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.

Evidence-based benchmarks for use of cancer surgery in high-income countries: a population-based analysis.

BACKGROUND: Estimating a population-level benchmark rate for use of surgery in the management of cancer helps to identify treatment gaps, estimate the survival impact of such gaps, and benchmark the workforce and other resources, including budgets, required to meet service needs. A population-based benchmark for use of surgery in high-income settings to inform policy makers and service provision has not been developed but was recommended by the Lancet Oncology Commission on Global Cancer Surgery. We aimed to develop and validate a cancer surgery benchmarking model. METHODS: We examined the latest clinical guidelines from high-income countries (Australia, the UK, the EU, the USA, and Canada) and mapped surgical treatment pathways for 30 malignant cancer sites (19 individual sites and 11 grouped as other cancers) that were notifiable in Australia in 2014, broadly reflecting contemporary high-income models of care. The optimal use of surgery was considered as an indication for surgery where surgery is the treatment of choice for a given clinical scenario. Population-based epidemiological data, such as cancer stage, tumour characteristics, and fitness for surgery, were derived from Australia and other similar high-income settings for 2017. The probabilities across the clinical pathways of each cancer were multiplied and added together to estimate the population-level benchmark rates of cancer surgery, and further validated with the comparisons of observed rates of cancer surgery in the South Western Sydney Local Health District in 2006-12. Univariable and multivariable sensitivity analyses were done to explore uncertainty around model inputs, with mean (95% CI) benchmark surgery rates estimated on the basis of 10 000 Monte Carlo simulations. FINDINGS: Surgical treatment was indicated in 58% (95% CI 57-59) of newly diagnosed patients with cancer in Australia in 2014 at least once during the course of their treatment, but varied by site from 23% (17-27) for prostate cancer to 99% (96-99) for testicular cancer. Observed cancer surgery rates in South Western Sydney were comparable to the benchmarks for most cancers, but were higher for some cancers, such as prostate (absolute increase of 29%) and lower for others, such as lung (-14%). INTERPRETATION: The model provides a new template for high-income and emerging economies to rationally plan and assess their cancer surgery provision. There are differences in modelled versus observed surgery rates for some cancers, requiring more in-depth analysis of the observed differences. FUNDING: University of New South Wales Scientia Scholarship, UK Research and Innovation-Global Challenges Research Fund.

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.

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.

Low CD34+ Cell Doses Are Associated with Increased Cost and Worse Outcome after Tandem Autologous Stem Cell Transplantation in Patients with Relapsed or Refractory Germ Cell Tumors.

Tandem autologous stem cell transplantation (ASCT) improves long-term survival of platinum-refractory germ cell tumors (GCT) patients. Studies, predominantly in lymphoma, showed that CD34+ cell doses > 5.0 × 106/kg/single transplant led to decreased resource utilization. Because most GCT patients have received prior cisplatin-based treatment, collecting >10 × 106 CD34+ cells/kg is challenging. We analyzed the effect of CD34+ cell dose on resource utilization and outcome in 131 GCT patients, median age 29.5 years (range, 16 to 58), undergoing tandem ASCT. Of 262 individual transplants performed, 120 were performed as inpatient and 142 as planned outpatient. Overall, median CD34+ dose per transplant was 3.1 × 106/kg (range, 0.8 to 16.0), with no significant difference between inpatient and outpatient transplants. Patients were divided into quartiles based on the CD34 cell dose infused: Q1, 0.8 to 1.9 × 106/kg; Q2, 2.0 to 2.9 × 106/kg; Q3, 3.0 to 4.1 × 106/kg; and Q4, 4.2 to 16.0 × 106/kg. For all patients higher CD34+ cell doses were associated with significantly shorter times to neutrophil (P <.001) and platelet recovery (P <.001). For inpatient transplants higher CD34+ doses were significantly associated with shorter length of hospital stay (P <.001), fewer days of filgrastim (P <.001), i.v. antibiotic (P = .012) and antifungal (P = .03) usage; and fewer RBC (P = .001) and platelet units transfused (P <.001), resulting in overall lower cost of care (P < .001). Of the 142 planned outpatient transplants, 100 admissions were required for a median length of hospital stay of 7.0 days (range, 1 to 18). Although there was no significant difference in the rates of hospitalization between patients in different CD34+ cell dose quartiles, a significant trend was observed for shorter hospitalization (P = .01) and fewer RBC (P = .002) and platelet (P = .005) transfusions with higher CD34+ cell dose quartile. Patients receiving CD34+ cell doses in the lowest dose quartile (Q1) had significantly worse progression-free survival and overall survival compared with patients receiving higher CD34+ cell doses. Overall, resource utilization, including cost of care, is significantly reduced when patients receive higher CD34+ cell doses, indicating greater efforts to improve peripheral blood stem cell collection in this population are needed.

