Sunitinib for Metastatic Renal Cell Carcinoma: Real-World Data from the STAR-TOR Registry and Detailed Literature Review.

INTRODUCTION: We evaluated the effectiveness and safety profile of the tyrosine kinase inhibitor sunitinib in patients with advanced or metastatic renal cell carcinoma (a/mRCC) in a real-world setting. METHODS: We analyzed data of adult a/mRCC patients treated with sunitinib. Data were derived from the German non-interventional post-approval multicenter STAR-TOR registry (NCT00700258). Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated using descriptive statistics and survival analyses for the entire cohort and patient subgroups. RESULTS: A total of 116 study sites recruited 702 patients treated with sunitinib (73.1% male; median age 68.0 years; median Karnofsky index 90%) between November 2010 and May 2020. The most frequent histological subtype was clear cell RCC (81.6%). Sunitinib was administered as first-line treatment in 83.5%, as second line in 11.7%, and as third line or beyond in 4.8% of the patients. Drug-related AEs and serious AEs were reported in 66.3% and 13.9% of the patients, respectively (most common AE: gastrointestinal disorders; 39.7% of all patients). CONCLUSIONS: This study adds further real-world evidence of the persisting relevance of sunitinib for patients with a/mRCC who cannot receive or tolerate immune checkpoint inhibitors. The study population includes a high proportion of patients with unfavorable MSKCC poor-risk score, but shows still good PFS and OS results, while the drug demonstrates a favorable safety profile. The STAR-TOR registry is also registered in the database of US library of medicine (NCT00700258).

Evaluation of Gas 6 as a Prognostic Marker in Papillary Renal Cell Carcinoma.

INTRODUCTION: Growth arrest-specific protein 6 (Gas 6) is a ligand that plays a role in proliferation and migration of cells. For several tumor entities, high levels of Gas 6 are associated with poorer survival. We examined the prognostic role of Gas 6 in renal cell carcinoma (RCC), especially in papillary RCC (pRCC), which is still unclear. METHODS: The patients' sample collection is a joint collaboration of the PANZAR consortium. Patients' medical history and tumor specimens were collected from n = 240 and n = 128 patients with type 1 and 2 pRCC, respectively. Expression of Gas 6 was determined by immunohistochemistry. RESULTS: In total, Gas 6 staining was evaluable in 180 of 240 type 1 and 110 of 128 type 2 pRCC cases. Kaplan-Meier analysis disclosed no significant difference in 5-year overall survival for all pRCC nor either subtype. Also, Gas+ and Gas- groups did not significantly differ in any tumor or patient characteristics. CONCLUSION: Gas 6 was not found to be an independent prognostic marker in pRCC. Future studies are warranted to determine if Gas 6 plays a role as prognostic marker or therapeutic target in pRCC.

Impact of mpMRI targeted biopsy on intraoperative nerve-sparing (NeuroSAFE) during robot-assisted laparoscopic radical prostatectomy.

BACKGROUND: The aim of our study was to evaluate the impact of prostate biopsy technique (transrectal ultrasound (US)-prostate biopsy (PBx) versus multiparametric magnetic resonance imaging (mpMRI) targeted prostate biopsy (MRI-PBx) on intraoperative nerve-sparing and the rate of secondary neurovascular-bundle resection (SNR) in patients undergoing robot-assisted laparoscopic radical prostatectomy (RARP). A real-time investigation with a frozen-section examination (NeuroSAFE) microscopically excluded or confirmed prostate cancer invasion of the nerve structures resulting in preservation of the neurovascular bundle or SNR. Additionally, we analyzed risk factors related to SNR, such as longer operation time and postoperative complications. METHODS: The total study cohort was stratified according to non-nerve-sparing versus nerve-sparing RARP. Patients with nerve-sparing approach were then stratified according to biopsy technique (PBx vs. MRI-PBx). Further, we compared PBx versus MRI-PBx according to SNR rate. RESULTS: We included a total of 470 consecutive patients, who underwent RARP for PCa at our institution between January 2016 and December 2019. Patients with a preoperative MRI-PBx had a 2.12-fold higher chance of successful nerve-sparing (without SNR) compared to patients with PBx (p < 0.01). Patients with preoperative MRI-PBx required 73% less intraoperative SNR compared to patients with PBx (p < 0.0001). Prior MRI-PBx is thus a predictor for successful nerve-sparing RARP approach. CONCLUSION: Preoperative MRI-PBx led to better oncological outcomes and less SNR. Young patients with good erectile function could benefit from a preoperative MRI-PBx before nerve-sparing RARP.

