Is Retroperitoneal Lymph Node Dissection the New Standard of Care for Stage II Seminoma?

According to researchers from the Indiana University School of Medicine, a leading institution in the treatment of testicular cancer, it may be time to include the use of retroperitoneal lymph node dissection (RPLND) as an option for patients with retroperitoneal disease following treatment for stage II seminoma.¹ Results from their study were published in the Journal of Clinical Oncology.

The current National Comprehensive Cancer Network guidelines recommend that patients with clinical stage II seminoma be managed with radiation therapy or chemotherapy.² Toxicities seen after radiation or chemotherapy include increased risk of developing cardiovascular disease and secondary malignancies, and several previous studies have indicated higher rates of mortality due to these secondary effects. Some recent evidence supports the use of RPLND for retroperitoneal-only disease.

In this retrospective study, the authors aimed to “confirm surgical efficacy and evaluate recurrences after primary RPLND for clinically significant IIA/IIB seminoma to determine if various clinical factors could predict recurrences.”

The study included men who underwent open primary RPLND between 2014 and 2021. RPLND was offered as an alternative to patients who wished to avoid toxicities related to radiation or chemotherapy. Patients had a maximum node size of approximately 3 cm and fewer than 3 positive lymph nodes. Exceptions were made for larger tumors in patients who wished to avoid chemotherapy toxicities or were poor candidates for chemotherapy. Patients who received adjuvant chemotherapy or carboplatin-containing chemotherapies were excluded. Patients with mildly elevated beta hCG were included in the study, while those with elevated alpha fetoprotein (AFP) were not.

All patients underwent surgical intervention within 4 to 6 weeks of staging studies and were followed for at least 6 months postoperatively. Follow-up included chest x-ray, computed tomography imaging, and serum tumor markers every 4 months for the first year, every 6 months for the second year, and then yearly for years 3 to 5.

The study’s primary outcome was recurrence-free survival (RFS), which was defined as radiographic evidence of metastatic disease or a rise in tumor markers. Secondary outcomes included investigating factors that may contribute to recurrence. The unilateral left-sided template included the left gonadal vessel and para-aortic nodes, including the borders superior of the diaphragmatic crus, left ureter laterally, aorta medially, and the common iliac artery inferiorly at the level where the ureter crosses over the common iliac artery. The left full template included the para-aortic, retroaortic, and interaortocaval lymph nodes. On the right side, the template included the gonadal vessel, paracaval and interaortocaval lymph nodes with borders of the diaphragmatic crus, right ureter, aorta, and the right common iliac artery inferiorly where the ureter crosses over. Templating was performed at the surgeon’s discretion.

The study included 67 patients with clinical stage IIA/IIB disease who underwent primary RPLND. The authors noted that 2 patients with pathologic stage IIB disease received adjuvant chemotherapy with 2 cycles of etoposide + cisplatin (EP) based on patient preference and a high number of positive nodes. Those patients did not experience recurrence during follow-up. Median patient age was of 37 years, and 54% of patients had a tumor size >4 cm on initial orchiectomy. A total of 52% of patients had rete testis invasion. Seventy-two percent of patients had stage I disease, 18% had stage IIA, and 10% had stage IIB. Twenty-one patients who were initially placed on active surveillance developed clinical stage IIA disease, and 34 developed clinical stage IIB disease.

Median time from orchiectomy to RPLND was 10.6 months. Out of the total cohort, 12 (18%) patients underwent immediate surgery, while 55 (82%) underwent a period of surveillance prior to surgery. Slightly more than half (54%) of patients underwent a unilateral template and 46% underwent a bilateral template. Several patients underwent modified procedures based on suspicious lymphadenopathy or patient-related factors (e.g., difficult surgery secondary to obesity), the authors noted. All patients who underwent unilateral template dissection maintained antegrade ejaculation. Sixteen patients who underwent bilateral template also underwent a nerve-sparing approach. Only 1 of those patients did not have antegrade ejaculation at 12 months. A total of 3 patients had a significant complication, including urine leak, chylous ascites, or pleural effusion.

