Clinical dilemmas in local and regional testis cancer.

At the Canadian Testis Cancer Workshop, the multidisciplinary management of testis cancer care was discussed. The two-day workshop involved urologists, medical and radiation oncologists, pathologists, radiologists, physician's assistants, residents, fellows, nurses, patients, and patient advocacy group members.This review summarizes the discussion regarding clinical dilemmas in local and regional testis cancer. We present cases that highlight the need for a coordinated approach to individualize care. Overarching themes include the importance of a multidisciplinary approach to testis cancer, willingness to involve a high-volume experienced center, and given that the oncological outcomes are excellent, a reminder that clinical decisions need to prioritize selecting a strategy with the least treatment-related morbidity when safe.

A Canadian approach to the regionalization of testis cancer: A review.

At the Canadian Testis Cancer Workshop, the rationale and feasibility of regionalization of testis cancer care were discussed. The two-day workshop involved urologists, medical and radiation oncologists, pathologists, radiologists, physician's assistants, residents and fellows, and nurses, as well as patients and patient advocacy groups.This review summarizes the discussion and recommendations of one of the central topics of the workshop - the centralization of testis cancer in Canada. It was acknowledged that non-guideline-concordant care in testis cancer occurs frequently, in the range of 18-30%. The National Health Service in the U.K. stipulates various testis cancer care modalities be delivered through supra-regional network. All cases are reviewed at a multidisciplinary team meeting and aspects of care can be delivered locally through the network. In Germany, no such network exists, but an insurance-supported online second opinion network was developed that currently achieves expert case review in over 30% of cases. There are clear benefits to regionalization in terms of survival, treatment morbidity, and cost. There was agreement at the workshop that a structured pathway for diagnosis and treatment of testis cancer patients is required.Regionalization may be challenging in Canada because of geography; independent administration of healthcare by each province; physicians fearing loss of autonomy and revenue; patient unwillingness to travel long distances from home; and the inability of the larger centers to handle the ensuing increase in volume. We feel the first step is to identify the key performance indicators and quality metrics to track the quality of care received. After identifying these metrics, implementation of a "networks of excellence" model, similar to that seen in sarcoma care in Ontario, could be effective, coupled with increased use of health technology, such as virtual clinics and telemedicine.

New treatments for stage I testicular cancer.

Clinical stage I represents the most frequent presentation of both seminoma and nonseminoma testicular cancer. Despite a survival rate of close to 100%, the management of patients with this disease stage is controversial. The recurrence rate is 10% to 20% for patients with stage I seminoma and 15% to 50% for those with stage I nonseminoma. A highly sensitive and specific biomarker of relapse that is applicable to both seminoma and nonseminoma, and able to drive a definitive risk-adapted management of the patients, still is not available. Lymphovascular invasion (LVI) in the orchiectomy specimen has been used as a risk factor in patients with stage I nonseminoma. However, with a risk of recurrence of 50% for LVI-positive patients and 15% for LVI-negative patients, the discriminative power of LVI is modest at best. Various management options exist. In the absence of a predictive biomarker for recurrence, active surveillance avoids overtreatment in 50% to 85% of patients, with no risk of long-term side effects in nonrelapsing patients and a preserved overall survival of almost 100% after specific treatment for recurrent disease. However, although active surveillance has been accepted as the preferred option for stage I seminoma and low-risk stage I nonseminoma, its role in high-risk stage I nonseminoma remains controversial.

Utilization of retroperitoneal lymph node dissection for testicular cancer in the United States: Results from the National Cancer Database (1998-2011).

