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.

Laparoscopic bilateral groin hernia repair with one large self-fixating mesh: prospective observational study with patient-reported outcome of urological symptoms and EuraHS-QoL scores.

BACKGROUND: Laparoscopic bilateral inguinal hernia repair may be completed with one large self-fixating mesh crossing the midline. No studies have investigated in detail whether preperitoneal mesh placement induces temporary or more lasting urinary symptoms. METHODS: Urinary and hernia-related symptoms were evaluated preoperatively and postoperatively at 1, 3 and 12 months using the ICIQ-MLUTS questionnaire and EuraHS-QoL score in patients undergoing bilateral inguinal hernia repair. RESULTS: One hundred patients were included. Voiding symptoms and bother scores were unchanged at 1 or 3 months, but there was significant improvement at 12 months compared with preoperative findings (symptoms P < 0.001; bother score P < 0.01). Incontinence symptoms improved at 1 month (P < 0.05) but not at 3 or 12 months, with a bother score significantly improved at 1 month (P < 0.01) and 12 months (P < 0.01). Diurnal and nocturnal frequency did not change significantly postoperatively, but 12 months nocturnal bother score was decreased (P < 0.05). EuraHS-QoL scores showed statistical significant improvement in all three domains for all measurements at the different follow-up moments compared to previous measurements. Postoperative symptoms were improved at 12 months, compared with preoperative pain scores (- 6.1), restriction of activity (- 10.1) and cosmetic scores (- 4.7) These findings were statistically significant (P < 0.001). At 12 months, there were no patients with severe discomfort (score ≥ 5) for any of the three domains. No recurrences were diagnosed with 95% clinical follow-up at 12 months. CONCLUSION: Laparoscopic bilateral groin hernia repair with one large preperitoneal self-fixating mesh did not cause new urinary symptoms and demonstrated significant improvement in voiding symptoms at 12 months. Incontinence and nocturnal bother score were significantly improved. CLINICAL TRIAL REGISTRY IDENTIFIER: Clinical.Trials.gov: NCT02525666.

Bladder Cancer Diagnosis and Follow-Up: The Current Status and Possible Role of Extracellular Vesicles.

Diagnostic methods currently used for bladder cancer are cystoscopy and urine cytology. Cystoscopy is an invasive tool and has low sensitivity for carcinoma in situ. Urine cytology is non-invasive, is a low-cost method, and has a high specificity but low sensitivity for low-grade urothelial tumors. Despite the search for urinary biomarkers for the early and non-invasive detection of bladder cancer, no biomarkers are used at the present in daily clinical practice. Extracellular vesicles (EVs) have been recently studied as a promising source of biomarkers because of their role in intercellular communication and tumor progression. In this review, we give an overview of Food and Drug Administration (FDA)-approved urine tests to detect bladder cancer and why their use is not widespread in clinical practice. We also include non-FDA approved urinary biomarkers in this review. We describe the role of EVs in bladder cancer and their possible role as biomarkers for the diagnosis and follow-up of bladder cancer patients. We review recently discovered EV-derived biomarkers for the diagnosis of bladder cancer.

Current trends in patient enrollment for robotic-assisted laparoscopic prostatectomy in Belgium.

BACKGROUND: During the last decade, an inverse stage migration has been observed in radical prostatectomy series at tertiary centers. However, it remains unclear whether similar trends can also be observed in solely robotic practices, including nonreferral centers. The aim of this study was to investigate the clinical and pathological trends in robotic-assisted laparoscopic prostatectomy (RALP) enrollment in Belgium over a period of 6 years through an analysis of a prospective registry. METHODS: A prospective, multicenter database was constructed: consecutive patients undergoing RALP in Belgium from 2010 to 2015 were enrolled, and 7366 men were analyzed. Variations in clinical and pathological variables were explored as a function of the enrollment year with proportional odds for categorical variables and with linear regressions for continuous variables. RESULTS: Net increases were observed in the prostate-specific antigen levels, cT stage, and biopsy Gleason scores across the study years (P < .001). The rate of low-risk prostate cancer (PCa) decreased from 36% in 2010 to 21% in 2015, whereas the rate of intermediate-risk PCa rose from 47% to 58%, and the rate of high-risk PCa rose from 17% to 21%. In parallel, the pT2 stage rate decreased from 76% to 64%, and the rate of Gleason 6 (3 + 3) cases was reduced from 45% to 23% (P < .001). Conversely, the pT3a stage rate rose from 16% to 24%, the pT3b stage rate rose from 7% to 11%, and the rate of Gleason 7 (4 + 3) cases rose from 7% to 21% (P < .0001). Finally, more patients underwent node dissection, and positive lymph nodes were increasingly diagnosed (from 3% in 2010 to 7% in 2015). CONCLUSIONS: During the last 6 years of RALP implementation in Belgium, there was a significant increase in the enrollment of intermediate- and high-risk PCa patients. This yielded a significant increase in adverse pathological characteristics. These results suggest a paradigm shift in PCa treatment, with radical robotic surgery increasing for intermediate- and high-risk patients. Cancer 2017;123:4139-4146. © 2017 American Cancer Society.

Prevalence and prognosis of low-volume, oligorecurrent, hormone-sensitive prostate cancer amenable to lesion ablative therapy.

OBJECTIVES: To describe the anatomical patterns of prostate cancer (PCa) recurrence after primary therapy and to investigate if patients with low-volume disease have a better prognosis as compared with their counterparts. MATERIALS AND METHODS: Patients eligible for an 18-F choline positron-emission tomography (PET)-computed tomography (CT) were enrolled in a prospective cohort study. Eligible patients had asymptomatic biochemical recurrence after primary PCa treatment and testosterone levels >50 ng/mL. The number of lesions was counted per scan. Patients with isolated local recurrence (LR) or with ≤3 metastases (with or without LR) were considered to have low-volume disease and patients with >3 metastases to have high-volume disease. Descriptive statistics were used to report recurrences. Cox regression analysis was used to investigate the influence of prognostic variables on the time to developing castration-resistant PCa (CRPC). RESULTS: In 208 patients, 625 sites of recurrence were detected in the lymph nodes (N1/M1a: 30%), the bone (18%), the prostate (bed; 11%), viscera (4%), or a combination of any of the previous (37%). In total, 153 patients (74%) had low-volume recurrence and 55 patients (26%) had high-volume recurrence. The 3-year CRPC-free survival rate for the whole cohort was 79% (95% confidence interval 43-55), 88% for low-volume recurrences and 50% for high-volume recurrences (P < 0.001). Longer PSA doubling time at time of recurrence and low-volume disease were associated with a longer time to CRPC. CONCLUSIONS: Three out of four patients with PCa with a 18-F choline PET-CT-detected recurrence have low-volume disease, potentially amenable to local therapy. Patients with low-volume disease have a better prognosis as compared with their counterparts. Lymph node recurrence was the most dominant failure pattern.

A European multicenter randomized noninferiority trial comparing 180 W GreenLight XPS laser vaporization and transurethral resection of the prostate for the treatment of benign prostatic obstruction: 12-month results of the GOLIATH study.

PURPOSE: We present the 1-year results of the GOLIATH prospective randomized controlled trial comparing transurethral resection of the prostate to GreenLight XPS for the treatment of men with nonneurogenic lower urinary tract symptoms due to prostate enlargement. The updated results at 1 year show that transurethral resection of the prostate and GreenLight XPS remain equivalent, and confirm the therapeutic durability of both procedures. We also report 1-year followup data from several functional questionnaires (OABq-SF, ICIQ-SF and IIEF-5) and objective assessments. MATERIALS AND METHODS: A total of 291 patients were enrolled at 29 sites in 9 European countries. Patients were randomized 1:1 to undergo GreenLight XPS or transurethral resection of the prostate. The trial was designed to evaluate the hypothesis that GreenLight XPS is noninferior to transurethral resection of the prostate on the International Prostate Symptom Score at 6 months. Several objective parameters were assessed, including maximum urinary flow rate, post-void residual urine volume, prostate volume and prostate specific antigen, in addition to functional questionnaires and adverse events at each followup. RESULTS: Of the 291 enrolled patients 281 were randomized and 269 received treatment. Noninferiority of GreenLight XPS was maintained at 12 months. Maximum urinary flow rate, post-void residual urine volume, prostate volume and prostate specific antigen were not statistically different between the treatment arms at 12 months. The complication-free rate at 1 year was 84.6% after GreenLight XPS vs 80.5% after transurethral resection of the prostate. At 12 months 4 patients treated with GreenLight XPS and 4 who underwent transurethral resection of the prostate had unresolved urinary incontinence. CONCLUSIONS: Followup at 1 year demonstrated that photoselective vaporization of the prostate produced efficacy outcomes similar to those of transurethral resection of the prostate. The complication-free rates and overall reintervention rates were comparable between the treatment groups.

Reliability of sentinel node procedure for lymph node staging in prostate cancer patients at high risk for lymph node involvement.

AIM: To investigate the reliability of a sentinel node (SN) procedure for nodal staging in prostate cancer (PCa) patients at high risk for lymph node (LN) involvement. MATERIAL AND METHODS: Seventy-four patients with localized prostate adenocarcinoma, who were clinically node-negative and had a risk of LN involvement of ≥ 10% (Partin tables), were prospectively enrolled. Upon intraprostatic 99mTc-nanocolloid injection, they underwent planar scintigraphy and SPECT imaging. Surgical removal of the SN, located by means of a gamma probe, was completed with a superextended LN dissection (seLND) as a reference and followed by radical prostatectomy. RESULTS: In total, 470 SN (median 6, IQR 3-9) were scintigraphically detected of which 371 (median 4, IQR 2-6) were located by gamma probe and selectively removed during surgery (79%). Histopathology confirmed LN metastases in 37 patients (50%) having 106 affected LN in total (median number per patient 2, IQR 1-4). Twenty-eight patients were node positive (N+) based on the analysis of the resected SN. However, the seLND that was performed as a reference revealed nine additional N+ patients resulting in a sensitivity of 76% (28/37). In total, 15 of 37 patients (41%) had metastases in SN only and could have been spared seLND to remove all affected nodes. CONCLUSION: We found a relatively low sensitivity when addressing the SN procedure for nodal staging in PCa patients at high risk for LN involvement. Importantly, only less than half of the N+ patients could have been spared a seLND to remove all affected lymphoid tissue.

Prognostic factors influencing prostate cancer-specific survival in non-castrate patients with metastatic prostate cancer.

BACKGROUND: In non-castrate prostate cancer (PCa), the prognostic value of the number of metastases on prostate cancer-specific survival (PCSS) is not well studied. METHODS: We retrospectively analyzed the medical records of 1,206 patients, referred for radiotherapy of the prostate (bed) following diagnosis of PCa. Distant metastases (nodal, skeletal, and/or visceral) developed in 121 patients following curative treatment, of which 80 with complete records were not castrated at time of metastasis. The treatment at time of metastases was androgen deprivation therapy (ADT; n = 22), active surveillance (n = 10) or metastasis-directed therapy (MDT; n = 48). Cox-regression analyses were used to examine the influence of different variables on PCSS. RESULTS: The median follow-up from primary PCa treatment was 6.9 years with a median interval from diagnosis to first metastatic event of 4.1 year (range: 0.2-15 years). The primary site of metastases was limited to lymph nodes (48%), bone (39%), and viscera (1%) or a combination (12%). Median PCSS from diagnosis of noncastrate metastases was 6.6 years (95% confidence interval [CI], 5.6-7.7 years). A longer premetastatic PSA doubling time (DT) (hazard ratio [HR] 0.73; 95% CI: 0.57-0.92), a lower number of metastases at first presentation (HR 1.07; 95% CI: 1.02-1.12) and pattern of metastatic spread (HR 3.6; 95% CI: 1.13-11.8 for extensive vs. minimal) were associated with improved PCSS. CONCLUSION: A longer PSA DT, involvement of nodes or axial skeleton and a lower number of metastases are associated with an improved PCSS in non-castrated patients developing metastases.

Surveillance or metastasis-directed Therapy for OligoMetastatic Prostate cancer recurrence (STOMP): study protocol for a randomized phase II trial.

BACKGROUND: Metastases-directed therapy (MDT) with surgery or stereotactic body radiotherapy (SBRT) is emerging as a new treatment option for prostate cancer (PCa) patients with a limited number of metastases (≤3) at recurrence - so called "oligometastases". One of the goals of this approach is to delay the start of palliative androgen deprivation therapy (ADT), with its negative impact on quality of life. However, the lack of a control group, selection bias and the use of adjuvant androgen deprivation therapy prevent strong conclusions from published studies.The aim of this multicenter randomized phase II trial is to assess the impact of MTD on the start of palliative ADT compared to patients undergoing active surveillance. METHODS/DESIGN: Patients with an oligometastatic recurrence, diagnosed on choline PET/CT after local treatment with curative intent, will be randomised in a 1:1 ratio between arm A: active surveillance only and arm B: MTD followed by active surveillance. Patients will be stratified according to the location of metastasis (node vs. bone metastases) and PSA doubling time (≤3 vs. > 3 months). Both surgery and SBRT are allowed as MDT. Active surveillance means 3-monthly PSA testing and re-imaging at PSA progression. The primary endpoint is ADT-free survival. ADT will be started in both arms at time of polymetastatic disease (>3 metastatic lesions), local progression or symptoms. The secondary endpoints include progression-free survival, quality of life, toxicity and prostate-cancer specific survival. DISCUSSION: This is the first randomized phase 2 trial assessing the possibility of deferring palliative ADT with MDT in oligometastatic PCa recurrence. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01558427.

Functional Outcomes and Quality of Life in High-risk Prostate Cancer Patients Treated by Robot-assisted Radical Prostatectomy with or Without Adjuvant Treatments.

BACKGROUND: Robot-assisted laparoscopic prostatectomy (RALP) is used frequently to treat prostate cancer; yet, prospective data on the quality of life and functional outcomes are lacking. OBJECTIVE: To assess the quality of life and functional outcomes after radical prostatectomy in different risk groups with or without adjuvant treatments. DESIGN, SETTING, AND PARTICIPANTS: The Be-RALP database is a prospective multicentre database that covers 9235 RALP cases from 2009 until 2016. Of these 9235 patients, 2336 high-risk prostate cancer patients were matched with low/intermediate-risk prostate cancer patients. INTERVENTION: Patients were treated with RALP only or followed by radiotherapy and/or hormone treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used a mixed-model analysis to longitudinally analyse quality of life, urinary function, and erectile function between risk groups with or without additional treatments. RESULTS AND LIMITATIONS: Risk group was not significant in predicting quality of life, erectile function, or urinary function after RALP. Postoperative treatment (hormone and/or radiotherapy treatment) was significant in predicting International Index of Erectile Function (IIEF-5), sexual activity, and sexual functioning. CONCLUSIONS: Risk group was not linked with clinically relevant declines in functional outcomes after RALP. The observed functional outcomes and quality of life are in favour of considering RALP for high-risk prostate cancer. Postoperative treatment resulted in lower erectile function measures without clinically relevant changes in quality of life and urinary functions. Hormone therapy seems to have the most prominent negative effects on these outcomes. PATIENT SUMMARY: This study investigated the quality of life, and urinary and erectile function in patients with aggressive and less aggressive prostate cancer after surgery only or in combination with hormones or radiation. We found that quality of life recovers completely, while erectile and urinary function recovers only partially after surgery. Aggressiveness of the disease had a minimal effect on the outcomes; yet, postoperative treatments lowered erectile function further.

Nutritional Supplement With Fermented Soy in Men With an Elevated Risk of Prostate Cancer and Negative Prostate Biopsies: General and Oncological Results From the Prospective PRAECAP Trial.

OBJECTIVE: To investigate the effect of a dietary supplement containing fermented soy on PSA, IPSS, changes in prostate volume and prostate cancer (PCa) development after a 6-month challenge in men at increased risk of PCa and negative previous biopsies. MATERIALS AND METHODS: Patients with an elevated risk of PCa, defined by either 1 of the following criteria: PSA >3 ng/mL, suspect lesion at digital rectal examination (DRE), suspect lesion at transrectal ultrasound (TRUS)/magnetic resonance imaging (MRI) and previous negative prostate biopsies (at least 8 cores) within 12 months before inclusion. Statistical analysis was carried out using a non-parametric 1-sided paired Wilcoxon rank sum test, chi-square test, and Fisher's exact test. RESULTS: In this trial, 94 patients were eligible for analysis. A PSA response was detected in 81% of the cases. In 25.8% (24/93) of patients, a decrease of at least 3 points on the IPSS was observed. The median prostate volume did not statistically change after 6 months (P = .908). Patients with PSA modulation required fewer investigations and had fewer positive biopsies (P <.001) and significantly fewer ISUP ≥3 lesions (P = .02). CONCLUSION: We observed a significantly lower PSA level after a 6-month challenge with a fermented soy-containing supplement, and an effect on IPSS in a subset of patients. Prescribing a fermented soy supplement in patients with an increased PCa risk could lead to a better selection of patients at real increased risk of having occult PCa.

