Real-world experience of water vapour therapy (Rezum) in patients with benign prostatic enlargement: a retrospective single-center study.

BACKGROUND: Water vapor thermal therapy (Rezum) is a minimally invasive treatment for benign prostatic enlargement (BPE). Studies reporting urodynamic results regarding the procedure are rare. Our study aimed to assess the effectiveness of Rezum on urinary outcome parameters in a consecutive series of patients and compare urodynamic data before and after treatment. METHODS: We retrospectively evaluated all the patients treated with Rezum between 07/2017 and 12/2023 at our institution. Patients who had more than one Rezum intervention, those who were unable to void (i.e., catheter-dependent patients), and those with insufficient data were excluded from the data analysis. Descriptive outcomes, such as symptom scores (IPSS, IPSS-QoL), peak flow in uroflowmetry (Qmax), post-micturition residual urine volume (PVR), and prostate volume (PVol), were analyzed. If available, preoperative and postoperative urodynamic results were evaluated. RESULTS: In total, 250 Rezum procedures were performed during the observational period. After applying the exclusion criteria, the data from 193 patients were included in the analysis. Patients achieved significant symptom relief as measured using the IPSS (46% reduction) and IPSS-QoL scores (41% reduction). Qmax improved by 4.8 ml/s, as the mean PVR significantly decreased by 50%. PVol and PSA values decreased by 30% and 27.5%, respectively. In 19/193 patients with a urodynamic evaluation, pre- and postoperative data analysis showed a significant reduction in the bladder outlet obstruction index (BOOI) by approximately 70%. CONCLUSIONS: Rezum is effective and can improve urinary symptoms. In appropriate patients, Rezum can significantly reduce the bladder outlet obstruction (BOO).

Rezum water vapor thermal therapy for treatment of lower urinary tract symptoms: A retrospective single-centre analysis from a German high-volume centre.

OBJECTIVE: Rezum is a minimal invasive surgical treatment for patients with lower urinary tract symptoms (LUTS) related to benign prostatic enlargement (BPE). The aim of our study was to assess safety and efficacy of the Rezum procedure in a consecutive series of patients. MATERIAL AND METHODS: A retrospective study was performed in a single tertiary care hospital in patients undergoing Rezum procedure between 2018 and 2020. All patients that underwent intervention because of drug-refractory moderate to severe LUTS were assessed. Descriptive outcomes such as symptoms scores (IPSS, IPSS-QoL), peak flow in uroflowmetry (Qmax), post-micturition residual urine volume (PVR) and prostate volume (PVol) were analysed. RESULTS: In total, 92 Rezum procedures were performed in the observational period. All interventions were competed without device- or procedure relates adverse events. Patients achieved a significant symptom relief as measured in IPSS (50% reduction, p<0.001, n = 35) and IPSS-QoL score (53% reduction, p<0.001, n = 35). Qmax improved by 7.3 ml/s from 10.6 ± 4.2 ml/s to 17.9 ± 9.3 ml/s (p = 0.003, n = 20) were as mean PVR significantly decreased by 136 ml from 175 ± 194.1 to 39 ± 62 ml (p = 0.007, n = 20). PVol significantly decreased by 40.3% from 73.9 ± 41.2 to 44.9 ± 29 ccm (p = 0.024, n = 17). All pre-interventional catheter-depending patients (28.3% of all patient) were catheter independent after six weeks. CONCLUSION: Rezum therapy is safe and effective and can be considered a viable treatment option for BPH related LUTS.

Perinephric Toxic Fat: Impact on Surgical Complexity, Perioperative Outcome, and Surgical Approach in Partial Nephrectomy.

