The Role of Surveillance versus Adjuvant Treatment in Stage I Germ Cell Tumors: Outcomes and Challenges

Author(s):  
Alan Horwich

Germ cell cancers of the testis arise in young adults, and, if identified in stage I, have an excellent prognosis. Thus, we should minimize management-related toxicities. Surveillance (observation) following orchiectomy can avoid further treatment; however, patients who experience relapse receive more treatment than what would have been used during initial adjuvant therapy. For the individual patient, it is important to be aware of their particular risk of relapse, the treatment they would receive for the treatment of relapse and the alternative adjuvant approaches. For seminoma, the risk of relapse during surveillance is 15% to 20%; the size of the primary tumor and the presence of rete testis invasion are prognostic factors. Most relapses occur within 3 years; however, approximately 10% occur more than 5 years after orchiectomy. The alternative adjuvant strategies are either one cycle of carboplatin or radiotherapy (RT), which reduce recurrence risk to less than 5%. The cure rate is around 99%, regardless of which management option is implemented. For stage I nonseminoma, the risk of relapse during surveillance in unselected series is 26% to 30%. Lymphovascular invasion and the amount of embryonal carcinoma are risk factors. Most relapses occur within the first year after orchiectomy, and relapse after 3 years is rare. Ninety percent of relapse patterns are classified as “good prognosis,” and cure rates are 99%. The alternatives to surveillance include adjuvant strategies such as one cycle of adjuvant bleomycin/etoposide/cisplatin (BEP) chemotherapy; however, evidence is emerging that a single cycle is effective. There is controversy whether to offer surveillance for all patients or to offer adjuvant chemotherapy to select patients.

2022 ◽  
Vol 14 (1) ◽  
Author(s):  
Melanie R. Müller ◽  
Aaron Burmeister ◽  
Margaretha A. Skowron ◽  
Alexa Stephan ◽  
Felix Bremmer ◽  
...  

Abstract Background Type II germ cell tumors (GCT) are the most common solid cancers in males of age 15 to 35 years. Treatment of these tumors includes cisplatin-based therapy achieving high cure rates, but also leading to late toxicities. As mainly young men are suffering from GCTs, late toxicities play a major role regarding life expectancy, and the development of therapy resistance emphasizes the need for alternative therapeutic options. GCTs are highly susceptible to interference with the epigenetic landscape; therefore, this study focuses on screening of drugs against epigenetic factors as a treatment option for GCTs. Results We present seven different epigenetic inhibitors efficiently decreasing cell viability in GCT cell lines including cisplatin-resistant subclones at low concentrations by targeting epigenetic modifiers and interactors, like histone deacetylases (Quisinostat), histone demethylases (JIB-04), histone methyltransferases (Chaetocin), epigenetic readers (MZ-1, LP99) and polycomb-repressive complexes (PRT4165, GSK343). Mass spectrometry-based analyses of the histone modification landscape revealed effects beyond the expected mode-of-action of each drug, suggesting a wider spectrum of activity than initially assumed. Moreover, we characterized the effects of each drug on the transcriptome of GCT cells by RNA sequencing and found common deregulations in gene expression of ion transporters and DNA-binding factors. A kinase array revealed deregulations of signaling pathways, like cAMP, JAK-STAT and WNT. Conclusion Our study identified seven drugs against epigenetic modifiers to treat cisplatin-resistant GCTs. Further, we extensively analyzed off-target effects and modes-of-action, which are important for risk assessment of the individual drugs.


2001 ◽  
Vol 40 (4) ◽  
pp. 536-540 ◽  
Author(s):  
Finn Edler von Eyben ◽  
Ebbe Lindegaard Madsen ◽  
Ole Blaabjerg ◽  
Per Hyltoft Petersen ◽  
Hans von der Maase ◽  
...  

Author(s):  
Darren R. Feldman

The state of the art management of germ cell tumors (GCT) in 2018 does not include novel agents targeting genomic alterations or exciting immunologic-based approaches but rather the avoidance of pitfalls in everyday practice. The relative rarity of GCT and high curability with correct management create the "perfect storm" for high-stakes errors to occur. This review focuses on several common pitfalls that should be avoided in staging and management of early-stage and advanced GCT in order to maximize patient outcomes. A particularly frequent misstep is to base treatment decisions on pre- rather than postorchiectomy tumor markers that, depending on marker directionality, can lead to either undertreatment with potentially inferior outcomes or overtreatment with excess toxicity. Another common mistake is the failure to consider the unique ability of GCT to differentiate and the distinct biology of teratoma (chemoresistance and lack of increased glucose uptake compared with normal tissue), which exerts a pervasive influence on nonseminoma management. This may lead to inappropriate use of PET scan to evaluate the postchemotherapy residual mass and, if negative, the conclusion that surgery is not needed whereas (FDG-negative) teratoma should be removed. It could also result in administration of additional unnecessary chemotherapy to patients with marker normalization but without robust radiographic response after 3 to 4 cycles of BEP. Finally, oncologists should strive to maintain standard chemotherapy doses, not substitute carboplatin for cisplatin, and refer to expert centers when expertise (e.g., RPLND) is not available locally in order to achieve optimal cure rates in advanced disease.


