TripleAiM1: a nationwide registry of de novo metastatic hormone-sensitive prostate cancer with prospective quality-of-life assessment.

INTRODUCTION: The treatment landscape for de novo metastatic hormone sensitive prostate cancer (mHSPC) is rapidly evolving. With an abundance of available treatment strategies, selecting the optimal strategy for an individual patient is becoming increasingly challenging. TripleAiM1 aims to evaluate the impact of mHSPC treatments on health-related quality of life (HRQoL) and to provide real-world data insights on diagnostics, treatment strategies, patient subgroups and related healthcare expenditure for mHSPC. The aspirational target of TripleAiM1 is that in the near future, a more tailored therapy can be offered based on the individual patient's wishes and needs in accordance with the overarching principle of value-based healthcare. METHODS AND ANALYSIS: We describe the TripleAiM1 study design; a nationwide registry comprising a retrospective and prospective cohort of patients with de novo mHSPC. Starting in May 2020, eligible patients are identified, selected and recruited in 14 participating hospitals in the Netherlands. Our hypothesis is that, in a real-world setting, differences in clinically meaningful HRQoL deterioration will be observed for treatment strategies over time. HRQoL data, assessed with patient-reported outcome measures, costs and clinical data will be collected for 24 months.For the retrospective cohort, all patients diagnosed with de novo mHSPC from January 2017 onwards are eligible for inclusion. Patient and tumour characteristics, imaging modalities and treatment patterns will be analysed descriptively to provide a real-world overview.Time-to-event endpoints will be assessed using the Kaplan-Meier method and regression models will be employed to analyse baseline characteristics associated with an increased likelihood of death, progression and HRQoL deterioration. Longitudinal mixed-effects models will be employed to assess change of patient-reported outcome scores from baseline until the end of follow-up. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Medical Research Ethics Committee, Twente. Study results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NL9719.

A Prospective Multicenter Comparison Study of Risk-adapted Ultrasound-directed and Magnetic Resonance Imaging-directed Diagnostic Pathways for Suspected Prostate Cancer in Biopsy-naïve Men.

BACKGROUND: European Association of Urology guidelines recommend a risk-adjusted biopsy strategy for early detection of prostate cancer in biopsy-naïve men. It remains unclear which strategy is most effective. Therefore, we evaluated two risk assessment pathways commonly used in clinical practice. OBJECTIVE: To compare the diagnostic performance of a risk-based ultrasound (US)-directed pathway (Rotterdam Prostate Cancer Risk Calculator [RPCRC] #3; US volume assessment) and a magnetic resonance imaging (MRI)-directed pathway. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective multicenter study (MR-PROPER) with 1:1 allocation among 21 centers (US arm in 11 centers, MRI arm in ten). Biopsy-naïve men with suspicion of prostate cancer (age ≥50 yr, prostate-specific antigen 3.0-50 ng/ml, ± abnormal digital rectal examination) were included. INTERVENTION: Biopsy-naïve men with elevated risk of prostate cancer, determined using RPCRC#3 in the US arm and Prostate Imaging Reporting and Data System scores of 3-5 in the MRI arm, underwent systematic biopsies (US arm) or targeted biopsies (MRI arm). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the proportion of men with grade group (GG) ≥2 cancer. Secondary outcomes were the proportions of biopsies avoided and GG 1 cancers detected. Categorical (nonparametric) data were assessed using the Mann-Whitney U test and χ2 tests. RESULTS AND LIMITATIONS: A total of 1965 men were included in the intention-to-treat population (US arm n = 950, MRI arm n = 1015). The US and MRI pathways detected GG ≥2 cancers equally well (235/950, 25% vs 239/1015, 24%; difference 1.2%, 95% confidence interval [CI] -2.6% to 5.0%; p = 0.5). The US pathway detected more GG 1 cancers than the MRI pathway (121/950, 13% vs 84/1015, 8.3%; difference 4.5%, 95% CI 1.8-7.2%; p < 0.01). The US pathway avoided fewer biopsies than the MRI pathway (403/950, 42% vs 559/1015, 55%; difference -13%, 95% CI -17% to -8.3%; p < 0.01). Among men with elevated risk, more GG ≥2 cancers were detected in the MRI group than in the US group (52% vs 43%; difference 9.2%, 95% CI 3.0-15%; p < 0.01). CONCLUSIONS: Risk-adapted US-directed and MRI-directed pathways detected GG ≥2 cancers equally well. The risk-adapted US-directed pathway performs well for prostate cancer diagnosis if prostate MRI capacity and expertise are not available. If prostate MRI availability is sufficient, risk assessment should preferably be performed using MRI, as this avoids more biopsies and detects fewer cases of GG 1 cancer. PATIENT SUMMARY: Among men with suspected prostate cancer, relevant cancers were equally well detected by risk-based pathways using either ultrasound or magnetic resonance imaging (MRI) to guide biopsy of the prostate. If prostate MRI availability is sufficient, risk assessment should be performed with MRI to reduce unnecessary biopsies and detect fewer irrelevant cancers.

