Multicentre, prospective study on local treatment of metastatic prostate cancer (LoMP study).

OBJECTIVES: To investigate the role of cytoreductive radical prostatectomy in addition to standard of care for patients with newly diagnosed metastatic prostate cancer. MATERIALS AND METHODS: This multicentre, prospective study included asymptomatic patients from 2014 to 2018 (NCT02138721). Cytoreductive radical prostatectomy was offered to all fit patients with resectable tumours, resulting in 40 patients. Standard of care was administered to 40 patients who were ineligible or unwilling to undergo surgery. The primary endpoint was castration resistant cancer-free survival at the time point of ≥50% events. The secondary endpoint was local event-free survival. Kaplan-Meier and Cox regression analyses with propensity-score analysis were applied. RESULTS: After a median (quartiles) follow-up of 35 (24-47) months, 42 patients became castration-resistant or died. The median castration resistant cancer-free survival was 53 (95% confidence interval [CI] 14-92) vs 21 (95% CI 15-27) months for cytoreductive radical prostatectomy compared to standard of care (P = 0.017). The 3-year estimates for local event-free survival were 83% (95% CI 71-95) vs 59% (95% CI 51-67) for cytoreductive radical prostatectomy compared to standard of care (P = 0.012). However, treatment group showed no significance in the multivariable models for castration resistant cancer-free survival (P = 0.5) or local event-free survival (P = 0.3), adjusted for propensity-score analysis. Complications were similar to the non-metastatic setting. Patients undergoing surgery were younger, with lower baseline prostate-specific antigen levels, alkaline phosphatase levels and metastatic burden. CONCLUSION: The present LoMP study was unable to show a difference between the two inclusion groups regarding castration resistant cancer-free survival for asymptomatic patients with newly diagnosed metastatic prostate cancer. These results validate previous evidence that, in well-selected and informed patients, cytoreductive radical prostatectomy is feasible and safe, with corresponding continence rates compared to the non-metastatic, high-risk setting. Whether cytoreductive radical prostatectomy could be a valuable option to achieve good local palliation needs to be further researched. Overall, the role of cytoreductive radical prostatectomy needs to be further explored in randomized studies to correct for potential bias.

Importance of metastatic volume in prognostic models to predict survival in newly diagnosed metastatic prostate cancer.

PURPOSE: To explore the prognostic importance of metastatic volume in a contemporary daily practice cohort of patients with newly diagnosed metastatic hormone-naive prostate cancer (mHNPC) and to develop a pragmatic prognostic model to predict survival for these patients. METHODS: Since 2014, 113 patients with newly diagnosed mHNPC were prospectively registered. Statistical analysis was performed using SPSS 25.0™ with two-sided p value < 0.05 indicating statistical significance. Univariate and multivariate cox regression analyses were performed to identify prognostic risk factors. Kaplan-Meier method with log-rank statistics was constructed to analyze difference in survival in the prognostic groups. Model performance was assessed using the Concordance-index (C-index) and cross-validated in R v3.4.1. High-volume mHNPC (HVD) was defined as the presence of visceral metastasis or ≥ 4 bone metastases with ≥ 1 appendicular lesion. RESULTS: Multivariate analysis identified HVD (p = 0.047) and elevated alkaline phosphatase (ALP) (p = 0.018) as independent prognostic risk factors for overall survival (OS). Consequently, three prognostic groups were created: a good (no risk factors), intermediate (1 risk factor) and poor prognosis group (2 risk factors). Median OS for the good, intermediate and poor prognosis group was not reached, 73 and 20 months (95% CI 9-31 months with p < 0.001 and Correspondence-index of 0.78), respectively. CONCLUSIONS: We developed a pragmatic and qualitative prognostic model consisting of three prognostic risk groups for OS in a daily practice cohort of patients with newly diagnosed mHNPC. Independent prognostic risk factors included in the model were HVD and abnormal ALP.

Discovery and validation of a serum microRNA signature to characterize oligo- and polymetastatic prostate cancer: not ready for prime time.

