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Diagnosis and Treatment of Testicular Cancer

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A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (28 February 2024) | Viewed by 24879

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Special Issue Editors

Dr. Luigi Napolitano

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Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples, Italy
Interests: andrology; male infertility; urologic oncology; testicular cancer; endourology; urolithiasis; human sexuality; extracorporeal shock wave lithotripsy; urological diagnostic techniques

Dr. Celeste Manfredi

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1. Unit of Urology, Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
2. Department of Urology, Rush University Medical Center, Chicago, IL, USA
Interests: urology; uro-oncology; andrology; sexual medicine; benign prostatic hyperplasia
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Special Issue Information

Dear Colleagues,

Germ-cell tumours (GCTs) represent a significant disease, with increasing incidence and a high burden of morbidity and mortality in men between the ages of 15 and 34 worldwide. Worldwide, testicular cancer accounts for approximately 72,000 diagnoses and 9000 deaths per year. Among GCTs, approximately 55–60% are pure seminomas and 40–45% are non-seminomas.

Clinical examination, scrotal ultrasound and high-resolution computed tomography are the diagnostic mainstays, but the clinical relevance of serum tumour markers is unsurpassed. Surgical procedures and chemotherapeutic treatment provide a high chance of recovery in the early stages. Despite the scientific progress, approximately 10% of metastatic testicular cancer remains incurable, and novel treatment approaches are warranted; furthermore, there is a lack of risk-stratifying biomarkers for follow-up, or biomarkers for predicting cisplatin resistance. The development of new tumour markers is currently an important and intensively ongoing issue. Some studies have reported a promising potential role of epigenetic modification and non-coding RNA microRNAs (miRNAs).

The goal of this Special Issue is to collate original articles, reviews, and meta-analyses from distinguished authors who have practical experience in researching innovations in the diagnosis, treatment, and prognosis of testicular cancer.

The specific interests of this Special Issue include:

Genesis and risk factors;
Epidemiological trends;
Advances in biomarkers;
Novel targeted treatments;
Long-term treatment side-effects;

Dr. Luigi Napolitano
Dr. Celeste Manfredi
Guest Editors

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Keywords

testicular cancer
seminoma
non-seminona
molecular markers
lymph node metastasis
diagnosis
systemic treatment

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Published Papers (8 papers)

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Research

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13 pages, 2360 KiB

Open AccessArticle

Cellular Senescence in Germ Cell Neoplasia In Situ (GCNIS) and Other Histological Types of Testicular Cancer

by Vasileios Tatanis, Dimitris Veroutis, Pavlos Pantelis, George Theocharous, Helen Sarlanis, Alexandros Georgiou, Francesk Mulita, Angelis Peteinaris, Anastasios Natsos, Napoleon Moulavasilis, Nikolaos Kavantzas, Athanassios Kotsinas and Ioannis Adamakis

Medicina 2024, 60(7), 1108; https://doi.org/10.3390/medicina60071108 - 8 Jul 2024

Viewed by 880

Abstract

Background and Objectives: The presence and contribution of senescent cells in premalignant lesions is well documented, but not in germ cell neoplasia in situ. The purpose of this study is to identify the presence of senescent cells in pre-malignant testicular conditions and in different histological types of testicular cancer. Materials and Methods: Thirty patients who underwent orchiectomy due to testicular tumors were included. Formalin-fixed paraffin-embedded (FFPE) testicular tissue for each patient was available. Sections from these specimens were examined by immunohistochemical analysis with the following markers: GL13 for cellular senescence, p21^WAF1/Cip1 for cell cycle arrest, and Ki67 for cell proliferation. Results: Thirteen (43.3%) suffered from seminoma with a mean total proportion of GCNIS senescence of 20.81 ± 6.81%. In the group of embryonal testicular tumors, nine (30%) patients were included, with an average rate of 6.64 ± 5.42% of senescent cells in GCNIS. One (3.3%) patient suffered from chondrosarcoma in which 7.9% of GL13+ cells were detected in GCNIS. Four (13.4%) patients suffered from teratoma and three (10%) from yolk sac tumors, while GCNIS senescence was detected in a range of 4.43 ± 1.78% and 3.76 ± 1.37%, respectively. Conclusions: Cellular senescence was detected in both germ cell neoplasia in situ and testicular cancer, but was more prevalent within the premalignant lesions. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Testicular Cancer)

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13 pages, 348 KiB

Open AccessArticle

Onco-TESE (Testicular Sperm Extraction): Insights from a Tertiary Center and Comprehensive Literature Analysis

by Lorenzo Cirigliano, Marco Falcone, Murat Gül, Mirko Preto, Carlo Ceruti, Natalia Plamadeala, Federica Peretti, Ilaria Ferro, Martina Scavone and Paolo Gontero