Diagnostic accuracy of 18F-fluciclovine PET/CT in primary lymph node staging of prostate cancer.

INTRODUCTION: To determine preoperative diagnostic accuracy of 18F-fluciclovine PET/CT-scan in detection (or exclusion) of lymph node metastases (LNM) in men with prostate cancer (PCa) in comparison to the histopathological results of the extended pelvic lymph node dissection (e-PLND). METHODS: A retrospective medical records-based cohort study, including 47 men with primary PCa who received 18F-fluciclovine PET/CT and subsequent e-PLND for lymph node staging. Incidence and number of visualized LNM, their locations and diameters on 18F-fluciclovine PET/CT were recorded in comparison to the histopathological results of the e-PLND as reference. Positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity and diagnostic accuracy of 18F-fluciclovine PET/CT were calculated on the basis of histopathology results after e-PLND. RESULTS: Forty-seven men were eligible for analysis. Median lymph node yield was 19 (range 10-70). A total of 996 lymph nodes were removed, and 59 metastases were found in 21 cases (45%). Preoperative PET was issued 'positive' in 11 men and in 9 of them (82%) this was histopathologically confirmed resulting in a PPV of 82% (95% CI, 51-96). On the contrary, PET was issued 'negative' in 36 cases, but in 12 of them (33%) metastases were detected in the e-PLND specimen, resulting in an NPV of 67% (95% CI, 50-80). The patient-based sensitivity was 43% (95% CI, 24-64) and the patient-based specificity rate was 92% (95% CI, 75-99), whereas overall diagnostic accuracy was established to be 70% in the present cohort. CONCLUSION: 18F-Fluciclovine PET/CT has a high specificity and positive predicted value for the presence of LNM in men with prostate cancer. However, the sensitivity and NPV seem to be limited to exclude the absence of LNM at a clinically acceptable level. Prospective evaluation is necessary to define patients who may benefit from 18F-fluciclovine PET/CT as a triage test for the indication for e-PLND.

Minimally invasive prostatic urethral lift: surgical technique and multinational experience.

BACKGROUND: Many men with benign prostatic hyperplasia (BPH) are dissatisfied with current treatment options. Although transurethral resection of the prostate (TURP) remains the gold standard, many patients seek a less invasive alternative. OBJECTIVE: We describe the surgical technique and results of a novel minimally invasive implant procedure that offers symptom relief and improved voiding flow in an international series of patients. DESIGN, SETTING, AND PARTICIPANTS: A total of 102 men with symptomatic BPH were consecutively treated at seven centers across five countries. Patients were evaluated up to a median follow-up of 1 yr postprocedure. Average age, prostate size, and International Prostate Symptom Score (IPSS) were 68 yr, 48 cm(3), and 23, respectively. SURGICAL PROCEDURE: The prostatic urethral lift mechanically opens the prostatic urethra with UroLift implants that are placed transurethrally under cystoscopic visualization, thereby separating the encroaching prostatic lobes. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were evaluated pre- and postoperatively by the IPSS, Quality-of-Life (QOL) scale, Benign Prostatic Hyperplasia Impact Index, maximum flow rate (Qmax), and adverse event reports including sexual function. RESULTS AND LIMITATIONS: All procedures were completed successfully with a mean of 4.5 implants without serious adverse effects. Patients experienced symptom relief by 2 wk that was sustained to 12 mo. Mean IPSS, QOL, and Qmax improved 36%, 39%, and 38% by 2 wk, and 52%, 53%, and 51% at 12 mo (p<0.001), respectively. Adverse events were mild and transient. There were no reports of loss of antegrade ejaculation. A total of 6.5% of patients progressed to TURP without complication. Study limitations include the retrospective single-arm nature and the modest patient number. CONCLUSIONS: Prostatic urethral lift has promise for BPH. It is minimally invasive, can be done under local anesthesia, does not appear to cause retrograde ejaculation, and improves symptoms and voiding flow. This study corroborates prior published results. Larger series with randomisation, comparator treatments, and longer follow-up are underway.

