Stage II A/B Seminomatous Germ Cell Tumors Clinical Trial
Official title:
Phase II Single-arm Trial to Evaluate Progression Free Survival With Primary Retroperitoneal Lymph-node Dissection (pRPLND) Only in Patients With Seminomatous Testicular Germ Cell Tumors With Clinical Stage IIA/B (PRIMETEST)
Primary objective:
to evaluate progression-free survival in patients with clinical stage II A/B seminomatous
germ cell tumor undergoing primary retroperitoneal lymph node dissection (RPLND) without
adjuvant treatment
Secondary objectives:
- overall survival
- perioperative complications (Clavien-Dindo score)
- quality of life (EORTC QLQ C30, EORTC QLQ TC26)
- long term sequelae
- rate of retrograde ejaculation
Standard treatment of patients with clinical stage IIA seminoma (isolated retroperitoneal
lymph nodes up to 2 cm) is radiotherapy (30Gy) and for clinical stage IIB (isolated
retroperitoneal lymph nodes 2-5 cm) is radiotherapy (36Gy, extended iliac field).
Alternatively, 3 courses of BEP are equal (1,2,3,4). According to the EAU guidelines 3
cycles of BEP can be substituted for 4 x PE in patients with contraindications for
bleomycin. Radiotherapy as well as chemotherapy has several side effects: multiple studies
show significant long term toxicity after cisplatin chemotherapy such as cardiotoxicity or
nephrotoxicity (5,6,7,8, 9). Patients after radiotherapy show a significant increased rate
of secondary malignancies during long term follow-up (relative risk between 1.3 and 1.4)
(13, 14).
There are no reliable data on recurrences of patients with seminoma in CS II who have
undergone surgery only. After the publication of Warszawski et al in 1997 primary RPLND in
seminoma has not been performed on a routine basis (10). However, seminoma metastasis
follows the same anatomical principles as non-seminoma and is primarily lymphatic. In
clinical stage I high risk seminoma patients the overall recurrence rate without adjuvant
therapy is ~ 30%, in CS IIB patients after radiotherapy at around 18%, respectively (11,12).
If seminoma stage II patients could achieve a less than 10% recurrence rate after surgery,
surveillance as well as a single course adjuvant chemotherapy would again be justified. The
overall burden of standard treatment with 3 or 4 courses of chemotherapy could thereby
considerably reduced. With a recurrence rate of > 30% (exceeding the upper border of the
confidence interval) every third patient would require surgery and chemotherapy and the
overall treatment burden would not justify this approach.
Thus, the hypothesis of this trial is currently an overtreatment of patients with low volume
metastasis either initially diagnosed or as recurrence with 3 courses BEP chemotherapy as
recommended standard treatment in most of these patients. In addition, surgical techniques
have evolved and laparoscopic robot-assisted RPLND seems possible in unilateral low stage
disease.
In order to clarify the role of primary RPLND in this patient cohort, the progression-free
survival has to be explored in a single arm non-randomized trial. Only if the recurrence
rate does not exceed the published figures further adjuvant treatment is justified. In a
subsequent trial patients may then be selected based on prognostic parameters to receive
surveillance after primary RPLND only or to be treated by 1 course of BEP in cases of higher
relapse figures. Therefore, this trial may serve as first step to improve the overall
treatment burden in patients with clinical stage II disease.
;
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment