The SWENOTECA group: A good example of continuous binational and multidisciplinary collaboration for patients with testicular cancer in Sweden and Norway

Objective: The aim of this article is to present the Swedish and Norwegian Testicular Cancer Group (SWENOTECA), with an emphasis on the history of SWENOTECA, organization, results and current status. Materials and methods: SWENOTECA was founded in 1981 as a binational organization open to hospitals in Sweden and Norway treating testicular cancer. It has since published treatment protocols for testicular cancer and prospectively registered patients with testicular cancer. Today, all hospitals in Norway and Sweden involved in the care of testicular cancer participate in SWENOTECA, and all patients with testicular cancer are prospectively registered in a population-based database. Results: Nine protocols with standardized guidelines on the diagnosis, treatment and follow-up of testicular cancer have been published. In addition to the guidelines, several studies have been performed or initiated within the scope of SWENOTECA. The details are presented in this article. Conclusions: SWENOTECA has been a very fruitful binational collaboration and has thoughtfully evolved over time. The group's continuous work and dedication have provided an example for other national and international cancer networks. The binational implementation of standardized guidelines has resulted in excellent patient outcomes, regardless of place of residence. Although testicular cancer is a relatively rare disease, the population-based binational organization of SWENOTECA has made it possible to publish some of the largest studies in the field of testicular cancer

Role of hexaminolevulinate-guided fluorescence cystoscopy in bladder cancer: critical analysis of the latest data and European guidance

Objective. Hexaminolevulinate (HAL) is an optical imaging agent used with fluorescence cystoscopy (FC) for the detection of non-muscle-invasive bladder cancer (NMIBC). Guidelines from the European Association of Urology (EAU) and a recent, more detailed European expert consensus statement agree that HAL-FC has a role in improving detection of NMIBC and provide recommendations on situations for its use. Since the publication of the EAU guidelines and the European consensus statement, new evidence on the efficacy of HAL-FC in reducing recurrence of NMIBC, compared with white light cystoscopy (WLC), have been published. Material and methods. To consider whether these new trials have an impact on the expert guidelines and on clinical practice (e. g. supporting existing recommendations or providing evidence for a change or expansion of practice), a group of bladder cancer experts from Denmark, Finland, Norway and Sweden met to address the following questions: What is the relevance of the new data on HAL-FC for clinical practice in managing NMIBC? What impact do the new data have on European guidelines? How could HAL-FC be used in clinical practice? and What further information on HAL-FC is required to optimize the management of NMIBC? Results and conclusions. This article reports the outcomes of the discussion at the Nordic expert panel meeting, concluding that, in line with European guidance, HAL-FC has an important role in the initial detection of NMIBC and for follow-up of patients to assess tumour recurrence after WLC. It provides practical advice, with an algorithm on the use of this diagnostic procedure for urologists managing NMIBC

Validation of a prediction model for post-chemotherapy fibrosis in nonseminoma patients

Objective - To validate Vergouwe's prediction model using the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) RETROP database and to define its clinical utility. Materials and methods - Vergouwe's prediction model for benign histopathology in post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) uses the following variables: presence of teratoma in orchiectomy specimen; pre-chemotherapy level of alpha-fetoprotein; β-Human chorionic gonadotropin and lactate dehydrogenase; and lymph node size pre- and post-chemotherapy. Our validation cohort consisted of patients included in RETROP, a prospective population-based database of patients in Sweden and Norway with metastatic nonseminoma, who underwent PC-RPLND in the period 2007–2014. Discrimination and calibration analyses were used to validate Vergouwe's prediction model results. Calibration plots were created and a Hosmer–Lemeshow test was calculated. Clinical utility, expressed as opt-out net benefit (NBopt-out), was analysed using decision curve analysis. Results - Overall, 284 patients were included in the analysis, of whom 130 (46%) had benign histology after PC-RPLND. Discrimination analysis showed good reproducibility, with an area under the receiver-operating characteristic curve (AUC) of 0.82 (95% confidence interval 0.77–0.87) compared to Vergouwe's prediction model (AUC between 0.77 and 0.84). Calibration was acceptable with no recalibration. Using a prediction threshold of 70% for benign histopathology, NBopt-out was 0.098. Using the model and this threshold, 61 patients would have been spared surgery. However, only 51 of 61 were correctly classified as benign. Conclusions - The model was externally validated with good reproducibility. In a clinical setting, the model may identify patients with a high chance of benign histopathology, thereby sparing patients of surgery. However, meticulous follow-up is required

Addressing nutritional requirements of ageing consumers in Asia-recommendations from an expert workshop