The Prognostic Impact of PD-L2 in Papillary Renal-Cell Carcinoma.

INTRODUCTION: Programmed death-1 ligand (PD-L1) has been often studied in different types of renal-cell carcinoma (RCC). For example, in clear-cell renal carcinoma it is well established that programmed death-1 receptor and PD-L1 are important prognostic markers. In contrast, the role of programmed death-2 ligand (PD-L2) as prognostic marker remains unclear. The aim of this study was to evaluate if PD-L2 expression could play a role as a prognostic marker for papillary RCC (pRCC). METHODS: The patients' sample collection was a joint collaboration of the PANZAR consortium. Patients' medical history and tumor specimens were collected from n = 240 and n = 128 patients with type 1 and 2 pRCC, respectively. Expression of PD-L2 was determined by immunohistochemistry. In total, PD-L2 staining was evaluable in 185 of 240 type 1 and 99 of 128 type 2 pRCC cases. RESULTS: PD-L2 staining was positive in 67 (36.2%) of type 1 and in 31 (31.3%) of type 2 pRCC specimens. The prevalence of PD-L2+ cells was significantly higher in high-grade type 1 tumors (p = 0.019) and in type 2 patients with metastasis (p = 0.002). Kaplan-Meier analysis disclosed significant differences in 5-year overall survival (OS) for patients with PD-L2- compared to PD-L2+ in pRCC type 1 of 88.4% compared to 73.6% (p = 0.039) and type 2 of 78.8% compared to 39.1% % (p < 0.001). However, multivariate analysis did not identify the presence of PD-L2+ cells neither in type 1 nor type 2 pRCC as an independent predictor of poor OS. DISCUSSION/CONCLUSION: PD-L2 expression did not qualify as an independent prognostic marker in pRCC. Future studies will have to determine whether anti-PD-L2-targeted treatment may play a role in pRCC and expression can potentially serve as a predictive marker for these therapeutic approaches.

Single- vs multiple-layer wound closure for flank incisions: results of a prospective, randomised, double-blinded multicentre study.

OBJECTIVE: To compare the incidence of postoperative flank bulges between patients with multiple-layer closure and single superficial-layer closure after retroperitoneal surgery via open flank incision in the SIngle versus MUltiple-LAyer wound Closure for flank incision (SIMULAC) trial. PATIENTS AND METHODS: The study was a randomised controlled, patient- and assessor-blinded, multicentre trial. Between May 2015 and February 2017, 225 patients undergoing flank incisions were randomised 1:1 to a multiple-layer closure (SIMULAC-I) or a single superficial-layer closure (SIMULAC-II) group. The primary outcome was the occurrence of a flank bulge 6 months after surgery. RESULTS: Overall, 177 patients (90 in SIMULAC-I, 87 in SIMULAC-II) were eligible for final assessment. The cumulative incidence of a flank bulge was significantly higher in the SIMULAC-II group (51.7%) compared to the SIMULAC-I group [34.4%; odds ratio (OR) 2.04, 95% confidence interval (CI) 1.11-3.73; P = 0.02]. Rate of severe postoperative complications (4.4% SIMULAC-I vs 10.3% SIMULAC-II; P = 0.21) or hernia (6.7% SIMULAC-I vs 10.3% SIMULAC-II; P = 0.59) was similar between the groups. There was no difference in pain (visual analogue scale) and the requirement for pain medication at 6 months postoperatively. Quality of life assessed with the European Quality of Life 5 Dimensions Questionnaire was higher in the SIMULAC-I group compared to the SIMULAC-II group at 6 months postoperatively, with a (median range) score of 80 (30-100) vs 75 (5-100) (P = 0.012). CONCLUSION: The overall risk of a flank bulge after flank incision is high. Multiple-layer closure after flank incision should be performed as a standard procedure.

Toxicities of axitinib, sunitinib and temsirolimus: implications for progression-free and overall survival in metastatic renal cell cancer.

