Management of Testicular Cancer

NYU Case of the Month, November 2018

Case of the Month Management of Testicular Cancer NYU Case of the Month, November 2018 James Wysock, MD NYU Langone Health and NYC Health + Hospitals/Bellevue, New York, NY [Rev Urol. 2018;20(4):179–181 doi: 10.3909/riu0824C] ® © 2019 MedReviews , LLC A 26-year-old healthy man in his usual state of health presented with painless left testicular fullness. He noted no dysuria or other lower urinary tract symptoms (LUTS), hematuria, or penile discharge. He had no history of recent scrotal or penile trauma. He is sexually active in a monogamous relationship. His medical history was pertinent for adrenal insufficiency secondary to congenital adrenal hyperplasia (CAH). His hormone levels were well controlled with oral prednisone and fludrocortisone. He had no prior surgical history and no family history of genitourinary malignancy. At the time of presentation, he noted that he was engaged to be married and that he had no children. Evaluation at NYU Langone Health Physical Examination On examination, he was found to be a normal, welldeveloped adult man. On testicular examination, a left lower pole testicular asymmetry without a discrete mass was noted. Both testes were non-tender, and no epididymal, scrotal, or inguinal abnormalities were noted. The remainder of his examination was normal. Laboratory Evaluation The patient’s alpha-fetoprotein was found to be at the upper limit of normal at 13 ng/mL; however, the remainder of his serum tumor markers were in the normal range. No other laboratory abnormalities were detected. Radiographic Evaluation The patient underwent testicular ultrasound, which demonstrated a 1.8 cm 3 1.6 cm 3 1.6 cm heterogeneous, intratesticular mass in the inferior left testicle (Figure 1). No other abnormalities were detected. Treatment Following administration of stress dose steroids, a left inguinal exploration with mobilization of the left spermatic cord was performed. A tourniquet was placed on the left spermatic cord and the left testicle was delivered into the operative field in standard fashion. The left testicle and spermatic cord were then isolated within a bowel bag. Intraoperative ultrasound was used to confirm the location of the left testicular mass. An incision was Figure 1. Scrotal sonogram demonstrating a 1.8 cm 3 1.6 cm 3 1.6 cm left testicular mass. Vol. 20 No. 4 • 2018 • Reviews in Urology • 179 4170018_00_RIU0824C_V4_rev03.indd 179 1/21/19 8:05 PM Management of Testicular Cancer continued made in the tunica albuginea to expose the contents of the left testicle. The left testicular mass was identified within a background of normal seminiferous tubules. A specimen was excised from the mass and sent for frozen section analysis. Frozen section confirmed presence of a germ cell tumor. The radical orchiectomy was then completed with same-day discharge. Pathology The histopathology of the patient’s testicle demonstrated a 1.7-cm tumor containing embryonal carcinoma. Vascular invasion was noted, as well as intratubular germcell neoplasm. Lymphovascular invasion was also noted. The patient’s spermatic cord margin was negative. The patient’s post-orchiectomy tumor markers were noted as normal. Further staging imaging with chest radiograph and CT of the abdomen and pelvis demonstrated no evidence of retroperitoneal or intrathoracic or metastatic disease. The patient was offered management options including surveillance, primary retroperitoneal lymph node dissection, or primary chemotherapy (bleomycin, etoposide, and cisplatin [BEP]). The patient initially elected surveillance. He underwent surveillance imaging per NCCN guidelines and his first CT a/p demonstrated new lymphadenopathy—1.9 cm 3 1.6-cm and 1.5 cm 3 1.1-cm aortocaval lymph nodes were identified (Figure 2). The patient’s tumor markers remained normal. After extensive counseling about treatment options and referral to a medical oncologist for further discussion, the patient elected to proceed with robotic full bilateral template retroperitoneal lymph node dissection (rRPLND) with Figure 2. CT a/p showing a 1.9 cm 3 1.6 cm interaortocaval lymph node. nerve sparing. Prior to surgery, the patient performed sperm banking. The patient’s surgery was uncomplicated, with minimal blood loss (EBL, 200 cc). The patient was discharged home on postoperative day 1, noting excellent pain control with oral pain medications. The patient’s final pathology demonstrated evidence of nodal disease in 4 of 64 nodes. Nodal disease was detected in 4 nodes in the interaortocaval lymph node packet (23 nodes resected from this region). The nodal disease measured approximately 2.5 cm and no extranodal extension was noted. These findings upgraded his pathologic staging to stage IIB from an initial clinical stage IA. Following these results, the patient underwent two cycles of EP which he tolerated without adverse events. On routine follow-up, he remains NED. Commentary Germ-cell tumors of the testicle are the most common solid tumor that presents in young men, with approximately 8700 new cases diagnosed annually.1 The treatment of testicular germcell tumors stands as a model for oncologic management, and these tumors remain one of the most successfully treatable cancers; modern protocols achieve 95% 5-year survival rates for all states of disease.2 As with many oncologic management paradigms, successful cancer control requires adherence to documented guidelines.3 The