New nonabsorbable stent versus a microsurgical procedure for vasectomy reversal: evaluating tissue reactions at the anastomosis in rabbits.

OBJECTIVE: To investigate whether a newly designed nonabsorbable polymeric stent for the reconstruction of the vas deferens provided less stricturing at the site of the anastomosis in comparison with the conventional microsurgical reconstruction of the vas deferens. DESIGN: Prospective randomized study in 26 rabbits, comparing the one-layer microscopic sutured procedure with a biocompatible stent. SETTING: University animal laboratory center. INTERVENTION(S): Pre- and postoperative average total sperm count, motility, and progressive motile sperm density (PMSD) levels were measured. Histologic sections were taken from the area of the anastomosis, testes, and epididymi after final semen analysis. MAIN OUTCOME MEASURE(S): Rates of stricture and semen parameters. RESULT(S): The vas deferens of the rabbits that received a stent showed an inflammatory reaction within the vas wall adjacent to the stent. Transmural histiocytic or eosinophilic reactions were seen in 2/13 (15%) of the stented animals, with atrophy of the epithelium. Histologic cross-sections of the stented vas deferens demonstrated patency. Microscopically sutured rabbits showed more partial obstructions at the site of the anastomosis (5/13 [38%]) with transmural infiltration of lymphocytes and histiocytes. Despite these partial obstructions the vasa were patent. There was a statistically significant difference in favor of the stent with respect to the total sperm count (P=.05). No differences were seen in motility (P=.057) or PMSD (P=.13). CONCLUSION(S): The newly developed stent provided patency rates comparable with the conventional one-layer microscopic procedure but showed significantly less stricturing of the anastomoses.

The use of a newly designed nonabsorbable polymeric stent in reconstructing the vas deferens: a feasibility study in New Zealand white rabbits.

OBJECTIVES: To investigate the use of a newly designed stent in the reconstruction of the vas deferens. MATERIALS AND METHODS: In 26 New Zealand White rabbits, 13 conventional one-layer microscopic reconstructions were compared with 13 stented reconstructions of the vas deferens. The newly designed nonabsorbable polymeric stent was shaped to facilitate the rejoining of the two loose ends of the vas deferens, using a central ridge to prevent migration. Semen was collected before and after surgery, using an artificial vaginal system (26 samples before and 115 after surgery). The individual and average total sperm count, motility and progressive motile sperm density (PMSD), were compared after surgery for both groups. After the final semen analysis, rabbits were killed and patency was assessed histologically at the site of the anastomosis. RESULTS: After an initial decline the mean total sperm count increased in both groups. The increase was significantly larger (P = 0.05) in the stented rabbits. The mean motility and PMSD showed no significant differences between both groups (P = 0.11 and 0.71, respectively). Histological examination of the anastomosed area showed partial obstruction (>50% narrowing of the original lumen) in five of the 13 conventionally treated rabbits, with no strictures in the stented group. Despite the narrowing in the conventional group the patency rates were not affected. The mean (range) operating time for the conventional and stented groups was 132 (99-168) and 98 (62-113) min, respectively (P < 0.001). CONCLUSIONS: The total sperm counts, motility and PMSD showed no or little difference after surgery between the conventional and stented rabbits. The stented reconstruction was easy, had no secondary stricturing and reduced the operating time.

A polymeric mini-stent designed to facilitate the vasectomy reversal operation. A rabbit model study.

Vasectomy has become popular since it is the safest surgical method for contraception. It is known that approximately 6% of the men that undergo vasectomy will seek reversal (vasovasostomy). This operation is, however, technically demanding and relatively time-consuming. This study was based on the hypothesis that a polymeric mini-stent can facilitate and accelerate vasovasostomies. A mini-stent was manufactured out of a crosslinked hydrogel biomaterial, which was synthesized from N-vinyl-pyrrolidinone (NVP), n-butylmethacrylate, and (triethyleneglycol) dimethacrylate. The device was tested with 28 rabbits, which were divided over two equal groups. In one group, the vasa deferentia were dissected and reanastomosed via microsurgical one-layer technique (end-to-end group). In the other group, the vasa deferentia were dissected and reattached through implantation of the mini-stent. Sperm counts revealed 100% patency in both groups, i.e. all vasovasostomies were successful. It was experienced that the operation was easier and faster in the case of the mini-stent, probably since the mini-stent keeps the lumens of both vas ends exactly in line during suturing. This study demonstrates the feasibility of the mini-stent. Further work is necessary to evaluate the utility of this approach for clinical vasovasostomies.