Comparative cost-effectiveness of contemporary treatment strategies for stage IIA seminoma.

BACKGROUND: The Surgery in Early Metastatic Seminoma (SEMS) trial examined retroperitoneal lymph node dissection as first-line treatment for patients with isolated 1-3 cm retroperitoneal lymphadenopathy. To date, the standard of care for these patients has been either chemotherapy or radiotherapy. Herein, we evaluated the relative cost-effectiveness of these management strategies. METHODS: A microsimulation model assessed the cost-effectiveness of retroperitoneal lymph node dissection, chemotherapy, and radiotherapy for stage IIA seminoma. Sensitivity analyses were performed to evaluate model robustness. Retroperitoneal lymph node dissection recurrence probabilities were obtained from the SEMS trial. All other probability and utility values were obtained from published literature. Primary outcomes included costs from a commercial insurer's perspective, effectiveness (quality adjusted life-years [QALYs]), and incremental cost-effectiveness ratios using a willingness-to-pay threshold of $100 000/QALY. RESULTS: At a lifetime horizon, the mean costs per patient for retroperitoneal lymph node dissection, radiotherapy, and chemotherapy were $58 469, $98 783, and $104 096, and the mean QALYs were 40.61, 40.70, and 39.15, respectively. Retroperitoneal lymph node dissection was found to be the most cost-effective approach because of high costs and accrued disutility of chronic toxicities associated with radiotherapy (cost-effectiveness ratios = $433 845/QALY) and chemotherapy (dominated). On 1-way sensitivity analyses, retroperitoneal lymph node dissection was no longer cost-effective if the probabilities of infertility and cardiovascular toxicity after radiotherapy were less than 13% and 16%, respectively, or if the 2-year probability of progression after retroperitoneal lymph node dissection was more than 26%. CONCLUSIONS: Retroperitoneal lymph node dissection was the most cost-effective treatment approach for stage IIA seminoma. These findings support clinical guideline consideration of including retroperitoneal lymph node dissection as a treatment option for well-selected patients with stage IIA seminoma.

H&E and OCT4/CD34 for the assessment of lympho-vascular invasion in seminoma and embryonal carcinoma.

BACKGROUND: Lymphovascular invasion (LVI) is a relevant prognostic factor in germ cell tumors of the testis (GCTT), and it is included in the pT stage. However, its detection on hematoxylin and eosin (H&E) slides is very challenging, and previous studies reported fair to moderate inter-observer agreement among dedicated uropathologists. In the present study, we tested H&E and a recently developed in-house double staining for OCT4/CD34 to detect LVI in GCTT. METHODS: Nine authors [5 non-uropathologists and 4 uropathologists] independently evaluated 34 consecutive and retrospectively enrolled cases of GCTT. We assessed the inter-observer agreement (Fleiss's Kappa) with both H&E and OCT4/CD34. Besides, we compared the consensus diagnosis on both H&E and OCT4/CD34-stained sections with the original diagnosis to evaluate the pT re-staging (McNemar test) and identify the sources of disagreement. RESULTS: The inter-observer agreement among uropathologists plus non-uropathologists was fair with both H&E (KF=0.398; p < 0.001) and OCT4/CD34 (KF=0.312; p < 0.001). OCT4/CD34 (KF=0.290; p < 0.001) slightly reduces the inter-observer agreement compared to H&E (KF=0.321; p < 0.001) for non-uropathologists; in contrast, OCT4/CD34 (KF=0.293; p < 0.001) significantly reduces the inter-observer agreement compared to H&E (KF=0.529; p < 0.001) for uropathologists, changing it from moderate to fair. Consensus diagnosis with H&E modified the LVI status of the original diagnosis in 8/34 (23.5 %) cases (p: 0.070), with pT re-staging in 2/34 (5.9 %) cases (p: 0.500). Consensus diagnosis with OCT4/CD34 modified the LVI status of the original diagnosis in 8/34 (23.5 %) cases (p: 0.289), with pT re-staging in 3/34 (8.8 %) cases (p: 0.250). The consensus diagnosis with OCT4/CD34 modified the consensus diagnosis with H&E in 8/34 (23.5 %) cases (p: 0.727), and these findings resulted in pT-restaging in 3/34 (8.8 %) cases (p: 0.500). The sources of disagreement among uropathologists were: H&E [artefactual clefts misinterpreted as LVI in 4/6 (66.7 %) cases and true foci of LVI misinterpreted as clusters of histiocytes within the vessels in 2/6 (33.3 %) cases], OCT4/CD34 [artefactual clefts misinterpreted as LVI in 2/8 (25 %) cases, true LVI misinterpreted as artefactual clefts in 2/8 (25 %) cases or floaters in 4/8 (50 %) cases]. CONCLUSIONS: OCT4/CD34 does not improve the inter-observer agreement for the assessment of LVI in OCT4(+) GCTT. Consensus diagnosis with H&E modifies the LVI status in a significant number of cases, resulting in changes of the pT stage in a relatively small subgroup. Consensus diagnosis with OCT4/CD34 provides little additional benefit since it cannot exclude mimickers of LVI such as floaters and artefactual clefts. These results argue against the adoption of this diagnostic tool for the routine assessment of OCT4(+) GCTT.