INTRODUCTION: To assess influencing factors on perinephric toxic fat (high Mayo Adhesive Probability [MAP] score) and the impact of high MAP scores on surgical complexity, perioperative outcome, and surgical approach in patients with localized renal tumors undergoing open (OPN) and robot-assisted partial nephrectomy (RAPN). METHODS: 698 patients were included in this study. Based on preoperative imaging, adherent perinephric fat (APF) was assessed to define MAP scores. Regression analyses assessed influencing parameters for high MAP scores (≥3), predictors of surgical outcome, and influencing factors on surgical approach. RESULTS: OPN was performed in 331 (47%) patients, and 367 (53%) patients underwent RAPN. Male gender (p < 0.001), age ≥65 (p < 0.001), and BMI ≥27.4 kg/m2 (p < 0.001) showed to be significantly influencing factors for the presence of APF. High MAP scores showed to be an influencing factor for a prolonged surgery duration (OR = 1.68, 95% CI 1.22-2.31, p = 0.002) and a significant predictor to rather undergo OPN than RAPN (OR = 1.5, 95% CI 1.05-2.15, p = 0.027). CONCLUSION: Older, male patients with high BMI scores have a higher risk for APF. The presence of APF increases surgery time and may have an impact on decision making regarding the preferred surgical approach.

Combination of PI-RADS score and mRNA urine test-A novel scoring system for improved detection of prostate cancer.

Available tests to detect clinically significant prostate cancer frequently lead to overdiagnosis and overtreatment. Our study assessed the feasibility of combining a urinary biomarker-based risk score (SelectMDx®) and multiparametric MRI outcomes in order to identify patients with prostate cancer on prostate biopsy with increased accuracy and reliability. Samples of 74 men with suspicion of prostate cancer and available multiparametric MRI were analysed in a prospective cross-sectional study design. First-voided urine for determination of HOXC6 and DLX1 mRNA levels was collected after digital rectal examination and prior to MRI/ultrasound fusion-guided prostate biopsy. All multiparametric MRI images were centrally reviewed by two experienced radiologists blinded for urine test results and biopsy outcome. The PI-RADS v2 was used. SelectMDx® score, PI-RADS and Gleason Sore were obtained. Associations between Gleason Score, PI-RADS scores and SelectMDx® were assessed using ANOVA and t-test. Sensitivity and specificity were assessed and evaluated as area-under-the-curve of the receiver operating characteristic. Upon biopsy, 59.5% of patients were diagnosed with prostate cancer, whereby 40.6% had high-grade prostate cancer (GS ≥ 7a). SelectMDx® scores were significantly higher for patients with positive biopsy findings (49.07 ± 25.99% vs. 22.00 ± 26.43%; p < 0.001). SelectMDx® scores increased with higher PI-RADS scores. Combining SelectMDx®, history of prior biopsy with benign histology and PI-RADS scores into a novel scoring system led to significant prostate cancer detection rates with tiered detection rate of 39%, 58%, 81% and 100% for Gleason grade group II, III, IV, and V, respectively. The area-under-the-curve for our novel sum score in receiver operating characteristic analysis was 0.84. The synergistic combination of two non-invasive tests into a sum score with increased sensitivity may help avoiding unnecessary biopsies for initial prostate cancer diagnosis. For confirmation, further prospective studies with larger sample sizes and univariate and multivariate regression analyses and decision curve analyses are required.

Efficacy of PSMA PET-Guided Radiotherapy for Oligometastatic Castrate-Resistant Prostate Cancer.

PURPOSE: To assess the outcome of radiotherapy (RT) to all PSMA ligand positive metastases for patients with castrate-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: A total of 42 patients developed oligometastatic mCRPC and received PSMA PET-guided RT of all metastases. The main outcome parameters were biochemical progression-free survival (bPFS), and second-line systemic treatment free survival (SST-FS). RESULTS: A total of 141 PSMA ligand-positive metastases were irradiated. The median follow-up time was 39.0 months (12-58 months). During the follow-up five out of 42 (11.9%) patients died of progressive mPCa. Five out of 42 (11.9%) patients showed no biochemical responses and presented with a PSA level ≥10% of the baseline PSA at first PSA level measurement after RT and were classified as non-responders. The median PSA level before RT was 4.79 ng/mL (range, 0.4-46.1), which decreased significantly to a median PSA nadir level of 0.39 ng/mL (range, <0.07-32.8; p=0.002). The median PSA level at biochemical progression after PSMA ligand-based RT was 2.75 ng/mL (range, 0.27-53.0; p=0.24) and was not significantly different (p=0.29) from the median PSA level (4.79 ng/mL, range, 0.4-46.1) before the PSMA ligand-based RT. The median bPFS was 12.0 months after PSMA ligand PET-based RT (95% CI, 11.2-15.8) and the median SST-FS was 15.0 months (95% CI, 14.0-21.5). CONCLUSION: In well-informed and closely followed-up patients, PSMA PET-guided RT represents a viable treatment option for patients with oligometastatic mCRPC to delay further systemic therapies.

