miR-371a-3p Predicting Viable Tumor in Patients Undergoing Retroperitoneal Lymph Node Dissection for Metastatic Testicular Cancer: The SWENOTECA-MIR Study.

PURPOSE: The SWENOTECA-MIR prospective multicenter study aims to assess the clinical value of miR-371a-3p as a novel marker in metastatic germ cell tumor patients undergoing retroperitoneal lymph node dissection (RPLND), to predict the presence of viable residual tumor. MATERIALS AND METHODS: A total of 114 patients (86 nonseminomas, 28 seminomas) who underwent surgery for presumed metastatic disease pre chemotherapy (primary RPLND) and post chemotherapy RPLND were included. The expression of miR-371a-3p was evaluated using reverse transcription-digital droplet polymerase chain reaction before and after RPLND. Pre- and postoperative miR-371a-3p levels were statistically compared, and optimism-corrected performance calculations compared with conventional serum tumor markers. Associations were evaluated by logistic regression. Patients who underwent primary RPLND were categorized into seminoma and nonseminoma groups. RESULTS: Among the seminoma patients (n = 24) undergoing primary RPLND, all had normal conventional markers. Six patients received adjuvant treatment before surgery. miR-371a-3p exhibited a sensitivity of 74%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 21% for viable tumor. The levels of miR-371a-3p significantly decreased after surgery. In the nonseminoma group (n = 18) treated with primary RPLND, 22% had elevated conventional markers and 3 had received prior adjuvant treatment. miR-371a-3p showed a sensitivity of 34%, specificity of 88%, positive predictive value of 67%, and negative predictive value of 62% for the primary nonseminoma patients. No association was observed between stage or prior adjuvant treatment and the outcome of the miR test. In the postchemotherapy group (n = 72), the miR-371a-3p sensitivity was 9%, reducing to 0 when excluding patients with seminoma (n = 4). Teratomas and benign histology were essentially negative. CONCLUSIONS: Our study highlights miR-371a-3p as a fairly sensitive and highly specific marker for prechemotherapy seminomas, outperforming conventional markers. However, in prechemotherapy nonseminomas as well as in postchemotherapy patients, we observed low sensitivity and no significant differences in miR-371a-3p levels before and after surgery, suggesting limited utility for miR-371a-3p in this context.

Molecular and histopathological characterization of seminoma patients with highly elevated human chorionic gonadotropin levels in the serum.

Approximately 30% of seminoma (SEM) patients present with moderately elevated human chorionic gonadotropin (hCG) levels at first diagnosis. In case of high hCG serum levels, the presence of a non-SEM component, i.e. choriocarcinoma (CC), may be assumed. To characterize cases described as pure seminoma with high serum hCG levels, tissue samples and DNA were analyzed. Patient files from an international registry were screened for patients with SEM and extraordinarily high hCG serum levels. IHC and qRT-PCR analysis was performed for markers of SEM, embryonal carcinoma (EC) and CC/trophoblast cells. The cell lines TCam-2 (SEM), 2102EP, NCCIT, NT2/D1 (EC) and JAR, JEG3 and BeWo (CC) were included for comparison. Of 1031 SEM patients screened, 39 patients (3.7%) showed hCG serum levels > 1000 U/l. Of these, tumor material for IHC and RNA for qRT-PCR was available from n = 7 patients and n = 3 patients, respectively. Median pre-orchiectomy serum hCG level was 5356 U/l (range: 1224-40909 U/L). Histopathologically, all investigated samples were classified as SEM with syncytiotrophoblast sub-populations. SEM cells were SALL4+ / OCT3/4+ / D2-40+, while syncytiotrophoblast cells were hCG+ / GATA3+ / p63+ and SOX2-/CDX2-. qRT-PCR analysis detected trophoblast stem cell markers CDX2, EOMES and TFAP2C as well as the trophectoderm-specifier TEAD4, but not GATA3. Additionally, SOX17 and PRAME, but not SOX2, were detected, confirming the pure SEM-like gene expression signature of the analyzed samples. In conclusion, excessively increased hCG serum levels can appear in patients with pure SEM. To explain detectable hCG serum levels, it is important to diagnose the subtype of a SEM with syncytiotrophoblasts.