Median follow-up was 22.4 months. Median time to recurrence was 11.8 months, and 17% of patients had a recurrence. Recurrence was managed with salvage chemotherapy and, in one case, a second RPLND with salvage chemotherapy. No significant recurrence differences were seen based on a nodal positive more than or less than 2. Of the patients who underwent unilateral templated RPLND, there were 8 recurrences compared with 3 distant recurrences in those who underwent a bilateral templated RPLND. Nearly 20% of patients who underwent bilateral template dissection had positive disease on the contralateral side.

The authors found that “2-year RFS for those with initial clinical stage I disease who were on surveillance for >12 months before developing clinical stage II disease was 92% compared with 59% for those with initial clinical stage I disease who were on surveillance for <12 months before developing clinical stage II disease and 62% for those presenting with stage II disease (log-rank P=.03). Median time to recurrence for those with clinical stage I disease with >12 months surveillance was 10.3 months, clinical stage I disease with <12 months was 11.8 months, and initial clinical stage II disease was 12.8 months. RFS was worse for stage I disease with a period of initial surveillance <12 months compared with >12 months (hazard ratio, 6.93; P=.02).”

According to the authors, this large, retrospective study demonstrated that many patients with clinical stage II seminoma can be managed with RPLND alone. Their results show a 2-year RFS rate of 80.2%. The study also showed that patients with clinical stage I disease who went on to progress to clinical stage II disease after 12 months following orchiectomy had a 2-year RFS rate of 92%. Patients who underwent bilateral template dissection had a lower rate of recurrence.

Many studies support the use of chemotherapy³ and radiotherapy,⁴ showing excellent 5-year progression-free survival. However, given the young age of these patients, there is a risk of secondary malignancies or development of cardiovascular disease. Recently, there has been support for using RPLND in this patient population, including from the SEMS trial.^5,6 This study also found that only 1 patient had N0 on final RPLND pathology, indicating a low rate of overtreatment.

The study isn’t without limitations, including the retrospective design and the fact that it took place at an institution with a very comprehensive testicular cancer treatment program, which means the study may not be reproducible. Still, the authors concluded the “data support the efficacy of RPLND as a primary treatment option for clinical stage IIA and IIB seminoma. The ideal surgical candidate seems to be a patient who develops clinical stage II disease after 12 months of surveillance.”

David Ambinder, MD is a urology resident at New York Medical College/Westchester Medical Center. His interests include surgical education, GU oncology and advancements in technology in urology. A significant portion of his research has been focused on litigation in urology.

References

1. Tachibana I, Alabd A, Tong Y, et al. Primary retroperitoneal lymph node dissection for stage II seminoma: is surgery the new path forward? J Clin Oncol. 2023;41(23):3930-3938. doi:10.1200/JCO.22.01822
2. Gilligan T, Lin DW, Aggarwal R, et al. Testicular Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2019;17(12):1529-1554. doi:10.6004/jnccn.2019.0058
3. Garcia-del-Muro X, Maroto P, Gumà J, et al. Chemotherapy as an alternative to radiotherapy in the treatment of stage IIA and IIB testicular seminoma: a Spanish Germ Cell Cancer Group study. J Clin Oncol. 2008;26(33):5416-5421. doi:10.1200/JCO.2007.15.9103
4. Glaser SM, Vargo JA, Balasubramani GK, Beriwal S. Stage II testicular seminoma: patterns of care and survival by treatment strategy. Clin Oncol (R Coll Radiol). 2016;28(8):513-521. doi:10.1016/j.clon.2016.02.008
5. Daneshmand S, Cary C, Masterson TA, et al. SEMS trial: result of a prospective, multi-institutional phase II clinical trial of surgery in early metastatic seminoma. J Clin Oncol. 2021;39:375. doi:10.1200/JCO.2021.39.6_SUPPL.375
6. Albers P, Lusch A, Che Y, Arsoc C, Niegisch G, Hiester A. The PRIMETEST trial: prospective phase II trial of primary retroperitoneal lymph node dissection (RPLND) in stage IIA/B patients with seminoma. J Clin Oncol. 2022;40:420. doi:10.1200/jco.2022.40.6_suppl.420