Bicentric Retrospective Analysis of en Bloc Resection and Muscularis Mucosae Detection Rate in Non-Muscle Invasive Bladder Tumors: A Real-World Scenario.

INTRODUCTION: For risk stratification of non-muscle invasive bladder cancer (NMIBC), the depth of stromal invasion can be further classified, where the lamina muscularis mucosae (MM) serves as a reference structure. While the overall identifiability of MM in standard transurethral specimens is low, en bloc resection may help in identification and overall orientation. The aims of this study were to report the detection rate of MM in en bloc resected bladder tumors (ERBT) and to provide real-world information on tissue stability and preservation of en bloc architecture during recovery and processing for histopathologic evaluation. METHODS: Thirty-four ERBT specimens were histologically re-evaluated with regard to MM detectability and structure as well as the presence of en bloc architecture and further histologic features. Associations with tumor size and energy source and within histologic parameters were assessed by standard Pearson's chi-squared analyses and Cramér's V effect size testing (V). RESULTS: The first parameter assessed was MM detection rate. In 19 out of 34 samples (56%) MM was detectable: scattered in 9 cases (26%), interrupted in 8 cases (24%) and continuous in 2 cases (6%). The second parameter assessed was preservation of en bloc architecture. In 11 out of 34 samples (32%), en bloc architecture could not be confirmed, and these samples served as a reference group for the detection of MM. Preservation of en bloc architecture was associated with an increased MM detection rate (MM in en bloc preserved 16/23, 70% vs. non-preserved 3/11, 27%; p = 0.020; V = 0.398) and with tumor size (p = 0.005; V = 0.595). Medium-sized tumors (1.1-2 cm) were best preserved. The choice of energy source did not show relevant association with en bloc architecture (p = n.s.). CONCLUSIONS: In line with recent publications, ERBT increases the MM detection rate considerably. However, a third of the ERBT specimens lost en bloc architecture during sample recovery and processing. Tumor size is a relevant factor, with optimal architecture preservation between 1 and 2 cm. Optimizing resection techniques, recovery, transport, and diagnostic processing of ERBT samples is warranted to verify the diagnostic value of MM-based substaging.

Checkpoint Inhibition for Metastatic Urothelial Carcinoma After Chemotherapy-Real-World Clinical Impressions and Comparative Review of the Literature.

Background: The introduction of checkpoint inhibitors is a long-awaited new option for a urothelial cancer with a poor prognosis. Apart from clinical studies, the data on real world experience is scarce. Methods: Patients for monotherapy with either Atezolizumab, Nivolumab or Pembrolizumab after chemotherapy were included. Adverse events and immune related adverse events as well as survival data and imaging analyses were recorded in a prospectively designed multi-center data base. Duration of response, progression free survival (PFS), and overall survival (OS) were estimated with the Kaplan-Meier method. Results: A total of 28 patients were included. The median follow-up was 8.0 (range, 0.7-41.7) months. Median PFS was 5.8 (95% CI, 2.3-NA) months. Median OS for all patients was 10.0 (95% CI, 8.0-NA) months. The overall response rate (ORR) was 21.4% (6 out of 28 patients). Adverse events were recorded in 20 (71.4%) of patients. Higher grade adverse events (≥Grade 3) were present in 11 (39.3%) patients. No therapy related deaths occurred during the observation period. A total of 13 (46.4%) patients had adverse events that were considered to be immune related. The most commonly affected organ was the thyroid gland with 21.4% of events. Conclusion: Our real-world clinical series confirms an objective response for about every fifth patient, promising OS and a low incidence for severe adverse events (≥Grade 3).

Efficacy of repeated PSMA PET-directed radiotherapy for oligorecurrent prostate cancer after initial curative therapy.

