Nerve-sparing radical prostatectomy using the neurovascular structure-adjacent frozen-section examination (NeuroSAFE): results after 20 years of experience.

OBJECTIVES: To evaluate the long-term oncological outcomes and functional results of the neurovascular structure-adjacent frozen-section examination (NeuroSAFE) during nerve-sparing (NS) radical prostatectomy (RP). MATERIALS AND METHODS: A 10-yr survival analysis on 11069 RPs performed with or without the NeuroSAFE, between January 2002 to June 2011 was carried out. In the NeuroSAFE cohort, the neurovascular structure-adjacent prostatic margins are removed and stained for cryo-sectioning during RP. In case of a PSM, partial or full removal of the neurovascular bundle was performed. The impact of NeuroSAFE on biochemical recurrence-free survival (BFS), salvage radiation therapy-free survival, metastasis-free survival, and prostate cancer-specific survival at 10 years was analyzed. 1-year (1-yr) erectile function (EF), 1-yr, and 2-yr continence rates were assessed in propensity score-based matched cohorts. RESULTS: Median follow-up was 121 (IQR: 73, 156) months. No differences in BFS between NeuroSAFE and non-NeuroSAFE were recorded (10-yr BFS: NeuroSAFE vs non-Neurosafe, pT2: 81% vs 84%, p = 0.06; pT3a: 58% vs. 63%, p = 0.6; ≥pT3b: 22% vs. 27%, p = 0.99). No differences were found between the two groups in terms of sRFS (pT2: p = 0.1; pT3a: p = 0.4; ≥pT3b: p = 0.4) (Fig. 1B, Table 2), and MTS (pT2: p = 0.3; pT3a: p = 0.6; ≥pT3b: p = 0.9). The NeuroSAFE-navigated patients reported a better 1-yr EF than non-NeuroSAFE (68% vs. 58%, p = 0.02) and no differences in 1-yr and 2-yr continence rates (92.4% vs. 91.8%, and 93.4% vs. 93%, respectively). The main limitation is the retrospective study design. CONCLUSIONS: While the NeuroSAFE approach did not show significant improvements in long-term oncologic or continence outcomes, it did provide an opportunity for a higher proportion of patients to improve postoperative functional results, possibly through increased nerve-sparing procedures.

Robot-assisted vs open retropubic radical prostatectomy: a propensity score-matched comparative analysis based on 15 years and 18,805 patients.

PURPOSE: To compare oncological, functional, and surgical outcomes of a large cohort of patients who underwent open retropubic radical prostatectomy (ORP) or robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: Data from 18,805 RPs performed with either the open or the robot-assisted approaches at a single tertiary referral center between 2008 and 2022 were analyzed. The impact of surgical approach on biochemical recurrence-free survival, salvage radiotherapy-free survival, and metastasis-free survival was analyzed by log-rank test and Kaplan-Meier analysis in a propensity score (PS)-based matched cohort. Intraoperative and postoperative surgical outcomes were assessed. One-week, 3-month, and 12-month continence rates and 12-month erectile function (EF) were analyzed. RESULTS: No statistically significant differences in oncological outcomes were found between ORP and RARP. A slight statistically significant difference in favor of RARP was noted in urinary continence at 3 months (RARP vs. ORP: 81% vs. 77%, p = 0.007) and 12 months (91% vs. 89.3%, p = 0.008), respectively. The rate of EF was statistically significantly higher (60%) after RARP than after ORP (45%, p < 0.001). CONCLUSION: Both RARP and ORP yielded similar oncological outcomes. RARP offered a slight advantage in terms of continence recovery, but its clinical significance may be less meaningful. RARP resulted in significantly improved postoperative EF, suggesting a potential influence of both surgical experience and minimally invasive approach.

Histopathological results of radical prostatectomy specimen of men younger than 50 years of age at the time of surgery: possible implications for prostate cancer screening programs?

