Unilateral Pelvic Lymph Node Dissection in Prostate Cancer Patients Diagnosed in the Era of Magnetic Resonance Imaging-targeted Biopsy: A Study That Challenges the Dogma.

PURPOSE: Bilateral extended pelvic lymph node dissection at the time of radical prostatectomy is the current standard of care if pelvic lymph node dissection is indicated; often, however, pelvic lymph node dissection is performed in pN0 disease. With the more accurate staging achieved with magnetic resonance imaging-targeted biopsies for prostate cancer diagnosis, the indication for bilateral extended pelvic lymph node dissection may be revised. We aimed to assess the feasibility of unilateral extended pelvic lymph node dissection in the era of modern prostate cancer imaging. MATERIALS AND METHODS: We analyzed a multi-institutional data set of men with cN0 disease diagnosed by magnetic resonance imaging-targeted biopsy who underwent prostatectomy and bilateral extended pelvic lymph node dissection. The outcome of the study was lymph node invasion contralateral to the prostatic lobe with worse disease features, ie, dominant lobe. Logistic regression to predict lymph node invasion contralateral to the dominant lobe was generated and internally validated. RESULTS: Overall, data from 2,253 patients were considered. Lymph node invasion was documented in 302 (13%) patients; 83 (4%) patients had lymph node invasion contralateral to the dominant prostatic lobe. A model including prostate-specific antigen, maximum diameter of the index lesion, seminal vesicle invasion on magnetic resonance imaging, International Society of Urological Pathology grade in the nondominant side, and percentage of positive cores in the nondominant side achieved an area under the curve of 84% after internal validation. With a cutoff of contralateral lymph node invasion of 1%, 602 (27%) contralateral pelvic lymph node dissections would be omitted with only 1 (1.2%) lymph node invasion missed. CONCLUSIONS: Pelvic lymph node dissection could be omitted contralateral to the prostate lobe with worse disease features in selected patients. We propose a model that can help avoid contralateral pelvic lymph node dissection in almost one-third of cases.

Risk and predictors of adverse pathology after radical prostatectomy in patients diagnosed with IUSP 1-2 prostate cancer at MRI-targeted biopsy: a multicenter analysis.

PURPOSE: Although active surveillance (AS) is recommended for low- to favorable intermediate-risk prostate cancer (PCa), risk of upgrading at radical prostatectomy (RP) is not negligible. Available studies based on systematic transrectal ultrasound biopsy might not be applicable to contemporary cohorts diagnosed with MRI-targeted biopsy (TB). The aim of the present study is to explore rates and risk factors for adverse outcomes (AO) at RP in patients with ISUP ≤ 2 PCa detected at TB with concomitant systematic biopsy (SB). METHODS: Multicenter, retrospective analysis of 475 consecutive patients with ISUP ≤ 2 PCa at MRI-TB + SB is treated with RP. AO were defined as ISUP upgrading, adverse pathology (upgrading to ISUP ≥ 3 and/or ≥ pT3 at RP, and/or pN1) (AP) or biochemical recurrence (BCR) in men with follow-up (n = 327). RESULTS: The rate of ISUP upgrading, upgrading ≥ 3, and AP were 39%, 21%, and 43%. Compared to ISUP2, men with ISUP1 PCa had a higher rate of overall upgrading (27 vs. 67%, p < 0.001), but less upgrading to ≥ 3 (27 vs. 10%, p < 0.001). AP was more common when ISUP2 was detected with a combined MRI-TB + SB approach compared to considering TB (p = 0.02) or SB (p = 0.01) alone. PSA, PSA density, PI-RADS, ISUP at TB, overall biopsy ISUP and EAU classification were predictors of upgrading to ISUP ≥ 3 and AP. The 1 year BCR-free survival was 94% with no differences in BCR rates between subgroups. CONCLUSION: Upgrading in ISUP ≤ 2 PCa remains prevalent even in men diagnosed in the MRI era. The use of MRI-TB with concomitant SB allows for the accurate identification of ISUP2 PCa and predicts the risk of AO at RP.

Impact of Age on Long-Term Urinary Continence after Robotic-Assisted Radical Prostatectomy.