PURPOSE: To assess the outcome of prostate cancer (PCa) patients diagnosed with oligorecurrent disease and treated with a first and a second PSMA (prostate-specific membrane antigen ligand) PET(positron-emission tomography)-directed radiotherapy (RT). PATIENTS AND METHODS: Thirty-two patients with oligorecurrent relapse after curative therapy received a first PSMA PET-directed RT of all metastases. After biochemical progression, all patients received a second PSMA PET-directed RT of all metastases. The main outcome parameters were biochemical progression-free survival (bPFS) and androgen deprivation therapy-free survival (ADT-FS). The intervals of BPFS were analyzed separately as follows: the interval from the last day of PSMA PET-directed RT to the first biochemical progression was defined as bPFS_1 and the interval from second PSMA PET-directed RT to further biochemical progression was defined as bPFS_2. RESULTS: The median follow-up duration was 39.5 months (18-60). One out of 32 (3.1%) patients died after 47 months of progressive metastatic prostate cancer (mPCa). All patients showed biochemical responses after the first PSMA PET-directed RT and the median prostate-specific antigen (PSA) level before RT was 1.70 ng/mL (0.2-3.8), which decreased significantly to a median PSA nadir level of 0.39 ng/mL (range <0.07-3.8; p = 0.004). The median PSA level at biochemical progression after the first PSMA PET-directed RT was 2.9 ng/mL (range 0.12-12.80; p = 0.24). Furthermore, the PSA level after the second PSMA PET-directed RT at the last follow-up (0.52 ng/mL, range <0.07-154.0) was not significantly different (p = 0.36) from the median PSA level (1.70 ng/mL, range 0.2-3.8) before the first PSMA PET-directed RT. The median bPFS_1 was 16.0 months after the first PSMA PET-directed RT (95% CI 11.9-19.2) and the median bPFS_2 was significantly shorter at 8.0 months (95% CI 6.3-17.7) after the second PSMA PET-directed RT (p = 0.03; 95% CI 1.9-8.3). Multivariate analysis revealed no significant parameter for bPFS_1, whereas extrapelvic disease was the only significant parameter (p = 0.02, OR 2.3; 95% CI 0.81-4.19) in multivariate analysis for bPFS_2. The median ADT-FS was 31.0 months (95% CI 20.1-41.8) and multivariate analysis showed that patients with bone metastases, compared to patients with only lymph node metastases at first PSMA PET-directed RT, had a significantly higher chance (p = 0.007, OR 4.51; 95% CI 1.8-13.47) of needing ADT at the last follow-up visit. CONCLUSION: If patients are followed up closely, including PSMA PET scans, a second PSMA PET-directed RT represents a viable treatment option for well-informed and well-selected patients.

Influence of short-term dexamethasone on the efficacy of 177 Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer.

BACKGROUND AND AIM: Corticosteroids alone or in combination therapy are associated with favorable biochemical responses in metastatic castration-resistant prostate cancer (mCRPC). We speculated that the intermittent addition of dexamethasone may also enhance the antitumor effect of radioligand therapy (RLT) with 177 Lu-prostate-specific membrane antigen (PSMA)-617. PATIENTS AND METHODS: Seventy-one patients with mCRPC were treated with 1 to 5 cycles of 177 Lu-PSMA-617 (6.0-7.4 GBq per cycle) at 6 to 8 weeks intervals. Based on the clinical decision (eg, in the case of vertebral metastases), 56% of patients received 4 mg of dexamethasone for the first 5 days of each cycle. Biochemical response rates, PSA decline and progression-free survival (PFS) were analyzed after one, three, and five cycles of RLT. RESULTS: PSA response rates were not significantly different between patients receiving 177 Lu-PSMA-617 plus dexamethasone and those receiving 177 Lu-PSMA-617 alone after one, three, and five cycles (33% vs 39%, P = .62; 45% vs 45%, P = 1.0; and 38% vs 42%, P = .81). However, there was a nonsignificant trend for a more pronounced PSA decline in patients with bone metastases receiving adjunct dexamethasone (-21% ± 50% vs +11% ± 90%, P = .08; -21% ± 69% vs +22% ± 116%, P = .07; -13% ± 76% vs +32% ± 119%, P = .07). Median PFS tended to be longer in patients with bone metastases receiving 177 Lu-PSMA-617 plus dexamethasone (146 vs 81 days; hazard ratio: 0.87 [95% confidence interval: 0.47-1.61]; P = .20). Multiple regression analysis showed that age (P = .0110), alkaline phosphatase levels (P = .0380) and adjunct dexamethasone (P = .0285) were independent predictors of changes in PSA in patients with bone metastases. CONCLUSIONS: We observed high response rates to 177 Lu-PSMA-617 RLT in men with mCRPC. The short-term addition of dexamethasone to 177 Lu-PSMA-617 had no striking antitumor effect but might enhance biochemical responses in patients with bone metastases. Future trials are warranted to test this hypothesis in a prospective setting.