INTRODUCTION: Prostate cancer (PCa) detection is usually achieved by PSA measurement and, if indicated, further diagnostics. The recent EAU guidelines recommend a first PSA test at the age of 50 years, if no family history of PCa or BRCA2 mutation exists. However, some men might harbor significant PCa at younger age; thus we evaluated the histopathological results of men treated with radical prostatectomy (RP) in their 40 s at our institution. MATERIALS AND METHODS: We relied on the data of all patients who underwent RP in our institution between 1992 and 2020 and were younger than 50 years at the time of surgery. The histopathological results are descriptively presented. Moreover, we tested the effect of a positive family history on the descriptive results. RESULTS: Overall, 1225 patients younger than 50 years underwent RP at our institution. Median age was 47 years. Most patients showed favorable histopathological characteristics. However, 20% of patients had extraprostatic disease (≥ pT3a), 15% had ISUP Gleason grade group ≥ 3, and 7% had positive lymph nodes (pN1). Patients with a known positive family history did not have a higher rate of adverse disease as their counterparts with a negative family history. DISCUSSION: Our data show that the majority of patients who were diagnosed with PCa at a very young age had favorable histopathological RP characteristics. However, a non-negligible proportion of patients already showed locally advanced disease and would have probably benefited from earlier PCa detection. This should be kept in mind when PCa screening recommendations are proposed.

Preprostatic lymph nodes in prostate cancer hot or not? Impact on oncological outcome after radical prostatectomy.

OBJECTIVE: To assess the impact of preprostatic lymph node invasion on prostate cancer patients' outcome after radical prostatectomy. It is known that invasion of pelvic lymph nodes is associated with worse oncological outcome, but little is known about invasion of preprostatic lymph nodes. We hypothesized that positive preprostatic lymph nodes may not be as harmful as positive pelvic lymph nodes. MATERIALS AND METHODS: A total of 11,107 consecutive patients treated for prostate cancer with radical prostatectomy between 2013 and 2017 were evaluated. 1575 (14.2%) had some type of lymph node invasion, 53 (0.5%) had only one positive preprostatic lymph node and 705 (6.3%) had only one positive pelvic lymph node. RESULTS: Median follow-up was 37.7 months (interquartile range: 24.6-58.7 months). Baseline characteristics of the overall cohort were not statistically significant between the preprostatic vs. pelvic lymph node invasion groups, except for robot-assisted operation (64.2 vs. 32.3%, p < 0.001) and count of removed lymph nodes (16 vs. 19, p < 0.001). There was no statistically significant difference in 3-years biochemical recurrence rate (56.2 vs. 65.8%, p = 0.5), 3-years metastases free survival rate (87.4 vs. 95.5%, p = 0.5) and overall cancer-specific mortality (1.9 vs 1.0%) between the two groups. CONCLUSIONS: Preprostatic lymph node invasion seems to have a similar harmful effect as pelvic lymph node invasion and thus, if detected, may alter treatment and follow-up strategy. Therefore, it is important to perform a histological analysis when removing the preprostatic tissue.

Concordance of biopsy and pathologic ISUP grading in salvage radical prostatectomy patients for recurrent prostate cancer.

PURPOSE: To investigate the concordance of biopsy and pathologic International Society of Urological Pathology (ISUP) grading in salvage radical prostatectomy (SRP) patients for recurrent prostate cancer. METHODS: Within a high-volume center database, we identified patients who underwent SRP for recurrent prostate cancer (PCa) between 2004 and 2020. Upgrading, downgrading, concordance, and any discordance between posttreatment biopsy ISUP and ISUP at SRP were tested. Logistic regression models were used to predict ISUP upgrading and ISUP discordance. Models were adjusted for prostatic specific antigen before SRP, age at surgery, initial prostatic specific antigen (PSA), type of primary treatment, time from primary PCa diagnosis to SRP, number of positive cores at biopsy, and original Gleason score. RESULTS: Overall, 184 patients with available biopsy and pathologic ISUP grading were identified. Of those, 17.4% (n = 32), 40.8% (n = 75), 19.6% (n = 36), and 22.2% (n = 41) harbored biopsy ISUP 1, ISUP 2, ISUP 3, and ISUP 4-5 grading, respectively. Pathologic ISUP 1, ISUP 2, ISUP 3, and ISUP 4-5 grading was recorded in 6.0% (n = 11), 40.8% (n = 75), 32.1% (n = 59), and 21.2% (n = 39), respectively. Median PSA before SRP was 5.5 ng/ml (interquartile range [IQR]: 3.1-8.1 ng/ml), median age at SRP was 65.1 years (IQR:60.7-69.4 years) and median time from original PCa diagnosis to SRP was 47 months (IQR: 27.3-85.2 months). Concordance of biopsy and pathologic ISUP was identified in 45.1% (n = 83). Conversely, any ISUP discordance, upgrading and downgrading of at least one ISUP group was identified in 54.9% (n = 101), 35.3% (n = 65), and 19.6% (n = 36). In logistic models, none of the preoperative characteristics was associated with upgrading or ISUP discordance (all p > 0.1). CONCLUSION: Discordance between biopsy and pathologic ISUP grading is common at SRP. However, in 45% of SRP cases biopsy ISUP is capable to predict pathologic ISUP. Further studies are necessary to identify characteristics for ISUP upgrading at SRP.

