Management of Testicular Cancer

Case of the Month Management of Testicular Cancer NYU Case of the Month, March 2017 James S. Wysock, MD Department of Urology, NYU Langone Medical Center, New York, NY [Rev Urol. 2017;19(1):56-59 doi: 10.3909/riu0757] ® © 2017 MedReviews , LLC A 27-year-old man presents with a painless right testicular mass. The patient has no significant medical history, no prior surgical history, and no family history of genitourinary malignancy. He is engaged to be married and has no children. Evaluation Testicular ultrasound demonstrated a 2.7 3 2.5 3 2.7-cm heterogeneous, solid mass in the right testicle (Figure 1). Staging imaging demonstrated a 7.5-mm right common iliac lymph node (Figure 2). Serum evaluation demonstrated an elevated β-human chorionic gonadotropin (hCG) and α-fetoprotein (AFP) (Table 1). Management Management options included surveillance, primary retroperitoneal lymph node dissection (RPLND), or primary chemotherapy (bleomycin, etoposide, and cisplatin [BEP]). The patient ultimately elected treatment with robotic bilateral infrahilar nerve-sparing RPLND. He performed sperm banking prior to surgery. The surgery was uncomplicated with minimal blood loss (estimated blood loss, 200 mL). A split and 56 • Vol. 19 No. 1 • 2017 • Reviews in Urology roll technique was performed using this minimally invasive technique. The patient was discharged home on postoperative day 1; he had excellent pain control with postoperative pain medications, and was without significant postoperative complaint. Two weeks following surgery, he reported that he had resumed regular activities. At 3-month followup, he reported a return of antegrade ejaculation. Final pathology results demonstrated no evidence of disease in 26 lymph nodes. Comment Treatment Options Testicular germ cell tumors are the most common solid tumor malignancy in adolescents and younger men,1 with an estimated 8700 new cases diagnosed annually.2 These tumors are also one of the most curable solid tumors, with a 5-year survival rate above 95%.3 Adherence to a guidelines-based approach is recommended to ensure adequate and timely treatment.1 Options for managing clinical stage I nonseminomatous germ cell tumors include active surveillance, primary chemotherapy, and RPLND. For men with risk factors for relapse (lymphovascular invasion, predominant embryonal carcinoma, or clinical Management of Testicular Cancer Figure 1. Testicular ultrasound demonstrating a 2.7 3 2.5 3 2.7-cm heterogeneous, solid mass in the right testicle. Figure 2. Staging imaging demonstrating a 7.5-mm right common iliac lymph node. TABLE 1 Before Orchiectomy After Orchiectomy Reference Range Lactic acid dehydrogenase (U/L) 130 130 100-200 a-Fetoprotein (ng/mL) 23.1 , 2.4 b-Human chorionic gonadotropin (IU/L) 190 , 0.5 , 6.1 0-3 stage $ T3), options are RPLND or chemotherapy.4 An additional consideration for this patient is the 7.5-mm right common iliac lymph node. Sensitivity for computed tomography detection of nodal metastases depends on the size criteria applied. For nodes $ 10 mm, sensitivity and specificity have been reported at 37% and 100%, respectively. However, using a nodal cutoff of $ 4 mm, sensitivity and specificity become 93% and 58%, respectively.5 Using a cutoff of 8 mm, sensitivity and specificity are both approximately 70%.6 Although this node does not meet strict criteria for enlargement, the measured size does raise concern for nodal disease and thus is a consideration in the treatment choice. The patient was counseled on the risk of disease recurrence in light of his orchiectomy pathology results. His risk of relapse was estimated at 40% to 50% given his predominant embryonal carcinoma.7 Each treatment option (surveillance, primary RPLND, and primary chemotherapy) was discussed in detail, including indicating that these three treatment options could achieve equivalent cure rates of approximately 99%.8 The surveillance protocol was explained, and the requirement for strict adherence given the patient’s high risk of recurrence was stressed. It was further explained that a relapse on surveillance would mean salvage chemotherapy of three to four cycles of BEP and exposure to considerably higher potential toxicity and morbidity. Primary chemotherapy with BEP was also explained. A randomized controlled trial comparing one cycle of BEP to primary RPLND demonstrated an improved 2-year recurrence-free survival for chemotherapy (99.46% vs 91.87%; P 