Biochemical Response of <0.1 ng/ml Predicts Therapy-free Survival of Prostate Cancer Patients following Prostate-specific Membrane Antigen-targeted Salvage Surgery.

BACKGROUND: In a subset of patients with oligorecurrent prostate cancer (PCa), salvage surgery with prostate-specific membrane antigen (PSMA) radioguided surgery (PSMA-RGS) seems to be of value. OBJECTIVE: To evaluate whether a lower level of postoperative prostate-specific antigen (PSA; <0.1 ng/ml) is predictive of therapy-free survival (TFS) following salvage PSMA-RGS. DESIGN, SETTING, AND PARTICIPANTS: This cohort study evaluated patients with biochemical recurrence after radical prostatectomy and oligorecurrent PCa on PSMA positron emission tomography treated with PSMA-RGS in three tertiary care centers (2014-2022). INTERVENTION: PSMA-RGS. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Postsalvage surgery PSA response was categorized as <0.1, 0.1-<0.2, or >0.2 ng/ml. Kaplan-Meier and multivariable Cox regression models evaluated TFS according to PSA response. RESULTS AND LIMITATIONS: Among 553 patients assessed, 522 (94%) had metastatic soft tissue lesions removed during PSMA-RGS. At 2-16 wk after PSMA-RGS, 192, 62, and 190 patients achieved PSA levels of <0.1, 0.1-<0.2, and >0.2 ng/ml, respectively. At 2 yr of follow-up, TFS rate was 81.1% versus 56.1% versus 43.1% (p < 0.001) for patients with PSA <0.1 versus 0.1-<0.2 versus >0.2 ng/ml. In multivariable analyses, PSA levels of 0.1-0.2 ng/ml (hazard ratio [HR]: 1.9, confidence interval [CI]: 1.1-3.1) and ≥0.2 ng/ml (HR: 3.2, CI: 2.2-4.6, p < 0.001) independently predicted the need for additional therapy after PSMA-RGS. The main limitation is the lack of a control group. CONCLUSIONS: For patients after salvage PSMA-RGS, a lower biochemical response (PSA <0.1 ng/ml) seems to predict longer TFS. This insight may help in counseling patients postoperatively as well as guiding the timely selection of additional therapy. PATIENT SUMMARY: We studied what happened to prostate cancer patients in three European centers who had salvage surgery using a special method called prostate-specific membrane antigen-targeted radioguidance. We found that patients who had low prostate-specific antigen levels soon after surgery were less likely to need further treatment for a longer time.

Impact of COVID-19 on the time to counseling and treatment of prostate cancer.

PURPOSE: This study investigates how the COVID-19 pandemic (CP) impacted the timeline between initial diagnosis (ID) of prostate carcinoma and subsequent therapy consultation (TC) or radical prostatectomy (RP) due to the implementation of a "minimal contact concept," which postponed clinical examinations until the day of admission. METHODS: We analyzed patient data from a tertiary care center from 2018 to September 2021. The focus was on comparing the time intervals from ID to TC and from ID to RP before and during the CP. RESULTS: Of 12,255 patients, 6,073 (61.6%) were treated before and 3,791 (38.4%) during the CP. The median time from ID to TC reduced from 37 days (IQR: 21 - 58d) pre-CP to 32 days (IQR: 20 - 50d) during CP (p < 0.001). Similarly, the time from ID to RP decreased from 98 days (IQR: 70 - 141d) to 75 days (IQR: 55 - 108d; p < 0.001) during the CP. There was a significant decrease in low-risk tumor cases at ID (18.9% vs. 21.4%; p = 0.003) and post-RP (4% vs. 6.7%; p < 0.001) during the CP. CONCLUSION: Our findings suggest that the COVID-19 pandemic facilitated more timely treatment of prostate cancer, suggesting potential benefits for both low-risk and aggressive tumor management through expedited clinical procedures.

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

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

Prevention of thromboembolic events after radical prostatectomy in patients with hereditary thrombophilia due to a factor V Leiden mutation by multidisciplinary coagulation management.

