Aging-related biomarkers in testicular cancer survivors after different oncologic treatments.

PURPOSE: Testicular cancer survivors (TCS) exposed to chemotherapy have an increased expression of CDKN2A/p16INK4a and a lymphocyte phenotype associated with immunosenescence. We seek to define whether the immunosenescent phenotype is associated with chemotherapy. METHODS: Case-control study of TCS, disease-free ≥3 months and stratified by primary treatment modality into orchiectomy only, chemotherapy, or bone marrow transplant (BMT). Each group was compared with age-matched healthy controls (HC). We measured the relative proportions of lymphocyte subpopulations using flow cytometry, levels of C-reactive protein, and relative expression of CDKN2A/p16INK4a quantified by qPCR. RESULTS: We included 65 patients; 19 were treated with orchiectomy only, 35 received different doses of chemotherapy, and 11 underwent BMT. The chemotherapy and BMT groups had decreased naïve CD4 cells compared to HC. The chemotherapy group showed increased central and effector memory CD4 cells, as well as effector and terminally differentiated CD8 cells, compared to HC. Chemotherapy (chemotherapy 1.84 vs. HC 0.92; p < 0.01) and BMT (BMT 6.96 vs. HC 1.25; p < 0.005) groups had higher expression of CDKN2A/p16INK4a compared to HC. The orchiectomy group showed no significant difference with HC (orchiectomy 1.73 vs. HC 1.01; p = 0.17). CRP levels were higher in all groups when compared with HC; in the orchiectomy group, they were only marginally increased (chemotherapy 0.22 vs. HC 0.06; p < 0.01; BMT 0.26 vs. HC 0.06; p < 0.01; orchiectomy 0.09 vs. HC 0.07; p < 0.01). CONCLUSIONS: Among TCS, only patients exposed to cytotoxic agents developed an immunosenescent phenotype. This finding supports the attribution of this alteration to the cytotoxic treatment.

Regional Differences in Stage III Nonseminoma Germ Cell Tumor Patients Across SEER Registries.

PURPOSE: We investigated regional differences in patients with stage III nonseminoma germ cell tumor (NSGCT). Specifically, we investigated differences in baseline patient, tumor characteristics and treatment characteristics, as well as cancer-specific mortality (CSM) across different regions of the United States. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database (2004-2018), patient (age, race/ethnicity), tumor (International Germ Cell Cancer Collaborative Group [IGCCCG] prognostic groups) and treatment (systemic therapy and retroperitoneal lymph dissection [RPLND] status) characteristics were tabulated for stage III NSGCT patients, according to 12 SEER registries representing different geographic regions. Multinomial regression models and multivariable Cox regression models testing for cancer-specific mortality (CSM) were used. RESULTS: In 3,174 stage III NSGCT patients, registry-specific patient counts ranged from 51 (1.5%) to 1630 (51.3%). Differences across registries existed for age (12%-31% for age 40+), race/ethnicity (5%-73% for others than non-Hispanic whites), IGCCCG prognostic groups (24%-43% vs. 14-24% vs. 3%-20%, in respectively poor vs. intermediate vs. good prognosis), systemic therapy (87%-96%) and RPLND status (12%-35%). After adjustment, clinically meaningful inter-registry differences remained for systemic therapy (84%-97%) and RPLND (11%-32%). Unadjusted 5-year CSM rates ranged from 7.1% to 23.3%. Finally in multivariable analyses addressing CSM, 2 registries exhibited more favorable outcomes than SEER registry of reference (SEER Registry 12): SEER Registry 4 (Hazard Ratio (HR): 0.36) and SEER Registry 9 (HR: 0.64; both P = .004). CONCLUSION: We identified important regional differences in patient, tumor and treatment characteristics, as well as CSM which may be indicative of regional differences in quality of care or expertise in stage III NGSCT management.

Cognitive function in long-term testicular cancer survivors: impact of modifiable factors.

