Discriminative capacity of guideline recommendations in the assessment of patients with asymptomatic microhematuria.

BACKGROUND & OBJECTIVE: Asymptomatic microhematuria (aMh) remains a diagnostic challenge in urological practice: while aMh is a risk factor of urothelial carcinoma (UC), prevalence of aMh is high. Guidelines were developed to permit risk stratification and reduce diagnostic workload. This study investigates the efficacy of several recommendations. MATERIAL & METHODS: Sixty hundred eight patients with newly diagnosed aMh without previous UC from an academic referral center (A; n = 320) and a private outpatient clinic (B; n = 288) were included. All patients underwent clinical workup including medical history, urine cytology, upper tract imaging and cystoscopy. Eleven former and current guidelines were applied to each patient individually; every patient was classified as either low risk (no further workup recommended) or high risk. Furthermore, a recently developed nomogram for hematuria assessment was included. RESULTS: The cohort comprised 142 females and 466 males (mean age 62 [range 18-92] years). Sixty-one patients (10.0%) were diagnosed with UC. Excluding the Swedish and recent NICE guideline generally advising against urologic workup, application of 9 other recommendations would have diagnosed all UCs and saved 1.6% to 16.1% of patients from workup. For the 2020 US guideline, solely applied to cohort B, 10.6% of patients were classified as low risk. The use of the nomogram would have saved 17.1% to 25% of patients from workup. CONCLUSIONS: Practical relevance of current guidelines is limited as they do not sufficiently identify patients not requiring clinical work up. Thus, guideline adherence may trigger overdiagnosis and even overtreatment. New ways of risk stratification are needed to improve aMh assessment.

Evaluation of [68Ga]Ga-PSMA PET/CT for therapy response assessment of [177Lu]Lu-PSMA radioligand therapy in metastasized castration refractory prostate cancer and correlation with survival.

PURPOSE: The aim of this retrospective study was to evaluate the use of [68Ga]Ga-PSMA PET/CT in therapy response assessment (TRA) of mCRPC patients treated with [177Lu]Lu-PSMA-617 and its correlation with overall survival (OS). METHODS: Thirty-nine patients were included in the study. Patient-/lesion-based early and late response assessment (ERA/LRA) was defined as PET2 (after two therapy cycles) vs. PET1 (before the first cycle) (n = 29) and end of treatment PET vs. PET1 (n = 17), respectively. PET-based response (PET parameters; modified (m) PERCIST/EORTC), biochemical response (ΔPSA; category-based) and category-based clinical response (CRA) was tested for correlation/agreement. PET-based TRA was correlated with OS. RESULTS: A significant correlation/agreement was shown between PET parameters and CRA as well as biochemical response in LRA of all lesions and between mPERCIST-based and category-based PSA response assessment in LRA (bone lesion-based, P = 0.045, κ = 0.184). At ERA, OS was significantly higher in CR/PR/SD compared to progressive disease applying mPERCIST/EORTC criteria (P = 0.0024). CONCLUSION: In [177Lu]Lu-PSMA-617-treated mCRPC patients OS of the group of CR/PR/SD was significantly higher compared to the progressive disease group (mPERCIST/EORTC) in ERA. Therefore, [68Ga]Ga-PSMA PET might serve as a complementary diagnostic tool for TRA offering prognostic value regarding OS.

Management of Germ Cell Tumours of the Testis in Adult Patients. German Clinical Practice Guideline Part I: Epidemiology, Classification, Diagnosis, Prognosis, Fertility Preservation, and Treatment Recommendations for Localized Stages.

INTRODUCTION: This is the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up on germ cell tumours (GCTs) of the testis in adult patients. We present the guideline content in two publications. Part I covers the topic's background, methods, epidemiology, classification systems, diagnostics, prognosis, and treatment recommendations for the localized stages. METHODS: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search was in March 2018) were provided. Thirty-one experts entitled to vote, rated the final clinical recommendations and statements. RESULTS: We provide 161 clinical recommendations and statements. We present information on the quality of cancer care and epidemiology and give recommendations for staging and classification as well as for diagnostic procedures. The diagnostic recommendations encompass measures for assessing the primary tumour as well as procedures for the detection of metastases. One chapter addresses prognostic factors. In part I, we separately present the treatment recommendations for germ cell neoplasia in situ, and the organ-confined stages (clinical stage I) of both seminoma and nonseminoma. CONCLUSION: Although GCT is a rare tumour entity with excellent survival rates for the localized stages, its management requires an interdisciplinary approach, including several clinical experts. Quality of care is highly related to institutional expertise and can be reassured by established online-based second-opinion boards. There are very few studies on diagnostics with good level of evidence. Treatment of metastatic GCTs must be tailored to the risk according to the International Germ Cell Cancer Collaboration Group classification after careful diagnostic evaluation. An interdisciplinary approach as well as the referral of selected patients to centres with proven experience can help achieve favourable clinical outcomes.

Systematic assessment of complications and outcome of radical cystectomy undertaken with curative intent in patients with comorbidity and over 75 years of age.

OBJECTIVE: To evaluate the complications, survival and oncological outcome of patients ≥75 years of age after radical cystectomy for muscle-invasive bladder cancer. PATIENTS AND METHODS: Between April 1993 and August 2010, 765 patients with muscle-invasive bladder cancer underwent radical cystectomy at one high-volume center. Of these, 70 patients were ≥75 years of age. All 70 patients had at least one severe systemic comorbidity with an American Society of Anesthesiologists score of 3. Primary endpoints of this retrospective study were overall and recurrence-free survival with a mean follow-up of 22 months (1-159). Perioperative parameters such as need for blood transfusions, hospital stay, mortality, short- and long-term complications were also assessed. Complications were graded according to the Clavien-Dindo classification. RESULTS: Perioperative complications occurred in 23/70 patients (33%) with a 30-day mortality rate of 1.4%. 16/70 patients (23%) developed late complications requiring hospitalization. Within 30 days of surgery, according to the Clavien-Dindo grading, 27% had no complications, 3% grade 1, 49% grade 2, 14% grade 3, 6% grade 4 and 1.4% grade 5 complications. Within 31-90 days after surgery, 76% had grade 1 complications, 3% grade 2, 6% grade 3, 9% grade 4 and 6% grade 4 complications. The calculated 5- and 8-year overall survival rates were 30 and 25%, respectively, with a recurrence-free survival rate of 52% at 5 and 42% at 8 years. CONCLUSIONS: Radical cystectomy is an appropriate and effective treatment for comorbid elderly patients. The oncological long-term outcome is the same as in younger patients while overall survival is comparatively lower. Mortality and complication-related morbidity are comparable to those in younger patients with modern perioperative management.

Incidence, prevention, and management of complications following percutaneous nephrolitholapaxy.

CONTEXT: Incidence, prevention, and management of complications of percutaneous nephrolitholapaxy (PNL) still lack consensus. OBJECTIVE: To review the epidemiology of complications and their prevention and management. EVIDENCE ACQUISITION: A literature review was performed using the PubMed database between 2001 and May 1, 2011, restricted to human species, adults, and the English language. The Medline search used a strategy including medical subject headings (MeSH) and free-text protocols with the keywords percutaneous, nephrolithotomy, PCNL, PNL, urolithiasis, complications, and Clavien, and the MeSH terms nephrostomy, percutaneous/adverse effects, and intraoperative complications or postoperative complications. EVIDENCE SYNTHESIS: Assessing the epidemiology of complications is difficult because definitions of complications and their management still lack consensus. For a reproducible quality assessment, data should be obtained in a standardized manner, allowing for comparison. An approach is the validated Dindo-modified Clavien system, which was originally reported by seven studies. No deviation from the normal postoperative course (Clavien 0) was observed in 76.7% of PNL procedures. Including deviations from the normal postoperative course without the need for pharmacologic treatment or interventions (Clavien 1) would add up to 88.1%. Clavien 2 complications including blood transfusion and parenteral nutrition occurred in 7%; Clavien 3 complications requiring intervention in 4.1.%; Clavien 4, life-threatening complications, in 0.6%; and Clavien 5, mortality, in 0.04%. High-quality data on complication management of rare but potentially debilitating complications are scarce and consist mainly of case reports. CONCLUSIONS: Complications after PNL can be kept to a minimum in experienced hands with the development of new techniques and improved technology. A modified procedure-specific Clavien classification should be established that would need to be validated in prospective trials.

Qualitative and quantitative assessment of urinary cytokeratin 8 and 18 fragments compared with voided urine cytology in diagnosis of bladder carcinoma.

OBJECTIVES: To evaluate the value of urine tests based on the detection of cytokeratins 8 and 18 for the diagnosis of bladder cancer compared with urine cytology. METHODS: Samples from 112 patients before transurethral resection (group 1), 40 patients before secondary surgical treatment (group 2), 29 healthy control subjects (group 3, controls), and 10 women with acute urinary tract infection (group 4, controls) were examined with the UBC Rapid and UBC II enzyme-linked immunosorbent assay (ELISA) tests and voided urine cytology. RESULTS: Of the 112 patients in group 1, 90 had transitional cell carcinoma. For the UBC Rapid, UBC ELISA, and cytology, the sensitivity and specificity was 64.4%, 46.6%, and 70.5% and 63.6%, 86.3%, and 79.5%, respectively. The cytology had the greatest accuracy (72.3%) compared with both cytokeratin tests (54.4% and 64.2%). For all three tests, sensitivity increased with tumor grade and stage. In group 2, 16 of 40 patients had residual carcinoma. The sensitivity was similar for all three tests, and the specificity of cytology was lower compared with its specificity in group 1 (47.9% versus 70.5% in group 1). In the controls with or without urinary tract infection, the specificity of cytology was greater than that of both other tests. The combination of the UBC ELISA test with cytology increased the sensitivity to 83% (specificity 68%). CONCLUSIONS: Both cytokeratin tests detected patients with transitional cell carcinoma, but were inferior to voided urine cytology in test quality.