Contemporary trends in management of stage 1 seminoma.

PURPOSE: Surveillance is now the preferred treatment strategy for patients with stage 1A/1B seminoma as reflected by the National Comprehensive Cancer Network guidelines. In this study, we aimed to describe trends in adjuvant management strategy for stage 1A/B seminoma from 2004 to 2016 using the National Cancer Database. MATERIALS AND METHODS: The database was queried for patients diagnosed with stage 1A/1B seminoma between 2004 and 2016. Staging was determined using the American Joint Committee on Cancer guidelines. Surveillance was defined as no treatment with chemotherapy or radiation within 60 days of diagnosis. Proportions of cancer patients utilizing surveillance, radiation, and single-agent chemotherapy were summarized annually. Kaplan-Meier survival analysis was used to compare overall survival between groups. RESULTS: 8,686 patients with stage 1A/1B seminoma met inclusion criteria over the course of the study period. Overall, 3,004 (34.6%) patients began adjuvant chemotherapy or radiation within 60 days. Utilization of surveillance increased from 39.8% in 2004 to 86.8% in 2016 while utilization of radiation decreased from 59.7% to 4.6%. High-volume centers adopted surveillance earlier than low-volume centers. CONCLUSION: This study describes trends in utilization of surveillance, chemotherapy, and radiotherapy for stage 1A/1B seminoma over 12 years. A major shift from utilization of adjuvant treatment to surveillance in patients with stage 1A/B seminoma is observed in this large national cancer database; a minority of patients now receive adjuvant treatment and risk-related toxicities. Survival analysis reveals similar survival at a median 5-year follow-up. The results provide insight into the time needed for clinical practice to adopt the preferred approach of surveillance over the time period studied.

Performance of formulae based estimates of glomerular filtration rate for carboplatin dosing in stage 1 seminoma.

BACKGROUND: Single cycle carboplatin, dosed by glomerular filtration rate (GFR), is standard adjuvant therapy for stage 1 seminoma. Accurate measurement of GFR is essential for correct dosing. Isotopic methods remain the gold standard for the determination of GFR. Formulae to estimate GFR have improved the assessment of renal function in non-oncological settings. We assessed the utility of these formulae for carboplatin dosing. METHODS: We studied consecutive subjects receiving adjuvant carboplatin for stage 1 seminoma at our institution between 2007 and 2012. Subjects underwent 51Cr-ethylene diamine tetra-acetic acid (EDTA) measurement of GFR with carboplatin dose calculated using the Calvert formula. Theoretical carboplatin doses were calculated from estimated GFR using Chronic Kidney Disease-Epidemiology (CKD-EPI), Management of Diet in Renal Disease (MDRD) and Cockcroft-Gault (CG) formulae with additional correction for actual body surface area (BSA). Carboplatin doses calculated by formulae were compared with dose calculated by isotopic GFR; a difference <10% was considered acceptable. RESULTS: 115 patients were identified. Mean isotopic GFR was 96.9 ml/min/1.73 m(2). CG and CKD-EPI tended to overestimate GFR whereas MDRD tended to underestimate GFR. The CKD-EPI formula had greatest accuracy. The CKD-EPI formula, corrected for actual BSA, performed best; 45.9% of patients received within 10% of correct carboplatin dose. Patients predicted as underdosed (13.5%) by CKD-EPI were more likely to be obese (p=0.013); there were no predictors of the 40.5% receiving an excess dose. CONCLUSIONS: Our data support further evaluation of the CKD-EPI formula in this patient population but clinically significant variances in carboplatin dosing occur using non-isotopic methods of GFR estimation. Isotopic determination of GFR should remain the recommended standard for carboplatin dosing when accuracy is essential.

Stage I testicular seminoma: a SEER analysis of contemporary adjuvant radiotherapy trends.

