Serum Levels of MicroRNA-371a-3p for Predicting the Histology of Postchemotherapy Residual Masses of Germ Cell Tumours.

BACKGROUND AND OBJECTIVE: Serum levels of microRNA-371a-3p (M371) represent a novel and sensitive biomarker of germ cell tumours (GCTs). This study analysed the utility of M371 to identify viable cancer (VC) in postchemotherapy (pc) residual masses with the underlying goal of avoiding overtreatment. METHODS: A multicentric, prospective diagnostic study was conducted in 180 GCT patients undergoing pc resection of residual masses. A correlation of M371 measurement results with the histological presence of VC in masses was found. A receiver operating characteristic analysis was performed for exploring the performance characteristics of the test. KEY FINDINGS AND LIMITATIONS: The sensitivity was found to be 68.9%, specificity 99.3%, area under the curve 0.813, positive predictive value 0.969, and negative predictive value 0.905; sensitivity is significantly associated with the percentage of VC in the mass. In specimens with ≤10% VC, there were 33.3% elevated M371 levels as opposed to 85.7% in specimens with >50% VC. Teratoma and somatic-type malignancy do not express M371. A lack of a central pathological review is a limitation. CONCLUSIONS AND CLINICAL IMPLICATIONS: The M371 test can identify 68.9% of patients with VC in pc masses. However, cases with <10% VC in the mass may escape detection. Teratoma does not express M371. The test alone cannot correctly identify patients requiring pc surgery, but it may be a tool for scheduling the extent of surgery. PATIENT SUMMARY: The microRNA-371a-3p (M371) test can identify about two-thirds of patients with viable cancer in residual metastatic masses following chemotherapy for germ cell tumours. Only masses with high percentages of viable cancer cells can be identified, and the histological subtype teratoma remains undetected with the test.

The Status of Spermatogenesis in Germ Cell Tumor Bearing Testis and Its Association with Metastatic Disease.

INTRODUCTION: We aimed to evaluate the status of spermatogenesis detected by histological examination of non-tumoral testicular tissues in tumor bearing testis and its association with advanced stage disease. PATIENTS AND METHODS: We retrospectively reviewed patients with testicular germ cell tumors (TGCTs) that undergone radical orchiectomy. All non-tumoral areas of the orchiectomy specimens were examined for the status of spermatogenesis. Patients were divided into two groups as localized (stage I) and metastatic (stage II-III) disease and analyzed separately for seminomatous (SGCT) and nonseminomatous germ cell tumors (NSGCT). RESULTS: Four hundred fifty-four patients were included in our final analysis. Of those, 195 patients had SGCT, and 259 patients had NSGCT. Three hundred and six patients had localized disease at the time of diagnosis. Median (Q1-Q3) age was 31 (26 - 38) years and 102 (22.5%) patients had normal spermatogenesis, 177 (39.0%) patients had hypospermatogenesis and 175 (38.5%) patients had no mature spermatozoa. On multivariate logistic regression analysis, embryonal carcinoma >50% (1.944, 95 %CI 1.054-3.585, P = .033) and spermatogenesis status (2.796 95% CI 1.251-6.250, P = .012 for hypospermatogenesis, and 3.907, 95% CI 1.692-9.021, P = .001 for absence of mature spermatozoa) were independently associated with metastatic NSGCT. However, there was not any variables significantly associated with metastatic SGCT on multivariate logistic regression analysis. CONCLUSION: Our study demonstrated that only 22.5% of patients with TGCTs had normal spermatogenesis in tumor bearing testis. Impaired spermatogenesis (hypospermatogenesis or no mature spermatozoa) and predominant embryonal carcinoma are associated with advanced stage NSGCT.

Primary Retroperitoneal Lymph Node Dissection for Clinical Stage II A/B Seminomas: A Systematic Review and Meta-Analysis.

