Differences in future life expectancy of testicular germ-cell tumor patients vs. age-matched male population-based controls.

BACKGROUND: It is unknown whether five-year overall survival (OS) differs and to what extent between testicular germ-cell tumor (TGCT) patients and age-matched male population-based controls. MATERIALS: We identified newly diagnosed (2004-2014) TGCT patients within Surveillance Epidemiology and End Results database 2004-2019. We compared OS between non-seminoma (NS-TGCT) and seminoma (S-TGCT) patients relative to age-matched male population-based controls based on Social Security Administration Life-Tables. Smoothed cumulative incidence plots displayed cancer-specific mortality (CSM) vs. other-cause mortality (OCM). RESULTS: Of all 20,935 TGCT patients, 43% had NS-TGCT and 57% had S-TGCT. Of NS-TGCT patients, 63% were stage I vs. 16% stage II vs. 21% stage III. Of S-TGCT patients, 86% were stage I vs. 8% were stage II vs. 6% stage III. Five-year OS differences between NS-TGCT patients vs age-matched male population-based controls were 97 vs. 99% (Δ = 2%) for stage I, 96 vs. 99% (Δ = 3%) for stage II, 76 vs 98% (Δ = 22%) for stage III. Five-year OS differences between S-TGCT patients vs age-matched male population-based controls were 97 vs. 98% (Δ = 1%) for stage I, 95 vs. 97% (Δ = 2%) for stage II, 87 vs. 98% (Δ = 11%) for stage III. OCM rates ranged from 1 to 3% in NS-TGCT patients and from 2 to 4% in S-TGCT patients. CONCLUSION: The OS difference between NS-TGCT patients vs. age-matched male population-based controls was invariably higher across all stages (2-22%) than for S-TGCT patients (1-11%). Reassuringly, OCM rates were marginal in stage I and stage II patients. Conversely, higher OCM rates were recorded in stage III patients.

Predictive factors of diagnostic delay and effect on treatment patterns in testicular germ cell tumor patients.

BACKGROUND: Increased time from clinical symptom onset to diagnosis of testicular germ cell tumor (GCT), termed diagnostic delay (DD), is associated with an increased likelihood of metastatic disease at presentation. We assessed the association of patient factors on DD and subsequent treatment patterns. METHODS: The records for patients undergoing orchiectomy at a tertiary care hospital and safety net county hospital between 2006 and 2018 were obtained. Demographic variables, clinical symptoms, and post-diagnosis parameters were queried. Patient factors were assessed for association with DD by using both univariate and multivariable analyses. The effect of the Patient Protection and Affordable Care Act (PPACA) on DD was also studied. RESULTS: 201 patients received orchiectomy, and median DD was 38 days (IQR 14.5-122.5). Patients with metastatic disease had increased DD compared to those with localized disease (76 vs. 31 days, P < 0.001). Increased DD was associated with presentation to the safety net hospital (P = 0.001), non-white (P = 0.025), emergency department presentation (P = 0.025), uninsured (P = 0.01), testicular pain (P = 0.019), and presentation before 2014 (P = 0.047). DD was independently associated with presentation before 2014 (P = 0.004) on multivariate analysis. DD >38 days (i.e., above the median) was associated with increased receipt of adjuvant therapy (P = 0.001). CONCLUSION: PPACA implementation is associated with earlier detection of testicular cancer. Our findings highlight the impact of health care legislation on improving access of care to young men with cancer. Delay in diagnosis can lead to increased stage at presentation and need for adjuvant treatment. Further research to identify and overcome sociodemographic factors associated with diagnostic delay may lead to decreased treatment-related morbidity.

A 25 year perspective on advances in the pathologic assessment and diagnosis of urologic cancers.

Over the past 25 years, diagnostic categories in genitourinary pathology have changed dramatically. Prostate cancer reporting incorporated numerous new variant categories, recognized the importance of intraductal carcinoma, and introduced the concept of Grade Groups. Pathologic diagnosis of bladder cancer not only added new variant categories, but also modified the grading of non-invasive urothelial neoplasms and refined staging definitions. Kidney cancer classification expanded from a handful of diagnostic categories to a broad array of additional cancer types defined by unique immunohistochemical and molecular findings. Segregation of penile carcinoma by human papillomavirus status more accurately reflected pathogenesis and helped improve prediction of cancer behavior. Testicular pathology research advanced understanding of germ cell tumor subtypes and their impact on patient outcomes. Finally, adrenal gland pathology has evolved to incorporate a broader recognition of morphological variation and risk factors associated with tumor progression. Taken together, changes in pathology over the past quarter century have revolutionized our approach to genitourinary cancers. This review seeks to highlight some of the many significant changes in genitourinary pathology that have occurred during the past 25 years and emphasize impacts on clinical outcomes or therapy, as relevant.

Population-based analysis of cost and peri-operative outcomes between open and robotic primary retroperitoneal lymph node dissection for germ cell tumors.