Objective: To examine the perioperative impact of factor V Leiden mutation on thromboembolic events' risk in radical prostatectomy (RP) patients. With an incidence of about 5%, factor V Leiden mutation is the most common hereditary hypercoagulability among Caucasians and rarer in Asia. The increased risk of thromboembolic events is three- to seven-fold in heterozygous and to 80-fold in homozygous patients. Methods: Within our prospectively collected database, we analysed 33 006 prostate cancer patients treated with RP between December 2001 and December 2020. Of those, patients with factor V Leiden mutation were identified. All patients received individualised recommendation of haemostaseologists for perioperative anticoagulation. Thromboembolic complications (deep vein thrombosis and pulmonary embolism) were assessed during hospital stay, as well as according to patient reported outcomes within the first 3 months after RP. Results: Overall, 85 (0.3%) patients with known factor V Leiden mutation were identified. Median age was 65 (interquartile range: 61-68) years. There was at least one thrombosis in 53 (62.4%) patients and 31 (36.5%) patients had at least one embolic event in their medical history before RP. Within all 85 patients with factor V Leiden mutation, we experienced no thromboembolic complications within the first 3 months after surgery. Conclusion: In our cohort of patients with factor V Leiden mutation, no thromboembolic events were observed after RP with an individualised perioperative coagulation management concept. This may reassure patients with this hereditary condition who are counselled for RP.

[Urinary incontinence after radical prostatectomy for prostate cancer-data from 17,149 patients from 125 certified centers]. / Harninkontinenz nach radikaler Prostatektomie beim Prostatakarzinom ­ aktuelle Daten von 17.149 Patienten aus 125 zertifizierten Zentren.

BACKGROUND: In addition to erectile dysfunction, urinary incontinence is the most common functional limitation after radical prostatectomy (RPE) for prostate cancer (PCa). The German S3 guideline recommends informing patients about possible effects of the therapy options, including incontinence. However, only little data on continence from routine care in German-speaking countries after RPE are currently available, which makes it difficult to inform patients. OBJECTIVE: The aim of this work is to present data on the frequency and severity of urinary incontinence after RPE from routine care. MATERIALS AND METHODS: Information from the PCO (Prostate Cancer Outcomes) study is used, which was collected between 2016 and 2022 in 125 German Cancer Society (DKG)-certified prostate cancer centers in 17,149 patients using the Expanded Prostate Cancer Index Composite Short Form (EPIC-26). Changes in the "incontinence" score before (T0) and 12 months after RPE (T1) and the proportion of patients who used pads, stratified by age and risk group, are reported. RESULTS: The average score for urinary incontinence (value range: 0-worst possible to 100-best possible) was 93 points at T0 and 73 points 12 months later. At T0, 97% of the patients did not use a pad, compared to 56% at T1. 43% of the patients who did not use a pad before surgery used at least one pad a day 12 months later, while 13% use two or more. The proportion of patients using pads differs by age and risk classification. CONCLUSION: The results provide a comprehensive insight into functional outcome 12 months after RPE and can be taken into account when informing patients.

EAU Biochemical Recurrence Risk Classification and PSA Kinetics Have No Value for Patient Selection in PSMA-Radioguided Surgery (PSMA-RGS) for Oligorecurrent Prostate Cancer.