INTRODUCTION: Retroperitoneal lymph node dissection (RPLND) for the treatment of testicular cancer is a relatively rare and complex operation that may contribute to differences in utilization. We sought to characterize the use of RPLND between different categories of cancer center facilities in the United States. MATERIALS AND METHODS: The National Cancer Database was queried for patients with germ cell tumors treated at different types of cancer centers between 1998 and 2011. The proportion of patients who underwent RPLND was stratified by stage and histology and then compared between treatment facilities. RPLND utilization was then compared between facility types as a function of time. RESULTS: A total of 59,652 patients met inclusion criteria and 5,475 (9.2%) underwent RPLND. The proportion of patients treated with RPLND for non-seminomatous germ cell tumor (NSGCT) was significantly different between cancer center types for all stages (P<0.001) and used most often in academic comprehensive cancer centers. There was no difference in the proportion of RPLND utilization for stage II and III seminoma stratified by treatment facility. There was a significantly decreased trend in the utilization of RPLND for stage I (P = 0.032) NSGCT whereas utilization was increased for stage III NSGCT (P≤0.001) over the study period. CONCLUSIONS: The proportion of patients undergoing RPLND for NSGCT varies significantly by the type of cancer center and is used most often in academic cancer centers. Utilization of RPLND decreased for stage I NSGCT and increased for stage III NSGCTs during the study period.

Patterns of Care and Survival Outcomes for Malignant Sex Cord Stromal Testicular Cancer: Results from the National Cancer Data Base.

PURPOSE: Sex cord stromal tumors of the testis comprise less than 5% of testicular neoplasms. Consequently, data regarding patterns of care and survival are sparse. Using a large national database, we sought to provide a more definitive analysis of outcomes and management of these malignancies. MATERIALS AND METHODS: Data were obtained from the National Cancer Data Base. Patients diagnosed from 1998 to 2011 with 2 of the most frequent sex cord stromal tumors of the testis, including Leydig and Sertoli cell tumors, were selected for study. Overall survival estimates were assessed by the Kaplan-Meier method. RESULTS: Of the 79,120 cases of testicular cancer between 1998 and 2011, 315 (0.39%) were primary malignant Leydig or Sertoli cell tumors. Median patient age was 43 years for both tumors. Of the 315 patients 250 (79%) had malignant Leydig cell tumors and 65 (21%) had malignant Sertoli cell tumors, of which 94% and 78%, respectively, were stage I. Overall survival at 1 and 5 years for stage I Leydig cell tumors was 98% (95% CI 96-100) and 91% (95% CI 85-96), and for stage I Sertoli cell tumors overall survival was 93% (95% CI 83-100) and 77% (95% CI 62-95), respectively (p = 0.015). Of patients with stage I Leydig and Sertoli cell tumors 94% and 84%, respectively, received no further treatment following orchiectomy. CONCLUSIONS: Five-year survival estimates of stage I Leydig and Sertoli cell tumors are significantly lower compared to those of stage I germ cell tumors with Sertoli cell tumors significantly worse than Leydig cell tumors. These differences in the survival of sex cord stromal tumors indicate the importance of large databases to evaluate the efficacy of treatment for rare neoplasms.

Enhancing Adolescent and Young Adult Oncology Research Within the National Clinical Trials Network: Rationale, Progress, and Emerging Strategies.

Adolescent and Young Adult Oncology (AYAO, including patients 15-39 years of age) is an emerging discipline in the field of cancer treatment and research. Poorer survival outcomes for this population and characteristic age-related challenges in care have called attention to the need for increased AYAO research. This chapter outlines pressing questions and reviews recent progress in AYAO research within the current organizational structure of the federal clinical trials enterprise, emphasizing how the United States National Cancer Institute's National Clinical Trials Network (NCTN) has created novel opportunities for collaborative AYAO research among the pediatric and adult NCTN groups. Potential strategies for expanding AYAO research, both within the NCTN and with other partners in the federal and advocacy domains are identified.

Patterns of relapse in patients with clinical stage I testicular cancer managed with active surveillance.