The aim of this study was to evaluate the association between axitinib, sunitinib and temsirolimus toxicities and patient survival in metastatic renal cell cancer patients. Overall survival (OS) and progression-free survival (PFS) of metastatic renal cell cancer patients from the prospective multicenter STAR-TOR study were assessed using multivariable Cox models. A total of 1195 patients were included (n = 149 axitinib; n = 546 sunitinib; n = 500 temsirolimus). The following toxicities significantly predicted outcomes: hand-foot skin reaction (hazard ratio [HR] = 0.29) for PFS with axitinib; stomatitis (HR = 0.62) and pneumonitis (HR = 0.23) for PFS with temsirolimus; stomatitis (HR = 0.52) and thrombocytopenia (HR = 0.6) for OS with temsirolimus; fatigue (HR = 0.71) for PFS with sunitinib; hand-foot skin reaction (HR = 0.56) and fatigue (HR = 0.58) for OS with sunitinib. In conclusion, in metastatic renal cell cancer, axitinib, sunitinib and temsirolimus demonstrate specific toxicities that are protective OS/PFS predictors.

Stereotactic Body Radiotherapy for Stage I Renal Cell Carcinoma: National Treatment Trends and Outcomes Compared to Partial Nephrectomy and Thermal Ablation.

PURPOSE: To assess use of stereotactic body radiotherapy (SBRT) for stage I renal cell carcinoma (RCC) and compare outcomes with thermal ablation and partial nephrectomy (PN). MATERIALS AND METHODS: The 2004-2015 National Cancer Database was investigated for histopathologically proven stage I RCC treated with PN, cryoablation, radiofrequency (RF) or microwave (MW) ablation, or SBRT. Patients were propensity score-matched to account for potential confounders, including patient age, sex, race, comorbidities, tumor size, histology, grade, tumor sequence, administration of systemic therapy, treatment in academic vs nonacademic centers, treatment location, and year of diagnosis. Overall survival (OS) was evaluated with Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models. RESULTS: A total of 91,965 patients were identified (SBRT, n = 174; PN, n = 82,913; cryoablation, n = 5,446; RF/MW ablation, n = 3,432). Stage I patients who received SBRT tended to be older women with few comorbidities treated at nonacademic centers in New England states. After propensity score matching, a cohort of 636 patients was obtained with well-balanced confounders between treatment groups. In the matched cohort, OS after SBRT was inferior to OS after PN and thermal ablation (PN vs SBRT, hazard ratio [HR] = 0.29, 95% confidence interval [CI] 0.19-0.46, P < .001; cryoablation vs SBRT, HR = 0.40, 95% CI 0.26-0.60, P < .001; RF/MW ablation vs SBRT, HR = 0.46, 95% CI 0.31-0.67, P < .001). Compared with PN, neither cryoablation nor RF/MW ablation showed significant difference in OS (cryoablation vs PN, HR = 1.35, 95% CI 0.80-2.28, P = .258; RF/MW ablation vs PN, HR = 0.64, 95% CI 0.95-2.55, P = .079). CONCLUSIONS: Current SBRT protocols show lower OS compared with thermal ablation and PN, whereas thermal ablation and PN demonstrate comparable outcomes.

Partial nephrectomy versus ablative techniques for small renal masses: a systematic review and network meta-analysis.

PURPOSE: To compare partial nephrectomy (PN), radiofrequency ablation (RFA), cryoablation (CRA) and microwave ablation (MWA) regarding oncologic, perioperative and functional outcomes. MATERIAL AND METHODS: The MEDLINE, EMBASE and COCHRANE libraries were searched for studies comparing PN, RFA, CRA or MWA and reporting on any-cause or cancer-specific mortality, local recurrence, complications or renal function. Network meta-analyses were performed. RESULTS: Forty-seven studies with 24,077 patients were included. Patients receiving RFA, CRA or MWA were older and had more comorbidities compared with PN. All-cause mortality was higher for CRA and RFA compared with PN (incidence rate ratio IRR = 2.58, IRR = 2.58, p < 0.001, respectively). No significant differences in cancer-specific mortality were evident. Local recurrence was higher for CRA, RFA and MWA compared with PN (IRR = 4.13, IRR = 1.79, IRR = 2.52, p < 0.05 respectively). A decline in renal function was less pronounced after RFA versus PN, CRA and MWA (mean difference in GFR MD = 6.49; MD = 5.82; MD = 10.89, p < 0.05 respectively). CONCLUSION: Higher overall survival and local control of PN compared with ablative therapies did not translate into significantly better cancer-specific mortality. Most studies carried a high risk of bias by selecting younger and healthier patients for PN, which may drive superior survival and local control. Physicians should be aware of the lack of high-quality evidence and the potential benefits of ablative techniques for certain patients, including a superior complication profile and renal function preservation. KEY POINTS: • Patients selected for ablation of small renal masses are older and have more comorbidities compared with those undergoing partial nephrectomy. • Partial nephrectomy yields lower all-cause mortality, which is probably biased by patient selection and does not translate into prolonged cancer-free survival. • The decline of renal function is smallest after radiofrequency ablation for small renal masses.