Aim and Objectives: We aimed to test the impact of age on long-term urinary continence (≥12 months) in patients undergoing robotic-assisted radical prostatectomy. Methods and Materials: We relied on an institutional tertiary-care database to identify the patients who underwent robotic-assisted radical prostatectomy between January 2014 and January 2021. Patients were divided into three age groups: age group one (≤60 years), age group two (61-69 years) and age group three (≥70 years). Multivariable logistic regression models tested the differences between the age groups in the analyses addressing long-term urinary continence after robotic-assisted radical prostatectomy. Results: Of the 201 prostate cancer patients treated with robotic-assisted radical prostatectomy, 49 (24%) were assigned to age group one (≤60 years), 93 (46%) to age group two (61-69 years) and 59 (29%) to age group three (≥70 years). The three age groups differed according to long-term urinary continence: 90% vs. 84% vs. 69% for, respectively, age group one vs. two vs. three (p = 0.018). In the multivariable logistic regression, age group one (Odds Ratio (OR) 4.73, 95% CI 1.44-18.65, p = 0.015) and 2 (OR 2.94; 95% CI 1.23-7.29; p = 0.017) were independent predictors for urinary continence, compared to age group three. Conclusion: Younger age, especially ≤60 years, was associated with better urinary continence after robotic-assisted radical prostatectomy. This observation is important at the point of patient education and should be discussed in informed consent.

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.

Impact of positive surgical margin length and Gleason grade at the margin on oncologic outcomes in patients with nonorgan-confined prostate cancer.

PURPOSE: Positive surgical margins (PSM) represent a poor prognostic factor at radical prostatectomy (RP). To investigate the impact of PSM, its length, the focality and the Gleason grade at the PSM, on the oncologic outcomes in nonorgan-confined RP patients. METHODS: Within a high-volume center database, we identified patients who harbored non-organ-confined (pT3) prostate cancer (PCa) at RP between 2010 and 2016. Only patients without lymph node invasion were included. Kaplan-Meier analyses and multivariable Cox regression models were used to test the effect of PSM on biochemical recurrence (BCR), metastasis, and cancer-specific death after RP in patients without adjuvant radiotherapy. RESULTS: Overall, 3705 patients were identified. Of those, 27.2% (n = 1007) harbored PSM. At 96 months after RP, BCR-free, metastasis-free and cancer-specific survival was 41.6 versus 57.5%, 82.7 versus 88.6%, and 94.7 versus 98.5% for patients with versus without PSM (all p < 0.001). BCR-free, metastasis-free and cancer-specific survival rates at 96 months were 56.7 versus 26.5% (p < 0.001), 94.4 versus 67.4% (p < 0.001), and 100.0 versus 87.1% (p < 0.01) for Gleason pattern 3 versus ≥ 4 at the margin and 45.0 versus 27.8% (p < 0.01), 83.3 versus 82.3% (p = 0.2), and 95.2 versus 92.7% (p = 0.3) for <4 mm versus ≥4 mm length of margin. In multivariable Cox models PSM was an independent predictor for BCR (hazard ratio [HR]:1.53, p < 0.001) and cancer-specific death (HR:2.75, p = 0.02). In subgroups of patients with PSM only, Gleason ≥ 4 at the margin (HR:1.60, p < 0.01) and length of PSM (HR:1.02, p < 0.05) was an independent predictor of BCR. CONCLUSION: PSM represents an independent predictor for worse oncologic outcome in nonorgan-confined PCa at RP. Gleason ≥ 4 at the margin was associated with the development of BCR, metastasis, and with cancer-specific death after RP. Next to margin status, Gleason at the margin and its length carry important information that should be reported for the specimen.

An Algorithm to Personalize Nerve Sparing in Men with Unilateral High-Risk Prostate Cancer.

PURPOSE: Current guidelines do not provide strong recommendations on preservation of the neurovascular bundles during radical prostatectomy in case of high-risk (HR) prostate cancer and/or suspicious extraprostatic extension (EPE). We aimed to evaluate when, in case of unilateral HR disease, contralateral nerve sparing (NS) should be considered or not. MATERIALS AND METHODS: Within a multi-institutional data set we selected patients with unilateral HR prostate cancer, defined as unilateral EPE and/or seminal vesicle invasion (SVI) on multiparametric (mp) magnetic resonance imaging (MRI), or unilateral International Society of Urologic Pathologists (ISUP) 4-5 or prostate specific antigen ≥20 ng/ml. To evaluate when to perform NS based on the risk of contralateral EPE, we relied on chi-square automated interaction detection, a recursive machine-learning partitioning algorithm developed to identify risk groups, which was fit to predict the presence of EPE on final pathology, contralaterally to the prostate lobe with HR disease. RESULTS: A total of 705 patients were identified. Contralateral EPE was documented in 87 patients (12%). Chi-square automated interaction detection identified 3 groups, consisting of 1) absence of SVI on mpMRI and index lesion diameter ≤15 mm, 2) index lesion diameter ≤15 mm and contralateral ISUP 2-3 or index lesion diameter >15 mm and negative contralateral biopsy or ISUP 1, and 3) SVI on mpMRI or index lesion diameter >15 mm and contralateral biopsy ISUP 2-3. We named those groups as low, intermediate and high-risk, respectively, for contralateral EPE. The rate of EPE and positive surgical margins across the groups were 4.8%, 14% and 26%, and 5.6%, 13% and 18%, respectively. CONCLUSIONS: Our study challenges current guidelines by proving that wide bilateral excision in men with unilateral HR disease is not justified. Pending external validation, we propose performing NS and incremental NS in case of contralateral low and intermediate EPE risk, respectively.