PURPOSE: To evaluate the performance of active surveillance as a management strategy in broad populations and to inform the development of surveillance schedules by individual patient data regarding timing and type of relapse. METHODS: Retrospective study including data from 2,483 clinical stage I (CSI) patients, 1,139 CSI nonseminoma and 1,344 CSI seminoma managed with active surveillance, with the majority treated between 1998 and 2010. Clinical outcomes including relapse and death, time distribution, extent of relapse and method of relapse detection observed on active surveillance were recorded. RESULTS: Relapse occurred in 221 (19%) CSI-nonseminoma and 173 (13%) CSI-seminoma patients. Median time to relapse was 4 months (range, 2-61 months), 8 months (range, 2-77 months) and 14 months (range, 2-84 months) for lymphovascular invasion-positive CSI nonseminoma, lymphovascular invasion-negative CSI nonseminoma and CSI seminoma. Most relapses were observed within the first 2 years/3 years after orchiectomy for CSI nonseminoma (90%)/CSI seminoma (92%). Relapses were detected by computed tomography scan/tumor-markers in 87%/3% of seminoma recurrences, in 48%/38% of lymphovascular invasion-negative and 41%/61% of lymphovascular invasion-positive patients, respectively. 90% of CSI-nonseminoma and 99% of CSI-seminoma relapses exhibited International Germ Cell Collaborative Group good-risk features. Three patients with CSI nonseminoma died of disease (0.3%). One patient with CSI seminoma and two patients with CSI nonseminoma died because of treatment-related events. Overall, advanced disease was seen in both early- and late-relapse patients. All late recurrences were cured with standard therapy. Five-year disease-specific survival was 99.7% (95% CI, 99.24% to 99.93%). CONCLUSION: Active surveillance for CSI testis cancer leads to excellent outcomes. The vast majority of relapses occur within 2 years of orchiectomy for CSI nonseminoma and within 3 years for CSI seminoma. Late and advanced stage relapse are rarely seen. These data may inform further refinement of rationally designed surveillance schedules.

Mesenteric lymphadenopathy in testicular germ cell tumor.

In approximately 25% of patients with testicular germ cell tumor (GCT), the cancer metastasizes to lymph nodes and distant organs. The initial lymphatic drainage site of GCTs is the retroperitoneum. GCTs rarely involve mesenteric lymph nodes. In this study, we report a case of a 32-year-old male patient with GCT and associated mesenteric lymphadenopathy.

Modeling Management Strategies for Clinical Stage I Seminoma: Direct and Indirect Costs for the First 5 Years.

INTRODUCTION: Clinical stage I seminoma can be managed with surveillance, chemotherapy or radiotherapy with similar survival rates. However, costs and side effects vary among these treatment modalities. We created a model to estimate the direct and indirect costs during the first 5 years of treatment for the 3 treatment strategies. METHODS: Markov model based analyses were conducted to compare the costs of the 3 management strategies during the first 5 years. In this model clinicians and patients were assumed to be 100% compliant with the 2012 NCCN Guidelines® for testicular cancer. Model parameters were collected from the Washington State CHARS (Comprehensive Hospital Abstract Reporting System), published literature and Medicare reimbursement amounts. A 5% annual health inflation rate was assumed. RESULTS: The model predicts an initial cost premium for carboplatin (1 cycle-$9,199.49; 2 cycles-$10,613.85) and radiotherapy ($9,532.80) compared with surveillance ($9,065.31). Radiotherapy (145.8 hours) and surveillance (123.0 hours) require more patient time than carboplatin (1 cycle-93.2 hours, 2 cycles-106.3 hours). When the direct and indirect costs are considered, the least expensive management strategy is surveillance. CONCLUSIONS: Surveillance is the most cost-effective management strategy for clinical stage I seminoma during the first 5 years of treatment. Although not evaluated in this analysis, costs of late side effects associated with radiotherapy and chemotherapy should be considered. Due to potentially minimal late side effects and superior cost-effectiveness, surveillance represents a safe, cost-effective and time effective option for the management of stage I seminoma.

Wisconsin Ginseng (Panax quinquefolius) to improve cancer-related fatigue: a randomized, double-blind trial, N07C2.