Neuroendocrine Differentiation and Response to PSMA-Targeted Radioligand Therapy in Advanced Metastatic Castration-Resistant Prostate Cancer: A Single-Center Retrospective Study.

Neuroendocrine differentiation is associated with treatment failure and poor outcome in metastatic castration-resistant prostate cancer. We investigated the effect of circulating neuroendocrine biomarkers on the efficacy of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT). Methods: Neuroendocrine biomarker profiles (progastrin-releasing peptide, neuron-specific enolase, and chromogranin-A) were analyzed in 50 patients commencing 177Lu-PSMA-617 RLT. The primary endpoint was a prostate-specific antigen response in relation to baseline neuroendocrine marker profiles. An additional endpoint was progression-free survival. Tumor uptake on posttherapeutic scans, a known predictive marker for response, was used as a control variable. Results: Neuroendocrine biomarker profiles were abnormal in most patients. Neuroendocrine biomarker levels did not predict treatment failure or early progression (P ≥ 0.13). By contrast, intense PSMA-ligand uptake in metastases predicted both treatment response (P = 0.0030) and reduced risk of early progression (P = 0.0111). Conclusion: Neuroendocrine marker profiles do not predict an adverse outcome from RLT. By contrast, high ligand uptake was confirmed to be crucial for achieving a tumor response.

Impact of double J stenting or nephrostomy placement during transurethral resection of bladder tumour on the incidence of metachronous upper urinary tract urothelial cancer.

BACKGROUND: Whether or not double J (DJ) stenting during transurethral resection of a bladder tumour (TURBT) harms patients with regard to possible metachronous upper urinary tract urothelial cancer (UUTUC) development remains controversial. This study evaluated the impact of DJ compared to nephrostomy placement during TURBT for bladder cancer (BCa) on the incidence of metachronous UUTUCs. METHODS: We retrospectively analysed 637 patients who underwent TURBT in our department between 2008 and 2016. BCa, UUTUC and urinary drainage data (retrograde/anterograde DJ and percutaneous nephrostomy) were assessed, along with the prevalence of hydronephrosis, and mortality. Chi-square and Fisher's exact test was performed for univariate analyses. Survival analysis was performed by the Kaplan-Meier method and log-rank tests. RESULTS: UUTUC was noted in 28 out of 637 patients (4.4%), whereas only eight (1.3%) developed it metachronously to BCa. Out of these, four patients received DJ stents, while four patients received no urinary drainage of the upper urinary tract. Placement of urinary drainage significantly correlated with UUTUC (50.0% vs. 17.9%; p = 0.041). DJ stenting significantly correlated with UUTUC (50.0% vs. 11%; p <  0.01), while no patient with a nephrostomy tube developed UUTUC. UUTUC-free survival rates were significantly lower for patients with DJ stents than for all other patients (p = 0.001). Patients with or without DJ stents had similar overall survival (OS) rates (p = 0.73), whereas patients with nephrostomy tubes had significantly lower OS rates than all other patients (p <  0.001). CONCLUSIONS: Patients with DJ stenting during TURBT for BCa might have an increased risk of developing metachronous UUTUC. This study indicated advantages in placing nephrostomy tubes rather than DJ stents; however, confirmation requires investigation of a larger cohort. Even so, the increased mortality rate in the nephrostomy group reflected hydronephrosis as an unfavourable prognostic factor.

Comparison of 68 Ga-PSMA ligand PET/CT versus conventional cross-sectional imaging for target volume delineation for metastasis-directed radiotherapy for metachronous lymph node metastases from prostate cancer.