No longer any role for routine follow-up chest x-rays in men with stage I germ cell cancer.

Following radical orchidectomy for testicular cancer, most patients undergo protocolled surveillance to detect tumour recurrences rather than receive adjuvant chemotherapy. Current United Kingdom national and most international guidelines recommend that patients require a chest x-ray (CXR) and serum tumour markers at each follow-up visit as well as regular CT scans; there is however, variation among cancer centres with follow-up protocols. Seminomas often do not cause tumour marker elevation; therefore, CT scans are the main diagnostic tool for detecting relapse. For non-seminomatous tumours, serum beta-HCG (HCG) and AFP levels are a very sensitive harbinger of relapse, but this only occurs in 50% of patients [1], and therefore, imaging remains as important. CXRs are meant to aid in the detection of lung recurrences and before the introduction of modern cross-sectional imaging in the early 1980s, CXRs would have been the only method of identifying lung metastasis. We examined the Thames Valley and Mount Vernon Cancer Centre databases to evaluate the role of CXRs in the 21st century for the follow-up of men with stage I testicular cancer between 2003 and 2015 to assess its value in diagnosing relapsed germ cell tumours. From a total of 1447 patients, we identified 159 relapses. All relapses were detected either by rising tumour markers or planned follow-up CT scans. Not a single relapse was identified on CXR. We conclude that with timely and appropriate modern cross-sectional imaging and tumour marker assays, the CXR no longer has any value in the routine surveillance of stage I testicular cancer and should be removed from follow-up guidelines and clinical practice. Omitting routine CXR from follow-up schedules will reduce anxiety as well as time that patients spend at hospitals and result in significant cost savings.

Unemployment risk and income change after testicular cancer diagnosis: A population-based study.

BACKGROUND: Among patients with cancer, returning to full working may serve as an indicator for return to normal lifestyle following illness, as opposed to unemployment or shifting to part-time work. The aim of the project was to clarify the association between unemployment risk and decreased income at 4 years after the diagnosis of testicular cancer (TC). PARTICIPANTS AND METHODS: A case control in a cohort study includes baseline measurement of people participating in the Israeli Central Bureau of Statistics 1995 National Census, and follow-up until 2011. Cancer incidence, employment status, and income level were ascertained through the Israel Cancer Registry and Tax Authority, respectively. A matched group was sampled from the population in the census. Binary logistic regression analyses were used to assess odds ratios (ORs) for study׳s outcomes, while controlling for age, ethnicity, education, and socioeconomic and employment status at 2 years before diagnosis. RESULTS: A total of 113 cases of TC and 468 persons in the matched group were included in the study after excluding persons who died during the study period. No association was found between TC and subsequent risk after the 4 years of unemployment (OR = 1.12, 95% CI: 0.65-1.95) or decreased income (OR = 1.41, 95% CI: 0.84-2.36). Predictors of subsequent unemployment were unemployment 2 years before diagnosis (OR = 6.91, 95% CI: 4.39-10.86) and increasing age (OR = 1.03 per year, 95% CI: 1.01-1.06). CONCLUSION: TC survivorship is not associated with subsequent unemployment or decreased income at 4 years after diagnosis.

Male reproductive disorders, diseases, and costs of exposure to endocrine-disrupting chemicals in the European Union.

INTRODUCTION: Increasing evidence suggests that endocrine-disrupting chemicals (EDCs) contribute to male reproductive diseases and disorders. PURPOSE: To estimate the incidence/prevalence of selected male reproductive disorders/diseases and associated economic costs that can be reasonably attributed to specific EDC exposures in the European Union (EU). METHODS: An expert panel evaluated evidence for probability of causation using the Intergovernmental Panel on Climate Change weight-of-evidence characterization. Exposure-response relationships and reference levels were evaluated, and biomarker data were organized from carefully identified studies from the peer-reviewed literature to represent European exposure and approximate burden of disease as it occurred in 2010. The cost-of-illness estimation utilized multiple peer-reviewed sources. RESULTS: The expert panel identified low epidemiological and strong toxicological evidence for male infertility attributable to phthalate exposure, with a 40-69% probability of causing 618,000 additional assisted reproductive technology procedures, costing €4.71 billion annually. Low epidemiological and strong toxicological evidence was also identified for cryptorchidism due to prenatal polybrominated diphenyl ether exposure, resulting in a 40-69% probability that 4615 cases result, at a cost of €130 million (sensitivity analysis, €117-130 million). A much more modest (0-19%) probability of causation in testicular cancer by polybrominated diphenyl ethers was identified due to very low epidemiological and weak toxicological evidence, with 6830 potential cases annually and costs of €848 million annually (sensitivity analysis, €313-848 million). The panel assigned 40-69% probability of lower T concentrations in 55- to 64-year-old men due to phthalate exposure, with 24 800 associated deaths annually and lost economic productivity of €7.96 billion. CONCLUSIONS: EDCs may contribute substantially to male reproductive disorders and diseases, with nearly €15 billion annual associated costs in the EU. These estimates represent only a few EDCs for which there were sufficient epidemiological studies and those with the highest probability of causation. These public health costs should be considered as the EU contemplates regulatory action on EDCs.