Significant reduction of lymphoceles after radical prostatectomy and pelvic lymph node dissection.

OBJECTIVES: To reduce the risk of symptomatic lymphocele (SLC), we present a technique using peritoneal fenestration that allows lymphatic fluid to drain into the abdomen, as SLC formation after open retropubic radical prostatectomy (ORP) with pelvic lymph node dissection (PLND) is a common adverse event. PATIENTS AND METHODS: We identified 1513 patients who underwent ORP with PLND between July 2018 and November 2019. Of those, 307 patients (20.3%) received peritoneal fenestration and 1206 (79.7%) no fenestration. The rate of LCs and the necessity for intervention were analysed by uni- and multivariable logistic regression (MLR) models. A propensity score matching was performed, as well. RESULTS: The median (interquartile range [IQR]) age was 65 (60-70) years. A median (IQR) of 16 (10-22) lymph nodes were dissected, 22 vs 14 lymph nodes in the fenestration vs non-fenestration group (P < 0.001). Overall, 189 patients (12.5%) were diagnosed with a LC after ORP, while 21 patients (6.8%) in the fenestration and 168 (13.9%) in the non-fenestration group had LCs (P = 0.001). In 70 patients (4.7%), LCs required further intervention, categorised as Clavien-Dindo Grade IIIa/b, with a smaller proportion in the fenestration group (2.9% vs 5.0% in the non-fenestration group, P < 0.001). There were no Clavien-Dindo Grade IV or V complications, in particular no abdominal complications in association with peritoneal fenestration observed. In MLR, peritoneal fenestration was associated with a reduced risk of LCs (odds ratio [OR] 0.33, 95% confidence interval [CI] 0.2-0.5; P < 0.001). The risk reduction was also shown after propensity score matching (OR 0.38, 95% CI 0.21-0.68; P = 0.001). The number needed to treat was 14. CONCLUSIONS: Peritoneal fenestration may decrease the rate of SLC after ORP with (extended) PLND. Therefore, it should be part of the operative strategy.

Comparison of intra- and postoperative analgesia and pain perception in robot-assisted vs. open radical prostatectomy.

PURPOSE: One of the advantages of minimally invasive surgery may be reduced postoperative pain and faster recovery. However, reliable comparisons of robot-assisted (RARP) vs. open radical prostatectomy (ORP) addressing perioperative pain regimen are scarce. METHODS: We identified 420 consecutive treated patients who underwent RARP (n = 254) vs. ORP (n = 166) for clinically localized prostate cancer in 2017. After 1:1 propensity score matching for age, body mass index, D'Amico risk classification and lymph node yield, intra- and postoperative pain medication doses, as well as pain perception expressed by the numeric rating scale were assessed in uni- and multivariable analyses. RESULTS: Median age was 64.9 years. Operation time was significantly shorter in ORP patients (155 vs. 175 min in RARP, p < 0.001). Overall, a median of 12.5 vs. 12 g of metamizol was administered in RARP vs. ORP patients (p = 0.2). Additionally, a median of 146.7 vs. 133.9 mg of morphine equivalent was administered in RARP vs. ORP patients (p < 0.001). The mean maximum pain perceived on day 0 was 3.2 vs. 3.6 in RARP vs. ORP patients (p = 0.1). It decreased within the following days, and again, no differences between the two groups were observed. All results were confirmed in multivariable analyses. CONCLUSIONS: When comparing RARP vs. ORP, a small increase in perioperative morphine administration at RARP may be expected. However, when assessing pain perception, no differences were observed between the two groups. Moreover, mean maximum pain perceived was very low, which may reassure patients, who are counselled for radical prostatectomy.