BACKGROUND: Safe, effective interventions to improve cancer-related fatigue (CRF) are needed because it remains a prevalent, distressing, and activity-limiting symptom. Based on pilot data, a phase III trial was developed to evaluate the efficacy of American ginseng on CRF. METHODS: A multisite, double-blind trial randomized fatigued cancer survivors to 2000mg of American ginseng vs a placebo for 8 weeks. The primary endpoint was the general subscale of the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) at 4 weeks. Changes from baseline at 4 and 8 weeks were evaluated between arms by a two-sided, two-sample t test. Toxicities were evaluated by self-report and the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) provider grading. RESULTS: Three hundred sixty-four participants were enrolled from 40 institutions. Changes from baseline in the general subscale of the MFSI-SF were 14.4 (standard deviation [SD] = 27.1) in the ginseng arm vs 8.2 (SD = 24.8) in the placebo arm at 4 weeks (P = .07). A statistically significant difference was seen at 8 weeks with a change score of 20 (SD = 27) for the ginseng group and 10.3 (SD = 26.1) for the placebo group (P = .003). Greater benefit was reported in patients receiving active cancer treatment vs those who had completed treatment. Toxicities per self-report and CTCAE grading did not differ statistically significantly between arms. CONCLUSIONS: Data support the benefit of American ginseng, 2000mg daily, on CRF over an 8-week period. There were no discernible toxicities associated with the treatment. Studies to increase knowledge to guide the role of ginseng to improve CRF are needed.

Testicular cancer survivorship: research strategies and recommendations.

Testicular cancer represents the most curable solid tumor, with a 10-year survival rate of more than 95%. Given the young average age at diagnosis, it is estimated that effective treatment approaches, in particular, platinum-based chemotherapy, have resulted in an average gain of several decades of life. This success, however, is offset by the emergence of considerable long-term morbidity, including second malignant neoplasms, cardiovascular disease, neurotoxicity, nephrotoxicity, pulmonary toxicity, hypogonadism, decreased fertility, and psychosocial problems. Data on underlying genetic or molecular factors that might identify those patients at highest risk for late sequelae are sparse. Genome-wide association studies and other translational molecular approaches now provide opportunities to identify testicular cancer survivors at greatest risk for therapy-related complications to develop evidence-based long-term follow-up guidelines and interventional strategies. We review research priorities identified during an international workshop devoted to testicular cancer survivors. Recommendations include 1) institution of lifelong follow-up of testicular cancer survivors within a large cohort setting to ascertain risks of emerging toxicities and the evolution of known late sequelae, 2) development of comprehensive risk prediction models that include treatment factors and genetic modifiers of late sequelae, 3) elucidation of the effect(s) of decades-long exposure to low serum levels of platinum, 4) assessment of the overall burden of medical and psychosocial morbidity, and 5) the eventual formulation of evidence-based long-term follow-up guidelines and interventions. Just as testicular cancer once served as the paradigm of a curable malignancy, comprehensive follow-up studies of testicular cancer survivors can pioneer new methodologies in survivorship research for all adult-onset cancer.

Testicular cancer: a prototypic tumor of young adults.

Testicular cancer is the most common solid tumor among males in the 20- to 39-year age range. Moreover, testicular cancer has unique biological associations, clinical features, and psychosocial impacts that establish this tumor as a prototypic malignancy of young adults. The biology of testicular germ cell tumors after puberty is distinctive. Epidemiologic patterns of testicular cancer suggest etiologic factors that may be congenital, racial, and geographic. The clinical management of a cancer common among young adults, but rare among adults in general, requires expertise so as not to jeopardize the high rates of survivorship associated with modern therapy. The concurrent but separate development of staging, prognostic systems, and treatment recommendations between the fields of pediatric and adult oncology highlights the need for increased integration and cooperation across these subspecialties. The high rate of survival, combined with the need for long-term monitoring for relapse or late effects, demonstrates the challenge of delivering longitudinal care in this mobile and active young adult population.