PURPOSE: Patients with clinical stage I testicular seminoma have historically been treated with adjuvant radiotherapy in the United States. However, nearly 80% of patients on surveillance will not experience relapse and even with relapse, salvage rates approach 100%. It remains unclear how practice patterns have changed with recently accumulating evidence and changes in guidelines. In a population based setting we evaluated contemporary trends and factors that may affect the use of adjuvant radiotherapy. MATERIALS AND METHODS: A total of 8,151 men diagnosed with stage I testicular seminoma from 2000 to 2009 were identified in the national SEER (Surveillance, Epidemiology, and End Results) registry. A multivariate regression model was constructed to analyze the association of year, age, race, socioeconomic status, SEER region, pathological stage and tumor size with the administration of adjuvant radiotherapy. RESULTS: The use of adjuvant radiotherapy decreased significantly from 2000 to 2009. In 2000, 74.7% of patients received radiation, compared with only 37.7% of patients in 2009 (p <0.0001). Later year of diagnosis was significantly associated with decreased odds of receiving adjuvant radiotherapy (p <0.0001, 2000 to 2005 vs 2006 to 2009, OR 0.40, 95% CI 0.36-0.44). Men age 35 years or older (p <0.0002, OR 1.20, 95% CI 1.09-1.32) and men in the highest socioeconomic index quartile (p <0.0001, OR 1.34, 95% CI 1.16-1.54) were more likely to receive adjuvant radiotherapy. CONCLUSIONS: The use of adjuvant radiotherapy for clinical stage I testicular seminoma has decreased significantly in the last decade. Older age and higher socioeconomic status are associated with higher rates of adjuvant radiotherapy.

An alternative treatment regimen of advanced seminoma with carboplatin, etoposide, and bleomycin instead of cisplatin-based therapy.

BACKGROUND: Cisplatin-based therapy is associated with acute and late toxicities. Therefore, a potentially less toxic carboplatin-based regimen was evaluated in patients with advanced seminoma. PATIENTS AND METHODS: Eighteen patients with advanced seminoma were treated on outpatient basis with carboplatin (AUC5) at day 1, etoposide (100 mgm(-2)) at days 1-5, and bleomycin (30 IU) at day 2 (CEB). Treatment was 3-weekly for a total of 4 cycles. Outcome and toxicities were analyzed. RESULTS: Median follow-up was 4 years and 7.5 months. Five-year progression-free survival was 86.6% (95% confidence interval (CI), 70.6%-100%), 5-year overall survival 100%, and 10-year overall survival 85% (95% CI, 63.3%-100%); 39% of all patients reached complete remission. Two patients underwent adjuvant treatment. Two patients relapsed; 1 is in ongoing remission 4 years after salvage therapy, the other died almost 6 years after CEB-therapy, despite multiple lines of salvage therapy. The main acute toxicity observed was hematologic. No late cardiovascular events or secondary malignancies were noted. CONCLUSION: CEB treatment is effective in advanced seminoma, showing minor toxicity. Progression-free and overall survival rates at 5 and 10 years are comparable to those achieved with cisplatin-based therapy. This indicates that carboplatin-combination therapy might be a good alternative to cisplatin-based therapy in the treatment of advanced seminomas.

Testicular seminoma metastasis to the gastrointestinal tract and the necessity of surgery.