INTRODUCTION: Chemotherapy and radiation therapy are considered standard treatments for stage II seminoma patients; however, these therapies are associated with long-term toxicities. Recently, retroperitoneal lymph node dissection has emerged as an alternative strategy, and the first three phase II trials were published in 2023 with promising results. The present study conducted a systematic review and meta-analysis to evaluate this surgery as an alternative treatment for stage IIA/B seminoma patients. PURPOSE: Seminomas are the most common testicular tumors, often affecting young adult males. Standard treatments for stage II seminomas include chemotherapy and radiation therapy, but these therapies are associated with long-term toxicities. Thus, identifying alternative strategies is paramount. Herein, we conducted a systematic review and meta-analysis to appraise the efficacy and safety of retroperitoneal lymph node dissection (RPLND) for treating this condition. METHODS: We systematically searched the PubMed, Embase, and Cochrane databases for studies evaluating RPLND as a primary treatment for stage II A/B seminomas. Using a random-effects model, single proportion and means and pooled 2-year recurrence-free survival rates with hazard rates and 95% CI were calculated. RESULTS: Seven studies were included, comprising 331 males with stage II seminomas. In the pooled analysis, the recurrence rate was 17.69% (95% CI 12.31-24.75), and the 2-year RFS rate was 81% (95% CI 0.77-0.86). The complication rate was 9.16% (95% CI 6.16-13.42), the Clavien-Dindo > 2 complication rate was 8.83% (95% CI 5.76-13.31), and the retrograde ejaculation rate was 7.01% (95% CI 3.54-13.40). The median operative time was 174.68 min (95% CI 122.17-249.76 min), median blood loss was 105.91 mL (95% CI 46.89-239.22 mL), and patients with no evidence of lymph node involvement ranged from 0-16%. CONCLUSIONS: Primary RPLNDs for treating stage IIA/B seminomas have favorable RFS rates, with low complication and recurrence rates. These findings provide evidence that this surgery is a viable alternative therapy for these patients.

Cryptorchidism and testicular cancer in the dog: unresolved questions and challenges in translating insights from human studies.

Cryptorchidism, the failure of one or both testes to descend into the scrotum, and testicular cancer show a strong correlation in both dogs and humans. Yet, long-standing medical debates persist about whether the location of undescended testes directly causes testicular cancer in humans or if both conditions stem from a common origin. Although testicular cancer is a prevalent disease in dogs, even less is known about its cause and correlation with testicular descent in this species. This review investigates the relation between these two disorders in dogs, drawing insights from human studies, and examines key biomarkers identified thus far. In addition, it explores potential causal links, including the impact of temperature on maturing testicular cells and a potential shared genetic origin. Notably, this literature review reveals significant differences between men and dogs in reproductive development, histological and molecular features of testicular tumors, and the prevalence of specific tumor types, such as Sertoli cell tumors (SCTs) in cryptorchid dogs and germ cell tumors (GCTs) in humans. These disparities caution against using dogs as models for human testicular cancer research and underscore the limitations when drawing comparisons between species. The paper concludes by suggesting specific research initiatives to enhance our understanding of the complex interplay between cryptorchidism and testicular cancer in dogs.

Extragonadal germ cell tumors: A clinicopathologic study with emphasis on molecular features, clinical outcomes and associated secondary malignancies.

Extragonadal germ cell tumors (EGCTs) are rare, representing <5% of all germ cell tumors (GCTs). Whilst EGCTs share morphological and immunohistochemical features with their gonadal counterparts, they tend to be more aggressive and are frequently associated with secondary somatic malignancies. The aim of our study was to evaluate the clinical, morphological and immunohistochemical features, and to analyze tumors for chromosomal abnormalities of 12p, in addition to any novel genetic alterations, in a series of EGCTs. Seventy-seven EGCTs were included. Anterior mediastinum was the most common anatomic site, followed by central nervous system, retroperitoneum, sacroccygeal area, and neck. Whole genome SNP array identified isochromosome 12p in 26% of tumors. Additional cytogenetic abnormalities included the presence of gain of chr 21 in 37% of tumors. Somatic-type malignancies were identified in 8% of patients. Disease progression (metastasis and/or recurrence) was documented in 8 patients, most of whom died from their relapse. Three patients who died of disease had somatic-type malignancies. Mediastinal seminomas had a significantly better overall survival when compared to mediastinal non-seminomatous GCTs. Our study demonstrates that EGCTs share similar histologic features, but diverse clinical outcomes compared to their gonadal counterparts. Outcomes vary according to anatomic location and histologic subtypes. Our data corroborate that somatic-type malignancies are frequently encountered in mediastinal EGCTs and that their presence portends a poorer prognosis.

Testicular seminoma presenting as a large conglomerate mass in abdomen.

