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.

Adherence to National Comprehensive Cancer Network® Guidelines for Testicular Cancer.

PURPOSE: Testicular cancer is the most common malignancy among young men and well established treatment guidelines exist to optimize outcomes. We characterized errors in the management of testicular cancer observed among patients seen at 3 referral centers in the United States. MATERIALS AND METHODS: We retrospectively reviewed data from 593 patients presenting with testicular cancer to 3 academic medical centers from 2007 to 2016. Nonguideline directed care was defined as management differing from National Comprehensive Care Network guideline recommendations. Cases of nonguideline directed care were systematically described. Patient and tumor characteristics were compared between guideline directed care and nonguideline directed care. Multivariable logistic regression was used to identify predictors of nonguideline directed care, and Cox regression modeling was used to assess the association between nonguideline directed care and relapse-free survival. RESULTS: Nonguideline directed care was identified in 177 of 593 (30%) patients. Inappropriate imaging (44%) and overtreatment (40%) were the most common classifications. Misdiagnosis (24%) and under treatment (16%) occurred relatively frequently, while inappropriate treatment (6%) was rare. Multivariable Cox regression modeling controlling for race, tumor stage and tumor histology identified nonguideline directed care as a significant predictor of relapse (HR 2.49, 95% CI 1.61-3.85, p <0.01). CONCLUSIONS: Nonguideline directed care of patients with testicular cancer is common, most frequently in the form of inappropriate imaging and overtreatment. Nonguideline directed care leads to delayed definitive therapy, unnecessary morbidity and higher rates of relapse.

Comparative analysis of the risk of radiation exposure and cost of reduced imaging intensity for surveillance of early-stage nonseminomatous germ cell tumors.

OBJECTIVE: To evaluate the surveillance recommendations for early-stage testis cancer and the risk of secondary malignancies due to increased radiation exposure. MATERIALS AND METHODS: Using National Comprehensive Cancer Network (NCCN) guidelines 2012 and 2014 for early-stage testicular cancer, the numbers of abdominal and pelvic computed tomography scans (CTAPs) and chest radiographies were calculated, and lifetime attributable risk for secondary malignancy was estimated using Biologic Effects of Ionizing Radiation VII organ-specific model for solid organ malignancy based on the initial age of exposure. Cost was based on the Centers for Medicare and Medicaid Services' cost estimates of CTAP and magnetic resonance imaging (MRI). RESULTS: The 2012 NCCN protocol uses a maximum of 17 CTAPs over 6 years, whereas 2014 guidelines suggest a maximum of 13 CTAPs. The radiation dosage in 2014 guidelines is decreased by 25% compared to the 2012 NCCN guidelines. The minimum number of CTAPs under the 2014 NCCN protocol reduced radiation dose by 38% compared to the maximum number, this compared to about 50% decrease from the 2012 NCCN guidelines. The median cost for a single CTAP with contrast is $369.30; median cost for a single MRI with contrast is $772.18. As compared to the 2012 protocol, the 2014 guidelines reduced CTAP cost by approximately 24%-54% for minimum and maximum CTAPs allowed. CONCLUSION: There is low, however nonzero, risk of secondary malignancy for surveillance in stage I testicular cancer. There is also a significant cost difference between protocols as well as between CT and MRI modalities.

Clinical features, presentation, and tolerance of platinum-based chemotherapy in germ cell tumor patients 50 years of age and older.

BACKGROUND: Germ cell tumors (GCTs) primarily affect adolescent and young adult men. Detailed clinical and treatment characteristics in older men are lacking. METHODS: Patients with GCT seen over a 20-year period at Memorial Sloan-Kettering Cancer Center were identified. Primary tumor site and histology were compared for patients aged ≥ 50 years at diagnosis versus younger men. For patients aged ≥ 50, individual chart review was performed and treatment delays, changes, and toxicities were recorded for those treated with first-line chemotherapy. RESULTS: Of 4235 diagnoses of GCT, 3999 (94.4%) were made at age < 50 versus 236 (5.6%) at age ≥ 50. Compared with patients diagnosed before age 50, older men more frequently had seminoma (62.7% versus 36.7%) and less frequently, nonseminoma (34.7% versus 63.2%) (P < .0001). Predominant histology switched from nonseminoma to seminoma around age 35. Distribution of primary sites also differed for older versus younger men (testis: 89.4% versus 92.9%; retroperitoneal: 3.8% versus 0.7%; CNS 0% versus 1.7%) except for mediastinal primary tumors, which remained constant across age groups. Fifty patients age ≥ 50 received first-line platinum-based chemotherapy; 30 experienced complications leading to treatment discontinuation, delay ≥ 7 days, or regimen change. Twenty-two (44%) patients experienced neutropenic fever, 6 despite prophylactic growth factor support. Estimated 5-year survival for chemotherapy-treated patients was 84.9%. CONCLUSIONS: Men aged ≥ 50 years comprise less than 10% of GCT diagnoses and have distinct clinical and histological characteristics as compared with younger patients. Although complications from chemotherapy occur frequently in older men, prognosis remains excellent when risk-directed treatment is administered with curative intent.