Features and management of men with pN1 cM0 prostate cancer after radical prostatectomy and lymphadenectomy: a systematic review of population-based evidence.

PURPOSE OF REVIEW: To investigate the features and optimal management of pN+ cM0 prostate cancer (PCa) according to registry-based studies. RECENT FINDINGS: Up to 15% of PCa patients harbor lymph node invasion (pN+) at radical prostatectomy plus lymph node dissection. Nonetheless, the optimal management strategy in this setting is not well characterized. SUMMARY: We performed a systematic review including n = 13 studies. Management strategies comprised 13 536 men undergoing observation, 11 149 adjuvant androgen deprivation therapy (aADT), 7,075 adjuvant radiotherapy (aRT) +aADT and 705 aRT. Baseline features showed aggressive PCa in the majority of men. At a median follow-up ranging 48-134months, Cancer-related death was 5% and overall-mortality 16.6%. aADT and aRT alone had no cancer-specific survival or overall survival advantages over observation only and over not performing aRT, respectively. aADT plus aRT yielded a survival benefit compared to observation and aADT, which in one study, were limited to certain intermediate-risk categories. Age, Gleason, Charlson score, positive surgical margins, pathological stage, and positive nodes number, but not prostate specific antigen, were most relevant prognostic factors. Our work further confirmed pN+ PCa is a multifaceted disease and will help future research in defining its optimal management based on different risk categories to maximize survival and patient's quality of life.

Catheterization Does Not Improve Course of Disease in Female Patients with Acute Cystitis or Pyelonephritis: Retrospective Analysis of >300 In-Hospital Treated Patients.

PURPOSE: Females with in-hospital treatment for acute cystitis (AC) or pyelonephritis may benefit from catheterization at admission. METHODS: All female patients with AC or pyelonephritis requiring in-hospital treatment at University Hospital Frankfurt (2004-2019) were retrospectively analyzed. Logistic regression models were used to predict the catheter value. RESULTS: Of 310 female patients, 40% harbored AC versus 60% pyelonephritis, of whom 62% and 74% received a catheter at admission: C-reactive protein (CRP) and white blood count (WBC) were significantly elevated in AC and pyelonephritis catheter versus no catheter patients (both p < 0.05). Time to CRP and WBC nadir did not differ between the AC catheter versus no catheter group (both p > 0.05). Conversely, time to CRP nadir was prolonged in pyelonephritis catheter patients. AC and pyelonephritis catheter patients exhibited a prolonged antibiotic treatment and length of stay (LOS, both p < 0.05). In multivariable analyses, CRP >5 ng/mL was a predictor for receiving a catheter in all patients. In AC, a positive urine culture and fever predicted, respectively, prolonged LOS or antibiotic treatment (all p < 0.05). CONCLUSION: Risk factors exist with regard to receiving a catheter and prolonged antibiotic treatment or LOS in females with AC or pyelonephritis. A catheter may not accelerate recovery or WBC nadir.

Effect of Extended Pelvic Lymph Node Dissection on Oncologic Outcomes in Patients with D'Amico Intermediate and High Risk Prostate Cancer Treated with Radical Prostatectomy: A Multi-Institutional Study.