PURPOSE: Patients with oligometastatic prostate cancer (PC) may benefit from metastasis-directed therapy (MDT), delaying disease progression and the start of palliative systemic treatment. However, a significant proportion of oligometastatic PC patients progress to polymetastatic PC within a year following MDT, suggesting an underestimation of the metastatic load by current staging modalities. Molecular markers could help to identify true oligometastatic patients eligible for MDT. METHODS: Patients with asymptomatic biochemical recurrence following primary PC treatment were classified as oligo- or polymetastatic based on 18F-choline PET/CT imaging. Oligometastatic patients had up to three metastases at baseline and did not progress to more than three lesions following MDT or surveillance within 1 year of diagnosis of metastases. Polymetastatic patients had > 3 metastases at baseline or developed > 3 metastases within 1 year following imaging. A model aiming to prospectively distinguish oligo- and polymetastatic PC patients was trained using clinicopathological parameters and serum-derived microRNA expression profiles from a discovery cohort of 20 oligometastatic and 20 polymetastatic PC patients. To confirm the models predictive performance, it was applied on biomarker data obtained from an independent validation cohort of 44 patients with oligometastatic and 39 patients with polymetastatic disease. RESULTS: Oligometastatic PC patients had a more favorable prognosis compared to polymetastatic ones, as defined by a significantly longer median CRPC-free survival (not reached versus 38 months; 95% confidence interval 31-45 months with P < 0.001). Despite the good performance of a predictive model trained on the discovery cohort, with an AUC of 0.833 (0.693-0.973; 95% CI) and a sensitivity of 0.894 (0.714-1.000; 95% CI) for oligometastatic disease, none of the miRNA targets were found to be differentially expressed between oligo- and polymetastatic PC patients in the signature validation cohort. The multivariate model had an AUC of 0.393 (0.534 after cross-validation) and therefore, no predictive ability. CONCLUSIONS: Although PC patients with oligometastatic disease had a more favorable prognosis, no serum-derived biomarkers allowing for prospective discrimination of oligo- and polymetastatic prostate cancer patients could be identified.

Fractional Carbon Dioxide Laser of Recent Surgical Scars in the Head and Neck Region: A Split-Scar, Evaluator-Blinded Study.

BACKGROUND: Postoperative scarring is a common cause of patient dissatisfaction. Several strategies have been developed to improve its clinical aspects. OBJECTIVE: To assess efficacy and safety of the 10,600 nm ablative fractional carbon dioxide (CO2) laser in the treatment of recent surgical scars in the head and neck region. METHODS AND MATERIALS: A prospective, randomized, single-blind intrapatient controlled study was conducted on 9 postoperative scars in the head and neck region. On half of the scar, 3 treatment sessions were performed. Physician/Patient Global Assessment (PhGA/PGA) and Patient and Observer Scar Assessment Scales (POSAS) were used to evaluate treatment efficacy. Safety was evaluated by registration of pain and adverse events. RESULTS: No statistically significant differences were noted in terms of PhGA or POSAS (observer). Patient Global Assessment (p = 0.058) and POSAS (patient) (p = 0.091) showed a trend toward better improvement of the treated half. Itch score (p = 0.046) and global end evaluation (patient) (p = 0.026) demonstrated a statistically significant difference in favor of the treated part. Adverse events were minor, and no long-term side effects were noted. CONCLUSION: The use of CO2 fractional laser is safe and is associated with high patient satisfaction. However, objective measurements could not confirm its efficacy in the treatment of recent surgical scars.

The Role of Cytoreductive Radical Prostatectomy in the Treatment of Newly Diagnosed Low-volume Metastatic Prostate Cancer. Results from the Local Treatment of Metastatic Prostate Cancer (LoMP) Registry.

