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Cancers
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Testicular Cancer
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Testicular Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 20633

Special Issue Editor

Dr. Joost L. Boormans

E-Mail Website1 Website2
Guest Editor
Erasmus MC, Rotterdam, Netherlands
Interests: testicular cancer; prognostic factors; retroperitoneal imaging and surgery; urothelial cancer; gene expression analysis; molecular oncology, urinary diagnostics

Special Issue Information

Dear Colleagues,

Testicular Cancer (TC) is the most commonly diagnosed malignant tumor in males between the ages of 16 and 40 years. The incidence of TC continues to rise, and the vast majority of TC patients are diagnosed with clinical stage I disease, either non-seminoma or seminoma testis. The aim of this Special Issue of Cancers is to address the following important clinical knowledge gaps regarding the diagnosis and management of clinical stage I TC: i) the impact of TC diagnosis on psychological and sexual wellbeing and fertility of patients; ii) the need for new and improved detection of prognostic markers to more accurately identify patients at the highest risk of relapse following orchiectomy; iii) controversies surrounding risk-adapted management of adjuvant treatment; and iv) the importance of long-term TC survivorship and monitoring of late side-effects. I sincerely hope this issue of Cancers will be read with great interest by clinicians, researchers, and patients.

Dr. Joost L. Boormans
Guest Editor

Manuscript Submission Information

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Keywords

  • testicular cancer
  • clinical stage I disease
  • prognosis
  • biomarkers
  • survivorship
  • risk-adapted management
  • psychological well-being

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Published Papers (7 papers)

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Research

12 pages, 642 KiB  
Article
The Polymorphisms of Genes Encoding Catalytic Antioxidant Proteins Modulate the Susceptibility and Progression of Testicular Germ Cell Tumor
by Uros Bumbasirevic, Nebojsa Bojanic, Marija Pljesa-Ercegovac, Marko Zivkovic, Tatjana Djukic, Milica Zekovic, Bogomir Milojevic, Boris Kajmakovic, Aleksandar Janicic, Tatjana Simic and Vesna Coric
Cancers 2022, 14(4), 1068; https://doi.org/10.3390/cancers14041068 - 20 Feb 2022
Cited by 8 | Viewed by 3188
Abstract
The simultaneous analysis of redox biomarkers and polymorphisms encoding for regulatory and catalytic antioxidant proteins was performed in order to evaluate their potential role in the development of testicular germ cell tumor (GCT), as well as the progression of the disease. NRF2 (rs6721961), [...] Read more.
The simultaneous analysis of redox biomarkers and polymorphisms encoding for regulatory and catalytic antioxidant proteins was performed in order to evaluate their potential role in the development of testicular germ cell tumor (GCT), as well as the progression of the disease. NRF2 (rs6721961), GSTM3 (rs1332018), SOD2 (rs4880) and GPX3 (rs8177412) polymorphisms were assessed in 88 patients with testicular GCT (52 with seminoma) and 88 age-matched controls. The plasma levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), thiol groups and the plasma activity of glutathione peroxidase were measured. A significant association between variant GPX3*TC+CC genotype and risk of overall testicular GCT, as well as seminoma development, was found. Moreover, carriers of variant SOD2*TT genotype were at almost 3-fold increased risk of seminoma development. Interestingly, combined SOD2*TT/GPX3*TC+CC genotype conferred a 7-fold higher risk for testicular GCT development. Finally, variant GSTM3*AC+CC genotype was associated with a higher risk for the development of advanced diseased. The presence of assessed genetic variants was not associated with significantly higher levels of redox biomarkers in both testicular GCT patients, as well as in those diagnosed with seminoma. In conclusion, the polymorphic expression of certain antioxidant enzymes might affect susceptibility toward testicular GCT development, as well as the progression of the disease. Full article
(This article belongs to the Special Issue Testicular Cancer)
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11 pages, 726 KiB  
Article
CNV Hotspots in Testicular Seminoma Tissue and Seminal Plasma
by Dora Raos, Irena Abramović, Miroslav Tomić, Alen Vrtarić, Tomislav Kuliš, Marijana Ćorić, Monika Ulamec, Ana Katušić Bojanac, Davor Ježek and Nino Sinčić
Cancers 2022, 14(1), 189; https://doi.org/10.3390/cancers14010189 - 31 Dec 2021
Cited by 2 | Viewed by 2286
Abstract
Seminoma (SE) is the most frequent type of testicular tumour, affecting predominantly young men. Early detection and diagnosis of SE could significantly improve life quality and reproductive health after diagnosis and treatment. Copy number variation (CNV) has already been associated with various cancers [...] Read more.
Seminoma (SE) is the most frequent type of testicular tumour, affecting predominantly young men. Early detection and diagnosis of SE could significantly improve life quality and reproductive health after diagnosis and treatment. Copy number variation (CNV) has already been associated with various cancers as well as SE. In this study, we selected four genes (MAGEC2, NANOG, RASSF1A, and KITLG) for CNV analysis in genomic DNA (gDNA), which are located on chromosomes susceptible to gains, and whose aberrant expression was already detected in SE. Furthermore, CNV was analysed in cell-free DNA (cfDNA) from seminal plasma. Analysis was performed by droplet digital polymerase chain reaction (ddPCR) on gDNA from SE and nonmalignant testicular tissue. Seminal plasma cfDNA from SE patients before and after surgery was analysed, as well as from healthy volunteers. The CNV hotspot in gDNA from SE tissue was detected for the first time in all analysed genes, and for two genes, NANOG and KITLG it was reflected in cfDNA from seminal plasma. Although clinical value is yet to be determined, presented data emphasize a potential use of CNV as a potential SE biomarker from a liquid biopsy. Full article
(This article belongs to the Special Issue Testicular Cancer)
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Graphical abstract