PURPOSE: Pelvic lymph node dissection represents the gold standard of lymph node staging in patients with prostate cancer. We sought to assess the effect of extended pelvic lymph node dissection on oncologic outcomes in patients with characteristics of D'Amico intermediate or high risk prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: In a multi-institutional database of 4 centers we identified 9,742 patients who underwent radical prostatectomy from 2000 to 2017 with or without pelvic lymph node dissection. Only patients with a greater than 5% probability of lymph node invasion according to the Briganti nomogram were included in study. We performed 2:1 propensity score matching to account for potential differences between the 2 cohorts. Cox regression models were used to test the effect of pelvic lymph node dissection on biochemical recurrence, metastasis and cancer specific mortality. RESULTS: Overall 707 patients (7.3%) did not undergo pelvic lymph node dissection, of whom 520 and 187 harbored D'Amico intermediate and high risk characteristics, respectively. A median of 14 lymph nodes (IQR 8-21) were removed in the pelvic lymph node dissection cohort and 1,714 of these cases (19.0%) harbored lymph node metastasis. After propensity score matching the biochemical recurrence-free, metastasis-free and cancer specific mortality-free survival rates were 60.4% vs 65.6% (p=0.07), 87.0% vs 90.0% (p=0.06) and 95.2% vs 96.4% (p=0.2) for pelvic lymph node dissection vs no pelvic lymph node dissection 120 months after radical prostatectomy. Multivariable Cox regression models adjusted for postoperative and preoperative tumor characteristics revealed that pelvic lymph node dissection performed at radical prostatectomy was no independent predictor of biochemical recurrence, metastasis or cancer specific mortality (all p ≥0.1). CONCLUSIONS: There was no significant difference in oncologic outcomes in patients with D'Amico high or intermediate risk prostate cancer in whom pelvic lymph node dissection was or was not performed at radical prostatectomy. The therapeutic value of pelvic lymph node dissection remains unclear.

Tumor characteristics, oncological and functional outcomes after radical prostatectomy in very young men ≤ 45 years of age.

PURPOSE: Age is an important prognostic factor for functional and oncological outcomes after radical prostatectomy (RP). Considering the long life-expectancy of young patients (≤ 45 years), it remains important to examine their outcomes. METHODS: Of 16.049 patients who underwent RP between 01/2006 and 12/2014 at the Martini-Klinik Prostate Cancer Center, 119 (0.7%) were ≤ 45. Known prognosticators were compared according to patient age at RP (categorical as ≤ 45, > 45 and ≤ 65, > 65 years). Kaplan-Meier plots and Cox-regressions analyzed oncological outcomes [biochemical recurrence (BCR)-free survival and metastasis-free survival (MFS)]. Logistic regressions were used for functional outcome. Urinary continence (UC) was defined as the use of 0 or 1 safety pad/day and potency as an IIEF-5 score of ≥ 18. RESULTS: Compared to their older counterparts, patients ≤ 45 years had more favorable tumor characteristics. Of all patients aged ≤ 45 years, 89% underwent bilateral and 9.3% unilateral nerve-sparing procedure. Five year BCR-free survival and MFS were 80.2% and 98.7% for patients ≤ 45 years, 72.8% and 95.0% for patients > 45 and ≤ 65 years and 70.5% and 94.9% for patients > 65 years. For the same groups, 1-year UC-rates were 97.4%, 89.4%, and 84.7% while 1.3%, 8.2%, and 11.6% used 1-2 pads/24 h. At 1-year, 75.6%, 58.6%, and 45.3% of preoperatively potent patients who underwent bilateral nerve-sparing were considered potent. Younger age was an independent predictor of favorable functional outcome also in multivariable analysis. CONCLUSIONS: Patients aged ≤ 45 years had more favorable tumor characteristics and oncological outcomes. Moreover, younger patients should be counseled about the excellent postoperative continence and potency rates.

Impact of positive surgical margin length and Gleason grade at the margin on biochemical recurrence in patients with organ-confined prostate cancer.