Functional MRI in patients with detrusor sphincter dyssynergia: Is the neural circuit affected?

AIMS: In recent years, the human brain-bladder control network has been visualized in different functional magnetic resonance imaging (fMRI) studies. The role of the brainstem and suprapontine regions has been elucidated. Especially the pontine region and the periaqueductal gray, as the central structures of the micturition circuit, were demonstrated. Detrusor sphincter dyssynergia (DSD) is a common problem in patients with neurological diseases. Residual urine and consecutive urinary tract infections with the risk of kidney damage remain a problem. In the present study, we used fMRI of the brain to compare the activation sites of patients with DSD with those of our previously published healthy controls with special emphasis on the brainstem region. METHODS: fMRI was performed in 11 patients with DSD who had an urge to void due to a filled bladder. In a nonvoiding model, they were instructed to contract or to relax the pelvic floor muscles repetitively. RESULTS: In patients with DSD, we could reproduce the activation sites found in healthy subjects, showing the regions in the brainstem as well as the other micturition-related areas. The activation of the pontine region was more rostral/dorsal compared with the healthy volunteers. CONCLUSION: Interestingly, we detected the well-known activation in the pontine region in the patients in the dorsal/rostral part compared with the more ventral activation in the healthy volunteers, suggesting that the L-region of the pontine micturition center is more prominent in cases of DSD.

Evaluation of the methoxy-X04 derivative BSC4090 for diagnosis of prodromal and early Alzheimer's disease from bioptic olfactory mucosa.

Alzheimer's disease (AD) pathology precedes the onset of clinical symptoms by several decades. Thus, biomarkers are required to identify prodromal disease stages to allow for the early and effective treatment. The methoxy-X04-derivative BSC4090 is a fluorescent ligand which was designed to target neurofibrillary tangles in AD. BSC4090 staining was previously detected in post-mortem brains and olfactory mucosa derived from AD patients. We tested BSC4090 as a potential diagnostic marker of prodromal and early AD using olfactory mucosa biopsies from 12 individuals with AD, 13 with mild cognitive impairment (MCI), and 10 cognitively normal (CN) controls. Receiver-operating curve analysis revealed areas under the curve of 0.78 for AD versus CN and of 0.86 for MCI due to AD versus MCI of other causes. BSC4090 labeling correlated significantly with cerebrospinal fluid levels of tau protein phosphorylated at T181. Using NMR spectroscopy, we find that BSC4090 binds to fibrillar and pre-fibrillar but not to monomeric tau. Thus, BSC4090 may be an interesting candidate to detect AD at the early disease stages.

Surgical approaches for treatment of ureteropelvic junction obstruction - a systematic review and network meta-analysis.