No study has comprehensively examined associated factors (adverse health outcomes, health behaviors, and demographics) affecting cognitive function in long-term testicular cancer survivors (TC survivors). TC survivors given cisplatin-based chemotherapy completed comprehensive, validated surveys, including those that assessed cognition. Medical record abstraction provided cancer and treatment history. Multivariable logistic regression examined relationships between potential associated factors and cognitive impairment. Among 678 TC survivors (median age = 46; interquartile range [IQR] = 38-54); median time since chemotherapy = 10.9 years, IQR = 7.9-15.9), 13.7% reported cognitive dysfunction. Hearing loss (odds ratio [OR] = 2.02; P = .040), neuropathic pain (OR = 2.06; P = .028), fatigue (OR = 6.11; P < .001), and anxiety/depression (OR = 1.96; P = .029) were associated with cognitive impairment in multivariable analyses. Being on disability (OR = 9.57; P = .002) or retired (OR = 3.64; P = .029) were also associated with cognitive decline. Factors associated with impaired cognition identify TC survivors requiring closer monitoring, counseling, and focused interventions. Hearing loss, neuropathic pain, fatigue, and anxiety/depression constitute potential targets for prevention or reduction of cognitive impairment in long-term TC survivors.

Mini-review: Evaluation and Management of Retroperitoneal Masses in Patients with Testicular Cancer.

Testicular germ cell tumours (GCTs) account for the majority of testicular malignancies. Seminomas and nonseminomas differ in prognosis and management strategies. While cisplatin-based chemotherapy has significantly improved survival rates, identification of residual masses after chemotherapy is crucial for determining further treatment and survival. For seminomas, spontaneous resolution of residual masses occurs in a significant percentage of cases. Fluorodeoxyglucose positron emission tomography (FDG PET) is recommended for evaluation of residual masses after chemotherapy. Retroperitoneal lymph node dissection (RPLND) offers therapeutic benefits but is challenging because of an increase in desmoplasia after chemotherapy. For nonseminomas, residual masses are common after chemotherapy, with surgical resection necessary for masses larger than 1 cm. FDG PET has limited utility, and timely surgical intervention is crucial for favourable outcomes. Teratoma, if left unresected, can lead to serious complications, including growing teratoma syndrome, malignant transformation, and late relapse. Extraretroperitoneal residual masses, particularly those containing teratoma, are associated with poorer prognosis. Surgical resection remains the mainstay treatment, with significantly higher progression-free and recurrence-free survival rates for fibrosis/necrosis in comparison to teratoma or viable cancer. Understanding the characteristics and management of residual masses after chemotherapy is paramount for optimising treatment strategies and improving patient outcomes in testicular GCT. PATIENT SUMMARY: We reviewed treatment options for patients with testicular cancer who still have tumour tissue in the lower abdomen after chemotherapy. Surgical removal of the tumour is the main option; removal of lymph nodes can also help, but may be difficult because of tissue reactions to chemotherapy. Survival rates differ according to the tumour type and are lower for tumours beyond the lower abdomen.

"Uncovering the unspoken": a narrative analysis of patients' experiences with testicular cancer.

BACKGROUND: The aim of this study was to understand the experiences of young men with a diagnosis of testicular cancer (TC) using a narrative approach, with the intention of informing models of care and support in clinical services. METHODS: TC patients were recruited to participate in one of four focus groups examining their lived experiences from diagnosis. Focus groups were recorded and transcribed and analyzed using a narrative approach. RESULTS: A total of 4 focus groups were held from March to May 2019, involving 21 participants. Participants were currently on treatment (n = 2), < 2 years from treatment completion (n = 7), or > 2 years from treatment completion (n = 12). Two overarching meta-themes were identified: Negotiating Identity (comprising "recovery, repair and control"; "breaking the news"; "threats to fertility and virility"; "multiple masculinities") and Needing to Adjust (comprising "trauma and post-traumatic growth"; "facing vulnerability"; "managing to cope"; "secrecy vs. privacy"). Shared themes relating to environments for support, conversations about cancer, and time stress were also identified. CONCLUSIONS: Despite the significant cure rates for testicular cancer, the psychosocial needs of patients diagnosed with TC are paramount and potentially long-lasting. Improved clinical care for these patients includes exploration of both physical and psychosocial concerns over multiple timepoints. Opportunities for peer support and mentorship may be essential to support these vulnerable patients.

