Seasonal Variations in the Diagnosis of Testicular Germ Cell Tumors: A National Cancer Registry Study in Austria.

We conducted a retrospective National Cancer Registry study in Austria to assess a possible seasonal variation in the clinical diagnosis of testicular germ cell tumors (TGCT). In total, 3615 testicular cancer diagnoses were identified during an 11-year period from 2008 to 2018. Rate ratios for the monthly number of TGCT diagnoses, as well as of seasons and half-years, were assessed using a quasi-Poisson model. We identified, for the first time, a statistically significant seasonal trend (p < 0.001) in the frequency of monthly newly diagnosed cases of TGCT. In detail, clear seasonal variations with a reduction in the tumor incidence during the summer months (Apr-Sep) and an increase during the winter months (Oct-Mar) were observed (p < 0.001). Focusing on seasonality, the incidence during the months of Oct-Dec (p = 0.008) and Jan-Mar (p < 0.001) was significantly higher compared to the months of Jul-Sep, respectively. Regarding histopathological features, there is a predominating incidence in the winter months compared to summer months, mainly concerning pure seminomas (p < 0.001), but not the non-seminoma or mixed TGCT groups. In conclusion, the incidence of TGCT diagnoses in Austria has a strong seasonal pattern, with the highest rate during the winter months. These findings may be explained by a delay of self-referral during the summer months. However, the hypothetical influence of vitamin D3 in testicular carcinogenesis underlying seasonal changes in TGCT diagnosis should be the focus of further research.

Management of Germ Cell Tumours of the Testes in Adult Patients: German Clinical Practice Guideline, PART II - Recommendations for the Treatment of Advanced, Recurrent, and Refractory Disease and Extragonadal and Sex Cord/Stromal Tumours and for the Management of Follow-Up, Toxicity, Quality of Life, Palliative Care, and Supportive Therapy.

OBJECTIVES: We developed the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up of germ cell tumours (GCT) of the testes in adult patients. We present the guideline content in 2 separate publications. The present second part summarizes therecommendations for the treatment of advanced disease stages and for the management of follow-up and late effects. MATERIALS AND 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 in March 2018), were provided. Thirty-one experts, who were entitled to vote, rated the final clinical recommendations and statements. RESULTS: Here we present the treatment recommendations separately for patients with metastatic seminoma and non-seminomatous GCT (stages IIA/B and IIC/III), for restaging and treatment of residual masses, and for relapsed and refractory disease stages. The recommendations also cover extragonadal and sex cord/stromal tumours, the management of follow-up and toxicity, quality-of-life aspects, palliative care, and supportive therapy. CONCLUSION: Physicians and other medical service providers who are involved in the diagnostics, treatment, and follow-up of GCT (all stages, outpatient and inpatient care as well as rehabilitation) are the users of the present guideline. The guideline also comprises quality indicators for measuring the implementation of the guideline recommendations in routine clinical care; these data will be presented in a future publication.

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.

Does Determining Tumor Markers from the Testicular Vein Enable Better Diagnosis and Prognosis?

INTRODUCTION: ß-HCG has been the only tumor marker evaluated in testicular vein (VT) blood until now. OBJECTIVE: To evaluate the correlation between the tumor markers ß-HCG, AFP, PLAP, and LDH from the VT and peripheral blood as well as their significance in predicting tumor recurrence and tumor stage. METHODS: Patients with testicular cancer undergoing orchiectomy were studied retrospectively over a period of 20 years. Tumor stage, tumor histology, time to tumor recurrence, and tumor markers from VT and peripheral blood were analyzed. Minimal follow-up was 2 years. Statistical analysis was performed by means of Cox- and logistic regression models and Spearman rank correlation coefficients. RESULTS: A total of 172 patients with an average follow-up of 9.9 years were investigated. The overall recurrence rate was 18% (seminoma patients 20.8%, nonseminoma patients 14.5%). Marker values measured from VT blood were higher than in peripheral blood and correlated strongly with the peripherally measured values. AFP obtained from peripheral blood was the only tumor marker allowing a statement on the recurrence probability. Tumor markers from VT blood showed no correlation with tumor stage. DISCUSSION/CONCLUSION: Tumor markers from VT blood are significantly higher than in peripheral blood. Tumor markers obtained from VT blood do not provide clinical advantage in terms of assessing tumor stage and recurrence probability.

The Correlation of Prostate Volume and Prostate-specific Antigen Levels With Positive Bacterial Prostate Tissue Cultures.