BACKGROUND: Radiotherapy to the prostate (RTp) prolongs survival for patients with low-volume, newly diagnosed metastatic prostate cancer (ndmPC). OBJECTIVE: to evaluate whether cytoreductive radical prostatectomy (cRP) is equally beneficial as RTp in low-volume ndmPC. DESIGN SETTING AND PARTICIPANTS: A multicenter prospective registry was established in 2014 to observe patients with ndmPC. Eligible patients were offered cRP or RTp. For this study we selected only patients with low-volume ndmPC (n = 109). Of these, 48, 26, and 35 patients underwent cRP, RTp, and no local therapy (NLT), respectively. Median follow-up was 32 mo (interquartile range 16-49). INTERVENTION: cRP was compared with RTp and NLT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS), cancer-specific survival (CSS), and local event-free survival (LEFS) were calculated using the Kaplan-Meier method. Factors prognostic for OS were identified using univariate and multivariate Cox regression analysis. RESULTS AND LIMITATIONS: The 2-yr OS was 93%, 100%, and 69%, and 2-yr CSS was 93%, 100%, and 75% for cRP, RTp, and NLT, respectively. The cRP and RTp groups had better OS compared to NLT and there was no significant difference between cRP and RTp. The 2-yr LEFS was 92%, 77%, and 60% for cRP, RTp, and NLT, respectively. The cRP group had better LEFS compared to RTp and NLT, and there was no significant difference between RTp and NLT. Advanced tumor stage, Eastern Cooperative Oncology Group performance status ≥2, and NLT were negative prognostic factors for OS. The main limitation is selection of fitter patients with less advanced tumors for cRP and the small sample size. CONCLUSIONS: For selected patients with low-volume ndmPC, cRP is able to achieve similar OS and CSS to RTp. cRP is effective in preventing local events due to disease progression. PATIENT SUMMARY: Patients with a low volume of newly diagnosed prostate cancer that has spread beyond the prostate gland might benefit from removal of the prostate, which we found was as effective as radiotherapy to the prostate in prolonging survival. Removal of the prostate is effective in preventing urinary problems caused by cancer progression.

Robot-assisted nephroureterectomy for upper tract urothelial carcinoma: results from three high-volume robotic surgery institutions.

Robot-Assisted NephroUreterectomy (RANU) represents a minimally invasive alternative to open NephroUreterectomy (NU) for management of Upper Tract Urothelial Carcinoma (UTUC) but its oncologic safety is still controversial. The objective of this study was to investigate the peri-operative, pathologic and oncologic outcomes of RANU for UTUC. From 2008 to 2017, 78 patients diagnosed with UTUC and elected for RANU at 3 high-volume robotic surgery centres were retrospectively assessed. Surgery was performed using da Vinci Si® and Xi® systems. RANU was done adhering to oncological principles as in open surgery. The outcomes of the study were: (1) peri-operative morbidity, namely intra- and post-operative complications, blood loss, length of hospital stay and operative time; (2) oncologic outcomes, namely overall survival (OS) and recurrence-free survival (RFS). Peri-operative overall complication rate was 24.4% and high-grade complication rate was 2.6%. Median blood loss, length of hospital stay and operative time were 124 ml, 4 days and 167 min. Lymphadenectomy was performed in 31 (41%) patients. Lymph-node involvement was present in 9 (29%) patients. At median follow-up of 15 months, 2- and 4-year OS were 79% and 66%, respectively, and RFS was 63% and 53%. Peritoneal dissemination was recorded in 1 (1.3%) patient with pT4N2R1 UTUC. Our study is limited by the relatively small cohort of patients and its retrospective character. RANU as minimally invasive treatment for patients with UTUC is safe and feasible. Post-operative morbidity is low and major complications are rare. Oncologic outcomes are acceptable and no evidence of increased risk of peritoneal dissemination is recorded. Long-term data are needed. RANU should be regarded as an alternative to open surgery for UTUC that can offer good peri-operative and oncologic results.

Primary versus Redo Urethroplasty: Results from a Single-Center Comparative Analysis.

OBJECTIVES: To explore the differences between primary and redo urethroplasty and to directly compare according stricture-free survival (SFS). Materials and Methods. Data of all male patients who underwent urethroplasty at Ghent University Hospital were collected between 2000 and 2018. Exclusion criteria for this analysis were age <18 years and follow-up <1 year. Two patient groups were created for further comparison: the primary urethroplasty (PU) group (no previous urethroplasty) and redo urethroplasty (RU) group (≥1 previous urethroplasty), irrespective of prior endoscopic treatments. A comparison between groups was performed using the Mann-Whitney U test and Fisher's Exact test. SFS was calculated using Kaplan-Meier statistics. A functional definition of failure, being the need for further urethral manipulation, was used. Uni- and multivariate Cox regression analyses were performed on the entire patient cohort. RESULTS: 805 patients were included. Median (IQR) follow-up of the PU (n = 556) and RU (n = 556) and RU (p=0.1). The RU group involved more penile strictures (p=0.1). The RU group involved more penile strictures (p=0.1). The RU group involved more penile strictures (p=0.1). The RU group involved more penile strictures (p=0.1). The RU group involved more penile strictures (p=0.1). The RU group involved more penile strictures (p=0.1). The RU group involved more penile strictures (p=0.1). The RU group involved more penile strictures (p=0.1). The RU group involved more penile strictures (. CONCLUSIONS: Several differences between primary and redo urethroplasties exist. Redo urethroplasty entails a distinct patient population to treat and is, in general, associated with lower stricture-free survival than primary urethroplasty, although more homogeneous series are required to corroborate these results. Prior urethroplasty and diabetes are independent risk factors for urethroplasty failure.