[Malignant mesothelioma of the vaginal testis: diagnostic and therapeutic considerations]. / Le mésothéliome malin de la vaginale testiculaire : aspects diagnostiques et thérapeutiques.

Mesothelioma of the testicular vagina is a rare malignant tumour, most often discovered by chance. The rarity of this type of tumour has not led to the development of specific guidelines. Median survival is estimated at 30 months. The lack of data and official recommendations makes surgical and medical management and follow-up difficult. Men who have not undergone radical orchiectomy die very rapidly after diagnosis. The remission rate at 1 year post-orchidectomy is 47 %, the recurrence rate at 1 year is 53 % and 92 % of relapses occur within 5 years post-operatively. The treatment option of hemiscrotectomy in the first instance has rarely been used; a second-look resection with negative margins may be proposed. The usefulness of adjuvant chemotherapy and/or radiotherapy has not been clearly demonstrated. Local recurrence is accompanied by metastasis in 85 % of cases. In the case of metastatic cancer (15 %), the retro-peritoneal, inguinal and iliac lymph nodes may be invaded. Follow-up by injected thoraco-abdomino-pelvic CT scan is recommended every 3 months for 2 years, then once a year for 3 years, for a total of 5 years of close follow-up. The long-term recurrence rate is 3 %.

Le mésothéliome de la vaginale testiculaire est une tumeur maligne rare et souvent de découverte fortuite. Sa rareté d'apparition n'a pas permis de développer des recommandations spécifiques. La survie médiane est estimée à 30 mois. Le manque de recommandations officielles rend sa prise en charge chirurgicale, médicale et son suivi difficiles. Les hommes n'ayant pas bénéficié d'orchidectomie radicale décèdent très rapidement après le diagnostic. Le taux de rémission à 1 an post-orchidectomie est de 47 %, le taux de récurrence à 1 an est de 53 % et 92 % des rechutes se font endéans les 5 ans post-opératoires. L'option thérapeutique par hémi-scrotectomie en première intention a rarement été pratiquée, une résection de «second look¼ en marges saines peut être proposée. L'utilité d'une chimiothérapie et/ou d'une radiothérapie adjuvante n'a pas été clairement démontrée. Une rechute locale est accompagnée de métastases dans 85 % des cas. En cas de cancer d'emblée métastatique (15 %), les relais ganglionnaires rétro-péritonéaux, inguinaux et iliaques peuvent être envahis. Un suivi par scanner thoraco-abdomino-pelvien injecté est recommandé tous les 3 mois pendant 2 ans, puis 1 fois par an pendant 3 ans pour un total de 5 ans. Le taux de récidive au long cours est de 3 %.

SEOM-GG clinical guidelines for the management of germ-cell testicular cancer (2023).

Testicular germ cell tumors are the most common tumors in adolescent and young men. They are curable malignancies that should be treated with curative intent, minimizing acute and long-term side effects. Inguinal orchiectomy is the main diagnostic procedure, and is also curative for most localized tumors, while patients with unfavorable risk factors for recurrence, or those who are unable or unwilling to undergo close follow-up, may require adjuvant treatment. Patients with persistent markers after orchiectomy or advanced disease at diagnosis should be staged and classified according to the IGCCCG prognostic classification. BEP is the most recommended chemotherapy, but other schedules such as EP or VIP may be used to avoid bleomycin in some patients. Efforts should be made to avoid unnecessary delays and dose reductions wherever possible. Insufficient marker decline after each cycle is associated with poor prognosis. Management of residual masses after chemotherapy differs between patients with seminoma and non-seminoma tumors. Patients at high risk of relapse, those with refractory tumors, or those who relapse after chemotherapy should be managed by multidisciplinary teams in experienced centers. Salvage treatment for these patients includes conventional-dose chemotherapy (TIP) and/or high-dose chemotherapy, although the best regimen and strategy for each subgroup of patients is not yet well established. In late recurrences, early complete surgical resection should be performed when feasible. Given the high cure rate of TGCT, oncologists should work with patients to prevent and identify potential long-term side effects of the treatment. The above recommendations also apply to extragonadal retroperitoneal and mediastinal tumors.