When is a Seminoma not a Seminoma? The Incidence, Risk Factors and Management of Patients With Testicular Seminoma With Discordant Elevated Serum Alpha-fetoprotein.

OBJECTIVE: To describe the incidence, clinical and demographic factors, and treatment patterns associated with discordant elevated alpha-fetoprotein (AFP) findings in patients with pure seminomatous histology. METHODS: We queried the National Cancer Database to identify patients with testicular germ cell tumors (GCT) diagnosed in 2011-2015. Patients were grouped based on histologic diagnosis and pre-operative serum AFP level. RESULTS: Of 18,616 patients diagnosed with testicular GCT, 53% (N = 9,849) had pure seminomatous histology, of whom 8.3% (N = 821) had an elevated serum AFP pre-operatively. Non-white patients with seminoma were more likely to have a pre-op elevated AFP (OR 1.42; 95% CI: 1.10-1.83); patients treated at higher volume centers were less likely to have a pre-op elevated AFP (0.66, 95% CI: 0.53-0.83). Patients with seminoma with elevated AFP received adjuvant radiation more frequently than those with NSGCT (Stage I: 15% vs 0.2%, P <.01; Stage II: 21.9% vs 0.1%, P <.01) and less frequently underwent retroperitoneal lymph node dissection (RPLND) (Stage 1: 1.9% vs 11.1% P <.01; Stage II: 8.8% vs 17.4%, P <.01). CONCLUSION: The detection of elevated serum alpha-fetoprotein (AFP) in patients with pure seminomatous testicular germ cell tumors (GCT) is a discordant finding that implies the presence of occult non-seminomatous GCT (NSGCT) elements. 8% of patients with pure seminomatous GCTs had diagnostically discordant elevated pre-operative AFP levels. Despite recommendations to manage these patients as NSGCT, patients with seminoma and elevated AFP were managed in a fashion comparable to those with seminoma and normal AFP levels.

Tumor markers and 18F-FDG PET/CT after orchiectomy in seminoma: Is there any correlation?

OBJECTIVE: The aim of our study was to analyze the potential relationship between tumor markers and 18F-fluorodoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) results in patients affected by seminoma. MATERIAL AND METHODS: 65 18F-FDG PET/CT scans of 41 patients with diagnosis of seminoma were analyzed and compared to alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG). PET/CT studies were analyzed qualitatively and measuring the maximum and mean standardized uptake value body weight max (SUVbwmax, SUVbwmean), maximum SUV lean body mass (SUVlbm), maximum SUV body surface area (SUVbsa), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of hypermetabolic lesions. All values were compared with serum markers. RESULTS: 31 PET/CT studies were true negative, 28 true positive, 6 false positive and 0 false negative with sensitivity of 100%, specificity of 84%, negative predictive value of 100%, positive predictive value of 82% and accuracy of 91%. No correlation between PET results and tumor marker levels was found and also between AFP and PET/CT semiquantitive parameters. All semiquantitative PET parameters were significantly related to hCG level. CONCLUSIONS: 18F-FDG PET/CT has good accuracy in evaluating patients with relapsed seminoma. HCG levels were significantly correlated with metabolic PET/CT parameters.

The prognostic significance of lactate dehydrogenase levels in seminoma patients with advanced disease: an analysis by the Global Germ Cell Tumor Collaborative Group (G3).

PURPOSE: The prognostic significance of lactate dehydrogenase (LDH) in patients with metastatic seminoma is not defined. We investigated the prognostic impact of LDH levels prior to first-line systemic treatment and other clinical characteristics in this subset of patients. METHODS: Files from two registry studies and one single-institution database were analyzed retrospectively. Uni- and multivariate analyses were conducted to identify patient characteristics associated with recurrence free survival (RFS), overall survival (OS), and complete response rate (CRR). RESULTS: The dataset included 351 metastatic seminoma patients with a median follow-up of 5.36 years. Five-year RFS, OS and CRR were 82%, 89% and 52%, respectively. Explorative analysis revealed a cut-off LDH level of < 2.5 upper limit of normal (ULN) (n = 228) vs. ≥ 2.5 ULN (n = 123) to be associated with a significant difference concerning OS associated with 5-years OS rates of 93% vs. 83% (p = 0.001) which was confirmed in multivariate analysis (HR 2.87; p = 0.004). Furthermore, the cut-off LDH < 2.5 ULN vs. ≥ 2.5 ULN correlated with RFS and CRR associated with a 5-years RFS rate and CRR of 76% vs. 86% (p = 0.012) and 32% vs. 59% (p ≤ 0.001), respectively. CONCLUSIONS: LDH levels correlate with treatment response and survival in metastatic seminoma patients and should be considered for their prognostic stratification.