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.

Primary mediastinal germ cell tumours with high prevalence of somatic malignancy: An experience from a single tertiary care oncology centre.

BACKGROUND: Primary mediastinal germ tumours (PMGCT) constitute, a mere 3-4% of all germ cell tumours (GCT). Although they account for approximately 16% of mediastinal tumours in adults and 19-25% in children as per western literature, there is hardly any large series on PMGCT reported from the Indian subcontinent. DESIGN: We have retrospectively analysed clinicopathological features of 98 cases of PMGCT diagnosed over 10 years (2010-2019) from a tertiary-care oncology centre. RESULTS: The study group (n = 98) comprised predominantly of males (n = 92) (M:F ratio-15:1), with an age range between 3 months to 57 years (median: 25 years). The tumours were predominantly located in the anterior mediastinum (n = 96). Broadly, Non-seminomatous germ cell tumours (NSGCT) were more common (n = 73, 74%) compared to pure seminoma (n = 25, 26%). Mixed NSGCT was the most common histological subtype (n = 30) followed by pure mature teratoma (n = 18), pure Yolk sac tumour (n = 13), mixed seminoma and NSGCT (n = 5), pure immature teratoma (n = 3) and GCT; NOS (n = 4). Interestingly, all female patients had exclusive teratomas. Nine cases revealed secondary somatic malignancy (5 carcinomas and 4 sarcomas). The majority of patients received neoadjuvant chemotherapy (n = 71). Surgical excision was performed in 60 patients. Follow up was available in 68 patients. NSGCT showed a poor prognosis as compared to seminoma (p value = 0.03) and tumours with somatic malignancies had a more aggressive clinical course. CONCLUSION: PMGCT was seen predominantly in young adult males and somatic malignancies were noted in as high as 9% of cases. Patient with somatic malignancy have aggressive clinical course, hence, extensive sampling and careful histopathological evaluation are recommended for the identification and definitive characterization.

Testicular cancer follow-up costs in Germany from 2000 to 2015.

PURPOSE: Advances in testicular cancer screening and therapy increased 10-year survival to 97% despite a rising incidence; eventually expanding the population of survivors requiring follow-up. We analyzed 10-year follow-up costs after testicular cancer treatment in Germany during 2000, 2008, and 2015. METHODS: Testicular cancer follow-up guidelines were extracted from the European Association of Urology. Per patient costs were estimated with a micro-costing approach considering direct and indirect medical expenses derived from expert interviews, literature research, and official scales of tariffs. Three perspectives covering costs for patients, providers, and insurers were included to estimate societal costs. Cost progression was compared across cancer histology, stage, stakeholders, resource use, and follow-up years. RESULTS: Mean 10-year follow-up costs per patient for stage I seminomatous germ-cell tumors (SGCT) on surveillance declined from EUR 11,995 in 2000 to EUR 4,430 in 2015 (p < 0.001). Advanced SGCT spending shrank from EUR 13,866 to EUR 9,724 (p < 0.001). In contrast, expenditure for stage II SGCT increased from EUR 7,159 to EUR 9,724 (p < 0.001). While insurers covered 32% of costs in 2000, only 13% of costs were reimbursed in 2015 (p < 0.001). 70% of SGCT follow-up resources were consumed by medical imaging (x-ray, CT, ultrasound, FDG-PET). Spending was unevenly distributed across follow-up years (years 1-2: 50%, years 3-5: 39%, years 5-10: 11%). CONCLUSIONS: The increasing prevalence of testicular cancer survivors caused German statutory insurers to cut per patient cost by up to 80% by budgeting services and decreasing reimbursement rates. The economic burden was gradually redistributed to patients and providers.