OBJECTIVE: To compare prostate volume and prostate-specific antigen (PSA) levels with bacterial growth in prostate tissue cultures. MATERIALS AND METHODS: Fifty male patients who underwent transurethral prostate resection were investigated prospectively. Resection chips from the prostate gland were added to brain-heart infusion medium and incubated. PSA levels were determined preoperatively at our urology ward. The prostate gland volume was estimated by transabdominal ultrasound examination preoperatively. RESULTS: Persons with positive bacterial prostate tissue cultures have a greater prostate volume. This is significant in patients with and without histopathologic signs of prostatitis. Persons with positive bacterial prostate tissue cultures have higher PSA values. This is significant in patients without histopathologic signs of prostatitis. CONCLUSION: People with positive bacterial prostatic tissue culture have a higher prostate volume in comparison with patients with negative culture findings and show a tendency toward increased PSA levels as well.

Renal Autotransplantation in Metachronous Solitary Contralateral Ureteral Metastasis from Renal Cell Carcinoma: A Case Report.

Ureteral metastasis of renal cell carcinoma (RCC) is rare and usually confined to the ipsilateral ureter. In literature, about 50 cases have been reported so far. Of these, only 14 metastasized metachronously to the contralateral ureter.A seventy-one-year-old man was hospitalized with recurrent painless severe haematuria. Seven years previously, he had undergone radical nephrectomy of the right kidney due to a clearcell renal cell carcinoma (cRCC), Fuhrman grad 2. Intravenous urography and a retrograde ureterogram revealed a filling defect (25 mm) in the left distal ureter, which we expected to be an urothelial carcinoma. Biopsy was not possible, due to ureteral stricture. Diagnostic workup revealed no other sites of metastasis. To preserve kidney function and quality of life we refrainedfrom performing nephroureterectomy and opted for an autotransplantation of the solitary left kidney with ureteral reimplantation in the bladder. We resected the ureter and histopathologicial examination showed a metastasis of cRCC, Fuhrman grade 2.Postoperatively, the patient developed an acute postrenal failure, hence a nephrostomy and a bladder catherization were performed. After this, the patient improved significantly and the drains could be removed. Currently the patient is free of complaints. The residual and contralateral ureter is a potential metastatic site after RCC. Autotransplantation is an option forsurgical treatment.

Prognostic role of N-cadherin expression in patients with non-muscle-invasive bladder cancer.

PURPOSE: To assess the role of N-cadherin as a prognostic biomarker in patients with non-muscle-invasive bladder cancer (NMIBC) treated with transurethral resection with or without adjuvant intravesical therapy. PATIENTS AND METHODS: Immunohistochemistry using monoclonal mouse antibody was used to evaluate the expression status of N-cadherin in 827 patients with NMIBC. N-cadherin was considered positive if any immunoreactivity with membranous staining was detected. Multivariable Cox regression models were performed to evaluate the prognostic effect of N-cadherin on survival outcomes. RESULTS: N-cadherin expression was observed in 333 patients (40.3%); it was associated with pT1 stage and high tumor grade (both were P<0.001). Median follow-up was 55 months (interquartile range: 18-106). On multivariable Cox regression analyses that adjusted for the effect of the standard clinicopathologic features, N-cadherin expression remained associated with recurrence-free survival (P = 0.007) but not progression-free survival (P = 0.3), cancer-specific survival (P = 0.2), or overall survival (P = 0.9). Adding N-cadherin to a model for prediction of disease recurrence modestly improved its discrimination from 72.8% to 73.4%. CONCLUSION: N-cadherin is expressed in approximately 2/5 patients with NMIBC. Its expression is associated with adverse pathological features and higher risk of disease recurrence but not progression. N-cadherin could be incorporated in predictive tools to assist in recurrence prediction helping thereby in patient selection regarding adjuvant therapies and follow-up planning.

Diversity of Bacterial Urine and Prostate Gland Tissue Cultures in Patients Undergoing Transurethral Prostate Gland Resection.

INTRODUCTION: The objective of this study was to identify the types of bacterial colonization of the prostate gland tissue and urine pre- and postoperatively in patients undergoing a transurethral resection (TUR) of the prostate gland. In addition, clinical symptoms and histopathological findings were included. MATERIAL AND METHODS: Forty three patients were investigated. Urine test strips and urine cultures were taken pre- and postoperatively and intraoperatively prostate resection chips were taken for culture. RESULTS: A positive bacterial culture was found in 20 of 43 (46.5%) patients. Preoperatively, a positive bacterial culture was found in 12 patients and postoperatively in 7 patients. Thirteen patients showed a positive culture of the prostate gland tissue. No patient showed the same bacterial isolates in all 3 samples. Postinterventionally, 6 patients of the group with positive bacterial cultures developed complications. From the group of patients without bacterial growth, only one patient developed a postoperative complication. CONCLUSION: The bacterial colonization in the 3 different cultures showed an inhomogeneous spectrum of bacteria without a reproducible pattern. Nevertheless, it clearly demonstrates that the group with a positive culture is at great risk to develop postoperative complications.