mainstay of testicular neoplasm management begins with radical orchiectomy.4 Although this procedure involves relatively modest short-term morbidity, loss of a testicle poses a risk for future fertility, hypogonadism, and selfimage.5,6 Consequently, careful consideration should be given to the differential diagnosis of a testicular mass before proceeding with radical orchiectomy. In addition to germ-cell tumors, the differential diagnosis of intratesticular tumors includes Leydigcell hyperplasia, Sertoli-cell tumors, lymphoma, metastatic disease, and epidermoid cysts.7 Often, these non–germ-cell tumors pose minimal to no oncologic risk. In the setting of CAH, a testicular adrenal rest tumor (TART) should be considered in the differential diagnosis of a testicular mass. Individuals with CAH often carry an autosomal recessive disorder resulting in deficient 21-α-hydroxylase (CYP21) and insufficient production of mineralocorticoids and glucocorticoids.8,9 With the loss of negative feedback, the pituitary gland produces excess adrenocorticotropin (ACTH).9 Although severe cases of CAH are often detected in neonatal screening, milder disease may not become clinically evident until later in childhood, in adolescence, and possibly in adulthood. Ectopic adrenal rest tissue may develop in several tissues, including the retroperitoneum, the ovaries, and the testes.10 This ectopic tissue most commonly becomes atrophic and rarely persists into adulthood. However, because of the excess ACTH produced during CAH, ectopic adrenal tissue receives excess growth signal and can subsequently hypertrophy. As a result, in individuals with CAH, the 180 • Vol. 20 No. 4 • 2018 • Reviews in Urology 4170018_00_RIU0824C_V4_rev03.indd 180 1/21/19 8:05 PM Management of Testicular Cancer frequency of detecting TART can be high, with documented prevalence rates as high as 94%.10,11 In addition, TART lesions commonly occur as multiple tumors and are also often bilateral. The peak incidence of TART detection in men is between 20 and 40 years of age, similar to germ-cell tumors.11 Given this patient’s long-standing history of CAH and the size of his left testis mass, we considered TART in the differential diagnosis especially because tumor markers were not definitively elevated. Thus, the decision was made to proceed to explore the testes and consider partial orchiectomy if intraoperative frozen section analysis confirmed the TART. The patient was extensively counseled on the procedure of partial orchiectomy and agreed to proceed. Partial Orchiectomy— Consideration for the Small Testicular Mass Widespread use of testicular ultrasound has resulted in increased detection of small testicular masses (STMs), defined as nonpalpable masses smaller than 25 mm.12 Several studies have demonstrated that the majority of incidentally detected STMs are benign, provided that tumor markers are not elevated.13-15 In a recent retrospective review of STMs, the rate of benign lesions increased as the lesion size decreased, ranging from 14.4% for masses of 2 to 3 cm, 33.3% for masses of 1 to 2 cm, and approximately 40% for masses of less than 1 cm.15,16 The technique for partial orchiectomy employs similar oncologic principles as for radical inguinal orchiectomy.17 The testis is delivered through an inguinal incision and the spermatic cord is secured with a tourniquet, facilitating conversion to radical orchiectomy as needed.18 To prevent tumor spillage or contamination, the testis is isolated from the operative field by a barrier before opening of tunica albuginea.16 Employing intraoperative ultrasound can assist with localization of the STMs.14,19 Cold ischemia can also be used. However, data on this technique are limited.20,21 Accurate intraoperative frozen section analysis (FSA) is fundamental to safe partial orchiectomy. Connolly and colleagues22 and Subik and colleagues23 reported positive and negative predictive values for FSA in the diagnosis of testicular malignancy of 94.2% and 92.6%, respectively. Similarly, Matei and colleagues reported sensitivity and specificity of 93% and 98% of FSA for testicular malignancy of STMs.24 Men with STMs should be carefully evaluated for the possibility of benign testicular masses. In this case, because the patient had a history of CAH, his normal serum tumor markers on presentation and the size of his testicular mass (,2 cm) raised the possibility that the mass was a TART. Maintaining attention to oncologic principles, intraoperative open testicular biopsy confirmed the presence of a germ cell tumor, and a radical orchiectomy was safely completed. The role of partial orchiectomy should only be considered in rare circumstances (eg, as bilateral testis tumors or testis tumors in solitary testicles), and in the setting of a normal contralateral testicle, radical orchiectomy remains the standard of care. However, when clinical suspicion of a benign testicular lesion is high, partial orchiectomy may provide a method for safe testis-sparing surgery. References 1. Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016;66:271-289. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017;67:7-30. Wymer KM, Pearce SM, Harris KT, et al. Adherence to National Comprehensive Cancer Network® Guidelines for Testicular Cancer. J Urol. 2016;197:684-689. Albers P, Albrecht W, Algaba F, et al. [EAU guidelines on testicular cancer: 2011 update. European Association of Urology]. 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