Discordance of retroperitoneal and thoracic histologic findings in patients with metastatic germ cell tumors at postchemotherapy residual tumor resection.

INTRODUCTION AND OBJECTIVES: Postchemotherapy residual tumor resection (PC-RTR) is an important part of the multimodal treatment for patients with metastatic germ cell tumors. Simultaneous retroperitoneal and thoracic metastases often require consecutive surgical procedures. This study analyzes the histologic findings after abdominal and thoracic surgery in order to tailor the sequence and intensity of surgery. PATIENTS AND METHODS: From a total of 671 PC-RTRs from 2008 to 2021 we analyzed 50 patients with stage III non-seminomatous germ cell tumor (NSGCT) who had undergone both retroperitoneal and thoracic postchemotherapy residual tumor resection after first-line and salvage chemotherapy. RESULTS: All patients included had stage III NSGCT. 39 and 11 patients received first-line and salvage chemotherapy, respectively. 45 (90%) patients received retroperitoneal resection first, followed by thoracic surgery. Three patients (6%) underwent thoracic surgery before retroperitoneal surgery and two patients (4%) underwent simultaneous surgery. Overall, the histology of retroperitoneal and thoracic specimens was discordant in 23% of cases. After first-line chemotherapy, of fourteen patients with necrosis in retroperitoneal histology, four patients had vital carcinoma in lung histology. In patients with teratoma in the retroperitoneum, the thoracic findings were concordant in most cases (78%). When teratomatous elements were also present in the orchiectomy specimen, concordance was 100%. After salvage chemotherapy, the discordance rate was 55%. CONCLUSION: The data presented in this study underline that retroperitoneal residual masses with necrosis cannot reliably predict histologic findings of thoracic specimens. Patients with teratoma in the retroperitoneum have a high likelihood of teratoma in the thoracic specimen.

The experience of fertility concerns in patients with testicular cancer: a qualitative study.

BACKGROUND: Testicular cancer usually occurs in young adult men between the ages of 20 and 40 years, which largely coincides with the age of men's reproductive intentions. However, a serious side effect of testicular cancer therapy could reduce the fertility of patients. PURPOSE: To explore the experience of fertility concerns in patients with testicular cancer. METHODS: A phenomenological research was conducted on 12 patients with testicular cancer. Data collection was from May 2023 to August 2023, and Colaizzi analysis method was used to analyze the data. RESULTS: Four themes were found: (1) multiple worries and negative emotions, (2) fertility decision-making faces many challenges, (3) self-coping strategies for facing fertility concerns, (4) unmet supportive care needs. CONCLUSION: Medical staff should pay attention to the fertility needs of patients with testicular cancer and provide relevant interventions and support to reduce their fertility concerns.

[A Case of Metastatic Prostate Cancer with Neuroendocrine Differentiation with Long-Term Survival after Multidisciplinary Therapy].

A 74-year-old man visited the urology clinic with the chief complaint of urinary retention in December 2014. Serum level of initial prostate specific antigen (PSA) was 50 ng/ml and he was diagnosed with Gleason Score 4＋4 prostate adenocarcinoma with regional lymphadenopathy (cT3aN1M0). PSA level had declined after the treatment with combined androgen blockade. In November 2018, he was diagnosed with castration resistant prostate cancer (CRPC) as local progression was detected by computed tomography (CT) while PSA level did not increase. Since local symptoms worsened, resulting in repeated hematuria after the treatment with enzalutamide, palliative radiation therapy to the prostate (45 Gy) was performed. Five months later, follow-up CT showed multiple metastasis in bilateral lung and left testicle. Serum level of neuron-specific enolase (NSE) was 24.4 ng/ml without an elevated in serum PSA level. He received rebiopsy of the prostate, but no malignant findings were observed. Consequently, bilateral orchiectomy was performed for diagnosis of left testicular tumor. Pathological examination revealed metastasis of neuroendocrine prostate cancer (NEPC). Chemotherapy using cisplatin and irinotecan was administered after orchiectomy. Complete response of lung lesions was achieved and serum level of NSE decreased within normal range. No recurrence has been confirmed for 4 years after the completion of chemotherapy.