BACKGROUND: Multiple surgical treatment options are available for the treatment of ureteropelvic junction obstruction (UPJO). The aim of this study is to compare the most frequently used technics in a comprehensive network approach. METHODS: A systematic literature search of the EMBASE, MEDLINE and COCHRANE libraries was conducted in January 2018. Publications were included that evaluated at least two of the following surgical techniques: open pyeloplasty (OP), endopyelotomy (EP), laparoscopic (LP) and robot assisted pyeloplasty (RP). Main outcomes were operative success, complications, urinary leakage, re-operation, transfusion rate, operating time, and length of stay. Network meta-analyses with random effects models simultaneously assessed effectiveness of all surgical techniques. RESULTS: A total of 26 studies including 3143 patients were analyzed. Compared with RP, EP and LP showed lower operative success rates (EP: OR = 0.09, 95%CI:0.05-0.19; p < 0.001; LP: OR = 0.51, 95%CI:0.31-0.84; p = 0.008). Compared with OP, LP and RP had lower risk for complications (LP: OR = 0.62; 95%CI:0.41-0.95; p = 0.027; RP: OR = 0.41; 95%CI:0.22-0.79; p = 0.007). Compared with RP, no significant differences were detected for urinary leakage or re-operation, transfusion rates. Compared with EP, RP yielded longer operating time (mean = 102.87 min, 95%CI:41.79 min-163.95 min, p = < 0.001). Further significant differences in operating times were detected when comparing LP to EP (mean = 115.13 min, 95%CI:65.63 min-164.63 min, p = < 0.001) and OP to EP (mean = 91.96 min, 95%CI:32.33 min-151.58 min, p = 0.003). CONCLUSIONS: Multiple surgical techniques are available for treatment of UPJO. RP has the highest rates of operative success and as well as LP lower complication rates than OP. Although surgical outcomes are worse for EP, its operating time is shorter than OP, RP, and LP. Surgeons should consider these findings when selecting the optimal treatment method for individual patients.

Enhancing PSMA-uptake with androgen deprivation therapy - a new way to detect prostate cancer metastases?

PURPOSE: 68Ga-PSMA PET/CT imaging is a promising modality for the staging of recurrent prostate cancer (PCa). Current evidence suggests limited diagnostic value of the 68Ga-PSMA PET/CT in PSA-levels ≤0.3ng/mL. Experimental data have demonstrated na increase in PSMA-expression in PCa metastases by androgen deprivation in vitro. The aim of the current study was to investigate a possible enhancing effect of PSMA with low-dose androgen deprivation in patients with BCR and low PSA-levels. MATERIALS AND METHODS: Five patients with PCa and BCR, following radical prostatectomy, underwent 68Ga-PSMA PET/CT. A consecutive 68Ga-PSMA PET/CT was performed 6 to 11 days after injection of 80mg of Degarelix (Firmagon®). We recorded PSA and testosterone serum-levels and changes of PSMA-uptake in 68Ga-PSMA PET/CT images. RESULTS: Median PSA prior 68Ga-PSMA PET/CT was 0.27ng/mL. All patients had a decrease in testosterone serum levels from median 2.95µg/l to 0.16µg/l following Degarelix injection. We observed an increase in the standardized uptake value (SUV) in PSMA-positive lymphogenous and osseous lesions in two patients following androgen deprivation. In another two patients, no PSMA positive signals were detected in either the fi rst or the second scan. CONCLUSION: Our preliminary results of this feasibility assessment indicate a possible enhancing effect of PSMA-imaging induced by low-dose ADT. Despite several limitations and the small number of patients, this could be a new approach to improve staging by 68Ga-PSMA PET/CT in PCa patients with BCR after primary therapy. Further prospective studies with larger number of patients are needed to validate our findings.

[The Joy of Being a Surgeon - How to Generate Enthusiasm in Undergraduate Medical Education - A Local Example: The "Göttinger Aufschneidertag"]. / Freude an der Chirurgie ­ Einblicke gewähren, Begeisterung wecken.

Offering a full-day program including practical courses and the possibility of direct exchange between medical students and university teachers, the "Göttinger Aufschneidertag" was launched to generate enthusiasm for surgery. Workshops comprising four surgical disciplines enable participants to gain insight into the craft of surgery. The program aims to create interest in surgery among medical students at an early point of their studies and to make them enjoy their profession.