Guidelines on Testicular Cancer: 2015 Update.

CONTEXT: This is an update of the previous European Association of Urology testis cancer guidelines published in 2011, which included major changes in the diagnosis and treatment of germ cell tumours. OBJECTIVE: To summarise latest developments in the treatment of this rare disease. Recommendations have been agreed within a multidisciplinary working group consisting of urologists, medical oncologists, and radiation oncologists. EVIDENCE ACQUISITION: A semi-structured literature search up to February 2015 was performed to update the recommendations. In addition, this document was subjected to double-blind peer review before publication. EVIDENCE SYNTHESIS: This publication focuses on the most important changes in treatment recommendations for clinical stage I disease and the updated recommendations for follow-up. CONCLUSIONS: Most changes in the recommendations will lead to an overall reduction in treatment burden for patients with germ cell tumours. In advanced stages, treatment intensification is clearly defined to further improve overall survival rates. PATIENT SUMMARY: This is an update of a previously published version of the European Association of Urology guidelines for testis cancer, and includes new recommendations for clinical stage I disease and revision of the follow-up recommendations. Patients should be fully informed of all the treatment options available to them.

Prevalence and incidence of clinical symptoms of the retroaortic left renal vein.

OBJECTIVE: To analyze the prevalence and incidence of clinical symptoms of retroaortic left renal vein (RLRV) diagnosed incidentally over 10 years by computed tomography (CT). PATIENTS AND METHODS: 7,929 consecutive patients (out- and inpatients) were studied with multidetector CT from January 2000 to April 2011. We retrospectively reviewed RLRV patients' medical records and analyzed their clinical characteristics. RESULTS: A total of 61 out of 7,929 patients had a RLRV, therefore the prevalence was 0.77%. Only 4 of 61 (6.6%) RLRV patients diagnosed by CT scan were clinically symptomatic. RLRV was associated with flank pain and microhematuria in one patient (1.6%), in another one with microhematuria only and in one with ureteropelvic junction obstruction. Furthermore, one patient suffered from arterial hypertension associated with a RLRV. CONCLUSIONS: RLRV is a rare finding, and only a small minority of RLRVs causes symptoms.

EAU guidelines on testicular cancer: 2011 update.

CONTEXT: On behalf of the European Association of Urology (EAU), guidelines for the diagnosis, therapy, and follow-up of testicular cancer were established. OBJECTIVE: This article is a short version of the EAU testicular cancer guidelines and summarises the main conclusions from the guidelines on the management of testicular cancer. EVIDENCE ACQUISITION: Guidelines were compiled by a multidisciplinary guidelines working group. A systematic review was carried out using Medline and Embase, also taking Cochrane evidence and data from the European Germ Cell Cancer Consensus Group into consideration. A panel of experts weighted the references, and a level of evidence and grade of recommendation were assigned. RESULTS: There is a paucity of literature especially regarding longer term follow-up, and results from a number of ongoing trials are awaited. The choice of treatment centre is of the utmost importance, and treatment in reference centres within clinical trials, especially for poor-prognosis nonseminomatous germ cell tumours, provides better outcomes. For patients with clinical stage I seminoma, based on recently published data on long-term toxicity, adjuvant radiotherapy is no longer recommended as first-line adjuvant treatment. The TNM classification 2009 is recommended. CONCLUSIONS: These guidelines contain information for the standardised management of patients with testicular cancer based on the latest scientific insights. Cure rates are generally excellent, but because testicular cancer mainly affects men in their third or fourth decade of life, treatment effects on fertility require careful counselling of patients, and treatment must be tailored taking individual circumstances and patient preferences into account.

A prospective, randomised EORTC intergroup phase 3 study comparing the oncologic outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma.