5 .0011).9 It was indicated that this approach offers excellent cancer control but carries an increased risk for long-term drug-associated toxicities, including cardiovascular, pulmonary, and renal side effects, and an increased risk of secondary malignancies.10 Finally, in discussing the risks and side effects of RPLND, it was explained that RPLND carries perioperative risks, including bleeding, infection, ileus, and chylous ascites.11 It was further explained that RPLND is the best method for assessing possible microscopic metastases; however, the rate of disease relapse following RPLND has been reported to be as high as 29%. The risk of overtreatment was also discussed.12 Vol. 19 No. 1 • 2017 • Reviews in Urology • 57 Management of Testicular Cancer continued Long-term Considerations of Treatment Choice The treatments available for clinical stage I nonseminomatous germ cell tumors achieve excellent cure rates,8 with a growing number of men achieving long-term survival. Given this robust survival, the longterm health impact of the treatment choice becomes critical to disease management. Long-term studies examining testicular cancer survivors reveal increased rates of cardiovascular disease, hypertension, renal failure, pulmonary disease, and secondary malignancies.13-15 In addition, survivors exhibit an overall increase in the rate of mortality.16 The rates of many of these complications are higher with chemotherapy than with surgery, suggesting a role for increased use of surgical options when possible.15 For example, Fung and colleagues17 reported a 40% increased rate of secondary cancers in men treated with chemotherapy compared with those treated with RPLND alone. Haugnes and colleagues18 observed a 3.1-fold increase in risk of myocardial infarction in men receiving BEP compared with a healthy matched population, and a 5.7-fold increase in coronary artery disease compared with men treated with RPLND alone. Platinum-based chemotherapy is also associated with long-term nephrotoxicity, resulting in an average long-term glomerular filtration rate approximately 21% below normal.19 An additional important longterm consideration for testicular cancer management is the impact on fertility. Median sperm concentration after orchiectomy is 40% lower than in healthy control subjects.20 In addition, the risk of hypogonadism appears to be highest following chemotherapy. Nord and associates21 reported a 4.9 relative risk of hypogonadism for men receiving chemotherapy compared with a relative risk 2.0 for men undergoing surgery alone. Regardless of treatment choice, men must be counseled on sperm banking before beginning postorchiectomy treatment. Robotic Retroperitoneal Lymph Node Dissection The choice of primary RPLND as the initial treatment for this patient rests on the goal of achieving disease control and minimizing exposure to chemotherapy. Although the use of a modified template versus a bilateral infrahilar template remains debated, the goal of the surgical approach is to maximize oncologic effectiveness and limit surgical risks. Given the estimated risk of up to 23% for nodal disease occurring outside a modified unilateral template and the increased risk of disease outside modified templates for right-sided tumors, the decision was made to proceed with a full bilateral infrahilar nerve-sparing robotic RPLND (R-RPLND).22 R-RPLND has gradually evolved to provide a minimally invasive approach to this complex surgery. The aim of R-RPLND is to replicate the surgical principles of open RPLND, such as the split and roll technique, and offer decreased pain and reduced length of hospital stay. The technique of R-RPLND allows for bilateral infrahilar nervesparing templates to be achieved in a single minimally invasive approach, as it did in this case. Early series using R-RPLND report excellent short-term outcomes, including decreased postoperative length of hospital stay and perioperative morbidity.23-25 As survivorship issues continue to present challenges for testicular cancer management, avoiding longterm complications of chemotherapy and radiation when possible is desirable. Improved surgical 58 • Vol. 19 No. 1 • 2017 • Reviews in Urology morbidity via R-RPLND will likely lead to increased use of this minimally invasive approach as a primary treatment option. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. Wymer KM, Pearce SM, Harris KT, et al. Adherence to National Comprehensive Cancer Network® guidelines for testicular cancer. J Urol. 2017;197(3 Pt 1):684-689. Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016;66:271-289. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67:7-30. Motzer RJ, Agarwal N, Beard C, et al. NCCN clinical practice guidelines in oncology: testicular cancer. J Natl Compr Cancer Netw. 2009;7:672-693. Hilton S, Herr HW, Teitcher JB, et al. CT detection of retroperitoneal lymph node metastases in patients with clinical stage I testicular nonseminomatous germ cell cancer: assessment of size and distribution criteria. AJR Am J Roentgenol. 1997;169:521-525. Hudolin T, Kastelan Z, Knezevic N, et al. Correlation between retroperitoneal lymph node size and presence of metastases in nonseminomatous germ cell tumors. Int J Surg Pathol. 2012;20:15-18. Vergouwe Y, Steyerberg EW, Eijkemans MJ, et al. Predictors of occult metastasis in clinical stage I nonseminoma: a systematic review. J Clin Oncol. 2003;21:4092-4099. Kollmannsberger C, Moore C, Chi KN, et al. Nonrisk-adapted surveillance for patients with stage I nonseminomatous testicular germ-cell tumors: diminishing treatment-related morbidity while maintaining efficacy. Ann Oncol. 2010;21:1296-1301. Albers P, Siener R, Krege S, et al; German Testicular Cancer Study Group. Randomized phase III trial comparing retroperitoneal lymph node dissection with one course of bleomycin and etoposide plus cisplatin chemotherapy in the adjuvant treatment of clinical stage I nonseminomatous testicular germ cell tumors: AUO trial AH 01/94 by the German Testicular Cancer Study Group. J Clin Oncol. 2008;26:29662972. Abouassaly R, Fossa SD, Giwercman A, et al. Sequelae of treatment in long-term survivors of testis cancer. Eur Urol. 2011;60:516-526. Subramanian VS, Nguyen CT, Stephenson AJ, Klein EA. Complications of open primary and postchemotherapy retroperitoneal lymph node dissection for testicular cancer. Urol Oncol. 2010;28:504-509. Hermans BP, Sweeney CJ, Foster RS, et al. Risk of systemic metastases in clinical stage I nonseminoma germ cell testis tumor managed by retroperitoneal lymph node dissection. J Urol. 2000;163:1721-1724. Meinardi MT, Gietema JA, van der Graaf WT, et al. Cardiovascular morbidity in long-term survivors of metastatic testicular cancer. J Clin Oncol. 2000;18:1725-1732. van den Belt-Dusebout AW, Nuver J, de Wit R, et al. Long-term risk of cardiovascular disease in 5-year survivors of testicular cancer. J Clin Oncol. 2006;24:467-475. Haugnes HS, Bosl GJ, Boer H, et al. Long-term and late effects of germ cell testicular cancer treatment and implications for follow-up. J Clin Oncol. 2012;30:3752-3763. Fosså SD, Gilbert E, Dores GM, et al. Noncancer causes of death in survivors of testicular cancer. J Natl Cancer Inst. 2007;99:533-544. Fung C, Fosså SD, Milano MT, et al. Solid tumors after chemotherapy or surgery for testicular nonseminoma: a population-based study. J Clin Oncol. 2013;31: 3807-3814. Haugnes HS, Wethal T, Aass N, et al. Cardiovascular risk factors and morbidity in long-term survivors of testicular cancer: a 20-year follow-up study. J Clin Oncol. 2010;28:4649-4657. Management of Testicular Cancer 19. 20. 21. Aass N, Fosså SD, Aas M, Lindegaard MW. Renal function related to different treatment modalities for malignant germ cell tumours. Br J Cancer. 1990;62:842-846. van Casteren NJ, Boellaard WP, Romijn JC, Dohle GR. Gonadal dysfunction in male cancer patients before cytotoxic treatment. Int J Androl. 2010;33:73-79. Nord C, Bjøro T, Ellingsen D, et al. Gonadal hormones in long-term survivors 10 years after treatment for unilateral testicular cancer. Eur Urol. 2003;44:322-328. 22. 23. Eggener SE, Carver BS, Sharp DS, et al. Incidence of disease outside modified retroperitoneal lymph node dissection templates in clinical stage I or IIA nonseminomatous germ cell testicular cancer. J Urol. 2007;177:937-942. Stepanian S, Patel M, Porter J. Robot-assisted laparoscopic retroperitoneal lymph node dissection for testicular cancer: evolution of the technique. Eur Urol. 2016;70:661-667. 24. 25. Williams SB, Lau CS, Josephson DY. Initial series of robot-assisted laparoscopic retroperitoneal lymph node dissection for clinical stage I nonseminomatous germ cell testicular cancer. Eur Urol. 2011;60:1299-1302. Cheney SM, Andrews PE, Leibovich BC, Castle EP. Robot-assisted retroperitoneal lymph node dissection: technique and initial case series of 18 patients. BJU Int. 2015;115:114-120. Vol. 19 No. 1 • 2017 • Reviews in Urology • 59