Mapping 3 procedure coding systems to the International Classification of Health Interventions (ICHI): coverage and challenges.

OBJECTIVE: To study the coverage and challenges in mapping 3 national and international procedure coding systems to the International Classification of Health Interventions (ICHI). MATERIALS AND METHODS: We identified 300 commonly used codes each from SNOMED CT, ICD-10-PCS, and CCI (Canadian Classification of Health Interventions) and mapped them to ICHI. We evaluated the level of match at the ICHI stem code and Foundation Component levels. We used postcoordination (modification of existing codes by adding other codes) to improve matching. Failure analysis was done for cases where full representation was not achieved. We noted and categorized potential problems that we encountered in ICHI, which could affect the accuracy and consistency of mapping. RESULTS: Overall, among the 900 codes from the 3 sources, 286 (31.8%) had full match with ICHI stem codes, 222 (24.7%) had full match with Foundation entities, and 231 (25.7%) had full match with postcoordination. 143 codes (15.9%) could only be partially represented even with postcoordination. A small number of SNOMED CT and ICD-10-PCS codes (18 codes, 2% of total), could not be mapped because the source codes were underspecified. We noted 4 categories of problems in ICHI-redundancy, missing elements, modeling issues, and naming issues. CONCLUSION: Using the full range of mapping options, at least three-quarters of the commonly used codes in each source system achieved a full match. For the purpose of international statistical reporting, full matching may not be an essential requirement. However, problems in ICHI that could result in suboptimal maps should be addressed.

Protein Biomarker Discovery Studies on Urinary sEV Fractions Separated with UF-SEC for the First Diagnosis and Detection of Recurrence in Bladder Cancer Patients.

Urinary extracellular vesicles (EVs) are an attractive source of bladder cancer biomarkers. Here, a protein biomarker discovery study was performed on the protein content of small urinary EVs (sEVs) to identify possible biomarkers for the primary diagnosis and recurrence of non-muscle-invasive bladder cancer (NMIBC). The sEVs were isolated by ultrafiltration (UF) in combination with size-exclusion chromatography (SEC). The first part of the study compared healthy individuals with NMIBC patients with a primary diagnosis. The second part compared tumor-free patients with patients with a recurrent NMIBC diagnosis. The separated sEVs were in the size range of 40 to 200 nm. Based on manually curated high quality mass spectrometry (MS) data, the statistical analysis revealed 69 proteins that were differentially expressed in these sEV fractions of patients with a first bladder cancer tumor vs. an age- and gender-matched healthy control group. When the discriminating power between healthy individuals and first diagnosis patients is taken into account, the biomarkers with the most potential are MASP2, C3, A2M, CHMP2A and NHE-RF1. Additionally, two proteins (HBB and HBA1) were differentially expressed between bladder cancer patients with a recurrent diagnosis vs. tumor-free samples of bladder cancer patients, but their biological relevance is very limited.

Biopsy and treatment decisions in the initial management of prostate cancer and the role of PCA3; a systematic analysis of expert opinion.

PURPOSE: The Prostate CAncer gene 3 (PCA3) assay may guide prostate biopsy decisions and predict prostate cancer (PCa) aggressiveness. This study explored the appropriateness of (1) PCA3 testing; (2) biopsy; (3) active surveillance (AS) and the value of the PCA3 Score for biopsy and AS decisions. METHODS: Using the RAND/UCLA appropriateness method, 12 urologists assessed the appropriateness of PCA3, biopsy and AS for theoretical patient profiles, constructed by combining clinical variables. They individually scored the appropriateness for all profiles using a 9-point scale. Based on the median score and extent of agreement, the appropriateness for each profile was calculated. RESULTS: The PCA3 Assay was mainly considered appropriate in men with ≥1 negative biopsy, PSA ≥ 3 ng/mL and life expectancy (LE) ≥10 years. A LE < 10 years, ≥2 negative biopsies and PCA3 Score <20 decreased biopsy appropriateness, while PSA ≥ 3 ng/mL and PCA3 Score >50 increased it. In men without a prior biopsy, LE ≥ 10 years and a suspicious DRE, PCA3 did not affect biopsy appropriateness. In other men, a PCA3 Score <20 discouraged biopsy, while a value ≥35 supported biopsy. AS was mainly considered appropriate if LE < 10 years, T1c PCa, ≤20% positive cores and PSA < 3 ng/mL. A PCA3 Score <20 pleads for and higher scores (particularly >50) against AS. CONCLUSIONS: These findings illustrate in which men PCA3 can be of additional value when taking biopsy and treatment decisions in clinical practice.