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.

Prognostic factors in malignant ovarian germ cell tumours (The Surveillance, Epidemiology and End Results experience 1978-2010).

PURPOSE: To evaluate the prognostic significance of age at diagnosis, extent of the disease (EOD) and socioeconomic (SES) and sociodemographic status (civil status, residency) on cause specific survival (CSS) in patients with malignant ovarian germ cell tumours (MOGCTs). To explore the cumulative incidence of a second cancer in 10-year MOGCT survivors. PATIENTS AND METHODS: 2541 patients with MOGCT, reported to the Surveillance, Epidemiology and End Results programme (1978-2010), were identified. The above mentioned prognostic factors were assessed separately for dysgerminoma and non-dysgerminoma, using Kaplan-Meier estimates and Cox Hazards Models, providing 95% confidence intervals (95% CI). RESULTS: Five-year CSS was 97% (95% CI, 96-98%), and 92% (95% CI, 91-93%), respectively for dysgerminoma, and non-dysgerminoma. Age >40 years at diagnosis and presence of metastases were significantly associated with cause specific mortality. Among non-dysgerminoma patients, decreasing SES (hazard ratio (HR), 1.59; 95% CI, 1.11-2.28) and treatment before 1990 (HR, 2.65; 95% CI, 1.83-3.85) increased mortality. In the adjusted analysis, patients from Michigan were almost 2.5 times more likely to die from MOGCT than patients from other states (HR, 2.48; 95% CI, 1.17-5.25). Second cancer was diagnosed in 10% of 10-year survivals who underwent radiotherapy and in 2% of survivals in non-radiotherapy group (p=.002). CONCLUSIONS: Increased attention should be directed towards the management of elderly MOGCT patients and those with non-dysgerminoma histology with low SES. Radiotherapy should be avoided as much as possible. Survival differences related to residency may occur when new cancer treatments are introduced.

Testicular cancer: a narrative review of the role of socioeconomic position from risk to survivorship.

BACKGROUND: Testicular cancer (TC) is one of the most curable cancers. Given survival rates of close to 100% with appropriate therapy, ensuring proper treatment is essential. We reviewed and summarized the literature on the association of socioeconomic position (SEP) along the cancer control spectrum from risk factors to survivorship. METHODS: We searched PubMed from 1966 to 2011 using the following terms: testicular cancer, testicular neoplasm, poverty, and socioeconomic factors, retrieving 119 papers. After excluding papers for the non-English (10) language and non-relevance (46), we reviewed 63 papers. We abstracted information on socioeconomic position (SEP), including occupation, education, income, and combinations of the 3. Five areas were examined: risk factors, diagnosis, treatment, survival, and survivorship. RESULTS: Most studies examined area-based measures, not individual measures of SEP. The majority of studies found an increased risk of developing TC with high SEP though recent papers have indicated increased risk in low-income populations. Regarding diagnosis, recent papers have indicated that lower levels of education and SEP are risk factors for later-stage TC diagnosis and hence higher TC mortality. For treatment, 1 study that examined the use of radiation therapy (RT) in stage I seminoma reported that living in a county with lower educational attainment led to lower use of RT. For survival (mortality), several studies found that men living in lower SEP geographic areas experience lower survival and higher mortality. CONCLUSION: The strongest evidence for SEP impact on testicular germ cell tumor (TGCT) was found for the risk of developing cancer as well as survival. The association of SEP with TGCT risk appears to have changed over the last decade. Given the highly curable nature of TGCT, more research is needed to understand how SEP impacts diagnosis and treatment for TGCT and to design interventions to address disparities in TGCT outcomes and SEP.

Carboplatin-based chemotherapy and surgery: a cost effective treatment strategy for malignant extracranial germ cell tumours in the developing world.