16 pages, 983 KiB  
Article
Cognitive Impairment in Long-Term Survivors of Testicular Cancer More Than 20 Years after Treatment
by Johannes Stelwagen, Andrea T. Meuleman, Sjoukje Lubberts, Gerrie Steursma, Lara M. Kruyt, Jan W. Donkerbroek, Coby Meijer, Annemiek M. E. Walenkamp, Joop D. Lefrandt, Sandra E. Rakers, Rients B. Huitema, Marianne A. A. de Jong, Erwin M. Wiegman, Alfons C. M. van den Bergh, Igle J. de Jong, Joost A. Agelink van Rentergem, Sanne B. Schagen, Janine Nuver and Jourik A. Gietema
Cancers 2021, 13(22), 5675; https://doi.org/10.3390/cancers13225675 - 12 Nov 2021
Cited by 5 | Viewed by 2141
Abstract
Background: Impaired cognition can be a late effect after treatment in long-term testicular cancer (TC) survivors, negatively affecting their daily life. However, little data is available beyond 20 years post-treatment. We assessed cognitive impairment in very long-term TC survivors after CT or RT [...] Read more.
Background: Impaired cognition can be a late effect after treatment in long-term testicular cancer (TC) survivors, negatively affecting their daily life. However, little data is available beyond 20 years post-treatment. We assessed cognitive impairment in very long-term TC survivors after CT or RT and compared the results with stage I TC survivors and controls. Methods: In this cross-sectional multicenter cohort study, we enrolled TC survivors (treated with orchiectomy followed by CT or RT or orchiectomy only)—with a follow-up duration ≥ 20 years—and age-matched healthy controls. Cognitive testing included the Auditory Verbal Learning Test, Letter Fluency Test, Category Fluency Test, and Trail Making Test. We used fasting blood samples to assess the presence of hypogonadism and measured cardiovascular aging parameters, including carotid pulse wave velocity (c-PWV) and advanced glycation end products (AGEs). Results: We included 184 TC survivors (66 CT patients, 53 RT patients, and 65 orchiectomy-only patients) and 70 healthy controls. The median follow-up was 26 years (range: 20–42). TC survivors had a lower combined score of the cognitive tests (mean cumulative Z-score −0.85; 95% CI −1.39 to −0.33) compared to controls (mean 0.67; 95% CI −0.21 to 1.57, p < 0.01). In univariate analysis, the presence of hypogonadism (β −1.50, p < 0.01), high c-PWV (β −0.35, p = 0.09), and high AGEs (β −1.27, p = 0.02) were associated with lower cognitive scores, while only AGEs (β −1.17, p = 0.03) remained a significant predictor in multivariate analysis (Model R2 0.31, p < 0.01). Conclusions: Long-term TC survivors performed worse on cognitive tests compared to controls. Physicians and patients should be informed about timely cardiovascular risk management and testosterone supplementation therapy during follow-up to reduce the risk of cognitive impairment. Trial Registration: NCT02572934. Full article
(This article belongs to the Special Issue Testicular Cancer)
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19 pages, 3670 KiB  
Article
Screening for the Key Proteins Associated with Rete Testis Invasion in Clinical Stage I Seminoma via Label-Free Quantitative Mass Spectrometry
by Lucia Borszéková Pulzová, Jan Roška, Michal Kalman, Ján Kliment, Pavol Slávik, Božena Smolková, Eduard Goffa, Dana Jurkovičová, Ľudovít Kulcsár, Katarína Lešková, Peter Bujdák, Michal Mego, Mangesh R. Bhide, Lukáš Plank and Miroslav Chovanec
Cancers 2021, 13(21), 5573; https://doi.org/10.3390/cancers13215573 - 8 Nov 2021
Cited by 5 | Viewed by 2678
Abstract
Rete testis invasion (RTI) is an unfavourable prognostic factor for the risk of relapse in clinical stage I (CS I) seminoma patients. Notably, no evidence of difference in the proteome of RTI-positive vs. -negative CS I seminomas has been reported yet. Here, a [...] Read more.