INTRODUCTION: Germ cell tumors rarely metastasize to the gastrointestinal (GI) tract with an incidence that is less than 5%. Germ cell tumors can be divided into two groups: pure seminomas and non-seminomas. Pure seminomas are characterized by their profound response to chemoradiation. Within the group of germ cell tumors, pure seminomas are least likely to metastasize to the GI tract with an incidence of less than 1%. The most frequent mode of metastasis to the GI tract is direct extension from the retroperitoneal lymph nodes, which drain the testes. Ileal and jejunal metastasis are more common due to their retroperitoneal locations as well as the fact that the testes have retroperitoneal lymphatic drainage. Due to the concern of retroperitoneal metastasis in germ cell tumors, retroperitoneal lymph node biopsies are advocated for accurate staging and diagnosis due to the possibility of occult involvement in these sites. Thus, amongst the GI sites for metastasis, the duodenum is the most uncommon location. The most common manifestations of GI metastasis are intestinal obstructions via volvulus or intussusception and not acute gastrointestinal bleeding. We present a case of chemoresistant pure testicular seminoma with metastasis to the duodenum with a complication of a massive upper GI bleed requiring emergent surgery. CONCLUSION: Chemotherapy has a 90% success rate in patients with pure seminomas, even in the setting of disseminated disease. However, pure seminomas with GI metastasis have a lower response rate (60%) to chemotherapy. While there are documented cases of pure seminomas presenting with duodenal bowel perforation, or jejunal occult bleeding, this, to our knowledge, is the first case of duodenal metastasis causing massive acute upper GI bleeding. Amongst the prognostic factors for seminomas, GI metastasis is listed as a poor prognostic factor with respect to chemotherapy. Given the poor response rate with chemotherapy in GI metastasis of seminomas, early surgical management should be considered in cases where GI metastasis occurs. A retroperitoneal lymph node biopsy should be highly considered in patients with a history of seminoma in the staging process, as occult lymph node involvement can lead to future gastrointestinal metastasis that is associated with a poorer prognosis.

SPECT/CT and a portable gamma-camera for image-guided laparoscopic sentinel node biopsy in testicular cancer.

UNLABELLED: The purpose of this study was to evaluate the utility of SPECT/CT and real-time intraoperative imaging with a portable γ-camera for laparoscopic sentinel node (SN) localization in stage I testicular cancer. METHODS: Ten patients with clinical stage I testicular cancer were studied between November 2006 and November 2010. Their mean age was 37 y (range, 25-50 y). The primary tumors were situated on the right side in 5 patients and on the left side in 5. After a funicular block with 2% lidocaine, an average dose of 80 MBq (range, 59-98 MBq) of (99m)Tc-nanocolloid in a volume of 0.2 mL was injected into the testicular parenchyma. Shortly after injection, a 10-min dynamic study was performed, followed by the acquisition of static planar images at 15 min and 2 h. SPECT/CT was performed at 2 h. After image fusion, SNs were visualized, and their exact anatomic location was determined. The SPECT/CT images were displayed in the operation room to guide SN detection using a laparoscopic γ-ray probe and a portable γ-camera. RESULTS: Lymphatic drainage to the retroperitoneum was seen in all patients. SPECT/CT identified interaortocaval or paracaval SNs in the 5 patients with right-sided tumors, one of whom had an additional SN adjacent to the testicular vessels. In all 5 patients with left-sided tumors, paraaortic SNs were visualized; a node along the testicular vessels was visualized in 2 of these 5. Twenty-six SNs were laparoscopically removed (range, 1-4 per patient). An SN contained metastases in 1 case. No recurrences developed in the 9 patients with a tumor-free SN during a median follow-up of 21 mo (range, 2-50 mo). CONCLUSION: SPECT/CT enables accurate anatomic localization of retroperitoneal SNs in patients with testicular cancer, facilitating their laparoscopic retrieval. Real-time image guidance by a portable γ-camera improves intraoperative SN detection and appears to identify (20%) additional SNs.

Randomized trial of carboplatin versus radiotherapy for stage I seminoma: mature results on relapse and contralateral testis cancer rates in MRC TE19/EORTC 30982 study (ISRCTN27163214).