Comparison of inflammation-based prognostic scores as predictors of survival outcomes in patients with germ cell tumors.

PURPOSE: The aim of this study was to compare the prognostic value of pretreatment inflammation-based scoring systems in terms of overall survival (OS) and progression-free survival (PFS) in patients with germ cell tumors (GCTs) receiving bleomycin, etoposide, and cisplatin (BEP) chemotherapy. MATERIALS AND METHODS: We evaluated 63 patients with GCTs retrospectively. The Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio, prognostic index, platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), systemic immune-inflammation index, and albumin-to-globulin ratio (AGR) were measured in all patients before chemotherapy. To assess the predictive ability of each scoring system, areas under the receiver operating characteristic curve were calculated, and multivariate analysis was performed to identify associations between the predictive scores and OS. RESULTS: Of all the inflammation-based scoring systems, the GPS had the greatest area under the curve (0.847) for predicting OS, followed by the PNI (0.829) and AGR (0.810). Kaplan-Meier analyses revealed that the GPS, PNI, and AGR were significantly associated with OS, whereas the GPS, PLR, and PNI were significantly associated with PFS. In the multivariate analysis, the GPS was an independent predictor of OS and PFS. CONCLUSIONS: We demonstrated that the GPS was the most valuable biomarker of OS and PFS in patients with GCTs.

Management of residual disease after chemotherapy in germ cell tumors.

PURPOSE OF REVIEW: Although testicular cancer remains a highly curable malignancy, challenges and uncertainty still remain in certain aspects of management. Residual disease after chemotherapy in patients with germ cell tumors (GCT) remains one of these challenges. We aim to highlight the recent literature on the management of residual disease after chemotherapy in GCT and the emerging innovations that may provide further guidance into this area. RECENT FINDINGS: A subset of patients with GCT will have residual disease after chemotherapy, and management of these patients involves highly skilled multidisciplinary experts including medical oncologists, surgeons, radiologists, and pathologists. Management options depend on histologic subtype, either seminoma or nonseminoma, and involve size criteria, possible further imaging modalities, and tumor markers. Even with these tools at highly specialized expert centers, uncertainty in management remains, and recent literature has explored the use of newer biomarkers to aid in these cases. SUMMARY: Postchemotherapy residual masses in GCT can prove to be complicated cases to manage. Balancing survival with quality of life outcomes is important and requires a multidisciplinary team experienced in treating GCT.

The relationship of neutrophil to lymphocyte ratio with testicular cancer

ABSTRACT Purpose: To assess the relationship between testicular germ cell tumors (TGCT) and neutrophil to lymphocyte ratio (NLR) and to determine whether this ratio can be used as a serum tumor marker. Material and Methods: Sixty-one patients with testicular germ cell tumors were included into the study. Patients were grouped as localized and non-localized. Histologically patients were categorized as seminoma and nonseminomatous germ cell tumors. Complete blood cell count was measured the day before surgery and at the postoperative 1st month. Preoperative and postoperative mean NLR values were compared. Results: Thirty-six patients (59%) had seminomas and 25 patients (41%) had nonseminomatous testicular cancer. Forty-five patients (73.8%) had localized and 16 patients (26.2%) had non-localized testicular cancer. There was a statistically significant difference between preoperative and postoperative mean NLR of the localized patients (p=0.001) but no such difference was detected for non-localized patients (p=0.576). Nineteen patients with localized seminomas had normal preoperative serum tumor markers. There was a significant difference between preoperative and postoperative mean NLR in this group of patients (p=0.010). Twenty-six patients with localized tumors had preoperative increased serum tumor markers which normalized after orchiectomy. Mean NLR of these patients significantly decreased from 3.10±2.13 to 1.62±0.59 postoperatively (p=0.010). Conclusions: NLR appears to be a useful marker for TGCT. It is successful in predicting localized and non-localized disease in early postoperative period.