PURPOSE: To assess the differences in the target volume (TV) delineation of metachronous lymph node metastases between 68 Ga-PSMA ligand PET/CT and conventional imaging in a comparative retrospective contouring study. PATIENTS AND METHODS: Twenty-five patients with biochemical prostate cancer recurrence after primary prostatectomy underwent 68 Ga-PSMA ligand PET/CT in addition to conventional imaging techniques such as CT and/or MR imaging for restaging. All patients were diagnosed with at least one lymph node metastasis. TVs were manually delineated in two different ways: (a) based on conventional imaging (CT/MRI) and (b) based on conventional imaging (CT/MRI) plus 68 Ga-PSMA ligand PET/CT. The size of TVs, overlap rates, and subjective assessment of the difficulty of TV delineation reported by the radiation oncologist (easy/moderate/difficult) were compared. RESULTS: With the additional information from PSMA ligand PET, 47 lymph node metastases were identified and included in the gross tumor volume (GTV). The median clinical target volume (CTV) of non-PET-based TV delineation was statistically larger than the CTV based on PET imaging (134.8 ml [range 6.9-565.2] versus 44.9 ml [range 4.9-481.3; p = 0.001]). The CTV based on CT/MRI enclosed only 81.3% (39/48) of PET-positive lymph nodes. The CT/MRI-based CTV did not enclose all PET-positive lymph nodes in 24% (6/25) of patients. In 12% (3/25) of patients, all PET-positive lymph nodes were outside of the CT/MRI-based CTV. The median overlap rates (TVPET/TVCT/MRIâ€¯× 100) were 45.7% (range 0-96.9) for the GTV and 71.7% (range 9.8-98.2) for the CTV. The assessment of difficulty of contouring revealed that contouring with the additional imaging information of the PET was categorized as easy/moderate in 92% (23/25) and as difficult in 8% (2/25) of the cases, whereas contouring based on CT/MRI without PET was categorized as difficult in 56% (14/25) and as easy/moderate in 44% of the cases (11/25; p = 0.003). CONCLUSION: 68 Ga-PSMA ligand PET/CT is superior to conventional cross-sectional imaging for the delineation of lymph node metastases from prostate cancer. PET-based TV delineation allows for smaller target volumes and should be considered the standard for irradiation of metachronous lymph node metastases in recurrent prostate cancer. Conventional imaging is not sufficiently sensitive for radio-oncological treatment concepts in oligometastatic prostate cancer.

Patterns of Progression After 68Ga-PSMA-Ligand PET/CT-Guided Radiation Therapy for Recurrent Prostate Cancer.

PURPOSE: To determine the patterns of progression after 68Ga prostate-specific membrane antigen (PSMA)-ligand positron emission tomography (PET)/computed tomography (CT)-guided radiation therapy (RT) for recurrent oligometastatic prostate cancer (PCa). METHODS AND MATERIALS: One hundred and eight patients with increased prostate-specific antigen levels, who received 68Ga-PSMA-ligand PET/CT-guided RT for recurrent oligometastatic disease after primary therapy for PCa were included. The biochemical progression-free survival and distant disease-free survival after PSMA-ligand PET/CT-guided RT were determined. The patterns of progression were determined using renewed 68Ga-PSMA-ligand PET/CT in patients with biochemical progression and compared with the clinical target volume of the 68Ga-PSMA-ligand PET/CT-guided RT. The frequency of infield and outfield relapses was recorded. RESULTS: A total of 97.2% (105 of 108) of patients showed a decrease in prostate-specific antigen levels after RT and were classified as biochemical responders. After the median follow-up of 18 months, 43.5% (47 of 108) of the patients experienced biochemical progression, resulting in an estimated biochemical progression-free survival of 16 months. Renewed 68Ga-PSMA-ligand PET/CT allowed localization of recurrent disease in 91.7% (33 of 36) of patients. Analysis of the patterns of progression resulted in a cumulative infield relapse rate of 12.1% (4 of 33) and a cumulative outfield relapse rate of 87.9% (29 of 33). The resultant median disease-free survival was 11 months. In terms of the pattern of progression, we observed a shift in the pattern of metastases toward skeletal involvement and distant lymph node metastases. Of these patients, 45.5% (15 of 33) were treated with further RT to delay initiation or escalation of systemic therapies. CONCLUSION: PSMA-ligand PET/CT-guided RT for relapsed PCa with limited tumor burden allowed individualization of treatment approaches, provided effective local control, and resulted in considerably prolonged biochemical progression-free survival. As indicated by the PSMA-ligand PET/CT-based patterns of progression, repeated PET/CT-guided RT may represent a treatment option in well-selected patients with relapse after RT for oligometastatic disease.

