13 Review Article The role of diagnostic imaging in the primary testicular cancer: initial staging, response assessment and surveillance Kerry L. Thomas, Daniel Jeong, Jaime Montilla-Soler, Sebastian Feuerlein Department of Diagnostic Imaging and Interventional Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA Contributions: (I) Conception and design: All authors; (II) Administrative support: None; (III) Provision of study materials or patients: All authors; (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: All authors; (VI): Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Dr. Kerry L. Thomas, MD. Department of Diagnostic Imaging and Interventional Radiology, H. Lee Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA. Email: [email protected]. Abstract: Testicular cancers are a group of uncommon malignancies that account for less than 1% of new cancer cases per year in the United States and globally. The disease typically affects men between the ages of 20–44, and the overwhelming majority of tumors are germ cell in origin. Most cases of testicular cancer are organ confined at diagnosis and have a good overall prognosis. Testicular cancers are staged by the tumor, node, metastasis, serum markers (TNMS) classification set forth by the American Joint Commission on Cancer staging. Diagnostic imaging plays a crucial role in initial staging, specifically in assessing the primary tumor prior to orchiectomy and evaluating for regional and/or distant metastasis. Multimodality imaging is used for initial staging, with ultrasound and computed tomography (CT) most commonly utilized. Diagnostic imaging is also important in evaluating response in patients who initially present with metastatic disease as well as in patients who are undergoing surveillance. Typically, CT is used for response assessment and surveillance, with magnetic resonance imaging (MRI) and positron emission tomography (PET) serving as adjunct modalities. This article reviews the role of various diagnostic imaging modalities and how they are employed in the diagnosis, staging, response assessment and surveillance of primary testicular cancer. Keywords: Diagnostic imaging; radiology; testicular cancer Submitted Feb 06, 2019. Accepted for publication Jun 19, 2019. doi: 10.21037/tau.2019.07.01 View this article at: http://dx.doi.org/10.21037/tau.2019.07.01 Introduction Testicular cancer most commonly affects young and middle-aged men with greater than two-thirds of cases Testicular cancers are a group of rare malignancies, being diagnosed in men aged 20–44 (mean age of diagnosis accounting for only 0.5% of new cancer cases in 2018 in 33) (1). In many developed countries, testicular cancer is the United States (USA). The global incidence of testicular cancer is similar to the USA, accounting for 0.8% of new the most common malignancy in men of this age group cancer cases in men in 2018 (1,2). The National Cancer (3,4). Men of Caucasian descent are more often affected Institute estimates there will be about 9,300 new cases than non-Caucasian men (5). In the majority of cases of testicular cancer diagnosed in 2018 (1). An estimated (68%), testicular cancer is limited to the testicle at time of 400 patients will die from their disease, accounting for 0.1% diagnosis, whereas the remaining 32% present with regional of all cancer-related deaths this year (1). While the rate of lymph node or distant metastasis (6). The overall 5-year new testicular cancers has increased both globally and in the survival for testicular cancer patients is 95.3% (1). USA in recent decades, mortality rates have been stable or Testicular cancers are classified as either germ cell or declining, particularly in developed countries (1,3,4). non-germ cell tumors. The majority are germ cell tumors, © Translational Andrology and Urology. All rights reserved. Transl Androl Urol 2020;9(Suppl 1):S3-S13 | http://dx.doi.org/10.21037/tau.2019.07.01 S4 Thomas et al. The role of diagnostic imaging in the primary testicular cancer lymphoma, the most common testicular malignancy in men over 60 years old, leukemia, sarcoma, fibroma, leiomyoma, vascular tumors and metastasis (9). Testicular cancers are most commonly staged using the American Joint Commission on Cancer’s (AJCC) tumor (T), nodal (N), and metastasis (M), TNM classification (10,11). The T stage is derived from pathologic analysis at orchiectomy while nodal and distant metastases are assessed via imaging studies (10). Testicular cancer also includes a unique, additional staging classification, the Figure 1 Seminoma. High-resolution testicular ultrasound with serum tumor marker (S) stage (10). Serum tumor markers color Doppler of the right testicle demonstrates a