The relationship of neutrophil to lymphocyte ratio with testicular cancer.

PURPOSE: To assess the relationship between testicular germ cell tumors (TGCT) and neutrophil to lymphocyte ratio (NLR) and to determine whether this ratio can be used as a serum tumor marker. MATERIAL AND METHODS: Sixty-one patients with testicular germ cell tumors were included into the study. Patients were grouped as localized and non-localized. Histologically patients were categorized as seminoma and nonseminomatous germ cell tumors. Complete blood cell count was measured the day before surgery and at the postoperative 1st month. Preoperative and postoperative mean NLR values were compared. RESULTS: Thirty-six patients (59%) had seminomas and 25 patients (41%) had nonseminomatous testicular cancer. Forty-five patients (73.8%) had localized and 16 patients (26.2%) had non-localized testicular cancer. There was a statistically significant difference between preoperative and postoperative mean NLR of the localized patients (p=0.001) but no such difference was detected for non-localized patients (p=0.576). Nineteen patients with localized seminomas had normal preoperative serum tumor markers. There was a significant difference between preoperative and postoperative mean NLR in this group of patients (p=0.010). Twenty-six patients with localized tumors had preoperative increased serum tumor markers which normalized after orchiectomy. Mean NLR of these patients significantly decreased from 3.10 ± 2.13 to 1.62 ± 0.59 postoperatively (p=0.010). CONCLUSIONS: NLR appears to be a useful marker for TGCT. It is successful in predicting localized and non-localized disease in early postoperative period.

Developing a Highly Specific Biomarker for Germ Cell Malignancies: Plasma miR371 Expression Across the Germ Cell Malignancy Spectrum.

PURPOSE: Our objective was to evaluate operating characteristics, particularly specificity and positive predictive value (PPV), by mapping plasma miR371 expression to actual clinical events in patients with a history of germ cell tumor. PATIENTS AND METHODS: One hundred eleven male patients with a history of or newly diagnosed germ cell tumors were evaluable. Biospecimens obtained before confirmed clinical events were analyzed for miR371 expression with blinding of providers and laboratory personnel to analytic results or clinical status, respectively. Cases (patients with clinically confirmed active germ cell malignancy [aGCM]) and controls (patients with no clinically confirmed aGCM) were assigned over the course of the management. Patients were assigned risk status (high, low, or moderate) based on the composite clinical picture at time points in management. RESULTS: Considering all cases and controls and results of prospectively obtained biosamples analyzed for miR371 expression, 46 (35%) of 132 samples had clinically confirmed aGCM over the course of management; 44 (96%) of these 46 patients had plasma miR371 expression (true positives) with no false positives. Two (4%) of 46 patients had no miRNA expression despite pathologic confirmation of aGCM (false negatives). Plasma miR371 expression in confirmed aGCM had a specificity, sensitivity, positive predictive value, and negative predictive value of 100%, 96%, 100%, and 98%, respectively. Interpretation of sensitivity and negative predictive value is limited by modest follow-up. Specificity and sensitivity were 100% and 98%, 100% and 92%, and 100% and 97% in the low-, moderate-, and high-risk groups, respectively, with a median follow-up time of 15 months. CONCLUSION: Plasma miR371 expression predicts aGCM with high specificity and positive predictive value. Although other operating characteristics of miR371 await longer follow-up for more complete definition, the findings of a highly specific liquid biopsy strongly support moving forward with large-scale, real-world clinical trials to further define full operating characteristics and to identify clinical utility and areas of patient benefit.

Serum Tumour Markers in Testicular Germ Cell Tumours: Frequencies of Elevated Levels and Extents of Marker Elevation Are Significantly Associated with Clinical Parameters and with Response to Treatment.

