[en] 

Purpose

: Testicular granulosa cell tumors (tGrCT) are rare sex cord-stromal tumors. This review aims to synthesize the available evidence regarding the clinical presentation and clinicopathological characteristics, treatment and outcomes.

Methods

: We conducted a systematic literature search using the most important research databases. Whenever feasible, we extracted the data on individual patient level.

Results

: From 7863 identified records, we included 88 publications describing 239 patients with tGrCT. The majority of the cases were diagnosed with juvenile tGrCT (166/239, 69%), while 73/239 (31%) patients were diagnosed with adult tGrCT. Mean age at diagnosis was 1.5 years (± 5 SD) for juvenile tGrCT, and 42 years (± 19 SD) for adult tGrCT. Information on primary treatment was available in 231/239 (97%), of which 202/231 (87%) were treated with a radical orchiectomy and 20/231 (9%) received testis sparing surgery (TSS). Local recurrence after TSS was observed in 1/20 (5%) cases. Metastatic disease was never observed in men with juvenile tGrCT but in 7/73 (10%) men with adult tGrCT. In 5/7 men with metastatic tGrCT, metastases were diagnosed at initial staging, while 2/7 patients developed metastases after 72 and 121 months of follow-up, respectively. Primary site of metastasis is represented by the retroperitoneal lymph nodes, but other sites including lungs, liver, bone and inguinal lymph nodes can also be affected. In comparison with non-metastatic adult tGrCT, men with metastatic adult tGrCT had significantly larger primary tumors (70 vs 24 mm, p 0.001), and were more likely to present with angiolymphatic invasion (57% vs 4%, p 0.002) or gynecomastia (29% vs 3%, p 0.019). In five out of seven men with metastatic disease, resection of metastases or platinum-based chemotherapy led to complete remission.

Conclusion

: Juvenile tGrCT represent a benign entity whereas adult tGCTs have metastatic potential. Tumor size, presence of angiolymphatic invasion or gynecomastia represent risk factors for metastatic disease. The published literature supports the use of testis sparing surgery but there is only limited experience with adjuvant therapies. In the metastatic setting, the reviewed literature suggests that aggressive surgical and systemic treatment might cure patients.

[en] Purpose: To provide guidance regarding follow-up procedures after initial treatment of early stage testicular seminoma (clinical stages (CS) I-II A/B) based on current published evidence complemented by expert opinion. Methods and Material: An interdisciplinary, multinational working group consisting of urologists, medical oncologists, and radiation oncologists analyzed the published evidence regarding follow-up procedures in various stages of seminomatous and nonseminomatous testicular cancers. Focusing on radiooncological aspects, the recommendations contained herein are restricted to early stage seminoma (with radiotherapy being a standard treatment option). In particular, extent, frequency, and duration of imaging at follow-up were analyzed concerning relapse patterns, risk factors, and mode of relapse detection. Results: Active surveillance, adjuvant carboplatin or radiotherapy are equally accepted options for CS I seminoma but they result in different relapse rates and patterns. Usually relapses occur within the first 2(-6) years. Routinely performed follow-up using computerized tomography (CT) after adjuvant treatment yield only low detection rates of recurrences. Therefore, there is no evidence to maintain routine examinations every 3-4 months. After treatment of stage IIA/B, detection rates of relapses or progression identified solely by routinely performed CT during follow-up are low. Conclusion: Considering lifelong cure rates of up to 99% for patients treated for seminoma CS I-IIA/B, the negative impact of unnecessary ionizing radiation exposure has to be considered. The presented recommendations for various follow-up scenarios for early stage seminoma strongly promote the restrictive use of imaging procedures that utilize ionizing radiation (especially CT), due to its potential to induce secondary malignancies. (orig.)

[en] 

Background

Treatment options for patients (pts) with multiply relapsed or refractory metastatic germ cell cancer (GCC) are limited. The mTOR inhibitor everolimus has been approved for the treatment of different solid tumors and was assessed in refractory GCC within this phase II RADIT trial of the German Testicular Cancer Study Group.

Methods

GCC pts progressing during cisplatin-based salvage chemotherapy, or relapsing after high-dose chemotherapy, or failing at least two lines of cisplatin-based chemotherapy were eligible. Prior combination chemotherapy with gemcitabine, oxaliplatin and paclitaxel, or a doublet combination of these drugs was mandatory. Primary endpoint was the progression-free survival rate at 12 weeks. Twenty-five evaluable pts were needed, assuming a 20% two-sided type 1 error and 95% power to reject the null hypothesis of 5% of patients being progression-free after 12 weeks. At least one pt among the first 13 pts being progression-free after 6 weeks was mandatory to complete recruitment. Secondary endpoints were objective response rate, disease control rate (SD + PR + CR), median progression-free survival (PFS), median overall survival (OS), and safety. The trial was registered at http://clinicaltrials.gov as NCT01242631.

Results

Twenty-five pts from six German centers were treated with everolimus 10 mg orally once daily until disease progression or unacceptable toxicity between December 2010 and January 2014. 12-week PFS rate was 0%, no objective responses were achieved, and only one pt had stable disease after 6 weeks on treatment as a prerequisite of completing patient accrual accounting for a 6-week disease control rate of 5.4%. Median PFS and OS were estimated at 7.4 weeks and 8.3 weeks, respectively. Toxicity was acceptable, with one treatment discontinuation due to adverse events, and no new safety signals detected.

Conclusions

Targeting the mTOR pathway with single-agent everolimus failed to produce clinically relevant responses in pts with heavily pretreated and/or cisplatin-refractory GCC.

[en] 

Purpose

: Outcomes of multiply relapsed, refractory germ-cell tumour (GCT) patients remain poor with an overall survival (OS) of a few months only. Thus, new therapeutic advances are urgently needed. Cabazitaxel has shown preclinical activity in platinum-resistant GCT models. Here, we report the first clinical case series of cabazitaxel treatment for platinum-refractory GCT.

Methods

: Data of multiply relapsed GCT patients receiving single-agent cabazitaxel were retrospectively analysed. Endpoints included 12-week progression-free survival (PFS) rate, disease control rate, tumour marker responses, median PFS and OS, and toxicity.

Results

: Cabazitaxel showed limited activity in 13 heavily pre-treated GCT patients. After a median follow-up of 23 weeks (IQR 29), 69% of patients were deceased. A median of 2 cycles of cabazitaxel (range 1–7) were applied. The 12-week PFS rate was 31%. Median PFS and OS were 7 and 23 weeks, respectively. Two patients achieved objective responses (15%), three patients (23%) achieved a tumour marker decline ≥ 50%, and the disease control rate was 39%. Cabazitaxel was well tolerated. CTCAE° III–IV haemato-toxicity was most common (54%), and dose reductions were scarce (15%).

Conclusion

: In this case series, cabazitaxel showed limited activity in heavily pre-treated GCT patients. Two-phase II studies are underway (NCT02115165, NCT02478502) prospectively assessing cabazitaxel in multiply relapsed GCTs.