The number of older persons in Asia is expected to triple by 2050. Ageing is associated with non-communicable chronic diseases, malnutrition, and geriatric syndromes, which influences the burden on the cost related to healthcare, health outcomes, and the quality of life. Experts in the field of older adult nutrition from Asia, Australia, and Europe were invited to participate in a two-day workshop to review the available data, current policies and programs for the ageing population in different countries of Asia to identify the gaps in knowledge and to develop recommendations for action. In Asia, most of the data pertaining to health status, nutritional status, and nutrient intake of the older persons were mainly obtained by conducting studies in nursing homes or hospitals and small cohort studies. There were limited country-specific data on this population. Moreover, the available data pertaining to different countries were difficult to compare due to differences in the reporting format and reference values used. Although nutrition initiatives and policies were realized and public education was conducted to support the older persons, most of these efforts targeted the general population rather than the older persons population segment. In healthcare management, a higher amount of education is required pertaining to the knowledge of nutritional requirements and appropriate feeding of the older persons to reduce underfeeding and its consequences. The expert group recommended the use of a systematic approach for reviewing data pertaining to different countries, initiatives, and programs to further evaluate the available data to underpin future research.</p

Population-Based Study of Treatment Guided by Tumor Marker Decline in Patients With Metastatic Nonseminomatous Germ Cell Tumor: A Report From the Swedish-Norwegian Testicular Cancer Group.

PURPOSE From 1995 to 2003, 603 adult patients from Sweden and Norway with metastatic testicular nonseminomatous germ cell tumor (NSGCT) were included prospectively in a population-based protocol with strict guidelines for staging, treatment, and follow-up. Patients with extragonadal primary tumor or previous treatment for contralateral testicular tumor were excluded. The basic strategy was to individualize treatment according to initial tumor marker response. METHODS Initial treatment for all patients was two courses of standard bleomycin, etoposide, and cisplatin (BEP), with tumor markers analyzed weekly. Good response was defined as a half-life (t(1/2)) for α-fetoprotein (AFP) of ≤ 7 days and/or for β-human chorionic gonadotropin (β-HCG) of ≤ 3 days. Patients with prolonged marker t(1/2) (ie, poor response) received intensification with addition of ifosfamide (BEP-if/PEI) in step 1. If poor response continued, the treatment was intensified with high-dose chemotherapy with stem-cell rescue as step 2. Results Overall, 99% of all patients with metastatic testicular NSGCT in the population were included in the protocol. Median follow-up was 8.2 years. Seventy-seven percent of the patients were treated with BEP alone; 18% received intensification step 1%, and 5% received intensification step 2. Grouped according to International Germ Cell Consensus Classification, 10-year overall survival was 94.7% in good-prognosis patients, 90.0% in intermediate-prognosis patients, and 67.4% in poor-prognosis patients. CONCLUSION With detailed treatment protocols and a dedicated collaborative group of specialists, treatment results comparable to those reported from large single institutions can be achieved at national level. With the treatment principles used in Swedish-Norwegian Testicular Cancer Group study SWENOTECA IV, the survival of intermediate-prognosis patients is remarkable and close to that of good-prognosis patients

Surgical Complications in Postchemotherapy Retroperitoneal Lymph Node Dissection for Nonseminoma Germ Cell Tumour : A Population-based Study from the Swedish Norwegian Testicular Cancer Group

BACKGROUND: Reports on perioperative complications after postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for nonseminoma germ cell tumour (NSGCT) are from experienced single centres, with a lack of population-based studies. OBJECTIVE: To assess the complications of bilateral and unilateral PC-RPLND. DESIGN, SETTING, AND PARTICIPANTS: A prospective, population-based, observational multicentre study included all patients with NSGCT who underwent PC-RPLND in Norway and Sweden during 2007-2014. Of a total of 318 patients, 87 underwent bilateral PC-RPLND and 231 underwent unilateral PC-RPLND. The median follow-up was 6 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Bilateral and unilateral PC-RPLND were compared for the outcomes of intra- and postoperative complications (graded by Clavien-Dindo) and retrograde ejaculation (with or without nerve-sparing surgery). Complications were reported as absolute counts and percentages. The χ2 test was used for comparisons. RESULTS AND LIMITATIONS: The incidence of intraoperative complications was higher for bilateral PC-RPLND than for unilateral PC-RPLND (14% vs 4.3%, p = 0.003), with ureteral injury as the most frequent reported complication (2% of the patients). Postoperative complications were more common after bilateral than after unilateral PC-RPLND (45% vs 25%, p = 0.001) with Clavien ≥3b reported in 8.3% and 2.2%, respectively (p = 0.009). Lymphatic leakage was the most common complication occurring in 11% of the patients. Retrograde ejaculation occurred more frequently after bilateral than after unilateral surgery (59% vs 32%, p < 0.001). Limitations of the study include reporting of retrograde ejaculation, which was based on a chart review. CONCLUSIONS: Intra- and postoperative complications including retrograde ejaculation are more frequent after bilateral PC-RPLND than after unilateral PC-RPLND. PATIENT SUMMARY: Lymph node dissection in patients with testicular cancer puts them at risk of complications. In this study, we present the complications after lymph node dissection

Surgical Complications in Postchemotherapy Retroperitoneal Lymph Node Dissection for Nonseminoma Germ Cell Tumour: A Population-based Study from the Swedish Norwegian Testicular Cancer Group