Testicular seminoma commonly occurs in young men aged between 15 and 45 years old. Those with testicular cancer may present with a lump or swelling in the testicle. If treated and managed early, patients can expect a greater than 95% success rate. However, advanced stages of testicular seminoma can lead to eventual metastasis. We present a 45-year-old male patient with a prior history of testicular seminoma who was admitted to the emergency department with abdominal distension and acute abdominal pain. The CT identified a rather sizable abdominal mass and the biopsy confirmed metastatic testicular seminoma. Lymphoma was considered as the other differential diagnosis. Abdominal metastasis is rare in patients with testicular seminoma and usually leads to a poor survival outcome. Our patient did not attend follow-up appointments postorchidectomy, likely resulting in abdominal metastasis of testicular seminoma. This demonstrates the importance of ongoing surveillance of seminoma patients, and the challenges associated with differentiating large abdominal conglomerate mass in the CT scan. This patient is currently on active chemotherapy with bleomycin, cisplatin, and etoposide.

Impact of teratoma on survival probabilities of patients with metastatic non-seminomatous germ cell cancer: Results from the IGCCCG Update Consortium.

AIMS: To resolve the ongoing controversy surrounding the impact of teratoma (TER) in the primary among patients with metastatic testicular non-seminomatous germ-cell tumours (NSGCT). PATIENTS AND METHODS: Using the International Germ Cell Cancer Collaborative Group (IGCCCG) Update Consortium database, we compared the survival probabilities of patients with metastatic testicular GCT with TER (TER) or without TER (NTER) in their primaries corrected for known prognostic factors. Progression-free survival (5y-PFS) and overall survival at 5 years (5y-OS) were estimated by the Kaplan-Meier method. RESULTS: Among 6792 patients with metastatic testicular NSGCT, 3224 (47%) had TER in their primary, and 3568 (53%) did not. In the IGCCCG good prognosis group, the 5y-PFS was 87.8% in TER versus 92.0% in NTER patients (p = 0.0001), the respective 5y-OS were 94.5% versus 96.5% (p = 0.0032). The corresponding figures in the intermediate prognosis group were 5y-PFS 76.9% versus 81.6% (p = 0.0432) in TER and NTER and 5y-OS 90.4% versus 90.9% (p = 0.8514), respectively. In the poor prognosis group, there was no difference, neither in 5y-PFS [54.3% in TER patients versus 55.4% (p = 0.7472) in NTER], nor in 5y-OS [69.4% versus 67.7% (p = 0.3841)]. NSGCT patients with TER had more residual masses (65.3% versus 51.7%, p < 0.0001), and therefore received post-chemotherapy surgery more frequently than NTER patients (46.8% versus 32.0%, p < 0.0001). CONCLUSION: Teratoma in the primary tumour of patients with metastatic NSGCT negatively impacts on survival in the good and intermediate, but not in the poor IGCCCG prognostic groups.

Rhabdomyosarcoma in Adults: De Novo or Conversion From Non-seminomas?

Rhabdomyosarcoma (RMS) is a highly sporadic, very aggressive, and fatal soft tissue tumor in adults. Although more common and treatable in the pediatric population, the occurrence of pleomorphic RMS in adults has a low incidence. Hence, it is not easy to treat. Surgery is the primary definitive treatment, along with radiation therapy, while adjuvant chemotherapy has recently gained popularity. We present an infrequent case of RMS in a patient with a recent history of mixed non-seminomatous germ-cell tumor testicular cancer. Therefore, it was challenging to treat the RMS as a new malignancy or as a recurrence of non-seminomatous testicular cancer. Our patient passed away, unfortunately, but we hope this case can help the minimal data in this regard in order to save more lives in the future.

Testicular Cancer Treatments and Sexuality: A Narrative Review.

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.

New insights on testicular cancer prevalence with novel diagnostic biomarkers and therapeutic approaches.

