Primary Retroperitoneal Lymph Node Dissection for Stage IB Nonseminomatous Germ Cell Tumor

NYU Case of the Month, April 2020

Case of the Month Primary Retroperitoneal Lymph Node Dissection for Stage IB Nonseminomatous Germ Cell Tumor NYU Case of the Month, April 2020 Richard S. Matulewicz, MD, MS Department of Urology, NYU Langone Health, Department of Population Health, NYU Grossman School of Medicine, New York, NY [Rev Urol. 2020;22(1):40–42] © 2020 MedReviews®, LLC A 29-year-old man presented to our office with a right-sided testicular mass that he had noticed several weeks prior. The mass was painless and had grown slightly larger since the patient had first noticed it. The patient denied any weight loss, back pain, sexual dysfunction, or other constitutional symptoms. He had no antecedent history of testicular trauma and did not report any personal or family history of undescended testes, pediatric hernia repairs, or testicular cancer. He is a never smoker and reported occasional alcohol use but denied any use of recreational drugs, including marijuana. The patient is married, has one young child, and desires future fertility. Evaluation and Treatment On examination, the patient was a healthy-appearing young man. Chest examination was without evidence of gynecomastia and lungs were clear to auscultation. Abdominal examination was benign, without tenderness or masses on deep palpation and free of costovertebral angle tenderness. Genitourinary examination was notable for a normal circumcised phallus. The left testis was descended, roughly 20 cc, and without tenderness or any palpable mass. The right testis was slightly atrophic, with a firm ∼2 cm nodular mass on the posterior aspect. There was no lower-extremity edema or palpable lymphadenopathy throughout. Serum tumor markers were notable for a slight elevation in beta-human chorionic gonadotropin (bHCG) (Table 1) and scrotal ultrasonography confirmed a 2.3 × 1.9 cm mass in the right testis (Figure 1). The patient was subsequently taken for a right-sided radical inguinal orchiectomy, which demonstrated a pT2 mixed nonseminomatous germ TABLE 1 Laboratory Test Results Pre-orchiectomy Post-orchiectomy (6 weeks) AFP (ng/mL) <2 <2 bHCG (IU/L) 20 <1 156 180 LDH (U/L) AFP, alpha-fetoprotein; bHCG, beta-human chorionic gonadotropin; LDH, lactate dehydrogenase. 40 • Vol. 22 No. 1 • 2020 • Reviews in Urology 4170020_11_RIU0870D_V1_rev02.indd 40 5/12/20 9:37 PM Primary Retroperitoneal Lymph Node Dissection To date, there have been no serum tumor marker elevations or radiographic relapses. Comment Figure 1. Scrotal ultrasound in long (left) and trans (right) orientations demonstrating a 2.3 × 1.9 cm heterogeneous, vascular mass in the right testis. Figure 2. Two adjacent imaging cuts of post-orchiectomy coronal CT scan images demonstrating no evidence of retroperitoneal lymphadenopathy (cN0). cell tumor (NSGCT) with embryonal carcinoma predominance and evidence of lymphovascular invasion (LVI). Complete staging with CT chest, abdomen, and pelvis imaging (Figure 2) demonstrated no concerning lymphadenopathy or evidence of metastatic disease. The patient was counseled on and chose to pursue cryopreservation of sperm. Post-orchiectomy tumor markers normalized (Table 1) and he recovered well after surgery. Management At the patient’s post-orchiectomy visit, we discussed the various adjuvant management options for pT2 embryonal predominant NSGCT with LVI (Stage IB). We discussed how two risk factors (LVI and embryonal NSGCT) placed him at a nearly 50% chance of relapse in subsequent years and how this made surveillance a less favorable strategy. After consultation with our medical oncology colleagues, he decided against chemotherapy and chose to pursue primary retroperitoneal lymph node dissection (RPLND). He underwent nervesparing bilateral RPLND with removal of 63 nodes, 1 of which was positive for a small, <1 cm focus of viable embryonal carcinoma (pN1). He recovered well from surgery and reported preserved antegrade ejaculation. Post RPLND, he was offered either surveillance or adjuvant chemotherapy (EPx2 or BEPx2) for his low-volume nodepositive disease and he chose to be managed with close monitoring. More than half of men diagnosed with NSGCT are clinical Stage I.1 After orchiectomy, there are several management options, including surveillance, systemic chemotherapy (BEPx1), and primary RPLND. The widely variable individual risk of relapse (11%–41%) for men with Stage I NSGCT makes this a controversial, and sometimes difficult, decision process for patients and urologists alike. Fortunately, regardless of the chosen initial management strategy, cancer- specific survival for all comers is between 98% and 99%. Therefore, decisions