OBJECTIVE: To assess the influence of biochemical recurrence (BCR) risk groups and PSA kinetics on the outcomes of radioguided surgery against prostate-specific membrane antigen (PSMA-RGS). Currently, neither BCR risk group nor PSA doubling time (PSA-DT), or PSA velocity (PSA-V) are actively assigned or relevant for counseling prior to PSMA-RGS. METHODS: We retrospectively analyzed PSMA-RGS cases for oligorecurrent prostate cancer between 2014 and 2023. BCR risk groups, PSA-DT, and PSA-V were analyzed as predictors for complete biochemical response (cBR, PSA < 0.2 ng/mL), BCR-free, and therapy-free survival (BCRFS, TFS). RESULTS: Of 374 included patients, only 21/374 (6%) and 201/374 (54%) were classified as low- and high-risk BCR (no group assignment possible in 152/374, 41%). A total of 13/21 (62%) patients with low- and 120/201 (60%) with high-risk BCR achieved cBR (p = 1.0). BCR classification was no predictor for BCRFS (HR:1.61, CI: 0.70-3.71, p = 0.3) or subsequent TFS (HR:1.07, CI: 0.46-2.47, p = 0.9). A total of 47/76 (62%) patients with PSA-DT ≤ 6 mo and 50/84 (60%) with PSA-DT > 6 mo achieved cBR (p = 0.4). PSA-DT was not associated with cBR (OR: 0.99, CI: 0.95-1.03, p = 0.5), BCRFS (HR: 1.00, CI: 0.97-1.03, p = 0.9), or TFS (HR: 1.02, CI: 0.99-1.04, p = 0.2). Consistent negative findings were recorded for PSA-V. CONCLUSIONS: The BCR risk groups and PSA kinetics do not predict the oncological success of PSMA-RGS performed at low absolute PSA values. Indolent low-risk BCR is rarely treated by PSMA-RGS.

Outcome of patients with epithelialized cavity formation after excessive vesicourethral anastomotic leak post radical prostatectomy.

PURPOSE: Excessive vesicourethral anastomotic leak (EVAL) is a rare but severe complication after radical prostatectomy (RP). Epithelialized vesicourethral cavity formation (EVCF) usually develops during prolonged catheterization. To our knowledge, there is no description of postoperative outcomes, complications, or functional assessment of these patients who received conservative therapy after EVAL. METHODS: We identified 70 patients (0.56%) with radiographic evidence of EVCF out of 12,434 patients who received RP in 2016-2020 at our tertiary care center. Postoperative radiographic cystograms (CG) were retrospectively re-examined by two urologists individually. We assessed urinary continence (UC), the need for intervention due to anastomotic stricture formation, urinary tract infection (UTI), and symphysitis during the first year of follow-up post-RP. RESULTS: The median age was 66 years [interquartile range (IQR) 61-70 years], the median body mass index was 27.8 kg/m2 (IQR 25.5-30.3 kg/m2), and the median prostate specific antigen before RP was 7.1 ng/ml (IQR 4.7-11.8 ng/ml). The median catheter insertion time was 44.5 days (IQR 35.2-54 days). One-year continence follow-up was available for 27 patients (38.6%), of which 22 (81.5%) reported the use of ≤ one pad, two patients reported the use of two (7.4%) pads/24 h, and three (11.1%) patients reported use > two pads/24 h. Overall, four (5.7%) patients needed surgical reintervention for anastomotic stricture, eight (11.5%) patients presented with symphysitis, and 55 (77.1%) presented with UTI. CONCLUSION: UC in 81.5% 1-year post-RP suggests that conservative treatment in EVAL is a treatment option with an acceptable outcome on UC and should be considered before reintervention for anastomotic insufficiency.

Advances, Limitations and Future Challenges in the Management of Immunotherapy for Hematological Diseases and Solid Tumors.

Our immune system is able to attack cancer cells by recognizing cellular mistakes and destroying them [...].

Feasibility, acceptability, and behavioral outcomes of a multimodal intervention for prostate cancer patients: Experience from the MARTINI lifestyle program.