BACKGROUND: Positive surgical margins (PSMs) represent a poor prognostic factor at radical prostatectomy (RP). To investigate the impact of PSM, its length, the focality, and the PSM Gleason, on biochemical recurrence (BCR) in organ-confined RP patients. METHODS: Within a high-volume center database, we identified patients who harbored organ-confined (pathologic stage T2 disease) prostate cancer (PCa) at RP (2010-2016). Kaplan-Meier analyses and multivariable Cox regression models were used to test the effect of the PSM on the BCR risk. RESULTS: Overall, 8770 patients were identified. Of those, 6.6% (n = 579) harbored PSM. BCR-free survival at 72 months after RP was 77.7% vs 89.0% for patients with vs without PSM (P < .001). BCR-free survival rates at 72 months were 77.4% vs 73.6% (P = .1) for unifocal vs multifocal PSM, 77.2% vs 71.8% (P = .03) for Gleason pattern 3 vs ≥4 at the margin and 88.4% vs 66.3% (P < .001) for <3 vs ≥3 mm length of margin. In multivariable Cox models PSM was an independent predictor for BCR (hazard ratio [HR] = 2.40, P < .001). However, in subgroups with PSM, only ≥3 mm PSM represented an independent predictor (HR = 1.93, P = .04), while focality and Gleason at the margin were no significant predictors. CONCLUSION: PSM represents an independent predictor for BCR in organ-confined PCa at RP. Moreover, Gleason ≥4 at the margin and ≥3 mm PSM length were associated with worse BCR-free survival. Closer surveillance of patients with organ-confined PCa at RP and PSM can help to identify those who qualify for early salvage radiotherapy.

Long-term incidence of secondary bladder and rectal cancer in patients treated with brachytherapy for localized prostate cancer: a large-scale population-based analysis.

OBJECTIVE: To examine the incidence and time trends of secondary bladder cancer (BCa) and rectal cancer (RCa) after brachytherapy (BT) relative to radical prostatectomy (RP). MATERIALS AND METHODS: Within the Surveillance, Epidemiology and End Results (SEER) database (1988-2015), we identified patients with localized PCa as an only or first primary cancer, who underwent BT or RP. Cumulative incidence plots and multivariable competing-risks regression (CRR) models were used. Sensitivity analyses focused on patients' age and year of diagnosis intervals and tested the effect of an unmeasured confounder. RESULTS: Of 318 058 patients with localized prostate cancer (PCa), 55 566 (18.4%) underwent BT. After propensity score-matching, 20-year secondary BCa incidence was 6.0% in patients who had undergone BT vs 2.4% in those who had undergone RP (P < 0.001) and the respective 20-year secondary RCa incidence was 1.1% vs 0.5% (P < 0.001). In multivariable CRR models, BT predicted higher secondary BCa (hazard ratio [HR] 1.58; P < 0.001) and RCa rates (HR 1.59; P < 0.001) vs RP. Sensitivity analyses replicated the same results after stratification according to age and showed HRs of decreasing magnitude for historical, intermediate and contemporary years of diagnosis. An unmeasured confounder with an HR of 2 would render the effect of BT statistically insignificant if it affected patients in the RP group with a ratio of 2 relative to those in the BT group. Finally, temporal trends showed a decrease of secondary 5-year BCa and RCa rates.> CONCLUSIONS: Brachytherapy predominantly increases the risk of secondary BCa and, to a lesser extent, that of RCa. Follow-up of such patients is therefore required. It is encouraging that both secondary BCa, and RCa rates, in particular, have recently decreased, RCa.

Survival effect of perioperative systemic chemotherapy on overall mortality in locally advanced and/or positive regional lymph node non-metastatic urothelial carcinoma of the upper urinary tract.

OBJECTIVES: To analyze the potential survival benefit of perioperative chemotherapy (CHT) in patients treated with nephroureterectomy (NU) for non-metastatic locally advanced upper tract urothelial carcinoma. METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2014), we identified 1286 patients with T3 or T4, N 0-3 M0 UTUC. Kaplan-Meier plots, as well as multivariable Cox regression models (MCRMs) relying on inverse probability after treatment weighting (IPTW) and landmark analyses, were used to test the effect of CHT vs no CHT on overall mortality (OM) in the overall population (n =1286), as well as after stratification according to lymph node invasion (LNI). RESULTS: Overall, 37.4% patients received CHT. The CHT rate was higher with LNI (62.2% vs 35.2%, p < 0.001). In MCRMs, testing for OM in the overall population, CHT was associated with lower rates of OM (HR 0.71, CI 0.58-0.87; p = 0.001). Similarly, in MCRMs testing for OM in patients with LNI, CHT achieved independent predictor status for lower OM (HR 0.61, CI 0.48-0.78; p < 0.001). Conversely, in MCRMs testing for OM in patients without LNI, no CHT effect was recorded (HR 0.72, CI 0.52-1.01; p = 0.05). All results were confirmed after IPTW adjustment and in landmark analyses. CONCLUSIONS: Our results represent a contemporary North American report indicating lower OM after CHT for patients with locally advanced non-metastatic upper tract urothelial carcinoma, specifically in patients with T3-T4, N1-N3, M0 disease. Validation of the current and of the previous study is required within a randomized prospective design.