Rete testis invasion (RTI) is an unfavourable prognostic factor for the risk of relapse in clinical stage I (CS I) seminoma patients. Notably, no evidence of difference in the proteome of RTI-positive vs. -negative CS I seminomas has been reported yet. Here, a quantitative proteomic approach was used to investigate RTI-associated proteins. 64 proteins were differentially expressed in RTI-positive compared to -negative CS I seminomas. Of them, 14-3-3γ, ezrin, filamin A, Parkinsonism-associated deglycase 7 (PARK7), vimentin and vinculin, were validated in CS I seminoma patient cohort. As shown by multivariate analysis controlling for clinical confounders, PARK7 and filamin A expression lowered the risk of RTI, while 14-3-3γ expression increased it. Therefore, we suggest that in real clinical biopsy specimens, the expression level of these proteins may reflect prognosis in CS I seminoma patients. Full article
(This article belongs to the Special Issue Testicular Cancer)
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10 pages, 1136 KiB  
Communication
Seasonal Variations in the Diagnosis of Testicular Germ Cell Tumors: A National Cancer Registry Study in Austria
by Gennadi Tulchiner, Nina Staudacher, Josef Fritz, Monika Hackl, Martin Pichler, Maximilian Seles, Shahrokh F. Shariat, David D’Andrea, Kilian Gust, Walter Albrecht, Karl Grubmüller, Stephan Madersbacher, Sebastian Graf, Lukas Lusuardi, Herbert Augustin, Andreas Berger, Wolfgang Loidl, Wolfgang Horninger and Renate Pichler
Cancers 2021, 13(21), 5377; https://doi.org/10.3390/cancers13215377 - 27 Oct 2021
Cited by 4 | Viewed by 2299
Abstract
We conducted a retrospective National Cancer Registry study in Austria to assess a possible seasonal variation in the clinical diagnosis of testicular germ cell tumors (TGCT). In total, 3615 testicular cancer diagnoses were identified during an 11-year period from 2008 to 2018. Rate [...] Read more.
We conducted a retrospective National Cancer Registry study in Austria to assess a possible seasonal variation in the clinical diagnosis of testicular germ cell tumors (TGCT). In total, 3615 testicular cancer diagnoses were identified during an 11-year period from 2008 to 2018. Rate ratios for the monthly number of TGCT diagnoses, as well as of seasons and half-years, were assessed using a quasi-Poisson model. We identified, for the first time, a statistically significant seasonal trend (p < 0.001) in the frequency of monthly newly diagnosed cases of TGCT. In detail, clear seasonal variations with a reduction in the tumor incidence during the summer months (Apr–Sep) and an increase during the winter months (Oct–Mar) were observed (p < 0.001). Focusing on seasonality, the incidence during the months of Oct–Dec (p = 0.008) and Jan–Mar (p < 0.001) was significantly higher compared to the months of Jul–Sep, respectively. Regarding histopathological features, there is a predominating incidence in the winter months compared to summer months, mainly concerning pure seminomas (p < 0.001), but not the non-seminoma or mixed TGCT groups. In conclusion, the incidence of TGCT diagnoses in Austria has a strong seasonal pattern, with the highest rate during the winter months. These findings may be explained by a delay of self-referral during the summer months. However, the hypothetical influence of vitamin D3 in testicular carcinogenesis underlying seasonal changes in TGCT diagnosis should be the focus of further research. Full article
(This article belongs to the Special Issue Testicular Cancer)
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Figure 1