Abiraterone and spironolactone in prostate cancer: a combination to avoid.

Objectives: Disease progression in metastatic castration-resistant prostate cancer (mCRPC) is dependent on androgen signaling. This case describes the complex adaptive androgen signaling mechanisms in mCRPC and illustrates that caution should be exercised when treating these patients with drugs influencing the androgen axis.Methods: Single case report and review of the literature.Results: We report the case of an 86-year-old man with mCRPC, treated with the secondary antihormonal agent abiraterone acetate. Following association of spironolactone to deal with symptoms related to mineralocorticoid excess, biochemical and radiographic disease progression occurred. Spironolactone was discontinued and 8 months after withdrawal, the patient continues to show a biochemical response to abiraterone.Conclusions: Although spironolactone generally exerts anti-androgenic effects, experimental evidence exists that it acts as an androgen receptor agonist in an androgen-depleted environment, capable of inducing prostate cancer proliferation. This is supported by the observations described in this case report. Therefore, spironolactone should be avoided in prostate cancer patients suffering from treatment-associated side effects of abiraterone.

Prospective Randomized Controlled Trial Exploring the Effect of TachoSil on Lymphocele Formation After Extended Pelvic Lymph Node Dissection in Prostate Cancer.

OBJECTIVE: To explore whether TachoSil, a hemostatic patch, can reduce the incidence of lymphocele formation. Development of a lymphocele is a frequent complication after pelvic lymph node dissection (PLND) for nodal staging in prostate cancer. MATERIALS AND METHODS: From 2013 to 2017, 100 patients with prostate cancer who were set to undergo a staging PLND before external beam radiotherapy (n = 50) or PLND concomitant with radical prostatectomy (RP) (n = 50) were prospectively randomized 1:1 between bilateral TachoSil placement or nonplacement. Primary end points were radiographic lymphocele development, lymphocele volume (1 week and 1 month postoperatively), and the duration and volume of postoperative catheter drainage. RESULTS: Patient, tumor, and surgical characteristics of the TachoSil and the control groups did not differ significantly. In total, 65 patients (65%) experienced a radiographic lymphocele up to 3 months after surgery: 29 (58%) in the TachoSil group and 36 (72%) in the control group (P = .34). Significantly less radiographic lymphoceles were observed 1 week postoperatively for patients who underwent sole PLND and 1 month postoperatively for patients who underwent PLND with RP in the TachoSil group compared with the control group (16% vs 48%, P = .024, and 24% vs 52%, P = .047, respectively). The other postoperative characteristics presented no significant differences between the 2 groups, neither for patients undergoing sole PLND nor for patients undergoing PLND with RP. CONCLUSION: Patients undergoing bilateral TachoSil placement after PLND seem less likely to develop a radiographic lymphocele early postoperatively. Nevertheless, the clinical relevance of the use of TachoSil remains highly debatable.

Metastatic burden in newly diagnosed hormone-naive metastatic prostate cancer: Comparing definitions of CHAARTED and LATITUDE trial.

OBJECTIVES: No uniformity exists in the definition of metastatic burden in metastatic hormone-naive prostate cancer (mHNPC) across clinical trials making their comparison challenging. We explored definition agreement and prognostic significance of bulky mHNPC according to the CHAARTED and LATITUDE trial. MATERIALS AND METHODS: Since 2014, 95 patients with newly diagnosed mHNPC were prospectively registered. For this study, they were categorized as having high-volume (HVD) vs. low-volume (LVD) and high-risk (HRD) vs. low-risk disease (LRD) according to the definition of CHAARTED and LATITUDE, respectively. Agreement was tested using Cohen's κ coefficient. The Kaplan-Meier method was used to compare castration-resistant prostate cancer-free survival (CRPC-FS) and overall survival (OS). Prognostic significance was analyzed using Cox regression models. RESULTS: In total, 44 (46%) and 46 (48%) patients showed HVD and HRD, respectively. Cohen's κ coefficient was 0.83 indicating "almost perfect" agreement (P<0.001). Median CRPC-FS was 40 (95% CI: 25-55) vs. 11 months (95% CI: 8-14) for LVD and HVD (P = 0.001); 40 (95% CI: 27-53) vs. 11 months (95% CI: 8-14) for LRD and HRD (P<0.001), respectively. Median OS was not reached vs. 51 months (95% CI: 0-102) for LVD and HVD (P = 0.001); not reached vs. 51 months (95% CI: 2-100) for LRD and HRD (P = 0.003), respectively. The prognostic significance of both definitions remained significant in the multivariate model for CRPC-FS (P = 0.012 and P = 0.003). CONCLUSIONS: There is an excellent agreement between the definitions of bulky mHNPC in the CHAARTED and LATITUDE trial. Both definitions have significant prognostic value for predicting worse CRPC-FS and OS.