Medicina 2023, 59(7), 1226; https://doi.org/10.3390/medicina59071226 - 29 Jun 2023

Cited by 3 | Viewed by 2221

Abstract

Background and Objectives: The peak of incidence of testicular cancer (TC) occurs among individuals in their reproductive age, emphasizing the importance of fertility preservation as an integral aspect of disease management. Sperm cryopreservation performed before orchiectomy is ineffective in azoospermic men, necessitating alternative approaches such as microdissection testicular sperm extraction (mTESE) at the time of orchiectomy (onco-mTESE) to obtain viable sperm. This study presents the findings from our institution’s experience with onco-mTESE and critically discusses our results in light of the existing body of literature. Materials and Methods: This is a tertiary center retrospective analysis of onco-mTESE procedures performed at a single center between December 2011 and July 2022. The included patients were post-puberal men with testicular tumors requiring orchiectomy, along with concomitant severe oligozoospermia or azoospermia. Bilateral mTESE was performed in all cases. Surgical outcomes, sperm retrieval rates, the usage of preserved viable sperm, assistive reproductive techniques’ results, and post-operative serum testosterone were recorded. Results: A total of nine patients were included, with a median age of 34 (IQR 29–36) years. All patients had germ cell tumors (GCTs), with seminomatous and non-seminomatous GCTs accounting for 44.4% (n = 4) and 55.6% (n = 5) of patients, respectively. Sperm retrieval occurred in three (33%) patients: one patient in the ipsilateral testis, one in the contralateral testis, and one in both testes. No complications were reported during the procedure, and no post-operative hypogonadism was observed. Among the three patients with successful sperm retrieval, an intracytoplasmic sperm injection (ICSI) was performed in two patients, resulting in two pregnancies, leading to one healthy live birth and one miscarriage. Conclusions: In the context of TC, it is essential to conduct a thorough evaluation of testicular function, including a semen analysis and cryopreservation. Onco-mTESE has proven its safety in preserving fertility in azoospermic cases while ensuring the efficacy of oncological treatment. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Testicular Cancer)

8 pages, 634 KiB

Open AccessArticle

Survival of Testicular Pure Embryonal Carcinoma vs. Mixed Germ Cell Tumor Patients across All Stages

by Cristina Cano Garcia, Andrea Panunzio, Stefano Tappero, Mattia Luca Piccinelli, Francesco Barletta, Reha-Baris Incesu, Kyle W. Law, Lukas Scheipner, Zhe Tian, Fred Saad, Shahrokh F. Shariat, Derya Tilki, Alberto Briganti, Ottavio De Cobelli, Carlo Terrone, Alessandro Antonelli, Severine Banek, Luis A. Kluth, Felix K. H. Chun and Pierre I. Karakiewicz

Medicina 2023, 59(3), 451; https://doi.org/10.3390/medicina59030451 - 24 Feb 2023

Cited by 2 | Viewed by 5104

Abstract

Background and Objectives: The impact of pure histological subtypes in testicular non-seminoma germ cell tumors on survival, specifically regarding pure embryonal carcinoma, is not well established. Therefore, this study aimed to test for differences between pure embryonal carcinoma and mixed germ cell tumor patients within stages I, II and III in a large population-based database. Materials and Methods: We relied on the Surveillance, Epidemiology and End Results (SEER) database (2004–2019) to identify testicular pure embryonal carcinoma vs. mixed germ cell tumor patients. Cumulative incidence plots depicted cancer-specific mortality that represented the main endpoint of interest. Multivariable competing risks regression models tested for differences between pure embryonal carcinoma and mixed germ cell tumor patients in analyses addressing cancer-specific mortality and adjusted for other-cause mortality. Results: Of 11,223 patients, 2473 (22%) had pure embryonal carcinoma. Pure embryonal carcinoma patients exhibited lower cancer-specific mortality relative to their mixed germ cell tumor counterparts for both stage III (13.9 vs. 19.4%; p < 0.01) and stage II (0.5 vs. 3.4%, p < 0.01), but not in stage I (0.9 vs. 1.6%, p = 0.1). In multivariable competing risks regression models, pure embryonal carcinoma exhibited more favorable cancer-specific mortality than mixed germ cell tumor in stage III (hazard ratio 0.71, p = 0.01) and stage II (hazard ratio 0.11, p < 0.01). Conclusions: Pure embryonal carcinoma exhibits a more favorable cancer-specific mortality profile relative to mixed germ cell tumor in stage II and III testicular cancers. Consequently, the presence of mixed germ cell tumor elements may be interpreted as a risk factor for cancer-specific survival. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Testicular Cancer)