Adjuvant Therapy in Stage I Testicular Cancer: Surveillance for All.

Given the remarkably high cure rates for clinical stage (CS) I testicular cancer, the toxicities and risks of adjuvant treatments, the cost effectiveness of surveillance, and the lack of reliable biomarkers to predict relapse, surveillance should be recommended for all patients with CS I testicular cancer.

Use of Risk Factors To Select Adjuvant Therapy Versus Surveillance for Testicular Nonseminoma and Seminoma Germ Cell Tumors.

New risk factors associated with relapse of stage I testicular cancer have been identified. These new factors reflect the risk of recurrence much better than previous parameters and can be used to assess the possible effect of adjuvant chemotherapy.

Review of Discordance Between American Urological Association and European Association of Urology Guideline Recommendations for Testicular Cancer.

We compared the American Urological Association and the European Association of Urology guidelines on testicular cancer. We identified a few differences, in particular for management of low-volume metastatic serum tumor marker-negative stage IIA/B seminoma and nonseminoma, and of advanced and relapsing disease. Overall the rate of concordance between the guidelines is high. PATIENT SUMMARY: We compared guidelines on testicular cancer published by the American Urological Association and the European Association of Urology. We found a high rate of agreement between the two guidelines, with some differences.

Urologic oncology considerations in transgender and gender diverse patients.

PURPOSE OF REVIEW: This review delves into the pressing issue of urologic oncology considerations within the transgender and gender-diverse (TGD) community. With estimates suggesting that TGD individuals constitute 0.3 to 0.5% of adults worldwide, and this number steadily rising, our review examines the barriers that impede the delivery of excellent quality care, particularly in the context of cancer diagnosis and treatment. RECENT FINDINGS: Recent findings highlight disparities in cancer screening, diagnosis, and treatment access for TGD individuals. These challenges are compounded by a dearth of research and the failure of healthcare systems to account for gender identity and its nuances in data collection. Main themes in the literature include the impact of gender-affirming hormone therapy and surgery on cancer risk, challenges in prostate cancer screening and management, and considerations pertinent to testicular and other urological cancers in TGD patients. SUMMARY: The implications for clinical practice and research are profound and emphasize the need for multidisciplinary approaches that cater to the unique healthcare needs of TGD individuals. This includes comprehensive strategies for inclusive and accurate data collection, alongside the development of evidence-based guidelines for cancer screening and management tailored specifically to this population.

Update on the Management of Low-stage Seminoma.

The contemporary paradigm of testicular cancer management is achieving high and durable cure rates while minimizing the burden of treatment given the potential long-term toxicities associated with radiation therapy and systemic therapies. The management of low-stage seminoma has seen significant changes in recent years. Nuances of surveillance strategies for stage I seminoma exist and continue to evolve. Emerging data show retroperitoneal lymph node dissection is a viable treatment option for selected patients with clinical stage IIA and IIB seminoma.

Regionalization of Testis Cancer Care-Is It Necessary?

Testicular germ cell tumors are rare genitourinary malignancies, but they represent the most common malignancies in men aged 15 to 30 years. Whereas the initial steps of management such as staging imaging studies, inguinal orchiectomy, and tumor marker can be performed elsewhere, the surgical and cytotoxic therapy needs to be done at reference centers. Regionalization of testis care has been shown to result in superior oncological outcome.

Testicular Cancer Survivorship and Fertility Preservation.

Testicular cancer disproportionally affects men of reproductive age making fertility an important aspect of testicular cancer survivorship. Men with testicular cancer have more semen parameter abnormalities and a higher incidence of infertility compared to the general population. All treatment options for testicular cancer negatively affect fertility with recovery rates varying by treatment. For these reasons, clinicians should offer sperm cryopreservation, ideally before orchiectomy to maximize the possibility of biologic paternity, if desired. Several innovations have positively impacted this space including direct-to-consumer cryopreservation and bench research demonstrating the feasibility of reintroducing testicular cells post-therapy.