Prognostic and Therapeutic Implications of Circulating Androgen Receptor Gene Copy Number in Prostate Cancer Patients Using Droplet Digital Polymerase Chain Reaction.

BACKGROUND: Resistance mechanisms in the androgen receptor (AR) signaling pathway remain key drivers in the progression to castration-resistant prostate cancer (CRPC) and relapse under antihormonal therapy. MATERIALS AND METHODS: We evaluated the circulating AR gene copy number (CN) gain using droplet digital polymerase chain reaction in 21 control and 91 prostate cancer serum samples and its prognostic and therapeutic implications in prostate cancer. RESULTS: In CRPC, AR CN gain was associated with faster progression to CRPC (P = .026), a greater number of previous treatments (P = .045), and previous chemotherapy (P = .016). Comparing patients with and without CN gain, the median progression-free survival (PFS) in the abiraterone subgroup was 1.7 months versus not reached (P = .004), and the median overall survival (OS) was 7 months versus 20.9 months (P = .020). In the enzalutamide subgroup, PFS was 1.7 versus 10.8 months (P = .006), and OS was 6.1 versus 16.5 months (P = .042). In the taxane subgroup, PFS was 3.2 versus 6.5 months (P = .093), and OS was 3.9 months versus not reached (P = .026). The presence of more AR copies correlated with shorter androgen deprivation (P = .002), abiraterone (P = .022), enzalutamide (P = .008), and taxane (P = .039) therapy. CONCLUSION: Circulating AR CN gain predicts for a poor prognosis in CRPC. It is a promising biomarker predetermining rapid CRPC progression and predicting worse abiraterone and enzalutamide outcomes. Furthermore, it is associated with multiple previous treatments and previous chemotherapy.

Cytoreductive Prostatectomy for Metastatic Prostate Cancer: First Lessons Learned From the Multicentric Prospective Local Treatment of Metastatic Prostate Cancer (LoMP) Trial.

OBJECTIVE: To prospectively evaluate patients with newly diagnosed metastatic prostate cancer in the context of the LoMP trial (which investigates the role of cytoreductive radical prostatectomy [cRP] in addition to standard of care [SoC]) and to provide a preliminary analysis of patient's characteristics, safety of cRP, and early local symptoms. PATIENTS AND METHODS: cRP was performed in asymptomatic patients with a resectable tumor and who were fit to undergo surgery (group A, n = 17). Only SoC was administered to patients with metastatic prostate cancer ineligible or unwilling to undergo cRP (group B, n = 29). At 3 months, surgical complications related to cRP and local symptoms for both groups were evaluated. RESULTS: Median operation time, blood loss, and hospital stay for cRP were 215 minutes (150-290), 250 mL (100-900), and 4 days (2-7), respectively. Respectively 5 (29.4%) and 2 (11.8%) patients suffered grades 1 and 2 complications within 3 months postoperatively. When compared with Group B, patients in group A were younger (64 vs 72 years, P = .005), had lower initial prostate-specific antigen (15.9 vs 156 µg/L, P = .002), and less high-volume metastatic disease (5.9% vs 69%, P <.001). At 3 months, 5 (29.4%) patients in group A reported stress urinary incontinence without any further local symptoms. In group B, respectively 2 (6.8%), 11 (37.9%), and 2 (6.8%) patients suffered urge incontinence, obstructive voiding needing medical intervention, and ureteric obstruction. CONCLUSION: In a group of well-selected patients, cRP is safe. These patients have more favorable characteristics compared with patients treated with only SoC. If only SoC can be offered, patients are at risk to suffer from local symptoms.