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14 pages, 3431 KiB

Open AccessArticle

Twenty Years’ Experience in Retroperitoneal Lymph Node Dissection for Testicular Cancer in a Tertiary Referral Center

by Angelo Mottaran, Amelio Ercolino, Lorenzo Bianchi, Pietro Piazza, Francesco Manes, Sasan Amirhassankhani, Marco Salvador, Francesco Chessa, Beniamino Corcioni, Alessandro Bertaccini, Riccardo Schiavina and Eugenio Brunocilla

Medicina 2023, 59(1), 133; https://doi.org/10.3390/medicina59010133 - 10 Jan 2023

Cited by 3 | Viewed by 2288

Abstract

Background and Objectives: The aim of this article is to present a single-surgeon, open retroperitoneal lymph node dissection (RPLND) series for testicular cancer in a high-volume center. Materials and Methods: We reviewed data from patients who underwent RPLND performed by an experienced surgeon at our institution between 2000 and 2019. We evaluated surgical and perioperative outcomes, complications, Recurrence-Free Survival (RFS), Overall Survival (OS), and Cancer-Specific Survival (CSS). Results: RPLND was performed in primary and secondary settings in 21 (32%) and 44 (68%) patients, respectively. Median operative time was 180 min. Median hospital stay was 6 days. Complications occurred in 23 (35%) patients, with 9 (14%) events reported as Clavien grade ≥ 3. Patients in the primary RPLND group were significantly younger, more likely to have NSGCT, had higher clinical N0 and M0, and had higher nerve-sparing RPLND (all p ≤ 0.04) compared to those in the secondary RPLND group. In the median follow-up of 120 (56–180) months, 10 (15%) patients experienced recurrence. Finally, 20-year OS, CSS, and RFS were 89%, 92%, and 85%, respectively, with no significant difference in survival rates between primary vs. secondary RPLND subgroups (p = 0.64, p = 0.7, and p = 0.31, respectively). Conclusions: Open RPLND performed by an experienced high-volume surgeon achieves excellent oncological and functional outcomes supporting the centralization of these complex procedures. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Testicular Cancer)

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Review

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12 pages, 346 KiB

Open AccessReview

Testicular Cancer Treatments and Sexuality: A Narrative Review

by Massimiliano Raffo, Angelo Di Naro, Luigi Napolitano, Achille Aveta, Simone Cilio, Savio Domenico Pandolfo, Celeste Manfredi, Chiara Lonati and Nazareno Roberto Suardi

Medicina 2024, 60(4), 586; https://doi.org/10.3390/medicina60040586 - 31 Mar 2024

Cited by 1 | Viewed by 1749

Abstract

The incidence of testicular cancer (TC) has been rapidly increasing over the past years. Diagnosis and early treatment have shown good oncological control, guaranteeing the patient different treatment approaches according to histology and tumor stage. Currently, physicians usually prioritize oncological outcomes over sexual outcomes and quality of life, considering as a first aim the overall survival of the patients; however, differently from other neoplasms, quality of life is still strongly affected among TC patients, and sexual outcomes are frequently compromised after each TC treatment. Several studies have suggested that each treatment approach may be associated with sexual dysfunctions, including erectile dysfunction, ejaculatory disorders, fertility issues, and hormonal changes. Since testicular cancer patients are more frequently young men, the subject of this work is substantial and should be analyzed in detail to help specialists in the management of this disease. The aim of the current narrative review is to generally describe every treatment for TC, including surgery, chemotherapy, radiotherapy, and retroperitoneal lymph node dissection, and to establish which sexual dysfunction may be specifically associated with each therapy. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Testicular Cancer)

23 pages, 456 KiB

Open AccessReview

Male Infertility and the Risk of Developing Testicular Cancer: A Critical Contemporary Literature Review

by Giuseppe Maiolino, Esaú Fernández-Pascual, Mario Alberto Ochoa Arvizo, Ranjit Vishwakarma and Juan Ignacio Martínez-Salamanca

Medicina 2023, 59(7), 1305; https://doi.org/10.3390/medicina59071305 - 14 Jul 2023