The Impact of Anxiety and Depression on Surgical and Functional Outcomes in Patients Who Underwent Radical Prostatectomy.

BACKGROUND: Depression and anxiety are associated with worse surgical outcomes and higher complication rates among various types of general or orthopedic surgeries. OBJECTIVE: To assess the impact of depression and anxiety on surgical, oncological, and functional outcomes in radical prostatectomy (RP) patients. DATA, SETTING, AND PARTICIPANTS: Retrospective analysis of 5862 RP patients (2014-2016). INTERVENTION: RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Baseline depression and anxiety were assessed using the Patient Health Questionnaire-4 (PHQ-4) and categorized into 0-2 (normal), 3-5 (mild), and ≥6 (moderate to severe) points. Surgical outcomes included length of hospital stay (LOS), blood loss, and complications (Clavien-Dindo grading). Functional outcomes included urinary incontinence (UI) and erectile dysfunction (ED). Oncological outcomes focused on biochemical recurrence (BCR). Kaplan-Meier plots, multivariable logistic analyses, and Cox regression analyses were used. RESULTS AND LIMITATIONS: Overall, 28% patients had abnormal PHQ-4 scores and 8% a score ≥6 points. Higher PHQ-4 was significantly associated with worse surgical outcomes (longer LOS and higher complication rates) and higher risk for UI. No statistically significant difference was found for ED. However, we observed a higher use of phosphodiesterase type 5 inhibitors and intracavernous injection therapies among men with PHQ-4 score of ≥3. BCR was not affected by PHQ-4. The main limitations are the retrospective design as well as the lack of information on concomitant medications or follow-up PHQ-4 scores. CONCLUSIONS: Higher PHQ-4 scores are significantly associated with worse surgical outcomes and higher risk for UI. Our study highlights the importance of preoperative depression and anxiety assessment to optimize quality of life and to reduce health-related costs. PATIENT SUMMARY: Patients with preoperative depression or anxiety are at higher risk for postoperative complications and urinary incontinence after radical prostatectomy.

Nuclear ELAC2 overexpression is associated with increased hazard for relapse after radical prostatectomy.

ELAC2 is a ubiquitously expressed enzyme potentially involved in tRNA processing and cell signaling pathways. Mutations of the ELAC2 gene have been found to confer increased prostate cancer susceptibility in families. ELAC2 protein expression was analyzed by immunohistochemistry in 9,262 patients and Kaplan-Meier curves of PSA recurrence-free survival were calculated in 8,513 patients treated with radical prostatectomy. Nuclear ELAC2 staining was observed in 60.8% of prostate cancers. It was weak in 26.3%, moderate in 26.6% and strong in 7.9%. Strong nuclear ELAC2 expression was associated with advanced tumor stage, nodal metastasis, higher Gleason grade, presence of TMPRSS2:ERG fusion, higher Ki67-labeling index and PTEN deletion. The difference in 1-, 5- and 10-year recurrence-free survival between strong and weak nuclear ELAC2 intensity is 7.2/13.8/17.6% in all cancers, 7.4/16.1/26.5% in the ERG negative subset, and 3.1/5.7/9.8% in the ERG positive subset. Regarding the univariate hazard ratio, PSA recurrence-free survival after prostatectomy for strong nuclear ELAC2 expression is 1.89 (1.64-2.10, p < 0.0001). It is independent of preoperative PSA-level, Gleason grade, pathological stage, surgical margin stage, and lymph node stage (multivariate hazard ratio 1.29 (1.11-1.49, p = 0.001). We conclude that nuclear ELAC2 expression is an independent prognostic marker for PSA recurrence-free survival after radical prostatectomy with a weak to moderate increase of the hazard ratio for biochemical relapse.

Prostate cancer prognosis in men with other malignancies prior to radical prostatectomy.