PURPOSE: To compare perioperative outcomes and perform the first cost analysis between open retroperitoneal lymph node dissection (O-RPLND) and Robotic-RPLND (R-RPLND) using a national all-payer inpatient care database. METHODS: Nationwide Inpatient Sample (NIS) was queried between 2013-2016 for primary RPLND and germ cell tumor. We compared cost, length of stay (LOS), and complications between O-RPLND and R-RPLND. Linear regression plots identified point of cost equivalence between R-RPLND and O-RPLND. A multivariable linear regression model was generated to analyze predictors of cost. RESULTS: 44 cases of R-RPLND and 319 cases of O-RPLND were identified. R-RPLND was associated with lower rate of complications (0% vs. 16.6%, p < 0.01) and shorter LOS [Median (IQR): 1.5 (1-3) days vs. 4 (3-6) days, p < 0.01]. Rates of ileus, genitourinary complications, and transfusions were lower with R-RPLND, but did not reach significance. On multivariable analysis, robotic approach independently contributed $4457, while each day of hospitalization contributed to an additional $2,431 to the overall model of cost. Linear regression plots determined point of cost equivalence between an R-RPLND staying a mean of 2 days was 4-5 days for O-RPLND, supporting the multivariable analysis. Total hospitalization cost was equivalent between R-RPLND and O-RPLND [Median (IQR): $15,681($12,735-$21,596) vs $16,718($11,799-$24,403), p = 0.48]-suggesting that the cost equivalency of R-RPLND is, at least in part, attributable to shorter LOS. CONCLUSION: While O-RPLND remains the gold standard and this study is limited by selection bias of a robotic approach to RPLND, our findings suggest primary R-RPLND may represent a cost-equivalent option with decreased hospital LOS in select cases.

Impact of circulating microRNA test (miRNA-371a-3p) on appropriateness of treatment and cost outcomes in patients with Stage I non-seminomatous germ cell tumours.

OBJECTIVES: To determine whether utilisation of a serum microRNA (miRNA) test could improve treatment appropriateness and cost-effectiveness for patients with Stage I non-seminomatous germ cell tumours (NSGCTs). PATIENTS AND METHODS: A decision tree model was built to investigate treatment course, clinical and cost outcomes for patients with Stage IA (T1N0M0S0) and IB (T2-4N0M0S0) NSGCT. The model compared outcomes and cost of standard approach using histopathology, conventional serum tumour markers and radiographic staging (standard model) to a miRNA-based approach using the standard model + post-orchidectomy serum miR-371a-3p (marker model). Probabilities of expected treatment and outcomes were based on presence/absence of cancer upon entering into the model. Overtreatment was defined as adjuvant chemotherapy or primary retroperitoneal lymph node dissection in a patient without cancer. Undertreatment was defined as initial surveillance for a patient with cancer. RESULTS: Utilising the miRNA marker-based approach, 26% of patients avoid overtreatment and 8% avoid undertreatment in Stage IA NSGCT; 27% avoid overtreatment and 23% avoid undertreatment in Stage IB disease. Appropriate treatment decision-making increased from 65% to 94% and 50% to 92% for Stage IA and IB, respectively. The miRNA-based approach remained cost-effective over a wide range of performance characteristics with savings of ~$1400 (American dollars)/patient for both Stage IA and IB disease. CONCLUSION: A miRNA-based approach may potentially select patients with Stage I NSGCT for correct treatment in a cost-effective manner. Identification of residual teratoma-only remains an issue. Prospective studies are necessary to validate these findings.

Adverse Surgical Outcomes Associated with Robotic Retroperitoneal Lymph Node Dissection Among Patients with Testicular Cancer.

Surgery for metastatic testicular disease has been an essential factor in the long-term cure rates for men with testicular germ cell tumors. Robotic approaches to retroperitoneal lymph node dissection (R-RPLND) have been proposed as an alternative to open surgery with few if any adverse events reported. We report the clinical course for five recent patients referred to our center for recurrences after R-RPLND, focusing on recurrence patterns, treatment burden, and treatment-related morbidity and mortality. The median time to recurrence after R-RPLND was 259d. The recurrence patterns after R-RPLND were aberrant from our past experience in managing recurrences after open RPLND. One man experienced an in-field recurrence located in close proximitry to an undivided lumbar vessel. Four patients had out-of-field recurrence in abnormal locations: pericolic space invading the sigmoid colon, peritoneal carcinomatosis with a perinephric mass, large-volume liver lesions with suprahilar disease extending into the retrocrural space, and lymph nodes in the celiac axis. The treatment burden was high: the five men were subjected to 12 different chemotherapy regimens and three underwent additional surgeries. Three patients developed significant cisplatin-induced toxicity. One patient died due to progression of testicular cancer after failing all chemotherapy and surgical options. PATIENT SUMMARY: We report our initial experience in managing patients with testicular cancer referred to our institution after robotic retroperitoneal lymph node dissection (RPLND). We found that the recurrences were highly variable and in unusual locations and were associated with a high treatment burden. We conclude that further investigation into the safety and long-term oncologic efficacy of robotic RPLND is necessary before widespread implementation.