INTRODUCTION: Although serum tumor markers beta human chorionic gonadotropin (bHCG), alpha-fetoprotein (AFP), and lactate dehydrogenase (LDH) are well-established tools for the management of testicular germ cell tumours (GCTs), there are only few data from contemporary cohorts of primary GCT patients regarding these biomarkers. Our aim was to evaluate marker elevations in testicular GCTs and to document their associations with various clinical characteristics. PATIENTS AND METHODS: A total of 422 consecutive patients with GCTs were retrospectively analysed regarding serum levels of bHCG, AFP, and LDH during the course of treatment. Additionally, the following characteristics were recorded: histology, age, laterality, clinical stage (CS), pT-stage, and tumour size. Marker elevations were first tabulated in dichotomized way (elevated: yes/no) in various subgroups and second as continuous measured serum values. Descriptive statistical methods were employed to look for differences among subgroups and for associations of elevations with clinical parameters. RESULTS: In all GCT patients, the frequencies of elevated levels of bHCG, AFP, LDH, and bHCG or AFP were 37.9%, 25.6%, 32.9%, and 47.6%; in pure seminomas 28%, 2.8%, 29.1%, and 30.3%; and in nonseminoma 53.0%, 60.1%, 38.7%, and 73.8%. Significant associations were noted with pT-stages >pT1, clinical stages >CS1, tumour size, and younger age. Frequencies of marker elevations dropped significantly after treatment, but LDH levels remained elevated in 30.5%-34.1%. Relapsing patients (n=27) had elevated levels of bHCG, AFP, and LDH in 25.9%, 22.2%, and 29.6%, respectively, thirteen of whom with a changed marker pattern. CONCLUSIONS: The classical GCT-biomarkers correlate with treatment success. Clinical utility is limited due to proportions of < 50% of patients with elevated levels and the low specificity of LDH. The elevation rates are significantly associated with histology, clinical and pT-stages, tumour size, and younger age. Individual marker patterns may change upon relapse. Clinically, ideal biomarkers are yet to be found.

What Is the Significance of Rete Testis Invasion by Malign Germ Cell Tumor and Does Hilum Predict Metastasis?

BACKGROUND: The significance of hilar soft tissue invasion of rete testis in malign germ cell tumors is still controversial on current guidelines. OBJECTIVES: We aimed to investigate the importance of hilar soft tissue involvement in germ cell tumors and evaluated the possibility of a risk factor such as rete testis. METHOD: Totally, 59 radical orchiectomy specimens operated between 2007 and 2015 at our clinics. All records were retrospectively researched. Patients' age, level of tumor markers, tumor size, histological subtype, clinical stage, presence or absence of carcinoma in situ, vascular/lymphatic and/or hilar soft tissue invasion, tumoral necrosis, number, site and diameter of metastasis, type of further treatment (radiotherapy or chemotheraphy) and follow-up period were recorded and evaluated for all patients. RESULTS: Twenty-six of totally 59 malign germ cell tumors were seminomatous and 33 were nonseminomatous (NS). Mean patients age was 38.54 years (range 17-89 years). Mean follow-up duration was 39.84 months (range 3-96). Serum tumor marker levels were found associated with rete testis invasion (p = 0.035). Hilar soft tissue invasion was significantly associated with vascular invasion (p = 0.001). As it was expected, vascular invasion was significantly associated with metastasis (p = 0.024). CONCLUSIONS: We concluded that there is a strong association between hilar soft tissue invasion and vascular invasion. Especially in NS germ cell tumors, hilar soft tissue involvement a risk factor for prognosis and to determine the need for additional treatment. According to our study, hilar soft tissue status should be reported on routine pathology report.

Serum Levels of MicroRNA-371a-3p (M371 Test) as a New Biomarker of Testicular Germ Cell Tumors: Results of a Prospective Multicentric Study.