OBJECTIVES: Cancer survivors are often diagnosed with subsequent prostate cancer. To improve medical care of these patients, we examined the oncological outcomes in men with prostate cancer and a cancer history. PATIENTS AND METHODS: We retrospectively analyzed data from 25,422 prostate cancer patients, who underwent a radical prostatectomy between 1992 and 2016. Patients with other malignancies were identified using medical records and self-administrated questionnaires. Cox regression and Kaplan Meier analysis of a propensity score-matched patient cohort were performed to examine biochemical recurrence-free survival, metastasis-free survival, overall survival and prostate cancer-specific survival. Competing risk analysis was used to estimate other-cause mortality, other cancer-specific mortality, and prostate cancer-specific mortality. Statistical analysis was performed using R. RESULTS: Of all patients, 6.4% were diagnosed with other malignancy prior to radical prostatectomy. Patients with tumor history were older (median: 66 years vs. 64 years., P< 0,001) and showed a higher tumor volume (median: 4.0 ml vs. 3.6 ml, P = 0.02) than patients without. The risk of biochemical recurrence and metastasis development after radical prostatectomy was similar. All-cause mortality was significantly increased (hazard ratio 2.0; 95% confidence interval 1.7-2.4), while prostate cancer-specific mortality was lower (hazard ratio 0.4; 95% confidence interval 0.23-0.87) in patients with additional malignancy. In a propensity score-matched cohort overall survival was significantly adverse (P< 0.001) and prostate cancer-specific survival was higher (P= 0.003) in patients with other malignancy prior to surgery. CONCLUSION: A higher other-cause mortality in men with tumor history should be concerned in the decision-making for medical care of prostate cancer patients in favor of reserved care strategies.

A comparative study of robot-assisted and open radical prostatectomy in 10 790 men treated by highly trained surgeons for both procedures.

OBJECTIVE: To compare oncological, functional and surgical outcomes of open retropubic radical prostatectomy (ORP) vs robot-assisted laparoscopic radical prostatectomy (RARP). PATIENTS AND METHODS: We identified 10 790 consecutive treated patients within our prospective database (2008-2016) who underwent either ORP (7007 patients) or RARP (3783). All procedures were performed by seven highly trained surgeons performing both surgical approaches regularly. Oncological (48-month biochemical recurrence [BCR] rate), functional (urinary continence, erectile function), and surgical outcomes (rate of nerve-sparing [NS] procedures, lymph node yield, surgical margin [SM] status, length of hospital stay [LOS], operation time, blood loss, transfusion rate, time to catheter removal) were assessed. Kaplan-Meier, multivariable Cox and logistic regression models were used to test for BCR and functional outcome differences. RESULTS: No statistically significant difference regarding oncological outcome distinguished between ORP vs RARP. For functional outcomes, the 1-week continence rates were higher in the ORP group (25.8% vs 21.8%, P < 0.001). At 3 months, no statistically significant differences were observed. At 12 months, continence rates were modestly higher in the RARP group (90.3% vs 88.8%, P = 0.01). This effect was no longer observed after stratification for age-groups. The 12-month potency rates were similar in ORP vs RARP (80.3% vs 83.6%, P = 0.33). For surgical outcomes, there was no significant difference in the rates of NS procedures, lymph node yield, SM status, and LOS. Conversely, operation time was shorter in ORP, and blood loss, transfusion rates and time to catheter removal were significantly lower in RARP. CONCLUSIONS: Both surgical approaches, performed in a high-volume centre by the same surgeons, achieve excellent, comparable oncological and functional outcomes. However, a modest advantage for RARP for surgical outcomes was observed, most likely attributable to its minimally invasive nature, and better teaching capabilities. Consequently, more than the surgical approach itself, the well-trained surgeon remains the most important factor to achieve satisfactory outcomes.

Perioperative management of direct oral anticoagulants in patients undergoing radical prostatectomy: results of a prospective assessment.