Cited by 5 | Viewed by 3089

Abstract

Background and Objectives: The relationship between male infertility (MI) and testicular cancer (TC) is bilateral. On one hand, it is well-established that patients diagnosed with TC have a high risk of pre- and post-treatment infertility. On the other hand, the risk of developing TC in male infertile patients is not clearly defined. The objective of this review is to analyze the histopathological, etiological, and epidemiological associations between MI and the risk of developing testicular cancer. This review aims to provide further insights and offer a guide for assessing the risk factors for TC in infertile men. Materials and Methods: A comprehensive literature search was conducted to identify relevant studies discussing the relationship between MI and the risk of developing TC. Results: The incidence rates of germ cell neoplasia in situ (GCNIS) appear to be high in infertile men, particularly in those with low sperm counts. Most epidemiological studies have found a statistically significant risk of developing TC among infertile men compared to the general or fertile male populations. The concept of Testicular Dysgenesis Syndrome provides an explanatory model for the common etiology of MI, TC, cryptorchidism, and hypospadias. Clinical findings such as a history of cryptorchidism could increase the risk of developing TC in infertile men. Scrotal ultrasound evaluation for testis lesions and microlithiasis is important in infertile men. Sperm analysis parameters can be useful in assessing the risk of TC among infertile men. In the future, sperm and serum microRNAs (miRNAs) may be utilized for the non-invasive early diagnosis of TC and GCNIS in infertile men. Conclusions: MI is indeed a risk factor for developing testicular cancer, as demonstrated by various studies. All infertile men should undergo a risk assessment using clinical examination, ultrasound, and semen parameters to evaluate their risk of TC. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Testicular Cancer)

11 pages, 346 KiB

Open AccessReview

Organ-Sparing Surgery for Testicular Germ Cell Tumors: A Current Perspective

by Esther García Rojo, Gianluca Giannarini, Borja García Gómez, Javier Amalio Feltes Ochoa, Félix Guerrero Ramos, Manuel Alonso Isa, Ricardo Brime Menendez, David Manuel Saenz Calzada, Juan Justo Quintas, Agustín Fraile, Celeste Manfredi and Javier Romero Otero

Medicina 2023, 59(7), 1249; https://doi.org/10.3390/medicina59071249 - 5 Jul 2023

Cited by 2 | Viewed by 2860

Abstract

Background and Objectives: We aimed to evaluate the oncological and functional outcomes of organ-sparing surgery for testicular germ cell tumors, a procedure that seeks to strike a balance between effective cancer control and organ preservation, in the treatment of testicular tumors. We aimed to discuss the surgical technique and complications, and determine the appropriate candidate selection for this approach. Material and Methods: A comprehensive literature search was conducted to identify relevant studies on organ-sparing surgery for testicular tumors. Various databases, including PubMed, Embase, and Cochrane Library, were used. Studies reporting on surgical techniques, complications, and oncologic and functional outcomes were included for analysis. Results: Current evidence suggests that organ-sparing surgery for testicular germ cell tumors can be considered a safe and efficacious alternative to radical orchiectomy. The procedure is associated with adequate oncological control, as indicated by low recurrence rates and low complication rates. Endocrine testicular function can be preserved in around 80–90% of patients and paternity can be achieved in approximately half of the patients. Candidate selection for this surgery is typically based on the following criteria: pre-surgery normal levels of testosterone and luteinizing hormone, synchronous or metachronous bilateral tumors, tumor in a solitary testis, and tumor size less than 50% of the testis. Conclusions: Organ-sparing surgery for testicular germ cell tumors offers a promising approach that balances oncological control and preservation of testicular function. Further research, including large-scale prospective studies and long-term follow-ups, is warranted to validate the effectiveness and durability of organ-sparing surgery and to identify optimal patient selection criteria. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Testicular Cancer)

17 pages, 412 KiB

Open AccessEditor’s ChoiceReview

Risk Factors for Testicular Cancer: Environment, Genes and Infections—Is It All?

by Sertac Yazici, Dario Del Biondo, Giorgio Napodano, Marco Grillo, Francesco Paolo Calace, Domenico Prezioso, Felice Crocetto and Biagio Barone

Medicina 2023, 59(4), 724; https://doi.org/10.3390/medicina59040724 - 7 Apr 2023

Cited by 26 | Viewed by 5537

Abstract

The incidence of testicular cancer is steadily increasing over the past several decades in different developed countries. If on one side better diagnosis and treatment have shone a light on this disease, on the other side, differently from other malignant diseases, few risk factors have been identified. The reasons for the increase in testicular cancer are however unknown while risk factors are still poorly understood. Several studies have suggested that exposure to various factors in adolescence as well as in adulthood could be linked to the development of testicular cancer. Nevertheless, the role of environment, infections, and occupational exposure are undoubtedly associated with an increase or a decrease in this risk. The aim of this narrative review is to summarize the most recent evidence regarding the risk factors associated with testicular cancer, starting from the most commonly evaluated (cryptorchidism, family history, infections) to the newer identified and hypothesized risk factors. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Testicular Cancer)

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