PURPOSE: Previous studies suggested that serum levels of microRNA (miR)-371a-3p (so-called M371 test) have a much higher sensitivity and specificity than the classic markers of testicular germ cell tumors (GCTs) and are applicable toward both seminoma and nonseminoma. We sought to confirm the usefulness of this test as a novel biomarker for GCT. PATIENTS AND METHODS: In a prospective, multicentric study, serum samples of 616 patients with testicular GCTs and 258 male controls were examined for serum levels of miRNA-371a-3p (miR levels) by quantitative polymerase chain reaction. The GCT population encompassed 359 patients with seminoma and 257 with nonseminoma; 371 had clinical stage I disease, 201 had systemic disease, and 46 had relapses. Paired measurements before and after orchiectomy were performed in 424 patients; 118 with systemic disease had serial measurements during treatment. miR levels were compared with those of ß-human chorionic gonadotropin, α-fetoprotein, and lactate dehydrogenase. RESULTS: For the primary diagnosis of GCT, the M371 test showed a sensitivity of 90.1%, a specificity of 94.0%, an area under the curve of 0.966 upon receiver operating characteristic analysis, and a positive predictive value of 97.2%. α-Fetoprotein, ß-human chorionic gonadotropin, and lactate dehydrogenase had sensitivities of less than 50% in seminoma and slightly higher sensitivities in nonseminomas. miR levels were significantly associated with clinical stage, primary tumor size, and response to treatment. Relapses had elevated miR levels that subsequently dropped to normal upon remission. Teratoma did not express miR-371a-3p. CONCLUSION: The M371 test outperforms the classic markers of GCT with both a sensitivity and a specificity greater than 90%. All histologic subgroups, except teratoma, express this marker. The test could be considered for clinical implementation after further validation.

Clinical and radiographic characterization of primary seminomas and nonseminomatous germ cell tumors.

BACKGROUND: Primary malignant mediastinal germ cell tumors (PMMGCTs) including seminomas and nonseminomatous germ cell tumors (NSGCTs) are rare, and sometimes the diagnosis is very difficult. PURPOSE: The purpose of this study is to compare the clinical characteristics, biomarkers, and imaging findings of seminomas and NSGCTs and to determine whether these features could help distinguish these two types of PMMGCT. MATERIAL AND METHODS: A retrospective study of 24 male patients with histopathologically proven PMMGCT was performed. We collected the information of computed tomography (CT) (the scan area ranged from the apex of lung to the costophrenic angles) and magnetic resonance imaging blood test and histology characteristics of these patients. RESULTS: Twelve of 24 cases were confirmed to be seminomas, whereas the other 12 cases were NSGCTs. Alfa-fetoprotein (AFP) was found to be elevated in all patients with NSGCT, whereas none of the patients with seminomas had elevated AFP level. Beta-human chorionic gonadotropin (ß-HCG) level was elevated in all the patients with seminomas (seven/seven), whereas in NSGCT only two of seven patients had elevated ß-HCG. Lactate dehydrogenase level was increased in five of the nine patients with seminomas, as well as in the eight patients with NSGCT. CT imaging revealed that 12 masses from the seminoma group were homogeneous, soft tissue opacity and showed minimal contrast enhancement. On the contrary, all 12 NSGCT cases showed cystic and solid masses; on contrast-enhanced CT, heterogeneous enhancement was found on the capsule of the tumor, septum, and solid masses. CONCLUSION: Seminomas and NSGCT showed different profiles of tumor biomarkers and radiographic features. Evidence from serum test, histopathological analysis, and imaging should be combined to ensure the accurate diagnosis of these two types of PMMGCT.

A Qualitative Analysis of the Impact of Carboplatin AUC 10 on Physical, Work Functioning and Bone Marrow Toxicity Among Seminoma Patients - A Single-centre Experience.

BACKGROUND: Single-agent carboplatin at area under the curve 10 (AUC10) is an effective treatment for metastatic seminoma. As far as we are aware of, there have been no studies reporting its effects on short-term quality of life. The objective was to study the efficacy, safety and tolerability, using health-related quality of life, of carboplatin AUC10 chemotherapy in patients with metastatic seminoma. PATIENTS AND METHODS: Forty-four patients with metastatic seminoma treated at Mount Vernon Cancer Centre with carboplatin AUC10 were included in this study. Response to treatment was determined by radiological imaging (Response Evaluation Criteria in Solid Tumors v 1.1) and serum tumour markers. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events Version 4.0. Quality of life treatment-related toxicities were assessed during treatment at pre-chemotherapy assessments. After treatment, toxicity was assessed using a defined telephone questionnaire consisting of four questions relating to hair loss, hearing impairment, days absent from work, and neuropathy. RESULTS: At a median follow-up of 27.5 (range=4-84) months, no patient had experienced relapse. Grade 3/4 neutropenia was seen in 15 (35%) patients, nine (21%) required prophylactic granulocyte colony-stimulating factor, 13 (30%) patients had grade 3/4 thrombocytopenia. Commonest non-haematological toxicities were fatigue in 28 (65%) and nausea 14 (33%) patients. They were grade 1 in 82% and 92% of cases, respectively. Six out of 44 (14%) had residual tinnitus. One patient had residual grade 1 peripheral neuropathy. Ten patients continued to work throughout treatment and two patients were retired. Of the remaining patients, 16 (37%), took fewer than 5 days off work. CONCLUSION: Carboplatin AUC10 is a safe and effective treatment for stage II/III seminoma with better health-related quality of life than experienced with combination cisplatin-based chemotherapy.