Assessment of Prognostic Factors of Racial Disparities in Testicular Germ Cell Tumor Survival in the United States (1992-2015).

OBJECTIVE: Testicular germ cell tumors (TGCT) are the most common cancer among men aged 15 to 39 years. Previous studies have considered factors related to TGCT survival rate and race/ethnicity, but histological type of the diagnosed cancer has not yet been thoroughly assessed. METHODS: The data came from 42,854 eligible patients from 1992 to 2015 in the Surveillance Epidemiology and End Results 18. Frequencies and column percent by seminoma and nonseminoma subtypes were determined for each covariates. We used Cox proportional hazard regression to assess the impact of multiple factors on post-diagnostic mortality of TGCT. RESULTS: Black males were diagnosed at a later stage, more commonly with local or distant metastases. The incidence of TGCT in black non-seminoma tumors increased most significantly. The difference in survival rates between different ethnic and histological subtypes, overall survival (OS) in patients with non-seminoma was significantly worse than in patients with seminoma. The most important quantitative predictor of death was the stage at the time of diagnosis, and older diagnostic age is also important factor affecting mortality. CONCLUSION: Histological type of testicular germ cell tumor is an important factor in determining the prognosis of testicular cancer in males of different ethnic groups.

Potential biomarkers for testicular germ cell tumour: Risk assessment, diagnostic, prognostic and monitoring of recurrence.

Testicular germ cell tumour (TGCT) is considered a relatively rare malignancy usually occurring in young men between 15 and 35 years of age, and both genetic and environmental factors contribute to its development. The majority of patients are diagnosed in an early-stage of TGCTs with an elevated 5-year survival rate after therapy. However, approximately 25% of patients show an incomplete response to chemotherapy or tumours relapse. The current therapies are accompanied by several adverse effects, including infertility. Aside from classical serum biomarker, many studies reported novel biomarkers for TGCTs, but without proper validation. Cancer cells share many similarities with embryonic stem cells (ESCs), and since ESC genes are not transcribed in most adult tissues, they could be considered ideal candidate targets for cancer-specific diagnosis and treatment. Added to this, several microRNAs (miRNA) including miRNA-371-3p can be further investigated as a molecular biomarker for diagnosis and monitoring of TGCTs. In this review, we will illustrate the findings of recent investigations in novel TGCTs biomarkers applicable for risk assessment, screening, diagnosis, prognosis, prediction and monitoring of the relapse.

Cost-effectiveness Analysis of Non-risk-adapted Active Surveillance for Postorchiectomy Management of Clinical Stage I Seminoma.

BACKGROUND: Cancer-specific survival for men with clinical stage I (CSI) seminoma approaches 100%, regardless of the management approach chosen after orchiectomy. Given the young age and high survival rate of these patients, there has been a shift toward minimizing treatment-related morbidity and cost. In this context, non-risk-adapted active surveillance (NRAS) has emerged as a desirable management strategy. OBJECTIVE: To evaluate the clinical, quality of life, and economic values of postorchiectomy NRAS for CSI seminoma. DESIGN, SETTING, AND PARTICIPANTS: We developed a decision analytic Markov model to estimate the costs and health outcomes of competing postorchiectomy management strategies for otherwise healthy 30-yr-old men with CSI seminoma. INTERVENTION: Real-world current practice, comprising active surveillance and adjuvant therapies (reference arm), was compared with empiric adjuvant radiotherapy (option 1), empiric adjuvant chemotherapy (option 2), risk-adapted active surveillance (RAAS; option 3), and NRAS (option 4). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Quality-adjusted life-years (QALYs), medical costs, incremental cost-effectiveness ratio, mortality, and unnecessary treatment avoidance were estimated over a 10-yr period. Uncertainties in model input values were accounted for using univariate, scenario, and probabilistic sensitivity analyses. RESULTS AND LIMITATIONS: NRAS dominated all other management options, offering the lowest per-patient health care cost ($3839) and the highest QALYs gained (7.74) over 10 yr. On probabilistic sensitivity analysis, NRAS had the highest chance of being most cost effective. Although NRAS resulted in the highest rate of salvage chemotherapy (20% vs 6% radiotherapy, 6% chemotherapy, 15% current practice, and 16% RAAS), it had the same mortality rate compared to current practice (2.5%). NRAS also allowed 80% of patients to avoid unnecessary treatment compared with 46% for current practice and 52% for RAAS. Study limitations included model simplifications, model parameter assumptions, as well as the absence of patient preference as a decision factor. CONCLUSIONS: NRAS maintains high cure rates for CSI seminoma, minimizes unnecessary treatment, and is cost effective compared with other management strategies. PATIENT SUMMARY: Clinical stage I (CSI) seminoma is one of the most common forms of testicular cancer. Surgery is the first step in the treatment of men with this disease, and some men may receive additional treatment with radiation or chemotherapy afterward. As most men are cured with surgery alone, non-risk-adapted active surveillance (NRAS), which involves routine monitoring with imaging and blood tests for disease recurrence after surgery, has become a desirable treatment option. Our study shows that in addition to maintaining high survival rates and avoiding unnecessary radiation and chemotherapy, NRAS is cost effective for the health care system.