BACKGROUND: Testicular cancer (TC), comprising merely 1% of male neoplasms, holds the distinction of being the most commonly encountered neoplasm among young males. RECENT FINDINGS: Most cases of testicular neoplasms can be classified into two main groups, namely germ cell tumors representing approximately 95% of the cases, and sex cord-stromal tumors accounting for about 5% of the cases. Moreover, its prevalence is on the rise across the globe. TC is a neoplastic condition characterized by a favorable prognosis. The advent of cisplatin-based chemotherapeutic agents in the latter part of the 1970s has led to a significant enhancement in the 5-year survival rate, which presently surpasses 95%. Given that TC is commonly detected before reaching the age of 40, it can be anticipated that these individuals will enjoy an additional 40-50 years of life following successful treatment. The potential causes of TC are multifactorial and related to different pathologies. Accurate identification is imperative to guarantee the utmost efficacious and suitable therapy. To a certain degree, this can be accomplished through the utilization of blood examinations for neoplastic indicators; nonetheless, an unequivocal diagnosis necessitates an evaluation of the histological composition of a specimen via a pathologist. CONCLUSION: TC is multifactorial and has various pathologies, therefore this review aimed to revise the prenatal and postnatal causes as well as novel diagnostic biomarkers and the therapeutic strategies of TC.

Expression of Immunotherapy Target PRAME in Cancer Correlates with Histone H3 Acetylation and Is Unrelated to Expression of Methylating (DMNT3A/3B) and Demethylating (TET1) Enzymes.

Background/Objectives: Preferentially expressed antigen in melanoma (PRAME), a member of the cancer testis antigen family, is a promising target for cancer immunotherapy. Understanding the epigenetic mechanisms involved in the regulation of PRAME expression might be crucial for optimizing anti-PRAME treatments. Methods: Three malignancies of different lineages (sinonasal melanoma, testicular seminoma, and synovial sarcoma), in which immunohistochemical (IHC) reactivity for PRAME is a common yet variable feature, were studied. The expression of PRAME, ten-eleven translocation demethylase 1 (TET1), and DNA methyltransferase (DNMT) 3A and 3B were evaluated using immunohistochemistry. Moreover, the expression of two epigenetic marks, 5-hydroxymethylcytosine (5hmC) and histone 3 acetylation (H3ac), was tested. Results: All PRAME-positive tumors expressed medium-to-high levels of H3ac but differed considerably with respect to other markers. In seminomas, PRAME expression correlated with TET1, but in melanomas and synovial sarcomas, it correlated with both DNMTs and DNMT3A, respectively. Conclusions: PRAME expression was not determined by a balance between the global expression of DNA methylating/demethylating enzymes. However, histone acetylation may be one of the epigenetic mechanisms involved in PRAME regulation. Thus, the therapeutic combination of histone deacetylase inhibitors and PRAME immunotherapy merits further investigation.

Prognostic factors for relapse in patients with clinical stage I testicular non-seminoma: A nationwide, population-based cohort study.

BACKGROUND: Approximately 30% of patients with clinical stage I non-seminoma (CSI-NS) relapse. Current risk stratification is based on lymphovascular invasion (LVI) alone. The extent to which additional tumor characteristics can improve risk prediction remains unclear. OBJECTIVE: To determine the most important prognostic factors for relapse in CSI-NS patients. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study including all patients with CSI-NS diagnosed in Denmark between 2013 and 2018 with follow-up until 2022. Patients were identified in the prospective Danish Testicular Cancer database. By linkage to the Danish National Pathology Registry, histological slides from the orchiectomy specimens were retrieved. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Histological slides were reviewed blinded to the clinical outcome. Clinical data were obtained from medical records. The association between prespecified potential prognostic factors and relapse was assessed using Cox regression analysis. Model performance was evaluated by discrimination (Harrell's C-index) and calibration. RESULTS: Of 453 patients included, 139 patients (30.6%) relapsed during a median follow-up of 6.3 years. Tumor invasion into the hilar soft tissue of the testicular hilum, tumor size, LVI and embryonal carcinoma were independent predictors of relapse. The estimated 5-year risk of relapse ranged from < 5% to > 85%, depending on the number of risk factors. After internal model validation, the model had an overall concordance statistic of 0.75. Model calibration was excellent. CONCLUSION AND RELEVANCE: The identified prognostic factors provide a much more accurate risk stratification than current clinical practice, potentially aiding clinical decision-making.

Iodine­125 seeds combined with carboplatin in the treatment of retroperitoneal metastatic seminoma: A case report and literature review.