Nineteen children with malignant extracranial germ cell tumours (MEGCT), were treated at our institution with a combination of carboplatin-based chemotherapy and surgery from 1992 to 2008. Seventeen are long term survivors. Chemotherapy was administered on an outpatient basis and required no monitoring of GFR or auditory function. There were no deaths from toxicity or infection. Blood product use was low. Carboplatin-based therapy achieved excellent results in our patient population and constitutes more than a US $1,800 saving per patient compared to regimens containing cisplatin. This has application in resource limited settings.

A comprehensive systematic review of testicular germ cell tumor surveillance.

BACKGROUND: Testicular cancer is the most common malignancy in men aged 15-34, and its incidence has been increasing over the past half-century. Survival for stage I testis cancer approaches 100% regardless of management strategy which is often dictated by other factors such as perceived morbidity. Advances in treatment have attempted to decrease morbidity and surveillance is thought to achieve this goal. METHODS: An English language literature search of MEDLINE from 1966 to December 2005 and CINAHL from 1982 to December 2005 was conducted using a broad search strategy. Comparative and descriptive original articles on outcomes of seminoma or NSGCT surveillance would be deemed eligible and review articles containing no original data were omitted. One hundred and thirty-eight articles were selected for formal review, during which a database was compiled that documented the first author, publication year, tumor histologic type, study purpose or topic(s), methodology, sample size, median follow-up, and relevant results. RESULTS: Most evidence for the efficacy of surveillance is from descriptive series or non-experimental comparative studies. Relapse occurs in approximately 28% and 17% of surveillance patients in NSGCT and seminoma, respectively, and cause-specific survival is approximately 98% and 100%, respectively. Compliance with surveillance ranges from poor to adequate, however there is no evidence that compliance impacts clinical outcome. Cost analyses have yielded inconsistent results when comparing treatment modalities. There is scant literature on quality of life and psychosocial issues and results are inconsistent. Active surveillance appears to be appropriate and perhaps optimal first line management of clinical stage I seminoma and non-seminomatous germ cell tumors. Further quantitative and qualitative research is warranted to deepen understanding of these issues that may impact treatment decision-making.

Laparoscopic versus open retroperitoneal lymph node dissection: a cost analysis.

PURPOSE: Laparoscopic retroperitoneal lymph node dissection is significantly less morbid than open retroperitoneal lymph node dissection but it is generally more costly due to longer operative time and disposable equipment. In response to budgetary pressure at our large county hospital we identified the cost components of laparoscopic retroperitoneal lymph node dissection that could be targeted to decrease procedure costs before expanding our laparoscopic retroperitoneal lymph node dissection program. MATERIALS AND METHODS: A comprehensive literature review of open and laparoscopic retroperitoneal lymph node dissection was performed and certain parameters were abstracted, including operative time and equipment, hospital stay, perioperative complications and surgical success rates. Using these data the projected overall cost and individual cost centers at our institution were compared for open and laparoscopic retroperitoneal lymph node dissection. Decision tree analysis models were devised to estimate the cost of each treatment using commercially available software. We performed 1 and 2-way sensitivity analysis to evaluate the effect of individual treatment variables on overall cost. Base case analysis involved a young man with clinical stage I nonseminomatous testicular cancer who was a candidate for retroperitoneal lymph node dissection. RESULTS: Based on a review of the costs at our institution open retroperitoneal lymph node dissection was a less costly procedure at $7,162 versus $7,804 for the laparoscopic approach. The slight cost superiority of the open approach was due to significantly lower costs associated with operating room time and equipment. On the other hand, the laparoscopic procedure showed a cost advantage for hospital stay. On 1-way sensitivity analysis laparoscopic dissection was less costly when operative time was less than 3.6 hours, hospitalization was less than 2.2 days or laparoscopic equipment costs were less than $768. On 2-way sensitivity analysis the laparoscopic approach was cost advantageous when performed in less than 5 hours or when the patient was discharged home within 2 days postoperatively. CONCLUSIONS: The primary cost variables for surgical treatment for testicular cancer include operative time, hospital stay and equipment cost. According to published data and decision tree analysis open retroperitoneal lymph node dissection is slightly less costly (less than $650) than laparoscopic retroperitoneal lymph node dissection for the surgical treatment of clinical stage I nonseminomatous testicular cancer at our institution. Our model identifies several measures that can be applied at any institution to render laparoscopic retroperitoneal lymph node dissection economically superior to the open approach.

Effect of duration of treatment on treatment outcome and cost of treatment for Wilms' tumor: a report from the National Wilms' Tumor Study Group.