Contemporary Assessment of Survival Rates in Stage I Testicular Seminoma: A Population-Based Comparison Between Surveillance and Active Treatment After Orchiectomy.

BACKGROUND: We tested contemporary surveillance and active treatment (AT) that included chemotherapy (CHT) and radiotherapy (RT) rates for stage I testicular seminoma patients, as well as cancer-specific mortality (CSM) and other-cause mortality (OCM) rates. PATIENTS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (1988-2015) we identified 11,206 stage I testicular seminoma patients. Surveillance versus CHT versus RT use rates were investigated using estimated annual percentage change (EAPC) analyses. After propensity score (PS) matching, cumulative incidence plots and multivariable competing risks regression models (MCRRMs) tested for CSM and OCM. RESULTS: Of all 11,206 patients, 4434 (40%), 918 (8%), and 5854 (52%), respectively, underwent surveillance, CHT, or RT after initial orchiectomy. Surveillance (EAPC: 7.5%; P < .001) and CHT (EAPC: 13.5%; P < .001) rates increased over time, whereas RT rates decreased (EAPC: -3.8%; P < .001). After PS matching, in MCRRMs surveillance was an independent predictor of CSM, relative to AT (hazard ratio [HR], 2.59; P = .04). Conversely, surveillance versus AT did not affect OCM (HR, 1.52; P = .051). All other analyses that focused on CSM and OCM, namely surveillance versus RT, surveillance versus CHT, and RT versus CHT resulted in nonsignificant differences (all P > .5). CONCLUSION: Surveillance and CHT use in stage I testicular seminoma rates increased, whereas RT rate decreased over time. A protective effect of AT defined as either RT or CHT was identified on CSM, relative to surveillance. This protective effect was not described for OCM. No differences in survival were recorded, when individual management strategies (surveillance vs. RT vs. CHT) were compared with each other.

Economy of Standards: European Association of Urology Guideline Changes Influence Treatment Costs in Stage I Testicular Cancer Patients.

OBJECTIVE: The study aimed to calculate direct medical costs (DMC) during the first year of diagnosis and to evaluate the impact of guideline changes on treatment costs in clinical stage (CS) I testicular germ cell tumor (TGCT) patients in a German healthcare system. MATERIALS AND METHODS: Healthcare expenditures as DMC during the first year of diagnosis for 307 TGCT patients in CS I treated at our institution from 1987 to 2013 were calculated from the statutory health insurance perspective using patient level data. Three periods were defined referring to the first European Association of Urology (EAU) guideline in 2001 as well as to subsequent major guideline changes in 2005 and 2010. Data source for cost calculations were the German Diagnosis Related Groups system for inpatient stays (version 2014) and the German system for reimbursement of outpatient care (EBM - Einheitlicher Bewertungsmaßstab, edition 2014). RESULTS: During our 25 years of study period, mean DMC in the first year after diagnosis for the entire cohort of TGCT patients in CS I almost halved from EUR 13.000 to EUR 6.900 (p < 0.001). From 1987 to 2001, DMC for CS I seminomatous germ cell tumor (SGCT) patients were EUR 13.790 ± 4.700. From 2002 to 2010, mean costs were EUR 10.900 ± 5.990, and from 2011 to 2013, mean costs were EUR 5.190 ± 3.700. For CS I non-seminomatous germ cell tumor (NSGCT) patients, from 1987 to 2001, mean DMC were EUR 11.650 ± 5.690. From 2002 to 2010, mean costs were EUR 11.230 ± 5.990, and from 2011 to 2013, mean costs were EUR 11.170 ± 7.390. Follow-up examinations became less frequent over time, which caused a significant cost reduction for NSGCT (p = 0.042) while costs remained stable for SGCT. When adding costs of relapse treatment, active surveillance (AS) was the most cost-effective adjuvant treatment option in CS I NSGCT whereas one course carboplatin or AS caused similar expenditures in SGCT patients. CONCLUSION: The introduction of the EAU guidelines in 2001 caused a decrease in DMC in CS I seminoma patients. This cost reduction mainly took place due to the declining importance of radiation therapy. No substantial changes were seen in patients with CS I NSGCT. Costs for follow-up care also diminished, but to a lesser degree. Even when considering expenditures for relapse treatment, AS remained cost-effective in CS I TCGT patients. Our data show that evidence-based medicine in TGCT can reduce DMC in the first year after diagnosis.