Cost Analysis of Noninvasive Blood-Based MicroRNA Testing Versus CT Scans for Follow-up in Patients With Testicular Germ-Cell Tumors.

BACKGROUND: Our group has developed a noninvasive blood-based microRNA (miRNA) test for improving diagnosis, disease monitoring, and relapse detection in malignant testicular germ-cell tumors (TGCTs). Performance analysis suggests the test is likely to have comparable sensitivity and specificity in detecting TGCT as computed tomography (CT), thus reducing the need for serial CT scans for follow-up monitoring, with associated reductions in cumulative radiation burden and second cancer risk. To facilitate clinical adoption, we undertook a cost analysis to identify the budget impact of replacing CT scans with miRNA testing within health care systems. METHODS: The TGCT aftercare pathway was mapped out using National Comprehensive Cancer Network guidelines. A Markov model was built to simulate the impact of the miRNA test on TGCT aftercare costs. Incidence, treatment probabilities, relapse rate, and death rate data were collected from published studies to populate the model. RESULTS: Applying our model to the US health care system, the miRNA test has the potential to save up to $69 million per year in aftercare expenses related to TGCT treatment, with exact savings depending on the adoption rate and test price. CONCLUSION: This analysis demonstrates the potential positive budget impact of adopting miRNA testing in place of CT scans in the clinical management of TGCTs.

Association of Human Development Index with global bladder, kidney, prostate and testis cancer incidence and mortality.

OBJECTIVES: To describe contemporary worldwide age-standardized incidence and mortality rates for bladder, kidney, prostate and testis cancer and their association with development. MATERIALS AND METHODS: We obtained gender-specific, age-standardized incidence and mortality rates for 184 countries and 16 major world regions from the GLOBOCAN 2012 database. We compared the mortality-to-incidence ratios (MIRs) at national and regional levels in males and females, and assessed the association with socio-economic development using the 2014 United Nations Human Development Index (HDI). RESULTS: Age-standardized incidence rates were 2.9 (bladder) to 7.4 (testis) times higher for genitourinary malignancies in more developed countries compared with less developed countries. Age-standardized mortality rates were 1.5-2.2 times higher in more vs less developed countries for prostate, bladder and kidney cancer, with no variation in mortality rates observed in testis cancer. There was a strong inverse relationship between HDI and MIR in testis (regression coefficient 1.65, R2 = 0.78), prostate (regression coefficient -1.56, R2 = 0.85), kidney (regression coefficient -1.34, R2 = 0.74), and bladder cancer (regression coefficient -1.01, R2 = 0.80). CONCLUSION: While incidence and mortality rates for genitourinary cancers vary widely throughout the world, the MIR is highest in less developed countries for all four major genitourinary malignancies. Further research is needed to understand whether differences in comorbidities, exposures, time to diagnosis, access to healthcare, diagnostic techniques or treatment options explain the observed inequalities in genitourinary cancer outcomes.

Role of imaging in testicular cancer: current and future practice.

The article provides a summary of the epidemiologic and clinical aspects of testicular malignancy. Current standard imaging and novel techniques are reviewed. Present data and clinical treatment trends have favored surveillance protocols over adjuvant radiation or chemotherapy for low-stage testicular malignancy. This has resulted in increasing numbers of imaging studies and the potential for increased long-term exposure risks. Understanding imaging associated risks as well as strategies to minimize these risks is of increasing importance. The development, validation and incorporation of alternative lower risk highly efficacious and cost-effective imaging techniques is essential.

Testicular self-examination and testicular cancer: a cost-utility analysis.

The United States Preventive Services Task Force (USPSTF) has recommended against testicular self-examinations (TSE) or clinical examination for testicular cancer screening. However, in this recommendation there was no consideration of the significant fiscal cost of treating advanced disease versus evaluation of benign disease. In this study, a cost-utility validation for TSE was performed. The cost of treatment for an advanced-stage testicular tumor (both seminomatous and nonseminomatous) was compared to the cost of six other scenarios involving the clinical assessment of a testicular mass felt during self-examination (four benign and two early-stage malignant). Medicare reimbursements were used as an estimate for a national cost standard. The total treatment cost for an advanced-stage seminoma ($48,877) or nonseminoma ($51,592) equaled the cost of 313-330 benign office visits ($156); 180-190 office visits with scrotal ultrasound ($272); 79-83 office visits with serial scrotal ultrasounds and labs ($621); 6-7 office visits resulting in radical inguinal orchiectomy for benign pathology ($7,686) or 2-3 office visits resulting in treatment and surveillance of an early-stage testicular cancer ($17,283: seminoma, $26,190: nonseminoma). A large number of clinical evaluations based on the TSE for benign disease can be made compared to the cost of one missed advanced-stage tumor. An average of 2.4 to 1 cost benefit ratio was demonstrated for early detected testicular cancer versus advanced-stage disease.