Inverse stage migration patterns in North American patients undergoing local prostate cancer treatment: a contemporary population-based update in light of the 2012 USPSTF recommendations.

PURPOSE: Recent studies demonstrated ongoing inverse stage migration in prostate cancer (PCa) patients towards more advanced and unfavorable tumors. The USPSTF grade D recommendation may impact this trend in North American patients. We assessed contemporary stage migration and treatment trends in a large North American cohort diagnosed with PCa 2009-2014. METHODS: Time-trend analyses were performed in patients within the Surveillance, Epidemiology, and End Results database, with complete data of clinical tumor stage, biopsy Gleason score, and validated PSA values, resulting in 211,645 assessable patients. Patients were stratified according to their different treatment methods [radical prostatectomy (RP), radiotherapy (RT), and no local treatment (NLT)] and according to clinical and pathological risk stratification (D'Amico and CAPRA-S score). RESULTS: Over time, proportions of D'Amico low-risk (LR) decreased, with an increase in intermediate-to-high-risk (IR/HR) patients. These trends were more distinct in men ≥ 70 years. NLT proportions increased, most notably in D'Amico LR and/or older patients. Conversely, RP proportions remained stable in younger HR and increased in older HR patients. Similar patterns were demonstrated in the RP-treated subgroup: D'Amico HR, pT3, and/or lymph-node invasion or CAPRA-S HR proportions increased from 23.5 to 30.8, 24.3 to 32.9, and 10.7 to 16.3% (each p ≤ 0.015). CONCLUSIONS: Inverse stage migration with increase of unfavorable PCa continues in most contemporary North American patients. However, a paradigm shift to treat LR patients with less invasive methods (NLT) was demonstrated. Contrary, HR patients increasingly undergo LT. Future studies with long-term follow-up might answer if inverse stage migration vs. treatment trends translate into different PCa metastases/mortality rates vs. proposed NLT benefits, particularly related to USPSTF-recommended reduced PSA screening.

Regional differences in total hospital charges between open and robotically assisted radical prostatectomy in the United States.

BACKGROUND: Robotically assisted radical prostatectomy (RARP) has become the most frequently used surgical approach for patients treated with radical prostatectomy (RP) for localized prostate cancer (PCa). Previous studies reported higher total hospital charges (THCs) for RARP than open RP (ORP). We hypothesized that based on increasing RARP surgical expertise, differences in THCs between RARP and ORP should have decreased or even disappeared in the United States in most contemporary years. PATIENTS AND METHODS: Within the National Inpatient Sample database (2008-2015), we identified patients who underwent RARP or ORP. Multivariable linear regression models with adjustment for clustering were used to test for differences in THCs. Subgroup analyses focused on geographical regions, defined as West, Midwest, South and Northeast. RESULTS: Of 83,693 RP patients, 51,363 (61.4%) underwent RARP. RARP rates increased from 13.1 to 81.5% (p = 0.04). Overall, median THCs were $11,898 vs. $10,162 (p < 0.001) for RARP vs. ORP, respectively. After adjustment for complications, length of stay and clustering, RARP was associated with higher THCs ($3124 more for each RARP, p < 0.001). Additional charges for RARP did not change over time (p = 0.3). However, additional charges for RARP were highest in the West ($4610, p < 0.001), followed by the Midwest ($3278, p < 0.001), the South ($2906, p < 0.001) and the Northeast ($2216, p < 0.001). CONCLUSION: RARP rates have increased exponentially from 13.1 to over 80%. Similar rates were identified across all four geographical regions. RARP THCs exceeded those of ORP. Finally, important regional differences in RARP THCs were identified and persisted even after most detailed adjustment for population differences.

Oncological and functional outcomes of a large Canadian robotic-assisted radical prostatectomy database with 10 years of surgical experience.