Prevalence and Management of Incidental Small Testicular Masses Discovered on Ultrasonographic Evaluation of Male Infertility.

PURPOSE: We report the safety of surveillance of small testicular masses incidentally discovered during evaluation of male infertility. MATERIALS AND METHODS: We retrospectively reviewed a prospectively collected database to identify patients with male infertility found to have incidental small testicular masses (hypoechoic lesions less than 10 mm) on scrotal ultrasound. The men were offered close surveillance with interval imaging and office followup. Patient and imaging characteristics were collected to compare the surveillance and surgical groups with additional comparisons between benign and malignant pathologies to elucidate predictors of underlying malignancy. RESULTS: Of 4,088 men in whom scrotal ultrasound was completed for male infertility evaluation 120 (2.9%) were found to have a subcentimeter testicular mass. Average followup was 1.30 years (range 0.1 to 16.9). A total of 18 men (15%) proceeded to extirpative surgery while 102 remained on surveillance at last followup. In those with at least 1 month of followup the mean lesion growth rate was -0.01 mm per year. Reasons for surgery included testicular exploration for infertility, mass growth, positive tumor markers, history of testis cancer, concerning imaging characteristics and patient choice. Six of the 18 men who underwent surgery were found to have malignancy, which was seminoma in all. All malignant lesions were greater than 5 mm on initial imaging and demonstrated vascularity, although size and vascularity were not significantly different from those of benign lesions on final pathology findings. No patients demonstrated advanced or recurrent disease. CONCLUSIONS: Small testicular masses are not uncommon, especially in the infertile male population. Most of these masses do not show significant growth during long-term evaluation and can be safely surveilled with close followup.

[Incidence and Risk Assessment of Tumor Lysis Syndrome in Patients with Advanced Germ Cell Cancer].

Tumor lysis syndrome (TLS) is a major oncological emergency. TLS is common in patients with hematological malignancies, but it can occur across a spectrum of cancer types. Germ cell tumors (GCT) have rapid cancer cell turnover and often present with bulky metastasis. The international TLS expert consensus panel has recommended guidelines for a medical decision tree to assign low, intermediate and high risk to patients with cancer at risk for TLS. GCT is classified as intermediate risk for TLS, and the patients who have other TLS risks factors are classified to be at high risk for TLS. In this study, we retrospectively analyzed 67 patients with metastatic GCT who were treated with induction chemotherapy at Tsukuba University Hospital between 2000 and 2013. Thirty-one, 15 and 21 patients were classified with good-, intermediate- and poor-prognosis disease, respectively, according to the International Germ Cell Cancer Collaborative Group criteria. Twelve patients (18%) were classified to be at high risk for TLS, and two patients were treated with allopurinol or rasburicase as prophylaxes for TLS. They did not show progression to laboratory TLS (L-TLS). In the remaining 10 TLS high-risk patients, three (30%) patients developed L-TLS after chemotherapy and started receiving oral allopurinol. As a result, no patients developed clinical TLS (C-TLS). In this study, 30% of TLS-high risk patients developed L-TLS without prophylactic treatment. Therefore, it is important to conduct TLS-risk stratification and consider prophylaxis such as rasburicase for advanced GCT patients at induction chemotherapy.

Management and outcomes of clinical stage IIA/B seminoma: Results from the National Cancer Data Base 1998-2012.

