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Testicular Germ Cell Tumors in Men with Down's Syndrome

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Testicular Germ Cell Tumors in Men with Down's Syndrome Central Annals of Mens Health and Wellness Bringing Excellence in Open Access Research Article *Corresponding author Jue Wang, Director of Genitourinary Oncology Section, University of Arizona Cancer Center at Dignity Health Testicular Germ Cell St. Joseph’s, Phoenix, AZ, 625 N 6th Street, Phoenix, AZ 85004, Tel: 1602-406-8222; Email: Tumors in Men with Down’s Submitted: 23 March 2018 Accepted: 29 March 2018 Syndrome: Delayed Diagnosis, Published: 31 March 2018 Copyright Comorbidities May Contribute © 2018 Wang et al. OPEN ACCESS to the Suboptimal Outcome Keywords • Testicular germ cell tumor (TGCT) 1 2,3,4 Emma Weatherford and Jue Wang * • Down’s syndrome (DS) 1Baylor University, USA • Delayed diagnosis 2Creighton University School of Medicine at St. Joseph’s Hospital and Medical Center, • Seminoma USA • Non seminomatous germ cell tumor; Orchiectomy 3 St. Joseph’s Hospital and Medical Center, USA • Chemotherapy 4Department of Genitourinary Oncology, University of Arizona Cancer Center at • Prognosis Dignity Health St. Joseph’s Hospital and Medical Center, USA Abstract Purpose: The main objective of this study was to determine the clinical features, treatment and prognosis of Down’s syndrome (DS) patients with testicular germ cell tumor (TGCT). Materials and methods: We conducted a pooled analysis of 43 Down’s syndrome patients diagnosed with TGCT published in literature between January 1985 and December 2016. Results: The median age was 30 years (range 2 – 50). A majority of tumors (67%) were seminomas. 26 (51%) patients were diagnosed as stage I, 14 (33%) and 7 (16%) as stage II and III, respectively. In the seminoma group, 18 patients (62%) were diagnosed with stage I, 9 (31%) with stage II and 2 (7%) with stage III. In the non-seminoma group, 4 patients (29%) were diagnosed with stage I, 5 (36%) with stage II and 5 (36%) with stage III. 26 out of 43 (60%) patients had documented comorbidities. The overall survival at 5 years for stage I was 100%, 76% for stage II and 68% for stage III. Conclusion: TGCT are often diagnosed at an advanced stage in patients with DS. In addition, patients often required modifications to standard treatment regimens due to their comorbidities. Delayed diagnosis, comorbidities may contribute to the suboptimal outcome in stage II/III TGCTs in DS patients. Emphasis education on community and care provider on prevalence of TGCT, early screening and detection, are needed to improve the outcome in this population. INTRODUCTION MATERIALS AND METHODS Testicular cancer, although relatively rare in the general Published data Search population, is the most common form of cancer among young Literature search based on PubMed search was performed men aged 15 to 35 [1,2]. The majority of testicular cancers are using the following keywords: “Testicular germ cell tumor testicular germ cell tumors (TGCT) [3-5]. The incidence of TGCT (TGCT)”, “Testicular cancer” and “Down’s syndrome”. Cases were has been observed to be higher among men with Down syndrome relative to the general population [6,7], despite the lower found through references in other reports or through a search incidence of most solid tumors among the Down’s syndrome ofinitially the Baylor identified University from alibrary search services. of PubMed; The fullfurther texts cases of reports were (DS) population [7]. However, there is a lack of published data regarding testicular cancer among men with DS, the available the abstract or a summary published in another source was used. information regarding clinical features, management, and were located when possible; when the full text was not available, treatment outcomes are limited [8-11]. Data extraction In order to better understand the differences in the clinical Information regarding the patient (patient age at diagnosis, manifestations and optimal management of testicular cancer presentation, and comorbidities), the tumor (discovery, among men with DS, we conducted a pooled analysis of 43 DS symptoms, tumor size, location, histology, and stage), patients diagnosed with TGCT published in literature [12-31], examination results (tumor markers, radiologic investigation, between January 1985 and December 2016. biopsy), treatment (treatment modalities, response), and the Cite this article: Weatherford E, Wang J (2018) Testicular Germ Cell Tumors in Men with Down’s Syndrome: Delayed Diagnosis, Comorbidities May Contribute to the Suboptimal Outcome. Ann Mens Health Wellness 2(1): 1010. Wang et al. (2018) Email: Central Bringing Excellence in Open Access outcome (evidence of metastases, vital status) were recorded, Table 1: The demographic and tumor characteristics of 43 Down's when available. syndrome Patients with TGCT published in literature between January 1985 and June 2016. Data analysis Descriptive statistics, such as frequency counts, medians, and Age (yr) N (%) ranges, were used to characterize the pooled sample. Survival was calculated according to the Kaplan-Meier method and the 20-29 <20 9 (21%) survival