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18th Meeting of the EAU Section of Oncological Urology (ESOU21)

ESOU 2021: Personalized Therapy to Reduce Treatment Morbidity in Testicular Cancer

(UroToday.com) Renowned testis cancer expert Dr. Peter Albers discussed personalized therapy to reduce treatment morbidity in testicular cancer at the rare tumors session of the European Association of Urology (EAU) Section of Oncological Urology (ESOU) 2021 Virtual meeting. Dr. Albers highlights that testicular cancer survivorship is heterogeneous across Europe ranging from 80% in Eastern Europe to 92% in Central Europe. As such, new problems have arisen over decades of testicular cancer survivors, including second malignancies and toxic deaths (ie. cardiovascular) as a result of treatment. According to Dr. Albers, there are 3 areas that need to be addressed in order to reduce treatment morbidity associated with testicular cancer:


  • Avoid unnecessary orchiectomy
  • Avoid unnecessary chemotherapy and surgery
  • Avoid unnecessary surgical trauma during post-chemotherapy retroperitoneal lymph node dissection
Dr. Albers stated that the indication for a radical orchiectomy is a tumor without relevant residual normal parenchyma in the setting of a seminoma or non-seminomatous germ cell tumors (NSGCT) with a normal contralateral testis. He notes, however, that when in doubt a frozen section can be helpful. Indications for organ-sparing surgery are as follows:

  • Metachronous secondary testicular tumor in a solitary testis, or
  • Synchronous bilateral testicular tumor, or
  • Tumor in a solitary testis (<30% of parenchyma), or
  • Suspicion of a potentially benign lesion
  • Benign tumor on a frozen section
  • Solitary testis
The advantages of organ-sparing surgery are preservation of (i) hormonal function (testosterone), (ii) improvement in fertility, and (iii) body image. Disadvantages of organ-sparing surgery include a risk of local recurrence and the potential for perioperative bleeding and infection.

Dr. Albers notes that there are two ways of avoiding unnecessary chemotherapy, including to not give adjuvant chemotherapy in scenarios where there is minimal risk of recurrence (CSI seminoma), and not giving adjuvant chemotherapy with inferior drugs (goal: no recurrence after adjuvant treatment). In a study pooling data from three randomized trials of patients with stage I seminoma, Mead et al.1 found that the noninferiority of the following treatments: 20 Gy of radiation therapy in the TE18 trial (HR of relapse 0.63, 90% CI 0.38-1.04) and carboplatin in the TE19 trial (HR of relapse 1.25, 90% CI 0.83-1.89). Furthermore, among 2,466 patients, there were only four recurrences (0.2%) after three years.

There is also an opportunity to avoid unnecessary chemotherapy in small volume seminoma metastasis. The PRIMETEST and SEMS trial are assessing the utility of primary retroperitoneal lymph node dissection (RPLND), specifically testing the efficacy of surgery and resection of metastasis in patients with clinical stage IIA (or extending to IIB?). Avoiding unnecessary surgery in patients with non-seminoma CS I is more clear-cut as diagnostic RPLND should be avoided for those with NSGCT CSI disease, except for the possible exception of high-risk NSGCT CSI. Dr. Albers highlights that 50% of patients with high-risk NSGCT CSI and there is no benefit from adjuvant BEP x1. However, he speculates that miRNA 371 may potentially change the game.

One way to avoid unnecessary surgical trauma during a post-chemotherapy RPLND according to Dr. Albers is due unilateral dissections in selected cases. Dr. Albers’ group published their experience with 504 post-chemotherapy RPLNDs, of which 171 patients had a template dissection:1

ESOU_RPLND.png



Patients undergoing template dissection had a mean tumor diameter of 4 cm (IQR 2.5-6.0 cm), with an 80% antegrade ejaculation rate, and 2-year recurrence-free survival rate of 91% (1 relapse in the contralateral retroperitoneum). Robotic-assisted post-chemotherapy RPLND in selected cases may also be justified. Dr. Albers’ group recently published their experience of 27 cases, with a reported 11% intra-operative complication rate, and 4% postoperative complication rate.2 He notes that larger registry studies are underway.

ESOU_RPLND2.png



Dr. Albers concluded noting that there has been a reduction in mortality from 70% at the time of Dr. Barnett Rosenberg inventing cisplatin in 1969, with continued reduction in mortality when Dr. Larry Einhorn invented PVB in 1974, down to 5% when Dr. John P. Donohue invented the nerve-sparing RPLND. The next goals are to avoid unnecessary treatment and the potential down-stream side effects.

Presented by: Peter Albers, MD, Professor of Urology, University of Dusseldorf, Dusseldorf, Germany

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md during the 18th Meeting of the EAU Section of Oncological Urology (ESOU21), January 29-31, 2021

References:

  1. Mead GM, Fossa SD, Oliver RTD, et al. Randomized trials in 2466 patients with stage I seminoma: Patterns of relapse and follow-up. J Natl Cancer Inst. 2011 Feb 2;103(3):241-249.
  2. Hiester A, Nini A, Arsov C, et al. Robotic Assisted Retroperitoneal Lymph Node Dissection for Small Volume Metastatic Testicular Cancer. J Urol. 2020 Dec;204(6):1242-1248.