BACKGROUND: Prostate cancer (PCa) is the most frequently diagnosed malignant tumor in men. The potential benefit of a healthy lifestyle contrasts sharply with the observed poor adherence to current international lifestyle guidelines. Thus, well-designed sustainable interventions of aftercare that can be translated into routine practice are highly recommended. The present pilot study aimed to evaluate the feasibility and acceptability of a multimodal lifestyle intervention program in PCa patients after radical prostatectomy (RP). METHODS: In a single-arm study, carried out at the Martini-Klinik of the University Medical Center Hamburg-Eppendorf, Germany, 59 eligible men with locally advanced PCa were recruited within 3-6 months after RP and assigned to a multimodal lifestyle program. The program consisted of 10 weekly 6-7 h course days, with a focus on dietary control, physical activity (per World Cancer Research Fund recommendations) and psychological support. Primary objectives were feasibility, acceptability, completion rate, and safety. In addition, changes in lifestyle, psychological well-being, clinical and laboratory values were assessed. The study was registered in the German Clinical Trials Register (No. DRK S00015288 [MARTINI-Lifestyle-cohort] [www.germanctr.de]). RESULTS: A high program acceptance was observed. Only three participants (5%) dropped out of the program prematurely. Personal feedback reflected appreciation for participation, personal gain through new knowledge and through the group experience. Without exception, all participants have taken part in follow-up examinations and no adverse events or incidents occurred. In addition, changes in lifestyle habits, clinical parameters and improved quality of life were detected. CONCLUSION: The MARTINI lifestyle program appears feasible and safe, and acceptance of the multimodal intervention was high among PCa patients. These encouraging results favor conducting a large multicenter trial to implement the program into routine practice and to evaluate the effectiveness of the intervention on survival and quality of life.

A Neural Network Model Combining [-2]proPSA, freePSA, Total PSA, Cathepsin D, and Thrombospondin-1 Showed Increased Accuracy in the Identification of Clinically Significant Prostate Cancer.

BACKGROUND: The Prostate Health Index (PHI) and Proclarix (PCLX) have been proposed as blood-based tests for prostate cancer (PCa). In this study, we evaluated the feasibility of an artificial neural network (ANN)-based approach to develop a combinatorial model including PHI and PCLX biomarkers to recognize clinically significant PCa (csPCa) at initial diagnosis. METHODS: To this aim, we prospectively enrolled 344 men from two different centres. All patients underwent radical prostatectomy (RP). All men had a prostate-specific antigen (PSA) between 2 and 10 ng/mL. We used an artificial neural network to develop models that can identify csPCa efficiently. As inputs, the model uses [-2]proPSA, freePSA, total PSA, cathepsin D, thrombospondin, and age. RESULTS: The output of the model is an estimate of the presence of a low or high Gleason score PCa defined at RP. After training on a dataset of up to 220 samples and optimization of the variables, the model achieved values as high as 78% for sensitivity and 62% for specificity for all-cancer detection compared with those of PHI and PCLX alone. For csPCa detection, the model showed 66% (95% CI 66-68%) for sensitivity and 68% (95% CI 66-68%) for specificity. These values were significantly different compared with those of PHI (p < 0.0001 and 0.0001, respectively) and PCLX (p = 0.0003 and 0.0006, respectively) alone. CONCLUSIONS: Our preliminary study suggests that combining PHI and PCLX biomarkers may help to estimate, with higher accuracy, the presence of csPCa at initial diagnosis, allowing a personalized treatment approach. Further studies training the model on larger datasets are strongly encouraged to support the efficiency of this approach.

Cohort Study of Oligorecurrent Prostate Cancer Patients: Oncological Outcomes of Patients Treated with Salvage Lymph Node Dissection via Prostate-specific Membrane Antigen-radioguided Surgery.