PURPOSE/OBJECTIVE: Disease-specific survival for testicular seminoma approaches 100%, even for those with node-positive disease. We sought to describe modern practice patterns, survival outcomes, and factors associated with postoperative therapy for patients with clinical stage (CS) IIA/B disease. METHODS AND MATERIALS: Data on patients diagnosed with CS IIA/B seminoma from 1998 to 2012 were extracted from the National Cancer Data Base. Demographic, clinical, treatment, and payer characteristics were evaluated using multivariate regression to identify factors associated with receipt of chemotherapy or radiation therapy (RT) within 6 months of orchiectomy. Five-year Kaplan-Meier overall survival (OS) by CS and treatment was calculated. A Cox proportional hazards regression for 5-year OS was performed. RESULTS: A total of 1885 patients were included; 38.5% received chemotherapy and 61.5% received RT. On multivariate analysis, factors associated with receipt of postorchiectomy RT rather than chemotherapy included CS IIA (odds ratio [OR], 3.04; P < .01) and community treatment setting (OR, 1.81-2.76; P < .01). Reduced likelihood of receiving RT was associated with Medicaid insurance (OR, 0.50; P < .01), more recent year of diagnosis (continuous OR, 0.93; P < .01), and primary pathologic tumor 3/4 stage (OR, 0.47; P < .01). On multivariate Cox regression, decreased 5-year OS was associated with receipt of chemotherapy in CS IIA patients (hazard ratio, 13.33; P < .01) but not in CS IIB patients (hazard ratio, 1.39; P = .45). For CS IIA, 5-year OS was 99.4% for orchiectomy and RT versus 91.2% for orchiectomy and chemotherapy (log-rank P < .01). For CS IIB, 5-year OS was 96.1% for orchiectomy and RT versus 92.8% for orchiectomy and chemotherapy (log-rank P = .08). CONCLUSIONS: Consistent with national guideline recommendations, our analysis supports preferred status for RT in CS IIA. In addition, these data also support use of RT for CS IIB. CS, treatment year, primary pathologic tumor stage, insurance, and facility type were associated with type of postoperative therapy. Longer follow-up to account for potential late effects of treatment is needed.

Disparities in Adolescent and Young Adult Survival After Testicular Cancer Vary by Histologic Subtype: A Population-Based Study in California 1988-2010.

PURPOSE: Testicular cancer is the most common cancer among adolescent and young adult (AYA) men 15-39 years of age. This study aims to determine whether race/ethnicity and/or neighborhood socioeconomic status (SES) contribute independently to survival of AYAs with testicular cancer. METHODS: Data on 14,249 eligible AYAs with testicular cancer diagnosed in California between 1988 and 2010 were obtained from the population-based California Cancer Registry. Multivariable Cox proportional hazards regression was used to examine overall and testicular cancer-specific survival and survival for the seminoma and nonseminoma histologic subtypes according to race/ethnicity, census-tract level neighborhood SES, and other patient and clinical characteristics. RESULTS: Compared with White AYAs, Hispanic AYAs had worse overall and testicular cancer-specific survival (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.07-1.37) and Black AYAs had worse overall survival (HR, 1.41; 95% CI, 1.01-1.97), independent of neighborhood SES and other demographic and clinical factors. Racial/ethnic disparities in survival were more pronounced for nonseminoma than for seminoma. AYAs residing in middle and low SES neighborhoods experienced worse survival across both histologic subtypes independent of race/ethnicity and other factors, while improvements in survival over time were more pronounced for seminoma. Longer time to treatment was also associated with worse survival, particularly for AYAs with nonseminoma. CONCLUSION: Among AYAs, race/ethnicity, and neighborhood SES are independently associated with survival after testicular cancer. Variation in disparities by histologic type according to demographic factors, year of diagnosis, and time to treatment may reflect differences in prognosis and extent of treatment for the two histologies.

Assessment of intravascular granulomas in testicular seminomas and their association with tumour relapse and dissemination.