PURPOSE: National Wilms' Tumor Study (NWTS)-4 was designed to evaluate the efficacy, toxicity, and cost of the administration of different regimens for the treatment of Wilms' tumor (WT). PATIENTS AND METHODS: Between August 6, 1986 and September 1, 1994, 905 previously untreated children aged younger than 16 years with stage II favorable histology (FH) WT (low-risk [LR]), stages III to IV FH WT, or stages I to IV clear-cell sarcoma of the kidney (high-risk[HR]) were randomized after the completion of 6 months of chemotherapy to discontinue (short) or continue for 9 additional months (long) treatment with chemotherapy regimens that included vincristine and either divided-dose (standard [STD]) courses (5 days) or single-dose (pulse-intensive [PI]) treatment with dactinomycin. HR patients also received either divided-dose (STD) courses (3 days) or single-dose (PI) treatment with doxorubicin. RESULTS: The 4-year relapse-free survival (RFS) rates after the second randomization for LR patients were 83.7% for the 190 patients treated with short and 88.2% for the 187 patients treated with long chemotherapy (P = .11). The 4-year RFS rates after the second randomization for HR FH patients were 89.7% for the 256 patients treated with short and 88.8% for the 246 patients treated with long chemotherapy (P = .87). The charge for treatment with the short PI treatment regimens for all children with stages I through IV FH WT was approximately one half of that with the long STD treatment regimens. CONCLUSION: The short administration schedule for the treatment of children with WT is no less effective than the long administration schedule and can be administered at a substantially lower total treatment cost.

Evaluation of optimal duration of chemotherapy in favorable-prognosis disseminated germ cell tumors: a Southeastern Cancer Study Group protocol.

Four courses of PVP16B (cisplatin plus etoposide [VP-16] plus bleomycin) has been standard chemotherapy for disseminated germ cell tumors at Indiana University and the Southeastern Cancer Study Group (SECSG) since 1984. We began a random prospective phase III study in patients with favorable-prognosis (minimal and moderate extent) disseminated germ cell tumors comparing four courses of PVP16B over 12 weeks to the identical dose PVP16B administered in three courses over 9 weeks. The categories of minimal and moderate disease constitute approximately two thirds of all disseminated germ cell tumors that require chemotherapy. One hundred eighty-four patients entered this trial, and all patients have a minimal follow-up of 1 year. Overall, 106 of 107 (99%) minimal extent and 73 of 77 moderate patients (95%) achieved an initial disease-free status (NED), confirming the favorable prognostic categories. Eighty-six of 88 patients (98%) randomized to three courses and 93 of 96 randomized to four courses (97%) of PVP16B achieved disease-free status. There have been ten relapses (5%), with five on each arm. Currently, 81 of 88 (92%) and 88 of 96 (92%) patients randomized to three v four courses of PVP16B are continuously disease-free. This study confirms the high cure rate with PVP16B in favorable-prognosis germ cell tumors. The deletion of the fourth course of PVP16B significantly reduces the toxicity, cost, and inconvenience of this curative regimen. We conclude that three courses of PVP16B is the preferred regimen for favorable-prognosis germ cell tumors.

Selecting initial therapy. Seminoma and nonseminoma.

About 80% of seminoma presents as low-stage disease. If clinical studies are negative, the usual initial therapy is "prophylactic" radiotherapy to the retroperitoneal zone. If clinical Stage II disease is evident, radiotherapy versus primary chemotherapy is being studied. Primary chemotherapy is treatment of choice for clinical Stage III disease. Postchemotherapy radiographic lesions are safe to follow without surgical extirpation as they are usually necrotic. Surveillance for clinical Stage I disease is another option. For nonseminoma, clinical Stage I disease has been managed with staging RPLND. But 70% of such cases will have negative nodes. Hence, primary surveillance studies are under way, with chemotherapy reserved for those who relapse clinically (estimated 95% survival). Sadly, surveillance has not been effective when applied on an ad hoc basis at the community level. Problems are compliance, delayed detection of relapse, nonreporting of failures. Clinical Stage II disease is managed with RPLND. Adjuvant, limited postoperative chemotherapy is an option versus no postoperative chemotherapy followed by full chemotherapy for those who relapse as Stage III disease later. Another option under study for Stage II disease is primary chemotherapy with RPLND surgery reserved for those who achieve only a partial remission.

Counting the costs of cancer therapy.

The costs of cancer treatment were estimated for five groups of cancer patients: those with operable breast cancer receiving adjuvant chemotherapy and patients with advanced breast cancer, ovarian cancer, germ cell cancer and small cell lung cancer. Cancer treatment costs were substantial but chemotherapy cost was a relatively minor item. Methods of limiting treatment costs are identified as reducing hospital stay, encouraging outpatient administration of chemotherapy and limiting the number of supernumary investigations. The cost of different cancer treatment options should be considered when management decisions are made.