circumscribed most commonly evaluated in testicular cancer include alpha mass in the inferior testicle. The mass is solid, homogenous and fetoprotein (AFP), beta human chorionic gonadotropin hypoechoic relative to the normal testicular parenchyma without (β-hCG) and lactate dehydrogenase (LDH) (11). The calcification or cystic spaces. International Germ Cell Cancer Collaborative Group has established risk classification for patients with advanced disease (12). Patients are classified into good, intermediate and poor risk, based on location of primary tumor, location of metastases and post-orchiectomy serum markers (10-12). Diagnostic imaging plays a pivotal role in the initial diagnosis and staging of testicular cancer as well as in assessment of treatment response and follow-up surveillance. This review focuses on the role of imaging in the diagnosis, staging and surveillance of testicular cancer. Initial diagnosis and staging Ultrasound Figure 2 Seminoma. High-resolution testicular ultrasound with color Doppler of the left testicle reveals a homogenous, hypoechoic Testicular cancer classically presents as a painless, palpable mass nearly replacing the entire left testicle and showing color mass and is most commonly initially evaluated with high flow, indicating a vascular mass. frequency ultrasound using a linear, high frequency transducer. Ultrasound has been shown to have greater than 90% sensitivity and specificity for detecting testicular with only 5–10% of cases classified as non-germ cell, or malignancy in the appropriate clinical setting (10,13). It can stromal tumors (6). Germ cell tumors are further divided localize a palpable mass as intra-testicular or extra-testicular into seminoma and nonseminomatous tumors with about as well as differentiate cystic lesions from solid masses 50% each seminoma and nonseminomatous lesions (6,7). (9,10). Ultrasound is also useful in assessing for clinically Nonseminomatous germ cell tumors (NSGCT) include: occult lesions in patients who present with metastatic embryonal carcinoma, yolk sac tumor, choriocarcinoma, disease and to evaluate the contralateral testis to exclude teratoma and mixed germ cell tumor (7). Seminomas tend bilateral, synchronous tumors, albeit rare, occurring in 2% to occur in older patients, have a better prognosis compared of seminoma (7,14). to nonseminomatous tumors, and are sensitive to radiation Typically, testicular seminoma presents as a unilateral and chemotherapy (8). Sex cord stromal tumors include mass that is homogenous and hypoechoic relative to Sertoli cell, Leydig cell and granulosa cell tumors, as well as surrounding testicular parenchyma (Figures 1,2). Cystic thecomas (5,9). While germ cell tumors are predominately spaces and calcifications are uncommon features, seen only malignant, primary sex cord and stromal tumors are in 10–30% of seminomas (9-10,15). Conversely, NSGCT malignant only in 10% (5). Other testicular tumors include are more likely heterogeneous in echogenicity with © Translational Andrology and Urology. All rights reserved. Transl Androl Urol 2020;9(Suppl 1):S3-S13 | http://dx.doi.org/10.21037/tau.2019.07.01 Translational Andrology and Urology, Vol 9, Suppl 1 January 2020 S5 A B C D Figure 3 Mature teratoma of the left testicle with abdominal metastasis. (A) Grayscale ultrasound image of the left testicle demonstrates a heterogenous mixed cystic and solid mass; (B) Doppler color image demonstrates internal color flow within the mass; (C) axial contrast enhanced CT shows the cystic components within the left testicular mass; (D) axial contrast enhanced CT of the abdomen shows a left para- aortic hypodense metastatic lesion. CT, computed tomography; LT, left; TRV, transverse. calcification and/or cystic components are not uncommon, to as is seen in contrast enhanced computed tomography occurring in up to 40% of patients (7,9) (Figures 3,4). (CT) and magnetic resonance imaging (MRI). Microbubble In some cases of germ cell tumor, only a small lesion or contrast agents are composed of tiny, injectable gas bubbles calcification may be seen or there may be no discreet mass in a supporting shell. The use of CEUS poses no risk of visible. This is thought to be due to outgrowing blood nephrotoxicity and does not use ionizing radiation, as is supply and resultant tumor regression (9,10). necessary in contrast, enhanced CT (13). An early experience Ultrasound cannot reliably differentiate tumor histology (9). study by Lock et al. showed promising results with CEUS, Ultrasound features of Leydig cell and granulosa cell where hyperenhancement of a testicular lesion had a tumors are similar to germ cell tumors, typically presenting positive predictive value (PPV) of