Development and validation of a haematuria cancer risk score to identify patients at risk of harbouring cancer.

BACKGROUND: A lack of consensus exists amongst national guidelines regarding who should be investigated for haematuria. Type of haematuria and age-specific thresholds are frequently used to guide referral for the investigation of haematuria. OBJECTIVES: To develop and externally validate the haematuria cancer risk score (HCRS) to improve patient selection for the investigation of haematuria. METHODS: Development cohort comprise of 3539 prospectively recruited patients recruited at 40 UK hospitals (DETECT 1; ClinicalTrials.gov: NCT02676180) and validation cohort comprise of 656 Swiss patients. All patients were aged >18 years and referred to hospital for the evaluation of visible and nonvisible haematuria. Sensitivity and specificity of the HCRS in the validation cohort were derived from a cut-off identified from the discovery cohort. RESULTS: Patient age, gender, type of haematuria and smoking history were used to develop the HCRS. HCRS validation achieves good discrimination (AUC 0.835; 95% CI: 0.789-0.880) and calibration (calibration slope = 1.215) with no significant overfitting (P = 0.151). The HCRS detected 11.4% (n = 8) more cancers which would be missed by UK National Institute for Health and Clinical Excellence guidelines. The American Urological Association guidelines would identify all cancers with a specificity of 12.6% compared to 30.5% achieved by the HCRS. All patients with upper tract cancers would have been identified. CONCLUSION: The HCRS offers good discriminatory accuracy which is superior to existing guidelines. The simplicity of the model would facilitate adoption and improve patient and physician decision-making.

Improved survival in metastatic germ-cell cancer.

Background: The prognostic score of the International Germ-Cell Cancer Collaborative Group (IGCCCG) in metastatic germ-cell cancers (mGCC) relies on treatments delivered before 1990. It is unclear, if this score is still relevant to contemporary cohorts of patients who receive modern-type chemotherapy and supportive care. Patients and methods: All patients who underwent cisplatin/etoposide-based first-line chemotherapy for mGCC at the University Hospital Zurich (USZ) between 1991 and 2016 were identified retrospectively. Clinical characteristics were extracted from medical charts and patients classified according to the IGCCCG score. International germ cell consensus classification: a prognostic factor-based staging system for metastatic germ cell cancers. J Clin Oncol 1997; 15: 594-603.). Progression-free survival (PFS) and overall survival (OS) probabilities at 5 years served as outcome parameters. Results: The study cohort consisted of 204 patients at a median age of 32 years and a median follow-up of 4.2 years. According to the IGCCCG score, PFS in the contemporary USZ cohort was 71% overall: 83% for good-risk, 69% for intermediate-risk and 30% for poor-risk patients, P < 0.001. OS for the entire cohort was 88%. In respect to OS, we observed no difference between good- and intermediate-risk patients (94% versus 91%, P = 0.62), but a statistically significant difference between those two risk groups and poor-risk patients, who had an OS of only 65%, P < 0.001. Conclusions: Within the contemporary USZ cohort of mGCC patients no improvements in PFS probabilities were observed compared with the ones predicted by the IGCCCG score for any prognostic category, but marked improvements in OS probabilities for intermediate- and poor-risk patients, possibly due to better salvage treatments.

Frequent PD-L1 expression in testicular germ cell tumors.

BACKGROUND: Many testicular germ cell cancers are curable despite metastatic disease, but about 10-15% of patients fail cisplatin-based first-line treatment. Immunotherapy is considered as additional treatment approach for these patients. Inhibition of the interaction between Programmed Death Receptor 1 (PD-1) and Programmed Death Receptor Ligand 1 (PD-L1) enhances T-cell responses in vitro and mediates clinical antitumour activity. We analysed the expression of PD-L1 in testicular germ cell tumours to evaluate its potential as target for immunotherapeutic strategies. METHODS: Immunohistochemistry was performed in 479 formalin-fixed paraffin-embedded specimens using a rabbit monoclonal antibody (E1L3N). The tissue microarray consisted of 208 pure seminomas, 121 non-seminomas, 20 intratubular germ cell neoplasia unclassified (IGCNU) and 20 specimens of non-neoplastic testicular tissue. RESULTS: Programmed Death Receptor Ligand-1 expression was found in 73% of all seminomas and in 64% of all non-seminomas. None of 20 IGCNU and none of 20 normal tissue specimens exhibited PD-L1 expression. PD-L1 positive stromal cells were only detected in seminomas, but not in non-seminomas. The anti PD-L1 antibody showed a pre-dominantly membranous staining pattern in testicular tumour cells, as well as expression in stromal cells. CONCLUSIONS: This frequent expression of PD-L1 in human testicular germ cell tumours suggests that patients with testicular germ cell tumours could profit from immunotherapeutic strategies using anti-PD1 and anti-PDL1 antibodies.

Validity and responsiveness of the Core Outcome Measures Index (COMI) for the neck.

PURPOSE: Patient-orientated outcome questionnaires are essential to evaluate treatment success. To compare different treatments, hospitals, and surgeons, standardised questionnaires are required. The present study examined the validity and responsiveness of the Core Outcome Measurement Index for neck pain (COMI-neck), a short, multidimensional outcome instrument. METHODS: Questionnaires were completed by patients with degenerative problems of the cervical spine undergoing cervical disc arthroplasty before (N = 89) and 3 months after (N = 75) surgery. The questionnaires comprised the EuroQol-Five Dimension (EQ-5D), the North American Spine Society Cervical Spine Outcome Assessment Instrument (NASS-cervical) and the COMI-neck. RESULTS: The COMI and NASS-cervical scores displayed no notable floor or ceiling effects at any time point whereas for the EQ-5D, the highest values [corrected] were reached in around 32.5% of patients at follow-up. With one exception (symptom-specific well-being), the individual COMI items and the COMI summary score correlated to the expected extent (R = 0.4-0.8) with the scores of the chosen reference questionnaires. The area under the curve (AUC) generated by ROC analysis was significantly higher for the COMI (0.96) than for any other instrument/subscale when self reported treatment outcome was used as the external criterion, dichotomised as "good" (operation helped a lot/helped) versus "poor" (operation helped only a little/didn't help/made things worse). The COMI had a high effect size (standardised response mean; SRM) (2.34) for the good global outcome group and a low SRM for the poor outcome group (0.34). The EQ-5D and the NASS-cervical lacked this ability to differentiate between the two groups, showing less distinct SRMs for good and poor outcome groups. CONCLUSIONS: This study provides evidence that the COMI-neck is a valid and responsive questionnaire in the population of patients examined. Further investigations should examine its applicability in other patient groups with less severe neck pain or undergoing other treatment modalities.