INTRODUCTION: Robotic-assisted radical prostatectomy (RARP) has grown to be the predominant global surgical approach to treat localized prostate cancer. However, there is still limited access to robotic technology and little data from Canadian cohorts. Herein, we report on our oncological and functional outcomes after 10 years of surgical experience. MATERIALS AND METHODS: Prospective data from 1,034 RARP cases performed by two high-volume experienced surgeons at two academic centers were collected from October 2006 to June 2017. Preoperative characteristics, surgical, oncological and functional outcomes were assessed up to 72 months postoperative. RESULTS: D'Amico risk distribution was 26.1%, 59.8% and 14.1% for low, intermediate and high risk prostate cancer. Median (interquartile range) operative time, blood loss and hospital stay were 170 minutes (145-200), 200 mL (150-300) and 1day (1-1), respectively and 1.4% received blood transfusion. Intraoperative complications occurred in 3.8%. Postoperatively, 32 (3.1%) and 138 (13.3%) men harbored major (Clavien III-IV) and minor complications (Clavien I-II), respectively. Among the 630 men (64.2%) with pT2 and 349 men (35.6%) with pT3 disease, stage-specific positive surgical margin rates were 15.7% and 39.0%, respectively. Urinary continence rates at 6, 12 and 72 months were 72.7%, 83.5% and 84.9%, respectively. In men without preoperative erectile dysfunction, potency was observed in 45.6%, 59.4% and 69.5% at 6, 12 and 72 months, respectively. Biochemical recurrence occurred in 105 patients (10.2%). CONCLUSION: Mid-term oncological outcomes in two large Canadian centers demonstrate comparable results to non-Canadian centers of excellence. RARP appears to be safe with acceptable surgical, oncological and functional outcomes in a publicly funded single-payer healthcare system.

Predictors of deviation in neurovascular bundle preservation during robotic prostatectomy.

INTRODUCTION: Neurovascular bundle (NVB) preservation during robot-assisted radical prostatectomy (RARP) directly affects patient functional outcomes. Despite careful surgical planning, many NVB preservation techniques are changed intraoperatively from their preoperative plan. Our objective was to identify risk factors predicting intraoperative change in NVB preservation technique during RARP. MATERIALS AND METHODS: Prospective data from 578 RARPs performed by a single surgeon between 2010 and 2017 at a tertiary care center. Side-specific NVB preservation technique was planned preoperatively. Surgical techniques were either complete nerve sparing (CNS), or incomplete nerve sparing (INS). Variables included age, tumor grade, prostate volume, number of lifetime biopsies, history of post-biopsy sepsis, and laterality. Variables were modeled in multivariable logistic regressions as potential predictors of deviation in surgical technique. Functional and oncological outcomes were also assessed. RESULTS: A total of 46.9% of cases underwent some intraoperative change in NVB preservation from their preoperative plan. A total of 37.7% of 880 prostate sides planned for CNS underwent unplanned INS. Older age, Gleason ≥ 3+4, post-biopsy sepsis, prostate volume, and left-sided dissections were significantly associated with unplanned INS. Number of lifetime biopsies was not a predictor of unplanned INS. Patients with an intraoperative change to INS had poorer potency and continence. Study limitations included the retrospective nature of analysis and lack of pathological assessment of NVB preservation. CONCLUSIONS: Age, Gleason ≥ 3+4, post-biopsy sepsis, prostate volume, and laterality were significant predictors of unplanned INS during RARP, which should guide patient counseling when discussing risks and functional outcomes. The number of lifetime biopsies did not predict unplanned INS, a valuable finding for patients on active surveillance. Our findings highlight the importance of careful preoperative planning and novel adjuncts such as multiparametric MRI.

Comparison of perioperative outcomes between open and minimally invasive nephroureterectomy: A population-based analysis.

OBJECTIVES: To examine intraoperative and postoperative morbidity and mortality, as well as the impact on length of stay and total hospital charges of minimally invasive nephroureterectomy compared with open nephroureterectomy in patients with upper tract urothelial carcinoma. METHODS: Within the National Inpatient Sample (2008-2013), we identified patients with non-metastatic upper tract urothelial carcinoma treated with either minimally invasive nephroureterectomy or open nephroureterectomy. We relied on inverse probability of treatment weighting to reduce the effect of inherent differences between open nephroureterectomy versus minimally invasive nephroureterectomy. Multivariable logistic regression, multivariable Poisson regression models and multivariable linear regression models were used. RESULTS: Between 2008 and 2013, we identified 3897 patients treated with either minimally invasive nephroureterectomy (1093 [28%]) or open nephroureterectomy (2804 [72%]). In multivariable logistic regression models, minimally invasive nephroureterectomy resulted in lower rates of overall (odds ratio 0.71, P < 0.001), wound (odds ratio 0.49, P = 0.01), intraoperative (odds ratio 0.55, P = 0.01), miscellaneous surgical (odds ratio 0.64, P = 0.008) and miscellaneous medical complications (odds ratio 0.77, P = 0.002). Furthermore, minimally invasive nephroureterectomy was associated with lower rates of transfusions (odds ratio 0.61, P < 0.001). In multivariable Poisson regression models, minimally invasive nephroureterectomy was associated with shorter length of stay (relative risk 0.88, P < 0.001). Finally, higher total hospital charges ($2500 more per patient) were recorded for minimally invasive nephroureterectomy. CONCLUSIONS: Intraoperative and postoperative morbidity, as well as length of stay, but not total hospital charges favor minimally invasive nephroureterectomy over open nephroureterectomy. These outcomes validate the safety and feasibility of minimally invasive nephroureterectomy in select upper tract urothelial carcinoma patients.