2017 ◽  
Vol 28 (2) ◽  
pp. 333-338 ◽  
Author(s):  
G. Mangili ◽  
C. Sigismondi ◽  
D. Lorusso ◽  
G. Cormio ◽  
M. Candiani ◽  
...  

1997 ◽  
Vol 4 (4) ◽  
pp. 321-327 ◽  
Author(s):  
Mariël E. Gels ◽  
Jan Marrink ◽  
Petra Visser ◽  
Dirk Th. Sleijfer ◽  
Jos H. J. Droste ◽  
...  

1997 ◽  
Vol 158 (2) ◽  
pp. 620-625 ◽  
Author(s):  
Axel Heidenreich ◽  
Noah S. Schenkmann ◽  
Isabell A. Sesterhenn ◽  
F. Kash Mostofi ◽  
William F. McCarthy ◽  
...  

2011 ◽  
pp. 28-35
Author(s):  
Giovanni Rosti ◽  
Ornella Carminati ◽  
Claudia Casanova ◽  
Giorgio Papiani

Germ cell tumors of the testes represent a unique paradigm of diseases which can be cured even in extremely advanced phase. Unfortunately, this makes them unique among adult solid tumors. Seminoma and non seminoma are relatively rare with approximatively 25,000 patients in Europe per year, but numbers are increasing world wide. Different strategies are needed depending on stage and prognostic scores. Seminoma is extremely sensitive to radiation therapy and chemotherapy, while all germ cell tumors show a very good response to chemotherapy. Clinical stage I seminoma is currently treated with radiation, single course carboplatin or surveillance policy. Clinical stage I non seminoma can also be approached with different strategies such as retroperitoneal lymph node dissection, observation or one-two courses of standard chemotherapy. Stage II seminoma may be treated with either radiation or chemotherapy, while for all advanced stages chemotherapy is mandatory. Since the mid-eighties PEB (Cisplatin, Etoposide and Bleomycin) is the regimen of choice and no other schedule has proved superior in terms of efficacy. Surgery on the residual disease is crucial to the whole strategy and should be performed or attempted in all cases. Consequently, the correct treatment strategy for these tumors does not depend only on the ability of a single physician, but on a skilled team specialized in this particular tumor. Second line therapies (VeIP, PEI, TIP) can cure 25%–40% of patients, but improved strategies for resistant tumors are desperately needed. High-dose chemotherapy has shown very good results in some studies while being less impressive in others. In any case, it should remain an option for relapsing patients and could be used in some cases of upfront chemotherapy in patients with slow marker decline, but this should only be considered in referring centers.


2017 ◽  
Vol 35 (11) ◽  
pp. 1203-1210 ◽  
Author(s):  
Furqan Shaikh ◽  
John W. Cullen ◽  
Thomas A. Olson ◽  
Farzana Pashankar ◽  
Marcio H. Malogolowkin ◽  
...  

Purpose To investigate whether event-free survival (EFS) can be maintained among children and adolescents with intermediate-risk (IR) malignant germ cell tumors (MGCT) if the administration of cisplatin, etoposide, and bleomycin (PEb) is reduced from four to three cycles and compressed from 5 to 3 days per cycle. Patients and Methods In a phase 3, single-arm trial, patients with IR MGCT (stage II-IV testicular, II-III ovarian, I-II extragonadal, or stage I gonadal tumors with subsequent recurrence) received three cycles of PEb. A parametric comparator model specified that the observed EFS rate should not be significantly < 92%. As recommended for trials that test a reduction of therapy, a one-sided P value ≤ .10 was used to indicate statistical significance. In a post hoc analysis, we also compared results to the EFS rate of comparable patients treated with four cycles of PEb in two prior studies. Results Among 210 eligible patients enrolled from 2003 to 2011, 4-year EFS (EFS4) rate was 89% (95% confidence interval, 83% to 92%), which was significantly lower than the 92% threshold of the comparison model ( P = .08). Among 181 newly diagnosed patients, the EFS4 rate was 87%, compared with 92% for 92 comparable children in the historical cohort ( P = .15). The EFS4 rate was significantly associated with stage (stage I, 100%; stage II, 92%; stage III, 85%; and stage IV, 54%; P < .001). Conclusion The EFS rate for children with IR MGCT observed after three cycles of PEb was less than that of a prespecified parametric model, particularly for patients with higher-stage tumors. These data do not support a reduction in the number of cycles of PEb from four to three. However, further investigation of a reduction in the number of cycles for patients with lower-stage tumors is warranted.


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