about adjuvant management should aim for cure while mitigating treatment side effects. Several clinical factors place a patient at higher risk for relapse and should be addressed in decision making, especially when considering surveillance. Orchiectomy pathological features such as LVI and advanced local stage (pT3-4) are well established as risk factors for relapse. In addition, histology with embryonal predominance increases the risk of relapse but has the benefit of being highly chemosensitive.2 Alternatively, a significant presence of teratoma should influence decisions toward surveillance or surgical management because these tumors are traditionally chemoresistant.3 In men without risk factors, surveillance is the preferred adjuvant management strategy because the 5-year relapse rate is roughly 11%, with a median time to recurrence at 8 to 9 months. Patients must be willing to accept the uncertainty associated with surveillance and be highly compliant given the Vol. 22 No. 1 • 2020 • Reviews in Urology • 41 4170020_11_RIU0870D_V1_rev02.indd 41 5/12/20 9:37 PM Primary Retroperitoneal Lymph Node Dissection continued close monitoring needed within the first 2 years, when the vast majority (∼90%) of relapses occur. The anxiety and aggregate radiation exposure associated with serial imaging should also not be ignored as risks when considering surveillance. In addition, in men who do relapse, compared with adjuvant chemo (BEPx1) there is an increase in treatment burden because salvage chemo regimens are risk based and at minimum EPx4 or BEPx3. However, the cure rate approaches 100%, even in those who relapse. For men with risk factors such as LVI, advanced local stage, or embryonal predominance, the 5-year relapse rate of those managed with surveillance can be up to 50%. Treatment with BEPx1 as an adjuvant option decreases the risk of relapse to between 1% and 3%. However, this strategy overtreats many men and is associated with secondary infertility, neuropathy, kidney damage, long-term cardiovascular sequelae, and increased risk of secondary cancers.4 Primary RPLND with nerve sparing is an attractive option for men with Stage IB NSGCT who are good surgical candidates. In expert hands, nerve sparing preserves antegrade ejaculation in nearly 97% of cases.5 A bilateral template is preferred because mapping studies have estimated that between 2% and 23% of men would have unresected disease outside of most unilateral template dissections.6 Unresected disease and subsequent relapse are associated with increased treatment burden (RPLND and full-dose chemotherapy) as well as only a 40% to 60% 5-year survival.7 An additional benefit of primary RPLND is that the retroperitoneum is surgically controlled, obviating the need for imaging after an initial postoperative scan. Patients can be followed with chest x-rays and serum tumor markers. As with our patient, surgery may also avoid the need for any systemic chemotherapy in patients with lowvolume node-positive disease. For those found to be pN1, a surveillance strategy is preferred over adjuvant chemotherapy because the 5-year risk of relapse is less than 10%.2 In summary, primary RPLND accurately stages and effectively treats early-stage NSGCT while minimizing the need for systemic therapies and optimizing long-term cure rates. References 1. 2. 3. 4. 5. 6. 7. Tandstad T, Dahl O, Cohn-Cedermark G, et al. Riskadapted treatment in clinical stage I nonseminomatous germ cell testicular cancer: the SWENOTECA management program. J Clin Oncol. 2009;27:2122–2128. Stephenson AJ, Bosl GJ, Bajorin DF, et al. Retroperitoneal lymph node dissection in patients with low stage testicular cancer with embryonal carcinoma predominance and/or lymphovascular invasion. J Urol. 2005;174:557–560, discussion 560. Sheinfeld J, Motzer RJ, Rabbani F, et al. Incidence and clinical outcome of patients with teratoma in the retroperitoneum following primary retroperitoneal lymph node dissection for clinical stages I and IIA nonseminomatous germ cell tumors. J Urol. 2003;170:1159–1162. van den Belt-Dusebout AW, de Wit R, Gietema JA, et al. Treatment-specific risks of second malignancies and cardiovascular disease in 5-year survivors of testicular cancer. J Clin Oncol. 2007;25:4370–4378. Large MC, Sheinfeld J, Eggener SE. Retroperitoneal lymph node dissection: reassessment of modified templates. BJU Int. 2009;104:1369–1375. 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, discussion 942–943. Sharp DS, Carver BS, Eggener SE, et al. Clinical outcome and predictors of survival in late relapse of germ cell tumor. J Clin Oncol. 2008;26:5524–5529. 42 • Vol. 22 No. 1 • 2020 • Reviews in Urology 4170020_11_RIU0870D_V1_rev02.indd 42 5/12/20 9:37 PM