AIMS: First, to determine the frequency of intravascular granulomas (IVGs) in seminomas and assess for the presence of entrapped seminoma cells. Second, to identify the relationship of this unusual form of vascular space invasion with tumour relapse and/or dissemination. METHODS: 86 cases of seminoma were reviewed to identify IVGs. Immunostaining for OCT3/4 and CD68 was performed. Pathological stage, presence of conventional vascular and rete testis invasion, parenchymal granulomas and follow-up were recorded. Multivariable analysis incorporating tumour size, vascular invasion (conventional granulomas and IVGs) and rete testis invasion was performed. RESULTS: IVGs were identified in 13 cases (13/86). CD68 confirmed histiocytes in all cases. OCT3/4 identified tumour cells in 9/13 seminomas. 27 patients had disease progression with either dissemination at presentation (n=11) or relapse (n=16). Of these 27 patients, 8 had IVG (29.6%). By comparison, 6 of 57 clinical stage 1 seminomas that did not relapse had IVG (10.53%). Multivariable analysis revealed that no single parameter was statistically significant at predicting tumour relapse and/or dissemination (size: HR 1.65; CI 0.71 to 3.82, p=0.24, rete testis invasion: HR 1.04; CI 0.48 to 2.26, p=0.92, lymphovascular space invasion/IVG: HR 1.62; CI 0.65 to 4.01, p=0.30). CONCLUSIONS: IVGs may represent a previously unrecognised form of vascular space invasion in seminomas. Studies on larger cohorts are needed to demonstrate its clinical value.

Interim (18)F-Fluorodeoxyglucose Positron Emission Tomography for Early Metabolic Assessment of Response to Cisplatin, Etoposide, and Bleomycin Chemotherapy for Metastatic Seminoma: Clinical Value and Future Directions.

BACKGROUND: In patients with metastatic seminoma, designing a risk-adapted strategy that may help personalize the burden of treatment and follow-up is required. PATIENTS AND METHODS: Patients who were administered cisplatin, etoposide, and bleomycin (PEB) were staged at baseline with computed tomography (CT), positron emission tomography (PET), and serum tumor markers. Restaging was then performed with PET after 2 cycles of PEB (PET2) and with CT after 3 to 4 cycles of treatment. The 20% cutoff of maximal standardized uptake value (SUVmax) changes and Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) criteria were applied to define the response. The Wilcoxon rank sum test was used to analyze the association between metabolic response and the shrinkage of target lesions. RESULTS: Between February 2009 and November 2013, 37 patients were enrolled. After 2 cycles of PEB, 27 patients (72.9%; 95% confidence interval [CI], 55.8-86.2) had a metabolic complete response (CR) and 10 patients had a partial response (PR; 27%; 95% CI, 13.8-44.1). A significant association was found between PET2 response and baseline (P = .003), final diameter (P < .001), and percentage of tumor shrinkage (P = .014) of target lesions. After 18 months' (interquartile range [IQR], 13-23) median follow-up, 2 patients with PET2 PR had relapsed disease; none of those with a CR had relapsed disease. CONCLUSIONS: A significant association was found between early metabolic response and tumor shrinkage in patients with advanced seminoma. Patients achieving a PET2 CR could be predicted not to need additional treatment after PEB, and simplifying their follow-up should be an end point. PET2 might also identify difficult to treat cases at an early stage.

Management trends in stage I testicular seminoma: Impact of race, insurance status, and treatment facility.

BACKGROUND: The management of stage I testicular seminoma is evolving rapidly. This study examined modern trends in the management of stage I testicular seminoma and the effects of sociodemographic factors on therapy choice. METHODS: Data from the National Cancer Data Base on 34,067 patients with stage I testicular seminoma who were treated between 1998 and 2011 were analyzed. Multivariate logistic regression models were used to assess factors associated with adjuvant management strategies. RESULTS: For patients with stage IA/B testicular seminoma, rates of observation after orchiectomy increased from 23.7% to 54.0%, the receipt of adjuvant chemotherapy increased from 1.5% to 16.0%, and the receipt of radiotherapy decreased from 70.8% to 28.8%. A similar pattern was seen in stage IS testicular seminoma, although these patients were more likely to receive adjuvant radiotherapy/chemotherapy (60.7% vs 44.8% for stage IA/B in 2011, P < .001). For patients with stage IA/B testicular seminoma, observation after orchiectomy was more common in racial minorities (odds ratio [OR] for blacks vs whites, 1.31, P < .001; OR for Hispanics vs whites, 1.39, P < .001) and in the uninsured (OR for uninsured vs privately insured, 1.33, P < .001) and less common at community centers (OR for community centers vs National Cancer Institute-designated cancer centers, 0.80, P = .044). In those with stage IA/B testicular seminoma who received adjuvant radiotherapy/chemotherapy, the receipt of chemotherapy was more common at academic centers and for patients with nonprivate insurance. CONCLUSIONS: Postorchiectomy observation in stage I testicular seminoma has increased significantly in recent years, as has the receipt of chemotherapy, whereas the receipt of radiotherapy has declined, particularly at academic centers. Race, insurance status, and facility type are strongly associated with the choice of adjuvant management.