Gender Specific Differences in Disease-Free, Cancer Specific and Overall Survival after Radical Cystectomy for Bladder Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: We summarize the evidence on gender specific differences in disease-free, cancer specific and overall survival after radical cystectomy for bladder cancer. MATERIALS AND METHODS: We performed a systematic literature search of MEDLINE®, Embase® and the Cochrane Library in July 2017. Studies evaluating gender specific differences in disease-free, cancer specific or overall survival after radical cystectomy for bladder cancer were included in study. Analyses included random effect meta-analysis, subgroup analyses, meta-influence and cumulative meta-analyses. Funnel plots and the Egger test were used to assess publication bias. RESULTS: Of the 3,868 studies identified during the literature search 59 published between 1998 and 2017 were included in analysis. Of the studies 30 in a total of 38,321 patients evaluated disease-free survival, 44 in a total of 69,666 evaluated cancer specific survival and 26 in a total of 30,039 evaluated overall survival. Random effect meta-analyses revealed decreased disease-free, cancer specific survival and overall survival in female patients than in their male counterparts. Pooled estimates showed a HR of 1.16 (95% CI 1.06-1.27, p = 0.0018) for disease-free survival, 1.23 (95% CI 1.15-1.31, p <0.001) for cancer specific survival and 1.08 (95% CI 1.03-1.12, p = 0.0004) for overall survival. Subgroup analyses confirmed impaired disease-free, cancer specific and overall survival in female patients in all strata. Publication bias was evident only for studies of cancer specific survival (Egger test p = 0.0029). After adjusting for publication bias by the trim and fill method the corrected pooled estimated HR of cancer specific survival was 1.13 (95% CI 1.05-1.21, p = 0.0012). CONCLUSIONS: Female patients who underwent radical cystectomy for bladder cancer demonstrated worse disease-free, cancer specific and overall survival than their male counterparts. The multifactorial etiology might include epidemiological differences, gender specific health care discrepancies and hormonal influences.

Quality of life after low-dose rate-brachytherapy for prostate carcinoma - long-term results and literature review on QLQ-C30 and QLQ-PR25 results in published brachytherapy series.

BACKGROUND: Patient-reported health-related quality of life (HRQOL) differs between treatment options for prostate carcinoma. Long-term HRQOL data in brachytherapy series are scarce. Therefore, we analyzed prostate-specific and general HRQOL in patients treated with brachytherapy for prostate carcinoma after long-term follow-up. METHODS: Two hundred ninety-six patients with prostate carcinoma were treated with brachytherapy (01/1998-11/2003). General and prostate-specific HRQOL were measured using EORTC-QLQ-C30 and EORTC-QLQ-PR25, respectively. Patients were asked to complete the questionnaires after a median follow-up of 141 (119-181) months. QLQ-C30 results were compared to the German reference population. QLQ-PR25 results were compared to an earlier follow-up after a median of 51 months (no published QLQ-PR25 reference population for comparison). Additionally, a literature review on HRQOL data in brachytherapy series was performed. RESULTS: One hundred six (35.8%) patients were lost to follow-up, 70 (23.6%) had died. 120 (40.5%) patients were contacted. 80 questionnaires were returned (27% of the original cohort; 91% of alive patients were ≥70 years). Sexual activity declined over time (mean scores: 40.5 vs. 45.5; p = 0.006), hormonal treatment-related symptoms, problems associated with incontinence aids, and burden of obstructive urinary symptoms did not differ significantly compared to the 51-month follow-up. General HRQOL was numerically better in our cohort as compared to the German reference population (> 16% relative difference for both age strata; < 70 and ≥70 years). CONCLUSIONS: Our results indicate that symptom-burden after long-term follow-up and associated prostate-specific HRQOL remains relatively stable from 51 to 141 months. General HRQOL in surviving patients was numerically better compared to the reference population.

Prospective, Controlled Study of Invasiveness and Post-Aggression Metabolism in Patients Undergoing Robotic-Assisted Radical Prostatectomy.

OBJECTIVES: To evaluate in a prospective, controlled, nonrandomized study the surgical stress and acute-phase systemic response in robotic-assisted laparoscopic prostatectomy (RALP) compared to open radical retro-pubic prostatectomy (ORRP) by measuring humoral mediators. METHODS: Forty consecutive patients undergoing either RALP or ORRP were prospectively included to assess the extent of systemic response. Blood samples were collected before surgery (T1), at the time of prostatectomy (T2), at the time of wound closure (T3), and 12 h (T4), 24 h (T5), and 48 h (T6) after surgery, and assayed for interleukins (IL-6 and IL-10), C-reactive protein (CRP), and hemoglobin. A 2-sided p < 0.05 was considered to indicate significance. RESULTS: Baseline levels of IL-6, IL-10, and CRP were comparable in both arms of the study. IL-6 and IL-10 increased in both groups during surgery and reached maximum levels at 12 and 24 h after surgery. The RALP and RRP groups differed significantly at T2 (p = 0.009), T3 (p = 0.046), T5 (p = 0.05) and T6 (p = 0.0007) for IL-6, and at T3 (p = 0.05) and T4 (p = 0.05) for IL-10. CRP levels differed significantly at 48 h postoperative (p = 0.0053). The maximum levels of all 3 mediators in the RALP group were significantly lower than those in the open surgery group. Patients in the RALP group experienced less pain from day 2 to 4 according to the Visual Analog Scale (p < 0.05). CONCLUSIONS: The study suggests that IL-6 and IL-10 are useful objective markers for surgical stress and that tissue trauma and activation of post-aggression metabolism seem to be less in RALP compared to ORRP.