INTRODUCTION AND OBJECTIVES: In the perioperative setting, temporary interruption of direct oral anticoagulants (DOACs) is recommended. However, the safety of these recommendations is based on non-urological surgical experiences. Our objective was to verify the safety of these recommendations in patients undergoing radical prostatectomy (RP). MATERIALS AND METHODS: Patients regularly receiving a DOAC and scheduled for RP at our institution were prospectively assessed. DOAC intake was usually stopped 48 h before surgery without any preoperative bridging therapy. Postoperatively, patients received risk-adapted low-molecular weight heparin (LMWH). On the third day after unremarkable RP, DOAC intake was restarted and the administration of LMWH was stopped. We assessed perioperative outcomes and 30-day morbidity. RESULTS: Thirty-two consecutive patients receiving DOAC underwent RP at our institution between 12/2017 and 07/2018. Time of surgery (median, 177 min) and intraoperative blood loss (median, 500 mL) were unremarkable. DOACs were restarted on the third postoperative day in 30 patients (94%). No patient had a significant hemoglobin level reduction after DOAC restart. Overall, 28% of patients experienced complications within 30 days after surgery. Most of which were minor (Clavien ≤ 2), three patients (9%), however, had Clavien ≥ 3 complications. CONCLUSION: Our report is the first to prospectively assess current guideline recommendations regarding DOAC restarting after major urological surgery. RP can safely be performed, if DOACs are correctly paused before surgery. Moreover, in case of an uneventful postoperative clinical course, DOACs can be safely restarted on the third postoperative day. A 9% Clavien ≥ 3 30-day morbidity warrants attention and should be further explored in future studies.

Upregulation of centromere protein F is linked to aggressive prostate cancers.

BACKGROUND: Centromere protein F (CENPF) is a key component of the kinetochore complex and plays a crucial role in chromosome segregation and cell cycle progression. Recent work suggests that CENPF upregulation is linked to aggressive tumor features in a variety of malignancies including prostate cancer. MATERIALS AND METHODS: Using a highly annotated tissue microarray, we analyzed CENPF protein expression from a cohort of 8,298 prostatectomized patients by immunohistochemistry to study its effect on prostate-specific antigen recurrence-free survival. RESULTS: CENPF overexpression was found in 53% of cancers, and was linked to higher Gleason grade, advanced pathological tumor stage, accelerated cell proliferation, and lymph node metastasis (p<0.0001, each). A comparison with other key molecular features accessible through the microarray revealed strong associations between CENPF overexpression and presence of erythroblast transformation-specific (ETS)-related gene (ERG) fusion as well as phosphatase and tensin homolog deletion (p<0.0001, each). CENPF overexpression was linked to early biochemical recurrence. A subset analysis revealed that this was driven by the ERG-negative subset (p<0.0001). This was independent of established preoperative and postoperative prognostic parameters in multivariate analyses. CONCLUSION: The results of our study identify CENPF overexpression as an important mechanism and a potential biomarker for prostate cancer aggressiveness.

Marked Prognostic Impact of Minimal Lymphatic Tumor Spread in Prostate Cancer.

BACKGROUND: Nodal metastasis (N1) is a strong prognostic parameter in prostate cancer; however, lymph node evaluation is always incomplete. OBJECTIVE: To study the prognostic value of lymphatic invasion (L1) and whether it might complement or even replace lymph node analysis in clinical practice. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of pathological and clinical data from 14 528 consecutive patients. INTERVENTION: Radical prostatectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The impact of L1 and N1 on patient prognosis was measured with time to biochemical recurrence as the primary endpoint. RESULTS AND LIMITATIONS: Nodal metastases were found in 1602 (12%) of 13 070 patients with lymph node dissection. L1 was seen in 2027 of 14 528 patients (14%) for whom lymphatic vessels had been visualized by immunohistochemistry. N1 and L1 continuously increased with unfavorable Gleason grade, advanced pT stage, and preoperative prostate-specific antigen (PSA) values (p<0.0001 each). N1 was found in 4.3% of 12 501 L0 and in 41% of 2027 L1 carcinomas (p<0.0001). L1 was seen in 11% of 9868 N0 and in 61% of 1360 N1 carcinomas (p<0.0001). Both N1 and L1 were linked to PSA recurrence (p<0.0001 each). This was also true for 17 patients with isolated tumor cells (ie, <200 unequivocal cancer cells without invasive growth) and 193 metastases ≤1mm. Combined analysis of N and L status showed that L1 had no prognostic effect in N1 patients but L1 was strikingly linked to PSA recurrence in N0 patients. N0L1 patients showed a similar outcome as N1 patients. CONCLUSIONS: Analysis of lymphatic invasion provides comparable prognostic information than lymph node analysis. Even minimal involvement of the lymphatic system has pivotal prognostic impact in prostate cancer. Thus, a thorough search for lymphatic involvement helps to identify more patients with an increased risk for disease recurrence. PATIENT SUMMARY: Already minimal amounts of tumor cells inside the lymph nodes or intraprostatic lymphatic vessels have a severe impact on patient prognosis.