Designing the selenium and bladder cancer trial (SELEBLAT), a phase lll randomized chemoprevention study with selenium on recurrence of bladder cancer in Belgium.

BACKGROUND: In Belgium, bladder cancer is the fifth most common cancer in males (5.2%) and the sixth most frequent cause of death from cancer in males (3.8%). Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of bladder cancer. This suggests that selenium may also be suitable for chemoprevention of recurrence. METHOD: The SELEBLAT study opened in September 2009 and is still recruiting all patients with non-invasive transitional cell carcinoma of the bladder on TURB operation in 15 Belgian hospitals. Recruitment progress can be monitored live at http://www.seleblat.org. Patients are randomly assigned to selenium yeast (200 µg/day) supplementation for 3 years or matching placebo, in addition to standard care. The objective is to determine the effect of selenium on the recurrence of bladder cancer. Randomization is stratified by treatment centre. A computerized algorithm randomly assigns the patients to a treatment arm. All study personnel and participants are blinded to treatment assignment for the duration of the study. DESIGN: The SELEnium and BLAdder cancer Trial (SELEBLAT) is a phase III randomized, placebo-controlled, academic, double-blind superior trial. DISCUSSION: This is the first report on a selenium randomized trial in bladder cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00729287.

Long-Term Outcomes and Genetic Predictors of Response to Metastasis-Directed Therapy Versus Observation in Oligometastatic Prostate Cancer: Analysis of STOMP and ORIOLE Trials.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The initial STOMP and ORIOLE trial reports suggested that metastasis-directed therapy (MDT) in oligometastatic castration-sensitive prostate cancer (omCSPC) was associated with improved treatment outcomes. Here, we present long-term outcomes of MDT in omCSPC by pooling STOMP and ORIOLE and assess the ability of a high-risk mutational signature to risk stratify outcomes after MDT. The primary end point was progression-free survival (PFS) calculated using the Kaplan-Meier method. High-risk mutations were defined as pathogenic somatic mutations within ATM, BRCA1/2, Rb1, or TP53. The median follow-up for the whole group was 52.5 months. Median PFS was prolonged with MDT compared with observation (pooled hazard ratio [HR], 0.44; 95% CI, 0.29 to 0.66; P value < .001), with the largest benefit of MDT in patients with a high-risk mutation (HR high-risk, 0.05; HR no high-risk, 0.42; P value for interaction: .12). Within the MDT cohort, the PFS was 13.4 months in those without a high-risk mutation, compared with 7.5 months in those with a high-risk mutation (HR, 0.53; 95% CI, 0.25 to 1.11; P = .09). Long-term outcomes from the only two randomized trials in omCSPC suggest a sustained clinical benefit to MDT over observation. A high-risk mutational signature may help risk stratify treatment outcomes after MDT.

Evaluation of the International Classification of Health Interventions (ICHI) in the coding of common surgical procedures.