Probability of metachronous testicular cancer in patients with biopsy-proven intratubular germ cell neoplasia depends on first-time treatment of germ cell cancer.

PURPOSE: To evaluate the probability of subsequent testicular cancer (STC) in patients with intratubular germ cell neoplasia unclassified (IGCNU) treated for first-time invasive germ cell cancer. PATIENTS AND METHODS: Sixty-one patients with germ cell testicular cancer or extragonadal germ cell cancer received follow-up from diagnosis of IGCNU to development of STC, initiation of IGCNU-definitive treatment (orchiectomy/radiotherapy), emigration, death, or end of follow-up. The probability of STC was assessed in subgroups according to chemotherapy burden. RESULTS: The probability of STC in the nonexposed patients was significantly increased compared with those exposed to chemotherapy (P = .05; 5-year probability of 54% [95% CI, 33% to 78%] and 23% [95% CI, 11% to 45%], respectively). In the group of patients treated with one to three cycles or no chemotherapy, the probability of STC was significantly increased compared with those exposed to four or more cycles (P = .03; 5-year probability of 42% [95% CI, 27% to 62%] and 22% [95% CI, 8% to 54%], respectively). Twenty-two of 22 patients were tumor-free and alive at a median of 56 months (range, 2 to 184 months) after diagnosis of STC. CONCLUSION: Platinum-based chemotherapy may reduce the probability of STC in patients with IGCNU, particularly in those treated with four or more cycles of chemotherapy. A watch-and-wait strategy for patients with IGCNU may be justified in selected patients with future plans for paternity.

Complementary and alternative medicine practitioners' standard of care: responsibilities to patients and parents.

In this article we explain (1) the standard of care that health care providers must meet and (2) how these principles apply to complementary and alternative medicine practitioners. The scenario describes a 14-year-old boy who is experiencing back pain and whose chiropractor performed spinal manipulation but did not recognize or take steps to rule out serious underlying disease-in this case, testicular cancer--either initially or when the patient's condition continued to deteriorate despite treatment. We use chiropractic care for a patient with a sore back as an example, because back pain is such a common problem and chiropracty is a common treatment chosen by both adult and pediatric patients. The scenario illustrates the responsibilities that complementary and alternative medicine practitioners owe patients/parents, the potential for liability when deficient care harms patients, and the importance of ample formal pediatric training for practitioners who treat pediatric patients.

[The future of uro-oncology: what needs to be done to secure its place in the field of urology?]. / Die Zukunft der Uroonkologie : Was muss geschehen, um den Bereich für die Urologie zu sichern?

The specialty of urology has changed considerably with regard to the subspecialty of uro-oncology and requires more than just knowledge of hormone therapy for metastatic prostate cancer and standard treatment of testicular tumors. Many oncology centers offer specialized and interdisciplinary treatment, but often the process of navigating through the jungle of diagnostic workup and treatment is inadequate. Thus, clinical centers for uro-oncology must include specialists in pharmacological therapy for cancer and drug development who will work closely with the department of urology.

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.

Quality of surveillance for stage I testis cancer in the community.

PURPOSE: Patients with clinical stage I testicular germ cell tumors have been managed with adjuvant radiotherapy, chemotherapy, or retroperitoneal lymph node dissection (RPLND). The use of surveillance-only strategies at referral centers has yielded survival outcomes comparable to those achieved with adjuvant therapy. We evaluated compliance with follow-up protocols developed at referral centers within the community. METHODS: We identified patients with stage I testis cancer within a large private insurance claims database and calculated compliance of follow-up test use with guidelines from the National Comprehensive Cancer Network. RESULTS: Surveillance was widely used in the community. Compliance with surveillance and postadjuvant therapy follow-up testing was poor and degraded with increasing time from diagnosis. Nearly 30% of all surveillance patients received no abdominal imaging, chest imaging, or tumor marker tests within the first year of diagnosis. Patients who elected RPLND were most compliant with recommended follow-up testing within the first year. Recurrence rates were consistent with previously reported literature, despite poor compliance. CONCLUSION: Surveillance is a widely accepted strategy in clinical stage I testicular cancer treatment in the community. However, follow-up care recommendations developed at referral centers are not being adhered to in the community. Although recurrence rates are similar to those of reported literature, the clinical impact of noncompliance on recurrence severity and mortality are not known. Further prospective work needs to be done to evaluate this apparent quality of care problem in the community.

Malignancies in beta-thalassemia patients: a single-center experience and a concise review of the literature.

