence rate between RALP and RRP 6 yr after surgery. However, in a subgroup analysis, we found a significant benefit for RALP regarding recurrence rate in the high-risk group. Larger studies with longer follow-up are needed to make a firm conclusion and to evaluate a possible survival benefit. PATIENT SUMMARY: In general, the oncological outcome is comparable between robotic and open radical prostatectomy 6 yr after surgery. For high-risk patients, our findings indicate that there is an advantage for robotics, but further studies with longer follow-up time is needed to make a firm conclusion.

Functional and Oncologic Outcomes Between Open and Robotic Radical Prostatectomy at 24-month Follow-up in the Swedish LAPPRO Trial.

BACKGROUND: The adoption of robot-assisted laparoscopic radical prostatectomy (RALP) has increased rapidly, despite lack of conclusive evidence of its superiority regarding long-term outcomes over open retropubic RP (RRP). In 2015, we reported on 12-mo follow-up from the LAPPRO trial showing a moderate advantage of RALP regarding erectile dysfunction. No significant differences were seen for urinary incontinence or surgical margin status. OBJECTIVE: To present patient-reported functional outcomes and recurrent and residual disease at 24-mo follow-up from the prospective multicenter LAPPRO trial. DESIGN, SETTING, AND PARTICIPANTS: A total of 4003 patients with clinically localized prostate cancer were recruited from 14 Swedish centers, seven performing RALP and seven RRP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Data were only analyzed for patients operated on by surgeons with >100 prior RPs. Adjusted odds ratios (AORs) were calculated using logistic regression, with adjustment for differences in patient mix. RESULTS AND LIMITATIONS: At 24 mo, there was a significant difference in erectile dysfunction in favor of RALP (68% vs 74%; AOR 0.72, 95% confidence interval [CI] 0.57-0.91; p=0.006). No significant difference was observed for incontinence (19% vs 16%; AOR 1.29, 95% CI 1.00-1.67; p=0.053) or recurrent or residual disease (13% vs 13%; AOR 0.79, 95% CI 0.59-1.07; p=0.13). We did not adjust for individual surgeon volume and experience, which is a potential limitation. CONCLUSIONS: Extended follow-up corroborated our previous report at 12 mo of a persistent RALP benefit regarding potency. PATIENT SUMMARY: LAPPRO is a Swedish trial comparing two different prostate cancer surgical techniques (robotic compared to open). At 24-mo follow-up after surgery there was a moderate advantage for the robotic technique regarding erectile dysfunction (potency), while there was a small but not significant difference in urinary leakage in favor of open surgery. We did not find any difference regarding cancer relapse.

PCA3 as a diagnostic marker for prostate cancer: a validation study on a Swedish patient population.

OBJECTIVE: Prostate cancer antigen 3 in urine (uPCA3) has been shown to perform better than total prostate-specific antigen in serum (tPSA) to predict prostate cancer (PCa) detection. The aim of this study was to validate the diagnostic precision of uPCA3 in a mixed set of patients with no previous history of PCa, including patients with previous negative biopsies. MATERIAL AND METHODS: The study included 62 men scheduled for prostate biopsy at Skåne University Hospital Malmö, Sweden. Urine samples were obtained according to the Progensa™ uPCA3 assay. Logistic regression and receiver operating characteristic curves were used to test associations between levels of biomarkers and prostate cancer. RESULTS: According to pathological examination of core needle biopsies, PCa was found in 18 out of 62 patients. A one-step increase in uPCA3 was associated with an increase in the odds of cancer of 1.026 (p = 0.005). Differences in the odds ratio between uPCA3 and tPSA were not statistically significant. A model using both markers did not increase prediction of event. Areas under the curve for uPCA3, tPSA and a model combining uPCA3 and tPSA did not differ significantly. No significant correlation was found between uPCA3 and tPSA or prostate volume. CONCLUSION: In this small set of mixed patients uPCA3 alone and tPSA performed equally well as diagnostic markers for PCa. A combination of the two markers did not improve the diagnostic performance. This study does not support a role for the uPCA3 urine test to replace or be added to tPSA in PCa detection.