BACKGROUND: In a subset of patients with recurrent oligometastatic prostate cancer (PCa) salvage surgery with prostate-specific membrane antigen (PSMA)-targeted radioguidance (PSMA-RGS) might be of value. OBJECTIVE: To evaluate the oncological outcomes of salvage PSMA-RGS and determine the predictive preoperative factors of improved outcomes. DESIGN, SETTING, AND PARTICIPANTS: A cohort study of oligorecurrent PCa patients with biochemical recurrence (BCR) after radical prostatectomy and imaging with PSMA positron emission tomography (PET), treated with PSMA-RGS in two tertiary care centers (2014-2020), was conducted. INTERVENTION: PSMA-RGS. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier and multivariable Cox regression models were used to assess BCR-free (BFS) and therapy-free (TFS) survival. Postoperative complications were classified according to Clavien-Dindo. RESULTS AND LIMITATIONS: Overall, 364 patients without concomitant treatment were assessed. At PSMA-RGS, metastatic soft-tissue PCa lesions were removed in 343 (94%) patients. At 2-16 wk after PSMA-RGS, 165 patients reached a prostate-specific antigen (PSA) level of <0.2 ng/ml. Within 3 mo, 24 (6.6%) patients suffered from Clavien-Dindo complications grade III-IV. At 2 yr, BFS and TFS rates were 32% and 58%, respectively. In multivariable analyses, higher preoperative PSA (hazard ratio [HR]: 1.07, 95% confidence interval [CI]: 1.02-1.12), higher number of PSMA-avid lesions (HR: 1.23, CI: 1.08-1.40), multiple (pelvic plus retroperitoneal) localizations (HR: 1.90, CI: 1.23-2.95), and retroperitoneal localization (HR: 2.04, CI: 1.31-3.18) of lesions in preoperative imaging were independent predictors of BCR after PSMA-RGS. The main limitation is the lack of a control group. CONCLUSIONS: As salvage surgery in oligorecurrent PCa currently constitutes an experimental treatment approach, careful patient selection is mandatory based on life expectancy, low PSA values, and low number of PSMA PET-avid lesions located in the pelvis. PATIENT SUMMARY: We looked at the outcomes from prostate cancer patients with recurrent disease after radical prostatectomy. We found that surgery may be an opportunity to prolong treatment-free survival, but patient selection criteria need to be very narrow.

Low Blood Levels of LRG1 Before Radical Prostatectomy Identify Patients with High Risk of Progression to Castration-resistant Prostate Cancer.

Background: After radical prostatectomy (RP), depending on stage, up to 40% of patients with prostate cancer (PCa) will experience biochemical failure (BF). Despite salvage therapy, approximately one-third of these patients will need permanent hormone therapy (pHT) and are at risk of progression to castration-resistant PCa (CRPC). Prognostic markers herald the need for neoadjuvant, adjuvant, or multimodal treatment. Objective: To evaluate the added value of blood LRG1 in predicting treatment failure in patients who have undergone radical prostatectomy (RP). Design setting and participants: We quantified LRG1 in serum or plasma sampled before radical prostatectomy from patients from the Martini-Klinik (Martini; n = 423), the Danish CuPCa cohort (CuPCa; n = 182), and Oslo University Hospital (OUH; n = 145). Outcome measurements and statistical analysis: The endpoints were BF, pHT, and CRPC. The association between LRG1 and survival outcomes was evaluated using Kaplan-Meier estimation and Cox proportional-hazards modeling. The added predictive value of LRG1 in nested models was estimated using the concordance index, time-dependent area under the receiver operating characteristic curve, and decision curve analysis. Results and limitations: In multivariable Cox models using preoperative characteristics, LRG1 was associated with an estimated lower risk of BF in the Martini cohort (adjusted hazard ratio [aHR] 0.68, 95% confidence interval [CI] 0.52-0.90) and in the CuPCa cohort (aHR 0.47, 95% CI 0.30-0.73). Using preoperative prognostic variables, our data showed that doubling of LRG1 was also associated with a lower risk of pHT receipt in the CuPCa cohort (aHR 0.43, 95% CI 0.20-0.93) and of CRPC development in the OUH cohort (aHR 0.32, 95% CI 0.15-0.69). Similar aHR values were observed using either preoperative or postoperative variables for all endpoints. Conclusions: PCa patients with high blood LRG1 are at lower risk of BF, pHT receipt, and progression to CRPC. Since LRG1 adds value to established prognostic models, new prognostic factor combinations including LRG1 should be considered in future studies. Patient summary: We measured concentrations of the blood-based protein LRG1 before surgery for prostate cancer. Patients with high LRG1 levels had better disease-free survival, suggesting that LRG1 can help in predicting prognosis.

New strategy for the identification of prostate cancer: The combination of Proclarix and the prostate health index.