21 pages, 3585 KiB  
Article
Combined Assessment of Immune Checkpoint Regulator VISTA on Tumor-Associated Immune Cells and Platelet-to-Lymphocyte Ratio Identifies Advanced Germ Cell Tumors with Higher Risk of Unfavorable Outcomes
by Rafał Pęksa, Michał Kunc, Marta Popęda, Michał Piątek, Michał Bieńkowski, Jolanta Żok, Anna Starzyńska, Adrian Perdyan, Marek Sowa, Renata Duchnowska and Wojciech Biernat
Cancers 2021, 13(8), 1750; https://doi.org/10.3390/cancers13081750 - 7 Apr 2021
Cited by 15 | Viewed by 3569
Abstract
In the current study, we aimed to investigate whether expression of immune checkpoint proteins (V-domain Ig suppressor of T cell activation (VISTA) and programmed death-ligand 1 (PD-L1)) and markers of systemic inflammation could predict progression/relapse and death in the cohort of 180 patients [...] Read more.
In the current study, we aimed to investigate whether expression of immune checkpoint proteins (V-domain Ig suppressor of T cell activation (VISTA) and programmed death-ligand 1 (PD-L1)) and markers of systemic inflammation could predict progression/relapse and death in the cohort of 180 patients with testicular germ-cell tumors (GCTs). Expression of PD-L1 and VISTA was assessed by immunohistochemistry utilizing tissue microarrays. To estimate systemic inflammation neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) were calculated. We found high PD-L1 and VISTA expression on tumor-associated immune cells (TAICs) in 89 (49.44%) and 63 (37.22%) of GCTs, respectively, whereas tumor cells besides trophoblastic elements were almost uniformly negative. High PD-L1 was associated with seminomatous histology and lower stage. Relapses in stage I patients occurred predominantly in cases with low numbers of PD-L1 and VISTA-expressing TAICs. In stage II/III disease, the combination of low VISTA-expressing TAICs and high PLR was identified as predictor of shorter event-free survival (HR 4.10; 1.48–11.36, p = 0.006) and overall survival (HR 15.56, 95% CI 1.78–135.51, p = 0.001) independently of tumor histology and location of metastases. We demonstrated that the assessment of immune checkpoint proteins on TAICs may serve as a valuable prognostic factor in patients with high-risk testicular GCTs. Further study is warranted to explore the predictive utility of these biomarkers in GCTs. Full article
(This article belongs to the Special Issue Testicular Cancer)
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14 pages, 282 KiB  
Article
Identifying the Need to Discuss Infertility Concerns Affecting Testicular Cancer Patients: An Evaluation (INDICATE Study)
by Esmée M. Krouwel, Thijs G. Jansen, Melianthe P. J. Nicolai, Sandra W. M. Dieben, Saskia A. C. Luelmo, Hein Putter, Rob C. M. Pelger and Henk W. Elzevier
Cancers 2021, 13(3), 553; https://doi.org/10.3390/cancers13030553 - 1 Feb 2021
Cited by 8 | Viewed by 2430
Abstract
Men with testicular cancer (TC) risk impaired fertility. Fertility is a major concern for TC patients due to diagnosis in almost always reproductive ages and high overall survival. This study assessed counselling in regards to the risk of impaired fertility and sperm cryopreservation. [...] Read more.
Men with testicular cancer (TC) risk impaired fertility. Fertility is a major concern for TC patients due to diagnosis in almost always reproductive ages and high overall survival. This study assessed counselling in regards to the risk of impaired fertility and sperm cryopreservation. A cross-sectional survey was performed on 566 TC patients diagnosed between 1995–2015. Of the 566 survivors, 201 questionnaires were completed (35.5%). Eighty-eight percent was informed about possible impaired fertility, 9.5% was not informed. The majority (47.3%) preferred the urologist to provide information. Collecting sperm was troublesome but successful for 25.6%, 4.8% did not succeed in collecting sperm. The reasons were high pressure due to disease, pain after surgery and uncomfortable setting. Due to impaired fertility, 19% of the respondents reported grief and 9.3% stated as being less satisfied in life. Sperm cryopreservation was performed by 41.3% (n = 83). One third (n = 63, 31.3%) had children after treatment, of which 11.1% made use of preserved sperm (n = 7). The results of this survey indicate the importance of timely discussion of fertility issues with TC patients. While being discussed with most men, dissatisfaction and grief may occur as a result of impaired fertility and a lack of counselling. Overall, 6.5% made use of cryopreserved sperm (n = 13). Men prefer their urologist providing counselling on fertility. Full article
(This article belongs to the Special Issue Testicular Cancer)
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