See the unseen: Mesorectal lymph node metastases in prostate cancer.

BACKGROUND: Our study is the first evaluation of nodal metastatic prostate cancer (PCa) to mesorectal lymph nodes (MLN) detected by (68) Ga-PSMA-PET/CT. METHODS: We retrospectively analyzed 76 consecutive PCa patients who underwent (68) Ga-PSMA-PET/CT: 61 PCa patients with biochemical recurrence (BCR) after curative treatment and 15 high-risk PCa before primary therapy. We assessed PET-positive MLN, which are indicative for PCa. RESULTS: We detected PET-positive lesions for PCa in (68) Ga-PSMA-PET/CT in 66 of 76 (87%) patients. Nodal disease was imaged in 47 of 66 (71%) patients. Indicative mesorectal nodal lesions for PCa were detected in 12 of 76 (15.8%) patients. The median number of PET-positive MLN was one per patient. Seven of twelve patients had recurrent PCa after radical prostatectomy with a median PSA value of 1.84 ng/ml (range 0.31-13). Five of twelve patients had untreated first diagnosed high-risk PCa with median PSA value of 90 ng/ml (range 4.6-93) at PET/CT, respectively. For all PET positive MLN a morphological correlate was found in CT (shortest diameter median 4 mm [range 4-21]; longest diameter median 7.5 mm [range 5-25]). After PET/CT, four patients with recurrent PCa received hormonal therapy, one patient was treated with directed radiation therapy of MLN, one patient received chemotherapy, and one patient was treated with pelvic lymph node dissection. Three high-risk PCa patients received hormonal therapy, and two patients were treated with adjuvant hormonal therapy after radical prostatectomy. CONCLUSIONS: Detection and exact location of nodal metastasis for PCa is crucial for the choice of treatment and the patient's prognosis. (68) Ga-PSMA-PET/CT seems to improve the detection of nodal metastasis in PCa, especially concerning mesorectal lymph nodes.

Biphasic 68Ga-PSMA-HBED-CC-PET/CT in patients with recurrent and high-risk prostate carcinoma.

PURPOSE: Binding of (68)Ga-PSMA-HBED-CC ((68)Ga-PSMA) at prostate cancer (PC) cells increases over time. A biphasic protocol may help separating benign from tumor lesions. The aim of this study was the retrospective evaluation of a diagnostic incremental value of a dual-time point (biphasic) (68)Ga-PSMA-PET/CT in patients with prostate cancer. METHODS: Retrospective analysis of 35 consecutive patients (49-78 years, median 71) with newly diagnosed PC (12/35) or recurrence of PC (23/35). PET/CT (Gemini TF16, Philips) was acquired 1 h and 3 h p. i. of 140-392 MBq (300 MBq median) (68)Ga-PSMA, followed by a diagnostic contrast CT. PET findings were correlated with histology or unequivocal CT findings. Semiquantitative PET data (SUVmax, SUV mean) were acquired and target-to-background-ratios (T/B-ratio) were calculated for benign and malign lesions for both time points. Size of lymph nodes (LN) on diagnostic CT was recorded. Statistical analysis was performed for assessment of significant changes of semiquantitative PET-parameters over time and for correlation of size and uptake of lymph nodes. RESULTS: One hundred and four lesions were evaluated. Sixty lesions were referenced by histology or unequivocal CT findings, including eight (13.3 %) histopathologically benign lymph nodes, 12 (20 %) histopathologically lymph node metastases, 12 (20 %) primary tumors, three (5 %) local recurrences, and 25 (41.7 %) bone metastases. Forty-four lesions were axillary LN with normal CT-appearance. Benign lesions had significantly lower SUVmax and T/B-ratios compared with malignant findings. Malign lesions showed a significant increase of both parameters over time compared to benign findings. There was no correlation between LN size and SUVmax. The sensitivity, specificity, the positive predictive value and negative predictive value of PET/CT regarding pelvic LN was 94 %, 99 %, 89 %, and 99.5 %, respectively. CONCLUSIONS: In contrast to benign tissues, the uptake of proven tumor lesions increases on (68)Ga-PSMA-PET/CT over time. A biphasic PET-study may lead to a better detection of tumor lesions in unequivocal findings.