Background Reports on perioperative complications after postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for nonseminoma germ cell tumour (NSGCT) are from experienced single centres, with a lack of population-based studies. Objective To assess the complications of bilateral and unilateral PC-RPLND. Design, setting, and participants A prospective, population-based, observational multicentre study included all patients with NSGCT who underwent PC-RPLND in Norway and Sweden during 2007–2014. Of a total of 318 patients, 87 underwent bilateral PC-RPLND and 231 underwent unilateral PC-RPLND. The median follow-up was 6 yr. Outcome measurements and statistical analysis Bilateral and unilateral PC-RPLND were compared for the outcomes of intra- and postoperative complications (graded by Clavien-Dindo) and retrograde ejaculation (with or without nerve-sparing surgery). Complications were reported as absolute counts and percentages. The χ2 test was used for comparisons. Results and limitations The incidence of intraoperative complications was higher for bilateral PC-RPLND than for unilateral PC-RPLND (14% vs 4.3%, p = 0.003), with ureteral injury as the most frequent reported complication (2% of the patients). Postoperative complications were more common after bilateral than after unilateral PC-RPLND (45% vs 25%, p = 0.001) with Clavien ≥3b reported in 8.3% and 2.2%, respectively (p = 0.009). Lymphatic leakage was the most common complication occurring in 11% of the patients. Retrograde ejaculation occurred more frequently after bilateral than after unilateral surgery (59% vs 32%, p < 0.001). Limitations of the study include reporting of retrograde ejaculation, which was based on a chart review. Conclusions Intra- and postoperative complications including retrograde ejaculation are more frequent after bilateral PC-RPLND than after unilateral PC-RPLND. Patient summary Lymph node dissection in patients with testicular cancer puts them at risk of complications. In this study, we present the complications after lymph node dissection

BladMetrix: a novel urine DNA methylation test with high accuracy for detection of bladder cancer in hematuria patients

Background Cystoscopy is the gold standard for bladder cancer detection, but is costly, invasive and has imperfect diagnostic accuracy. We aimed to identify novel and accurate DNA methylation biomarkers for non-invasive detection of bladder cancer in urine, with the potential to reduce the number of cystoscopies among hematuria patients. Results Biomarker candidates (n = 32) were identified from methylome sequencing of urological cancer cell lines (n = 16) and subjected to targeted methylation analysis in tissue samples (n = 60). The most promising biomarkers (n = 8) were combined into a panel named BladMetrix. The performance of BladMetrix in urine was assessed in a discovery series (n = 112), consisting of bladder cancer patients, patients with other urological cancers and healthy individuals, resulting in 95.7% sensitivity and 94.7% specificity. BladMetrix was furthermore evaluated in an independent prospective and blinded series of urine from patients with gross hematuria (n = 273), achieving 92.1% sensitivity, 93.3% specificity and a negative predictive value of 98.1%, with the potential to reduce the number of cystoscopies by 56.4%. Conclusions We here present BladMetrix, a novel DNA methylation urine test for non-invasive detection of bladder cancer, with high accuracy across tumor grades and stages, and the ability to spare a significant number of cystoscopies among patients with gross hematuria

Initial surveillance in men with marker negative clinical stage IIA non-seminomatous germ cell tumours

Objectives: To assess whether extended surveillance with repeated computed tomography (CT) scans for patients with clinical stage IIA (CS IIA; &lt;2 cm abdominal node involvement) and negative markers (Mk−) non-seminomatous germ cell tumours (NSGCTs) can identify those with true CS I. To assess the rate of benign lymph nodes, teratoma, and viable cancer in retroperitoneal lymph node dissection (RPLND) histopathology for patients with CS IIA Mk− NSGCT. Patients and methods: Observational prospective population-based study of patients diagnosed 2008–2019 with CS IIA Mk− NSGCT in the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) registry. Patients were managed with surveillance, with CT scans, and tumour markers every sixth week for a maximum of 18 weeks. Patients with radiological regression were treated as CS I, if progression with chemotherapy, and remaining CS IIA Mk− disease with RPLND. The end-point was the number and percentage of patients down-staged to CS I on surveillance and rate of RPLND histopathology presented as benign, teratoma, or viable cancer. Results: Overall, 126 patients with CS IIA Mk− NSGCT were included but 41 received therapy upfront. After surveillance for a median (range) of 6 (6–18) weeks, 23/85 (27%) patients were in true CS I and four (5%) progressed. Of the remaining 58 patients with lasting CS IIA Mk− NSGCT, 16 received chemotherapy and 42 underwent RPLND. The RPLND histopathology revealed benign lymph nodes in 11 (26%), teratoma in two (6%), and viable cancer in 29 (70%) patients. Conclusions: Surveillance with repeated CT scans can identify patients in true CS I, thus avoiding overtreatment. The RPLND histopathology in patients with CS IIA Mk− NSGCT had a high rate of cancer and a low rate of teratoma