Human Chorionic Gonadotropin Assays for Testicular Tumors: Closing the Gap between Clinical and Laboratory Practice.

BACKGROUND: Clinical practice guidelines recommend the measurement of human chorionic gonadotropin (hCG) and/or hCGß in serum for management of testicular germ cell tumors (GCTs). These guidelines, however, disregard relevant biochemical information on hCG variants to be detected for oncological application. We set out to provide a critical review of the clinical evidence together with a characterization of the selectivity of currently marketed hCG immunoassays, identifying assays suitable for management of GCTs. CONTENT: Evidence sources in the available literature were critically appraised. Most instances of misdiagnosis and mismanagement of testicular GCTs have been associated with hCG results. According to the clinical evidence, 36% of patients with seminoma show an exclusive hCGß increase, and 71% of patients with nonseminomatous GCTs (NSGCTs) show an increase of intact hCG and/or hCG + hCGß, whereas the hCGß increase in NSGCTs is variable according to the tumor stage and histology. SUMMARY: hCG + hCGß assays that display an equimolar recognition of hCG and hCGß, or at least do not overtly underestimate hCGß, may be employed for management of testicular GCTs. Assays that underestimate hCGß are not recommended for oncological application. In addition to the hCG + hCGß assay in service, an additional assay with broader selectivity for other hCG variants should be considered when false-negative or false-positive results are suspected on the basis of clinical data.

Pure Testicular Seminoma with Non-Pathologic Elevation of Alpha Fetoprotein: A Case Series.

BACKGROUND: Pure testicular seminoma does not express alpha fetoprotein (AFP). However, seminoma patients with mildly elevated serum AFP levels are increasingly reported. As this finding may prompt unwarranted treatment measures, we reviewed our experience with AFP levels in seminoma. PATIENTS AND METHODS: We retrospectively registered AFP levels in 254 consecutive seminoma patients, and in 196 male controls with non-malignant diseases. In those with elevated AFP levels, we re-examined the orchiectomy specimens histologically. We reviewed the clinical course and looked for hepatic disorders. RESULTS: Elevated AFP levels were found in 5 patients (1.97%, 95% CI 0.19-3.68) and in 4 controls (2.04%, 95% CI 0.06-4.02). The elevations were modest and kept elevated throughout the clinical course. No hepatic disorders were recorded. Histologically, pure seminoma was confirmed. CONCLUSION: Unspecific AFP elevations occur in about 2% of seminoma patients. Care-givers should be aware of this particular subgroup of seminoma patients to avoid unwarranted treatment burden.

Serum Levels of MicroRNA371a-3p: A Highly Sensitive Tool for Diagnosing and Staging Testicular Germ Cell Tumours: A Clinical Case Series.

INTRODUCTION: MicroRNA (miR)371a-3p was suggested to be a sensitive and specific new serum biomarker of germ cell tumours (GCTs); however, its clinical usefulness remains unproven. PATIENTS, METHODS: In 312 consecutive cases with various testicular diseases, serum levels of miR371a-3p were measured. Measurement results became available only after completion of treatment. Five patients with testicular seminoma were selected for review because of unanticipated clinical courses. RESULTS: In each two patients, elevated miR levels heralded undetected primary testicular GCT and metastases despite inconclusive radiological findings. In one case, a normal miR371a-3p level correctly pointed to the absence of metastases contrary to clinical assessment. In all cases, knowledge about the miR371a-3p levels would have altered the clinical management. CONCLUSIONS: These cases highlight the exceptional usefulness of the new GCT biomarker. In contrast to classical markers, miR371a-3p can identify primary testicular GCT. The marker can aid in clinical decision making in cases with ambiguous clinical findings.