Thalassemia represents the world's most common monogenic disease, characterized by absence of or decreased globin chain production. The lifespan of thalassemia patients has been extended as a result of current supportive treatment. We report three cases of cancer (non-Hodgkin lymphoma, Hodgkin disease, and seminoma) in thalassemic patients. Factors that may contribute to the pathogenesis of cancer seem to be infections and iron overload through mechanisms of oxidative damage; immunomodulation or coexistence of the two diseases may only be coincidental.

[Testicular germ-cell tumour: diagnosis and treatment]. / Tumeurs germinales séminomateuses du testicule: diagnostic et traitement.

Among germ cell tumours, seminomas hold a particular status related to their radio-sensitivity. Although radiotherapy remains the best treatment for Localized tumours of stage 1, in some cases, surveillance or chemotherapy may presently be considered as alternative therapies. Due to Long-term radiotherapy-related adverse effects, in particular the risk of second non-germ malignancies or cardiac morbidity, both dose and irradiation field are reduced in case of lymphatic retroperitoneal extension. Chemotherapy is the preferential treatment in more advanced stages, either with retroperitoneal bulky disease or with metastatic extension. Its efficacy allows Limiting surgical indications on residual masses, relying partly on the follow-up data of positron emission transaxial tomography assessment.

[Postoperative radiologic evaluation in uroradiology. Part 2: Bladder, prostate, and testis]. / Postoperative Bildgebung in der Uroradiologie. Teil 2: Blase, Prostate und Hoden.

Radiologists, especially uroradiologists, must retain abreast of rapid developments in urologic therapy and operative techniques in order to critically assess postoperative changes. Part 2 of this review will cover therapy and postoperative evaluation in bladder surgery, surgery in prostate cancer, and retroperitoneal disease associated with testicular tumors. Using the appropriate modality at the appropriate time during the postoperative course is discussed. A variety of alternatives are available to perform urinary diversion after radical cystectomy. Knowledge of operative techniques and postoperative anatomy are mandatory for interpretation of postoperative radiologic findings.

Surgical removal of a seminoma from a black sea bass.

An adult black sea bass was examined because of abdominal distention and decreased appetite. A large abdominal swelling was evident and was firm on palpation. Differential diagnoses included neoplasia, abscess or granuloma, hematoma, or swim bladder abnormality. Diagnostic tests included survey radiography, positive-contrast radiography, and computed tomography. The sea bass was anesthetized with tricaine methanesulfonate. A ventral midline abdominal incision was made, and adhesions to the mass were gently dissected. The fish recovered without complications. Radiography was repeated 8 weeks after surgery, and there was no evidence of mass regrowth. To the authors' knowledge, this is the first report of a barium enema being performed in a fish. Although surgical procedures are performed more commonly on fish for research, a few reports of clinical surgical cases have been described. Our experience supports the conclusions of other reports that certain surgical procedures can be performed safely in fish.

Differential diagnosis of testicular mass by cytological examination of seminal fluid collected by ejaculation or prostatic massage.

The cytological examination of the seminal fluid of 3 patients with painless testicular masses was performed using an ordinary conventional technique. Neoplastic cells appeared in the ejaculate or fluid from prostatic massage of all patients. The final pathologies were seminoma, choriocarcinoma and mixed teratocarcinoma. Malignant cells were no longer found in the seminal fluid after orchiectomy. This sample, noninvasive technique plus further flow cytometric study of cellular DNA contents is a great help in the preoperative differential diagnosis of testicular masses.

Phosphorus-31 MRS of human testicular function and viability.

The current clinical use of magnetic resonance spectroscopy (MRS) is explored with attention to testicular function and pathology. Magnetic resonance spectroscopy provides insights into metabolic processes that are occurring in vivo. Information on these processes were, until now, only obtained through the use of invasive procedures such as biopsy, with the attendant undesired side effects. Phosphorus-31 (31P) MRS of the testes can provide unique metabolic information noninvasively and may provide clinicians with an alternative to the invasive procedures. The practical applicability of 31P MRS to the study of human infertility and testicular pathologies is described in some very preliminary studies.

Is SP-1 a marker for testicular cancer?

We measured the serum levels of the pregnancy-associated protein SP-1 by radioimmunoassay in 91 patients with a diagnosis of germ cell testicular cancer. Sixty-seven of the men had active disease, and of these, 52 per cent had elevated levels of SP-1. In contrast, all 24 patients with inactive disease had normal levels. Elevations of SP-1 were associated more often with elevated levels of human chorionic gonadotropin than with elevated levels of alpha-fetoprotein, but elevated SP-1 levels also occurred in patients with normal levels of both of these established tumor markers. We studied serial samples from 21 patients, and in 5 the SP-1 level provided clinically valuable information not provided by the other two markers. SP-1 is a clinically useful marker in germ cell testicular cancer. Further studies are needed to determine the role of the two forms of protein, alpha and beta, and to define the conditions under which the SP-1 level is elevated.