BACKGROUND: Nephron-sparing surgery (NSS) can safely be performed with slightly higher complication rates than radical nephrectomy (RN), but proof of oncologic effectiveness is lacking. OBJECTIVE: To compare overall survival (OS) and time to progression. DESIGN, SETTING, AND PARTICIPANTS: From March 1992 to January 2003, when the study was prematurely closed because of poor accrual, 541 patients with small (≤5 cm), solitary, T1-T2 N0 M0 (Union Internationale Contre le Cancer [UICC] 1978) tumours suspicious for renal cell carcinoma (RCC) and a normal contralateral kidney were randomised to NSS or RN in European Organisation for Research and Treatment of Cancer Genito-Urinary Group (EORTC-GU) noninferiority phase 3 trial 30904. INTERVENTION: Patients were randomised to NSS (n=268) or RN (n=273) together with limited lymph node dissection (LND). MEASUREMENTS: Time to event end points was compared with log-rank test results. RESULTS AND LIMITATIONS: Median follow-up was 9.3 yr. The intention-to-treat (ITT) analysis showed 10-yr OS rates of 81.1% for RN and 75.7% for NSS. With a hazard ratio (HR) of 1.50 (95% confidence interval [CI], 1.03-2.16), the test for noninferiority is not significant (p=0.77), and test for superiority is significant (p=0.03). In RCC patients and clinically and pathologically eligible patients, the difference is less pronounced (HR=1.43 and HR=1.34, respectively), and the superiority test is no longer significant (p=0.07 and p=0.17, respectively). Only 12 of 117 deaths were the result of renal cancer (four RN and eight NSS). Twenty-one patients progressed (9 after RN and 12 after NSS). Quality of life and renal function outcomes have not been addressed. CONCLUSIONS: Both methods provide excellent oncologic results. In the ITT population, NSS seems to be significantly less effective than RN in terms of OS. However, in the targeted population of RCC patients, the trend in favour of RN is no longer significant. The small number of progressions and deaths from renal cancer cannot explain any possible OS differences between treatment types.

Proposal for a standardized PSA doubling-time calculation.

PURPOSE: Prostate-specific antigen (PSA) doubling-time (PSA-DT) is an important indicator of progression and survival in men with prostate cancer. Three major limitations regarding PSA-DT determination may lead to inconsistent results: the variety of mathematical methods currently applied, the non-standardized handling of input variables and the potential lack of accuracy due to PSA variability. The aim of this project was to develop a reproducible PSA-DT determination tool which simultaneously provides a PSA-DT error estimation. MATERIALS AND METHODS: An internet-based PSA-DT calculation tool via nonlinear optimization implementing the least squares error method using the most recent three PSA values was developed. PSA-DT calculation error is estimated via randomly disturbed measurement data streams (n=65) based on a variable (5-25%) PSA variability. RESULTS: According to a simulation in five men, PSA-DT was calculated to be between 1.7 and 15 month (mean: 6.3 month) and determined with another standard tool between 1.3 and 14.5 month (mean: 4.2 month). CONCLUSION: We present a defined, open and reproducible PSA-DT calculation and PSA-DT error estimation tool based on a standardized PSA data input. This tool is not better compared to other methods but is scientifically standardized and freely accessible via the following internet address: http://adam.drahtwarenhandlung.at/webapp/mg2008/chapter_prostata4/example_psa.

European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): part II.

OBJECTIVES: The first consensus report that had been presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, The Netherlands. METHODS: Medical oncologists, urologic surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference and incorporated the new data into updated and revised guidelines. As for the first meeting the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. RESULTS: The second part of the consensus paper includes the treatment of metastasised disease, residual tumour resection, salvage therapy, follow-up, and late toxicities. CONCLUSIONS: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early-stage as well as of advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged.

Using PSA to guide timing of androgen deprivation in patients with T0-4 N0-2 M0 prostate cancer not suitable for local curative treatment (EORTC 30891).

OBJECTIVE: EORTC trial 30891 compared immediate versus deferred androgen-deprivation therapy (ADT) in T0-4 N0-2 M0 prostate cancer (PCa). Many patients randomly assigned to deferred ADT did not require ADT because they died before becoming symptomatic. The question arises whether serum prostate-specific antigen (PSA) levels may be used to decide when to initiate ADT in PCa not suitable for local curative treatment. METHODS: PSA data at baseline, PSA doubling time (PSADT) in patients receiving no ADT, and time to PSA relapse (>2 ng/ml) in patients whose PSA declined to <2 ng/ml within the first year after immediate ADT were analyzed in 939 eligible patients randomly assigned to immediate (n=468) or deferred ADT (n=471). RESULTS: In both arms, patients with a baseline PSA>50 ng/ml were at a>3.5-fold higher risk to die of PCa than patients with a baseline PSA12 mo. Time to PSA relapse after response to immediate ADT correlated significantly with baseline PSA, suggesting that baseline PSA may also reflect disease aggressiveness. CONCLUSIONS: Patients with a baseline PSA>50 ng/ml and/or a PSADT<12 mo were at increased risk to die from PCa and might have benefited from immediate ADT, whereas patients with a baseline PSA<50 ng/ml and a slow PSADT (>12 mo) were likely to die of causes unrelated to PCa, and thus could be spared the burden of immediate ADT.