Survival benefit of local versus no local treatment for metastatic prostate cancer-Impact of baseline PSA and metastatic substages.

BACKGROUND: To test whether local treatment (LT), namely radical prostatectomy (RP) or brachytherapy (BT) still confers a survival benefit versus no local treatment (NLT), when adjusted for baseline PSA (bPSA). To further examine whether the effect of LT might be modulated according to bPSA and M1 substages. METHODS: Of 13 906 mPCa patients within the SEER (2004-2014), 375 underwent RP, 175 BT, and 13 356 NLT. Multivariable competing risks regression (MVA CRR) analyses after 1:2 propensity score matching assessed the impact of LT versus NLT on cancer specific mortality (CSM). Interaction analyses tested the association between treatment type and bPSA within different M1 substages. RESULTS: MVA CRR analyses revealed lower CSM rates for LT (RP [HR: 0.55, CI: 0.44-0.70, P < 0.001] and BT [HR: 0.63, CI: 0.49-0.83, P < 0.001]) compared to NLT. A significant interaction existed between bPSA and treatment type, in M1b patients only. Here, LT conferred a survival benefit when bPSA was <60 ng/mL with maximum benefit when bPSA was <40 ng/mL. No survival benefit existed for M1b patients above the 60 ng/mL bPSA threshold and for M1c patients, regardless of bPSA. For M1a patients, LT conferred a survival benefit compared to NLT. However, dose-response according to bPSA could not be tested, due to insufficient sample size. CONCLUSIONS: Our observations provide new insight regarding the pivotal effect of bPSA and M1 substages on CSM, when LT is contemplated. While M1a patients benefited from LT, the survival benefit was modulated by bPSA in M1b patients and no survival benefit existed in M1c patients.

Extent of lymph node dissection improves survival in prostate cancer patients treated with radical prostatectomy without lymph node invasion.

PURPOSE: To assess the effect of pelvic lymph node dissection (PLND) extent on cancer-specific mortality (CSM) in prostate cancer (PCa) patients without lymph node invasion (LNI) treated with radical prostatectomy (RP). METHODS: Within the Surveillance, Epidemiology, and End results (SEER) database (2004-2014), we identified patients with D'Amico intermediate- or high-risk characteristics who underwent RP with PLND, without evidence of LNI. First, multivariable logistic regression models tested for predictors of more extensive PLND, defined as removed lymph node count (NRN) ≥75th percentile. Second, Kaplan-Meier analyses and multivariable Cox regression models tested the effect of NRN ≥75th percentile on CSM. Finally, survival analyses were repeated using continuously coded NRN. RESULTS: In 28 147 RP and PLND patients without LNI, 67.3% versus 32.7% exhibited D'Amico intermediate- or high-risk characteristics. The median NRN was 6 (IQR 3-10), the 75th percentile defined patients with NRN ≥11. Patients with NRN ≥11 had higher rate of cT2/3 stage (29.8 vs 26.1%), GS ≥8 (25.7 vs 22.4%), and respectively more frequently exhibited D'Amico high-risk characteristics (34.6 vs 32.1%). In multivariable logistic regression models predicting the probability of more extensive PLND (NRN ≥11), higher biopsy GS, higher cT stage, higher PSA, more recent year of diagnosis, and younger age at diagnosis represented independent predictors. At 72 months after RP, CSM-free rates were 99.5 versus 98.1% for NRN ≥11 and NRN ≤10, respectively and resulted in a HR of 0.50 (P = 0.01), after adjustment for all covariates. Similarly, continuously coded NRN achieved independent predictor status (HR: 0.955, P = 0.01), where each additional removed lymph node reduced CSM risk by 4.5%. CONCLUSION: More extensive PLND at RP provides improved staging information and consequently is associated with lower CSM in D'Amico intermediate- and high-risk PCa patients without evidence of LNI. Hence, more extensive PLND should be recommended in such individuals.