curves were compared by univariate analysis with the 30-39 12 (28%) >39 14 (33%) from the date of TGCT diagnosis to the date of death. Statistical Median Age (Range) 30 (2-50) 8 (19%) long-rank test. Overall survival (OS) was defined as the time Comorbidities performed using SPSS ver. 15.0 (SPSS Inc., Chicago, IL). Yes significance was defined as a p-value<0.05. All analyses were No 26 (60%) RESULTS Crytorchidism 17 (40%) Patient and Tumor Characteristics Yes No 27(62.8) Forty-three DS patients with adequate clinical and pathologic 16(37.2%) Histology Seminoma Embryonic carcinoma data were included in final analysis. A majority (61%) of patients 29 (67%) Choriocarcinoma presented between the ages of 20 and 39; the median age was 5 (12%) Yolk sac tumor 30 years (range 2 years – 50 years). Many patients (60%) had 0 (0%) Teratoma one or more reported comorbidities. Sixteen patients (37%) 1 (2%) Mixed had a history of cryptorchidism in one or both testes. 24(56%) 0 (0%) involved left side testis including 4(9%) were bilateral. 20 7 (16%) Stage (46%) patients presented with findings of swelling of the Not specified 1 (2%) I documentedscrotum; 7(16%) comorbidities. presented Table with 1swelling shows theof the demographic groin; 6(14%) and II with abdominal or flank pain.26 out of 43 (60%) patients had 22 (51%) tumor characteristics of these patients with TGCT published in III literature. 14 (33%) AFP Levels: seminoma / nonseminoma 7 (16%) Elevated Normal 0 (0%) / 8 (57%) A majority of tumors (67%) were seminomas. The remainders Unknown 15 (52%) / 2 (14%) were nonseminomas, of which 12% were embryonic carcinomas β-hCG Levels: seminoma / nonseminoma 14 (48%) / 4 (29%) and 16% were mixed germ cell tumors. In the seminoma group, Elevated 18 patients (62%) were diagnosed with stage I, 9 (31%) with Normal 7 (24%) / 4 (29%) stage II and 2 (7%) with stage III. In the non-seminoma group, 4 Unknown patients (28%) were diagnosed with stage I, 5 (36%) with stage 8 (28%) / 5 (36%) 14 (48%) / 5 (36%) IITreatment and 5 (36%) and with adverse stage III. effects III. Figure 1c presents the survival by histology at presentation. Treatment regimens and patient outcomes are presented nonseminoma. There was no significant difference between seminoma and in Table 2. A majority of DS patients (51%) received standard disease. Both of these patients presented with advanced radiotherapy.treatment. All Eightpatients reports underwent state thatorchiectomy. the patient In addition,received Three DS patients (7%) died due to progression of their 51% of DS patients received chemotherapy and 19% received another patient presented at stage IIB, no additional therapy or stage (two stage III and received nonstandard chemotherapy; modified treatment due to comorbidities (such as reduced complications during treatment. Two of these patients died during the period of follow-up due to causes unrelated to cancer. duringglomerular chemotherapy, filtration rate). while Five thepatients remainder (12%) experiencedsuccessfully radiotherapy following orchiectomy). Two DS patients (5%) died completed their therapy. DISCUSSION Testicular cancers (TC) are rare in the general population, Outcome mainly young adults between the ages of 15 to 35 years [1,2]. accounting for 1% of all human malignancy, but affect reportedThe majority outcome. of When DS patients only cases (67%) with showed recorded no outcomesevidence their chemosensitivity, multidisciplinary management, and of disease at the end of follow-up. Seven cases (16%) had no establishedAlthough TC follow-up in general approach shows and excellent salvage curetherapies rates [3-5], based delay on in diagnosis of a testicular cancer may result in an advanced stage Figureare considered, 1b presents 86% the ofsurvival patients by stagesurvived at presentation. their cancer. The Figure OS at of disease at diagnosis, which may affect disease free and overall 1a presents the cancer specific survival of patients in this study. survival [32]. 5 years for stage I was 100%, 76% for stage II and 68% for stage Ann Mens Health Wellness 2(1): 1010 (2018) 2/5 Wang et al. (2018) Email: Central Bringing Excellence in Open Access Table 2: Treatment and Patient Outcome of 43 Down's syndrome Patients with TGCT published in literature between January 1985 and June 2016. (A) Variable Orchiectomy Value N (%) Yes No 43 (100%) Chemotherapy 0 (0%) Yes No 22 (51%) Radiotherapy 21 (49%) Yes No 8 (19%) Outcome 35 (81%) NED DOC 29 (67%) DOD 2 (5%) (B) DOT 3 (7%) NS 2 (5%) 7 (16%) Note: AWD, alive with disease; DOC, died due to another condition; DOD, died of disease progression; DOT, died during treatment; NA, not available; NED, no evidence of disease; NS, not specified Emerging epideminologic and clinical evidences suggests that men with DS experience a higher frequency of testicular cancer than the general population [6-9]. The presentation of testicular cancer is similar to that of nondisabled persons: painless nodule and a swelling of the scrotum. Due to intellectual disability, indivuduals with DS may not adequately convey their symptoms and pain, often leading to delayed diagnosis and potentially worse outcome [9].
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