OBJECTIVE: To evaluate the International Classification of Health Interventions (ICHI) in the clinical and statistical use cases. MATERIALS AND METHODS: We identified 300 most-performed surgical procedures as represented by their display names in an electronic health record. For comparison with existing coding systems, we coded the procedures in ICHI, SNOMED CT, International Classification of Diseases (ICD)-10-PCS, and CCI (Canadian Classification of Health Interventions), using postcoordination (modification of existing codes by adding other codes), when applicable. Failure analysis was done for cases where full representation was not achieved. The ICHI encoding was further evaluated for adequacy to support statistical reporting by the Organisation for Economic Co-operation and Development (OECD) and European Union (EU) categories of surgical procedures. RESULTS: After deduplication, 229 distinct procedures remained. Without postcoordination, ICHI achieved full representation in 52.8%. A further 19.2% could be fully represented with postcoordination. SNOMED CT was the best performing overall, with 94.3% full representation without postcoordination, and 99.6% with postcoordination. Failure analysis showed that "method" and "target" constituted most of the missing information for ICHI encoding. For all OECD/EU surgical categories, ICHI coding was adequate to support statistical reporting. One OECD/EU category ("Hip replacement, secondary") required postcoordination for correct assignment. CONCLUSION: In the clinical use case of capturing information in the electronic health record, ICHI was outperformed by the clinically oriented procedure coding systems (SNOMED CT and CCI), but was comparable to ICD-10-PCS. Postcoordination could be an effective and efficient means of improving coverage. ICHI is generally adequate for the collection of international statistics.

The Multicenter, Randomized, Phase 2 PEACE V-STORM Trial: Defining the Best Salvage Treatment for Oligorecurrent Nodal Prostate Cancer Metastases.

Optimal local treatment for nodal oligorecurrent prostate cancer is unknown. The randomized phase 2 PEACE V-STORM trial will explore the best treatment approach in this setting. Early results on the acute toxicity profile are projected to be published in quarter 3, 2021.

Development and external validation of a nomogram to predict lymph node invasion after robot assisted radical prostatectomy.

BACKGROUND: Prediction of lymph node invasion (LNI) after radical prostatectomy has been rarely assessed in robotically assisted laparoscopic radical prostatectomy (RALP) series. We aimed to develop and externally validate a pretreatment nomogram for the prediction of LNI following RALP in patients with high- and intermediate-risk prostate cancer. METHODS: 1654 RALP patients were prospectively collected between 2009 and 2016 from academic and community hospitals. We included patients with intermediate- and high-risk prostate cancer who underwent pelvic lymph node dissection (e-PLND). Logistic regression analysis was applied to construct a nomogram to predict LNI. Centers were randomly assigned to the training cohort (80%) and validation cohort (20%). The discriminative accuracies were evaluated by the areas under the curve and by the calibration plot. The net benefit of the nomogram to predict LNI was assessed by decision curve analysis and a cut-off was proposed. RESULTS: In total, 14% of the patients in our cohort had pN1 disease. Applying logistic regression analysis, the following covariates were chosen to develop the nomogram: initial PSA, clinical T stage, biopsy Gleason sum, and proportion of positive biopsy cores. The nomogram showed a median discriminative accuracy of 73% and excellent calibration. The net benefit of the model ranged between 7% and 51% predicted risk of LNI. A cut-off to perform e-PLND was set at 7%. This would permit a 29% of avoidable e-PLND, missing 9.4% of patients with LNI. CONCLUSIONS: We developed and externally validated a nomogram to predict LNI in patients treated with RALP from a prospective, multi-institutional, nationwide series. A risk of LNI > 7% is proposed as cut-off above which e-PLND is recommended.

A Trial-Based Cost-Utility Analysis of Metastasis-Directed Therapy for Oligorecurrent Prostate Cancer.

The optimal management of patients with oligorecurrent prostate cancer (PCa) is unknown. There is growing interest in metastasis-directed therapy (MDT) for this population. The objective was to assess cost-utility from a Belgian healthcare payer's perspective of MDT and delayed androgen deprivation therapy (ADT) in comparison with surveillance and delayed ADT, and with immediate ADT. A Markov decision-analytic trial-based model was developed, projecting the results over a 5-year time horizon with one-month cycles. Clinical data were derived from the STOMP trial and literature. Treatment costs were derived from official government documents. Probabilistic sensitivity analyses showed that MDT is cost-effective compared to surveillance (ICER: €8393/quality adjusted life year (QALY)) and immediate ADT (dominant strategy). The ICER is most sensitive to utilities in the different health states and the first month MDT cost. At a willingness-to-pay threshold of €40,000 per QALY, the cost of the first month MDT should not exceed €8136 to be cost-effective compared to surveillance. The Markov-model suggests that MDT for oligorecurrent PCa is potentially cost-effective in comparison with surveillance and delayed ADT, and in comparison with immediate ADT.