OBJECTIVES: Prostate health index (PHI) and, more recently, Proclarix have been proposed as serum biomarkers for prostate cancer (PCa). In this study, we aimed to evaluate Proclarix and PHI for predicting clinically significant prostate cancer (csPCa). PATIENTS AND METHODS: Proclarix and PHI were measured using samples of 344 men from two different centers. All patients underwent prostate biopsy, and among those, 188 men with PCa on biopsy had an additional radical prostatectomy (RP). All men had a prostate-specific antigen (PSA) between 2 and 10 ng/ml. Evaluation of area under the curve (AUC) and performance at predefined cut-offs of Proclarix and PHI risk scores as well as the linear combination thereof was performed to predict csPCa. PSA density was used as an independent comparator. RESULTS: The cohort median age and PSA were 65 (interquartile range [IQR]: 60-71) and 5.6 (IQR: 4.3-7.2) ng/ml, respectively. CsPCa was diagnosed in 161 (47%) men based on the RP specimen. ROC analysis showed that Proclarix and PHI accurately predicted csPCa with no significant difference (AUC of 0.79 and 0.76, p = 0.378) but significantly better when compared to PSA density (AUC of 0.66, p < 0.001). When using specific cut-offs, Proclarix (cut-off 10) revealed higher specificity and positive predictive value than PHI (cut-off 27) at similar sensitivities. The combination of Proclarix and PHI provided a significant increase in the AUC (p ≤ 0.007) compared to the individual tests alone and the highest clinical benefit was achieved. CONCLUSION: Results of this study show that both Proclarix and PHI accurately detect the presence of csPCa. The model combining Proclarix and PHI revealed the synergistic effect and improved the diagnostic performance of the individual tests.

Management of Patients Receiving Direct Oral Anticoagulants Scheduled for Radical Prostatectomy: An Update of a Prospective Assessment.

BACKGROUND: In the perioperative setting, temporary interruption of direct oral anticoagulants (DOACs) is mandatory. However, the safety of these recommendations is largely based on nonurological surgical experiences. OBJECTIVE: To verify the safety of these recommendations in patients undergoing radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: A total of 5317 patients underwent RP in our tertiary care centre between December 2017 and February 2020. Of them, 107 consecutive patients had DOACs in standard preoperative medication. DOAC intake was stopped 2-3 d before RP. Postoperatively, patients received weight- and risk-adapted low-molecular-weight heparin (LMWH). DOAC intake was restarted, and administration of LMWH was stopped the 3rd day after surgery. For comparison, we performed 1:2 propensity-score matching (DOAC:non-DOAC), which resulted in 321 consecutive patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Perioperative outcomes and 30-d morbidity were compared between both cohorts. The Wilcoxon rank sum test and the Pearson's chi-square test were used. RESULTS AND LIMITATIONS: The median age of patients with DOACs was 68 yr. Sixty-six patients (61.7%) stopped DOAC intake 48 h and 41 patients (38.3%) 72 h before RP. In comparison with the matching cohort, the median blood loss during RP, median duration of surgery, and median duration of hospitalisation did not differ in a statistically significant fashion. Similarly, there was no significant difference in 30-d morbidity between groups. Importantly, the rate of bleeding and thromboembolic complications did likewise not differ significantly, though it is a nonrandomised and retrospective study. CONCLUSIONS: Standardised perioperative management of DOACs is important to minimise bleeding and thromboembolic complications. RP can be performed with a low perioperative complication risk if patients are adherent to our presented algorithm. PATIENT SUMMARY: We looked at peri- and postoperative complications and compared direct oral anticoagulant (DOAC) and non-DOAC patients. We found no significant difference in thromboembolic and bleeding complications between the groups. We conclude that our regime is safe.

CHD1 loss negatively influences metastasis-free survival in R0-resected prostate cancer patients and promotes spontaneous metastasis in vivo.