PURPOSE: Initial results of a randomized trial comparing carboplatin with radiotherapy (RT) as adjuvant treatment for stage I seminoma found carboplatin had a noninferior relapse-free rate (RFR) and had reduced contralateral germ cell tumors (GCTs) in the short-term. Updated results with a median follow-up of 6.5 years are now reported. PATIENTS AND METHODS: Random assignment was between RT and one infusion of carboplatin dosed at 7 × (glomerular filtration rate + 25) on the basis of EDTA (n = 357) and 90% of this dose if determined on the basis of creatinine clearance (n = 202). The trial was powered to exclude a doubling in RFRs assuming a 96-97% 2-year RFR after radiotherapy (hazard ratio [HR], approximately 2.0). RESULTS: Overall, 1,447 patients were randomly assigned in a 3-to-5 ratio (carboplatin, n = 573; RT, n = 904). RFRs at 5 years were 94.7% for carboplatin and 96.0% for RT (RT-C 90% CI, 0.7% to 3.5%; HR, 1.25; 90% CI, 0.83 to 1.89). One death as a result of seminoma (in RT arm) occurred. Patients receiving at least 99% of the 7 × AUC dose had a 5-year RFR of 96.1% (95% CI, 93.4% to 97.7%) compared with 92.6% (95% CI, 88.0% to 95.5%) in those who received lower doses (HR, 0.51; 95% CI, 0.24 to 1.07; P = .08). There was a clear reduction in the rate of contralateral GCTs (carboplatin, n = 2; RT, n = 15; HR, 0.22; 95% CI, 0.05 to 0.95; P = .03), and elevated pretreatment follicle-stimulating hormone (FSH) levels (> 12 IU/L) was a strong predictor (HR, 8.57; 95% CI, 1.82 to 40.38). CONCLUSION: These updated results confirm the noninferiority of single dose carboplatin (at 7 × AUC dose) versus RT in terms of RFR and establish a statistically significant reduction in the medium term of risk of second GCT produced by this treatment.

Stage I seminoma: what should a practicing uro-oncologist do in 2009?

Testicular tumors are uncommon, but they continue to represent an important group of malignancies in young men. It is the most common solid malignancy in males between the ages of 20 and 35, and primary germ cell tumors are the most common histological type. In the United States in 2008, approximately 4800 cases of seminoma, approximately 4100 of which were stage I disease were projected after the completion of staging investigations. Remarkable progress has been made in the treatment of testicular seminoma over the past 25 years. Management options of stage I seminoma include radiotherapy, surveillance, or adjuvant chemotherapy. Standard management until recent years has been adjuvant retroperitoneal radiotherapy. Although providing excellent long term results, this approach has been associated with increased risk of gonadal toxicity, development of secondary malignancies and an increased risk of cardiovascular disease. The use of surveillance in management of patients with stage I seminoma is therefore becoming more frequent as it minimizes the burden of treatment and maintains the cure rate at virtually 100%. Adjuvant chemotherapy using Carboplatin has been investigated as an alternative management approach. However, the long term outcomes of patients managed with Carboplatin are not yet clear and this strategy should only be used in a study setting. It has been suggested that more patients with stage I seminoma will die of their treatment than of their cancer; therefore, the thrust of modern management should be to maintain 100% cure while minimizing the burden of treatment.

Synchronous appearance of germ cell tumor and papillary carcinoma of the thyroid.

Synchronous appearance of 2 different malignancies in one patient is a rare phenomenon. We describe our experience of 2 patients with synchronous malignancies of the testis and thyroid gland, and of a third patient who developed a thyroid neoplasm unrelated to recent treatment for a germ cell tumor. The medical records of 3 male patients treated for both a germ cell tumor and a thyroid cancer between 1989 and 1994 were reviewed. Two patients with nonseminomatous germ cell tumor received postoperative chemotherapy after orchiectomy and developed a papillary carcinoma of the thyroid during treatment. A third patient, who received radiation therapy for a clinical stage 1 seminoma, recurred with biopsy proven seminoma in the neck in association with a thyroid nodule 2 years later. All 3 patients had their thyroid cancer treated by surgical resection, and one received adjuvant radioactive iodine. Two of the patients are currently alive and disease-free. One patient died of pulmonary complications that stemmed from bleomycin toxicity. Synchronous appearance of germ cell tumor and papillary carcinoma of the thyroid has not been previously described. Genetic predisposition may play a role in the development of such simultaneous neoplasms.