Postoperative complications of contemporary open and robot-assisted laparoscopic radical prostatectomy using standardised reporting systems.

OBJECTIVES: To analyse time trends and contemporary rates of postoperative complications after radical prostatectomy (RP) and to compare the complication profile of open RP (ORP) and robot-assisted laparoscopic RP (RALP) using standardised reporting systems. PATIENTS AND METHODS: Retrospective analysis of 13 924 RP patients in a single institution (2005-2015). Complications were collected during hospital stay and via standardised questionnaire 3 months after, and grouped into eight schemes. Since 2013, the revised Clavien-Dindo classification was used (n = 4 379). Annual incidence rates of different complications were graphically displayed. Multivariable logistic regression analyses compared complications between ORP and RALP after inverse probability of treatment weighting (IPTW). RESULTS: After the introduction of standardised classification systems, complication rates have increased with a contemporary rate of 20.6% (2013-2015). While minor Clavien-Dindo grades represented the majority (I: 10.6%; II: 7.9%), severe complications (Grades IV-V) were rare (<1%). In logistic regression analyses after IPTW, RALP was associated with less blood loss, shorter catheterisation time, and lower risk of Clavien-Dindo Grade II and III complications. CONCLUSION: Our results emphasise the importance of standardised reporting systems for quality control and comparison across approaches or institutions. Contemporary complication rates in a high-volume centre remain low and are most frequently minor Clavien-Dindo grades. RALP had a slightly better complication profile compared to ORP.

Integrating Tertiary Gleason 5 Patterns into Quantitative Gleason Grading in Prostate Biopsies and Prostatectomy Specimens.

BACKGROUND: Presence of small (tertiary) Gleason 5 pattern is linked to a higher risk of biochemical recurrence in prostate cancer. It is unclear, however, how to integrate small Gleason 5 elements into clinically relevant Gleason grade groups. OBJECTIVE: To analyze the prognostic impact of Gleason 5 patterns in prostate cancer and to develop a method for integrating tertiary Gleason 5 patterns into a quantitative Gleason grading system. DESIGN, SETTING, AND PARTICIPANTS: Prostatectomy specimens from 13 261 consecutive patients and of 3295 matched preoperative biopsies were available. Percentages of Gleason 3, 4, and 5 had been recorded for each cancer. Outcome measurements and statistical analysis: RESULTS AND LIMITATIONS: Our data demonstrate that minimal Gleason 5 areas have strong prognostic impact in Gleason 7 carcinomas, while further expansion of the Gleason 5 pattern population has less impact. We thus defined an integrated quantitative Gleason score (IQ-Gleason) by adding a lump score of 10 to the percentage of unfavorable Gleason pattern (Gleason 4/5) if any Gleason 5 was present and by adding another 7.5 points in case of a Gleason 5 fraction >20%. There was a continuous increase of the risk of prostate-specific antigen recurrence with increasing IQ-Gleason. This was also true for subgroups with identical Cancer of the Prostate Risk Assessment Postsurgical scores (p<0.0001) or Gleason grade groups (p<0.0001). CONCLUSIONS: The IQ-Gleason represents a simple and efficient approach for combining both quantitative Gleason grading and tertiary Gleason grades in one highly prognostic numerical variable. PATIENT SUMMARY: Prostatectomy specimens (13 261) were analyzed to estimate the relevance of small Gleason 5 elements in prostate cancers. Even the smallest Gleason 5 areas markedly increased the risk of prostate-specific antigen recurrence after surgery. Larger fractions of Gleason 5 patterns had less further impact on prognosis. Based on this, a numerical Gleason score (integrated quantitative Gleason score) was defined by the percentages of Gleason 4 and 5 patterns, enabling a refined estimate of patient prognosis.