Prediction of Locally Advanced Urothelial Carcinoma of the Bladder Using Clinical Parameters before Radical Cystectomy--A Prospective Multicenter Study.

INTRODUCTION: We aimed at developing and validating a pre-cystectomy nomogram for the prediction of locally advanced urothelial carcinoma of the bladder (UCB) using clinicopathological parameters. MATERIALS AND METHODS: Multicenter data from 337 patients who underwent radical cystectomy (RC) for UCB were prospectively collected and eligible for final analysis. Univariate and multivariate logistic regression models were applied to identify significant predictors of locally advanced tumor stage (pT3/4 and/or pN+) at RC. Internal validation was performed by bootstrapping. The decision curve analysis (DCA) was done to evaluate the clinical value. RESULTS: The distribution of tumor stages pT3/4, pN+ and pT3/4 and/or pN+ at RC was 44.2, 27.6 and 50.4%, respectively. Age (odds ratio (OR) 0.980; p < 0.001), advanced clinical tumor stage (cT3 vs. cTa, cTis, cT1; OR 3.367; p < 0.001), presence of hydronephrosis (OR 1.844; p = 0.043) and advanced tumor stage T3 and/or N+ at CT imaging (OR 4.378; p < 0.001) were independent predictors for pT3/4 and/or pN+ tumor stage. The predictive accuracy of our nomogram for pT3/4 and/or pN+ at RC was 77.5%. DCA for predicting pT3/4 and/or pN+ at RC showed a clinical net benefit across all probability thresholds. CONCLUSION: We developed a nomogram for the prediction of locally advanced tumor stage pT3/4 and/or pN+ before RC using established clinicopathological parameters.

Personalized Treatment Strategy in "Low-Risk Prostate Cancer Active Surveillance Candidates" Using Irreversible Electroporation: Prospective Evaluation of Feasibility, Morbidity, Functional and Oncological Outcomes.

PURPOSE: To evaluate the morbidity, functional and oncological outcome of irreversible electroporation (IRE) as a focal therapy for prostate cancer (PCa) when used in "active surveillance (AS)" candidates refusing standard treatment options. MATERIALS AND METHODS: IRE was performed under general anaesthesia, and the transurethral catheter was removed one day after intervention in all patients. Pre- and post-interventional voiding parameters (measured by International Prostate Symptom Score Questionnaire [IPSS], uroflowmetry and post-void residue) were compared. Follow-up (FU) was observed over a minimum of six months, including oncological outcome (controlled by multiparametric magnetic resonance imaging, rebiopsy, prostate-specific antigen dynamic as well as the need and type of secondary treatment) and general functional outcome (International Index of Erectile Function Questionnaire, satisfaction of the procedure). RESULTS: Twenty-four patients refusing AS or standard treatment with a median FU of 18.7 months were included. IPSS showed nine patients with mild, 12 with moderate and two with severe obstructive voiding symptoms pre-intervention (focal IRE). Median IPSS pre-IRE was 9 points, 8.5 (p=0.341) at six months and 10 (p=0.392) after 12 months, respectively. Pre-IRE maximum urinary flow (Qmax) (median: 16.1±8.0 mL/sec) and Qmax after catheter removal (16.2±7.6 mL/sec) did not differ significantly (p=0.904). Thirteen PCa recurrences occurred (54.2%). Out-of-lesion-PCa was found in 12/13 patients (92.3%), while 4/13 patients showed in-lesion-PCa recurrence simultaneously (30.8%). In one patient, there was an in-lesion-PCa recurrence only (7.7%). Six out of 24 patients (25.0%) received a secondary treatment. All patients were satisfied with the IRE procedure. CONCLUSIONS: Focal IRE underperforms regarding the overall oncological outcome and should not be offered as an equivalent therapy to established curative treatment strategies. Nevertheless, under a strict FU regimen, its lack of significant additional morbidity compared to an active surveillance strategy makes IRE a feasible alternative for low-risk PCa in highly selected patients as a personalised approach.