The outcome of prostate cancer (PCa) patients is highly variable and depends on whether or not distant metastases occur. Multiple chromosomal deletions have been linked to early tumor marker PSA recurrence (biochemical relapse, BCR) after radical prostatectomy (RP), but their potential role for distant metastasis formation is largely unknown. Here, we specifically analyzed whether deletion of the tumor suppressor CHD1 (5q21) influences the post-surgical risk of distant metastasis and whether CHD1 loss directly contributes to metastasis formation in vivo. By considering >6800 patients we found that the CHD1 deletion negatively influences metastasis-free survival in R0 patients (HR: 2.32; 95% CI: 1.61, 3.33; p < 0.001) independent of preoperative PSA, pT stage, pN status, Gleason Score, and BCR. Moreover, CHD1 deletion predicts shortened BCR-free survival in pT2 patients and cancer-specific survival in all patients. In vivo, CHD1 loss increases spontaneous pulmonary metastasis formation in two distinct PCa models coupled with a higher number of multicellular colonies as compared to single-cell metastases. Transcriptome analyses revealed down-regulation of the PCa-specific metastasis suppressor and TGFß signaling regulator PMEPA1 after CHD1 depletion in both tested PCa models. CHD1 loss increases the risk of postoperative metastasis in R0-resected PCa patients and promotes spontaneous metastasis formation in vivo.

A novel serum biomarker quintet reveals added prognostic value when combined with standard clinical parameters in prostate cancer patients by predicting biochemical recurrence and adverse pathology.

The objective was to determine the prognostic utility of a new biomarker combination in prostate cancer (PCa) patients undergoing Radical Prostatectomy (RP). Serum samples and clinical data of 557 men who underwent RP for PCa with pathological stage (pT) <3 at Martini Clinic (Hamburg, Germany) were used for analysis. Clinical Grade Group and clinical stage was determined using biopsy samples while tumor marker concentrations were measured in serum using immunoassays. The prognostic utility of the proposed marker combination was assessed using Cox proportional hazard regression and Kaplan-Meier analysis. The performance was compared to the Cancer of the Prostate Risk Assessment (CAPRA) score in the overall cohort and in a low-risk patient subset. A multivariable model comprising fibronectin 1, galectin-3-binding protein, lumican, matrix metalloprotease 9, thrombospondin-1 and PSA together with clinical Grade Group (GG) and clinical stage (cT) was created. The proposed model was a significant predictor of biochemical recurrence (BCR) (HR 1.29 per 5 units score, 95%CI 1.20-1.38, p<0.001). The Kaplan-Meier analysis showed that the proposed model had a better prediction for low-risk disease after RP compared to CAPRA (respectively 5.0% vs. 9.1% chance of BCR). In a pre-defined low risk population subset, the risk of BCR using the proposed model was below 5.2% and thus lower when compared to CAPRA = 0-2 (9%), GG<2 (7%) and NCCN = low-risk (6%) subsets. Additionally, the proposed model could significantly (p<0.001) discriminate patients with adverse pathology (AP) events at RP from those without. In conclusion, the proposed model is superior to CAPRA for the prediction of BCR after RP in the overall cohort as well as a in a pre-defined low risk patient population subset. It is also significantly associated with AP at RP.

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

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

Evaluation of Risk Factors for Adverse Functional Outcomes after Radical Prostatectomy in Patients with Previous Transurethral Surgery of the Prostate.

INTRODUCTION: A history of transurethral surgery of the prostate is generally considered as a risk factor of adverse functional outcomes after radical prostatectomy (RP). We tested whether the risk of postoperative urinary incontinence (UIC) and erectile dysfunction (ED) after RP could be further substantiated in such patients. MATERIALS AND METHODS: We tested the effect of the following variables on UIC and ED rates 1 year after RP: residual prostate volume after transurethral desobstruction, the time from transurethral desobstruction to RP, the type of transurethral desobstruction (TURP vs. laser enucleation), age, and nerve-sparing surgery (yes vs. no). UIC was defined as usage of any pad except a safety pad. ED was defined as no sexual intercourse possible. RESULTS: Overall, 216 patients treated with RP between 2010 and 2019 in a tertiary care center were evaluated. All patients had previously undergone transurethral desobstruction. Regarding UIC analyses, only time from transurethral desobstruction to RP significantly influenced UIC rates (p = 0.003). Regarding ED rates, none of the tested variables reached statistical significance. CONCLUSION: The risk of UIC and ED after RP is substantial in men who had previously undergone transurethral desobstruction. The time from transurethral desobstruction to RP significantly impacts on the postoperative UIC rates. This observation should be further explored in future studies.