Short- and Long-term Functional Outcomes and Quality of Life after Radical Prostatectomy: Patient-reported Outcomes from a Tertiary High-volume Center.

BACKGROUND: Results from population-based studies and the Prostate Testing for Cancer and Treatment trial reported worse urinary continence (UC) and erectile function (EF) for radical prostatectomy (RP) patients compared with their radiation or active surveillance counterparts. OBJECTIVE: To investigate functional outcomes for patients undergoing RP in a high-volume center. DATA, SETTING, AND PARTICIPANTS: A total of 8573 consecutive RP patients (2008-2012) were analyzed. INTERVENTION: RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Standardized questionnaires assessing EF, UC, and quality of life (QoL), were completed at baseline and annually thereafter. UC was defined as use of 0 or 1 safety pad/d, whereas the regular use of 1 pad/d was considered incontinent. EF was defined as ≥3 points in the International Index of Erectile Function question two. QoL was assessed using the EORTC-QLQ-C30 Global Health/QoL item. Statistics relied on comparison of means and proportions. RESULTS AND LIMITATIONS: EF and UC rates significantly decreased after RP. Overall, 12-mo, 24-mo, and 36-mo EF rates were 45%, 51%, and 53%, but reached up to 65.7% in preoperatively potent patients with bilateral nerve sparing. At 36 mo, 13% reported problems in their partnership. However, at the same time point, 77% were satisfied with their sexual intercourse. UC rates were 89.1%, 91.3%, and 89.0% at 12-mo, 24-mo, and 36-mo postoperatively. Mean EORTC-QLQ-C30 scores ranged from 74 to 79 and remained constant compared to baseline. CONCLUSIONS: Although varying definitions hinder direct comparisons to other studies, functional outcomes seemed favorable for patients undergoing RP in a high-volume center and most patients reported excellent QoL. PATIENT SUMMARY: Results of functional outcomes (urinary continence and potency) after radical prostatectomy are better in a high-volume center compared with those obtained from population-based data, and most patients report excellent quality of life after radical prostatectomy.

Functional Outcomes and Quality of Life After Radical Prostatectomy Only Versus a Combination of Prostatectomy with Radiation and Hormonal Therapy.

BACKGROUND: While the optimal use and timing of secondary therapy after radical prostatectomy (RP) remain controversial, there are limited data on patient-reported outcomes following multimodal therapy. OBJECTIVE: To assess the impact of additional radiation therapy (RT) and/or androgen deprivation therapy (ADT) on urinary continence, potency, and quality of life (QoL) after RP. DESIGN, SETTING, AND PARTICIPANTS: Among 13150 men who underwent RP from 1992 to 2013, 905 received RP + RT, 407 RP + ADT and 688 RP + RT + ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Urinary function, sexual function, and overall QoL were evaluated annually using self-administered validated questionnaires. Propensity score-matched and bootstrap analyses were performed, and the distributions for all functional outcomes were analyzed as a function of time after RP. RESULTS AND LIMITATIONS: Patients who received RP + RT had a 4% higher overall incontinence rate 3 yr after surgery, and 1% higher rate for severe incontinence (>3 pads/24h) compared to matched RP-only patients. ADT further increased the overall and severe incontinence rates by 4% and 3%, respectively, compared to matched RP + RT patients. RP + RT was associated with an 18% lower rate of potency compared to RP alone, while RP + RT + ADT was associated with a further 17% reduction compared to RP + RT. Additional RT reduced QoL by 10% and additional ADT by a further 12% compared to RP only and RP + RT, respectively. The timing of RT after RP had no influence on continence, but adjuvant compared to salvage RT was associated with significantly lower potency (37% vs 45%), but higher QoL (60% vs 56%). Limitations of our study include the observational study design and potential for selection bias in the treatments received. CONCLUSIONS: Secondary RT and ADT after RP have an additive negative influence on urinary function, potency, and QoL. Patients with high-risk disease should be counseled before RP on the potential net impairment of functional outcomes due to multimodal treatment. PATIENT SUMMARY: Men with high-risk disease choosing surgery upfront should be counseled on the potential need for additional radiation and or androgen deprivation, and the potential net impairment of functional outcomes arising from multimodal treatment.