DNA methylation of neural EGFL like 1 (NELL1) is associated with advanced disease and the metastatic state of renal cell cancer patients.

Recent studies have shown that NELL1 expression is silenced epigenetically in human renal cell cancer (RCC) tissues and in RCC cell lines. However, it remains unknown whether NELL1 promoter methylation observed in clinical specimens might be associated with the clinicopathology or survival of patients with RCC. We analyzed NELL1 DNA methylation in tissues from patients with RCC and in adjacent normal renal tissues. In addition, we evaluated NELL1 methylation in cell lines derived from different urogenital tumors (prostate cancer, urothelial cancer and RCC). We performed regression analyses to determine whether NELL1 methylation is associated with clinicopathological parameters and recurrence­free survival (RFS). This cross­sectional study included 98 patients with RCC and 63 paired tumor and adjacent normal tissue samples. We analyzed a locus in the intron 1 region of NELL1 with pyrosequencing. We performed in silico analysis of NELL1 methylation in the TCGA Kidney Renal Clear Cell Carcinoma (KIRC) data set (n=284 patients), which served as a validation study. Statistical analyses were performed with the two­sided paired t­test for paired tumor and adjacent normal samples. We used logistic regression for subgroup comparisons and Cox regression for RFS comparisons. The mean methylation level was 6.8% higher in RCC tissues compared to paired adjacent normal tissues (paired t­test, P<0.001). Methylation levels in RCC were associated with advanced disease (P=0.002), the presence of distant metastases (P=0.004), and shorter RFS (P=0.035, HR: 4.15). In silico validation with TCGA KIRC data for adjacent loci also demonstrated that high relative methylation levels were associated with adverse clinicopathology and shortened RFS. Our results suggest that NELL1 methylation contributes to RCC disease progression. This finding could provide a clinical marker to complement recent functional analyses in tumor models.

Is there an anti-androgen withdrawal syndrome for enzalutamide?

BACKGROUND: The anti-androgen withdrawal syndrome (AAWS) can be seen in one-third of patients after discontinuation of first-generation non-steroidal anti-androgen therapy. With the introduction of new agents for anti-androgen therapy as well as alternate mechanisms of action, new therapeutic options before and after docetaxel chemotherapy have arisen (Ohlmann et al. in World J Urol 30(4):495-503, 2012). The question regarding the occurrence of an enzalutamide withdrawal syndrome (EWS) has not been evaluated yet. In this study, we assess prostate-specific antigen (PSA) response after discontinuation of enzalutamide. METHODS: In total 31 patients with metastatic castration-resistant prostate cancer (mCRPC) underwent an enzalutamide withdrawal and were evaluated. Data were gathered from 6 centres in Germany. Patients with continuous oral administration of enzalutamide with rising serum PSA levels were evaluated, starting from enzalutamide withdrawal until subsequent therapy was initiated, follow-up ended or death of the patient occurred. Statistical evaluation was performed applying one-sided binomial testing using R-statistical software, version 3.0.1. RESULTS: Mean withdrawal follow-up was 6.5 weeks (range 1-26.1 weeks). None of the 31 patients showed a PSA decline. Mean relative PSA rise over all patients was 73.9 % (range 0.5-440.7 %) with a median of 44.9 %. CONCLUSIONS: If existent, an AAWS is at least very rare for enzalutamide in patients with mCRPC after taxane-based chemotherapy and does not play a clinical role in this setting. This may be attributed to the different pharmacodynamics of enzalutamide. Longer duration of therapy or a longer withdrawal interval may reveal a rare EWS in the future.