Circulating Vitamin D and Selenium Levels and Outcome in Prostate Cancer Patients: Lessons from the MARTINI-Lifestyle Cohort.

BACKGROUND: Dietary agents, in particular vitamin D (Vit D) and selenium, are widely used by prostate cancer (PCa) patients to improve cancer outcomes. OBJECTIVE: To investigate whether plasma Vit D and selenium levels prior to radical prostatectomy (RP) are associated with worse pathologic tumor characteristics and increased risk of disease recurrence. DESIGN, SETTING, AND PARTICIPANTS: A total of 3849 men with PCa scheduled for RP in the Martini-Klinik at the University Hospital Hamburg-Eppendorf, Hamburg, Germany, between January 2014 and December 2018 were included in this study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Age, and clinical and laboratory values were collected prior to RP. Biochemical recurrence (BCR) was defined as prostate-specific antigen (PSA) ≥0.2 µg/l and rising after RP. Kaplan-Meier plots depicted BCR-free survival. Cox regression models (adjusted for age, preoperative PSA, pT stage, pN stage, pGG, surgical margin status, and year of surgery) tested the relationship between oncologic outcomes and Vit D and selenium levels. RESULTS AND LIMITATIONS: Median plasma Vit D and selenium levels were 19.3 and 71 µg/l, respectively. Circulating Vit D and selenium levels correlated inversely with PSA values. Histologic grade, pT stage, and pN stage were not associated with Vit D and selenium levels at the time of RP. In the overall cohort, BCR-free survival at 3 yr of follow-up was 82.9%. When stratified according to median Vit D levels, BCR-free survival at 3 yr of follow-up was 82.7% and 83.0% (p ≤ 0.59). Upon stratification according to median selenium levels, BCR-free survival was 82.2% and 83.7% (p = 0.19). In a multivariable Cox regression model predicting BCR, lower Vit D and selenium levels were not independent predictors of BCR. CONCLUSIONS: Plasma Vit D and selenium levels prior to RP were not associated with BCR-free survival. PATIENT SUMMARY: The results of the MARTINI-Lifestyle cohort could not show a correlation between the occurrence of biochemical recurrence of prostate cancer after radical prostatectomy and the serum levels of vitamin D and selenium. A recommendation should therefore be made to compensate for a potential deficiency and not with the expectation of a reduction in the risk of progression.

EGFR as a stable marker of prostate cancer dissemination to bones.

BACKGROUND: Prostate cancer (PCa) is among the most commonly diagnosed malignancies in men. Although 5-year survival in patients with localised disease reaches nearly 100%, metastatic disease still remains incurable. Therefore, there is a need for markers indicating metastatic dissemination. METHODS: EGFR overexpression (EGFRover) was tracked in 1039 primary tumours, circulating tumour cells from 39 d'Amico high-risk patients and metastatic samples from 21 castration-resistant PCa cases. EGFR status was compared to clinical parameters and multiple molecular factors were assessed using immunohistochemistry and gene ontology analysis. The functional aspect of EGFR was evaluated by plating PC-3 cells on soft and rigid matrices. RESULTS: EGFRover was found in 14% of primary tumours, where it was associated with shorter metastasis-free survival and was an independent indicator of worse overall survival. EGFRover correlated with a pro-migratory and pro-metastatic phenotype of tumour cells as well as rich collagen fibre content. All circulating tumour cells (detected in 13% of cases) were positive for EGFR, independent of their EMT-related phenotype. EGFRover was more prevalent in castration-resistant bone metastases (29% of patients) and supported growth of human PCa cells on rigid matrices mimicking bone stiffness. CONCLUSIONS: EGFRover is a stable, EMT-independent marker of PCa disseminating to rigid organs, preferentially bones.