Testicular seminoma is a relatively rare malignant tumor, with the most common site of recurrence and metastasis being the retroperitoneal lymph nodes. Since seminoma is highly sensitive to radiotherapy and chemotherapy, even if it metastasizes, its cure rate is still >95%. However, the long-term toxicity and side effects of radiotherapy and chemotherapy cannot be ignored. Iodine-125 seeds represent a low-energy radioactive source that kills tumor cells while protecting the surrounding normal tissues, and brachytherapy using iodine-125 seeds has been widely used for the treatment of various malignancies. In addition, carboplatin can be used as an alternative to cisplatin-based combination chemotherapy to reduce the incidence of pulmonary toxicity, neurological damage and renal toxicity. In the present study, a case in which iodine-125 seeds were implanted for the treatment of retroperitoneal metastatic seminoma is reported. The patient was diagnosed with postoperative recurrence of seminoma that metastasized to the retroperitoneal lymph nodes. Since the tumor was large and surrounded blood vessels, surgical intervention and external radiotherapy were not considered. Moreover, considering the potential long-term toxic side effects of standard chemotherapy, a treatment plan for the patient using iodine-125 seed implantation combined with carboplatin (AUC7) therapy was finally formulated. No disease recurrence or toxic reactions occurred during the 3-year follow-up after treatment. The present case therefore demonstrated the antitumor efficacy and reduced toxicity of iodine-125 seeds combined with carboplatin for treating seminoma.

Neutropenic Enterocolitis in a Metastatic Seminoma Patient With Streptococcus gallolyticus Bacteremia.

Neutropenic enterocolitis (NEC), also referred to as typhlitis, is a condition associated with a high mortality risk and primarily manifests in immunocompromised patients. It is characterized by ulceration, edema, and hemorrhage affecting the bowel wall. The underlying cause of NEC is postulated as an immunocompromised condition that facilitates bacterial infiltration through compromised bowel mucosa. The high mortality rate is attributable to bowel necrosis, culminating in perforation and sepsis. This report describes a case involving a patient with metastatic seminoma who exhibited seizure-like activity, fever, Streptococcus gallolyticus bacteremia, and NEC. The patient underwent treatment involving broad-spectrum antibiotics and filgrastim. The patient's neutropenia resolved leading to discharge on oral antibiotics. The case reported is unique, as it links NEC to Streptococcus gallolyticus and seminoma. Streptococcus gallolyticus has not been previously associated with NEC.

Malignant ovarian and testicular germ cell tumors: Common characteristics but different prognoses.

Both ovarian and testicular germ cell tumors (GCTs) arise from the primordial germ cell and share many similarities. Both malignancies affect mainly young patients, show remarkable responsiveness to cisplatin-based therapy, and have an excellent prognosis, which also highlights the importance of minimizing long-term side effects. However, certain differences can be noted: The spreading of the disease differs, and the staging system and treatment recommendations are dissimilar. Moreover, the prognosis for ovarian GCTs is significantly inferior to that for testicular cancer, as exemplified in this review comparing the survival in Swedish patients diagnosed with testicular (1995-2022) and ovarian (1990-2018) GCTs. The 5-year overall survival in ovarian GCTs was 85.2%, versus 98.2% for testicular GCTs. How can this be explained? One reason may be the difference in knowledge, experience, and evidence because the incidence rate of testicular cancer is more than 15 times that of ovarian GCTs. Given the rarity of the disease in women and the lack of established guidelines, a comprehensive understanding of the disease and treatment decisions is challenging. The main objective of this review is to derive insights from testicular GCTs (seminoma and non-seminoma) by reviewing etiological, tumor biological, and clinical knowledge, and to thereafter suggest actions for ovarian GCTs based on this. We hypothesize that by adopting specific treatment strategies from testicular GCTs-including de-escalating adjuvant chemotherapy for low-risk patients and implementing more standardized and intensive treatment protocols in cases of relapse-we can improve the prognosis and minimize long-term side effects in ovarian GCT patients.

Survival differences in non-seminoma testis cancer patients according to race/ethnicity.

BACKGROUND: Historic evidence suggests that non-Caucasian race/ethnicity predisposes to higher testis cancer-specific mortality (CSM) in non-seminoma. However, it is unknown, whether higher CSM in non-Caucasians applies to Hispanics or Asians or African-Americans, or all of the above groups. In contemporary patients, we tested whether CSM is higher in these select non-Caucasian groups than in Caucasians, in overall and in stage-specific comparisons: stage I vs. stage II vs. stage III. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (2004 -2019) was used. Kaplan-Meier plots and multivariable Cox regression models tested the effect of race/ethnicity on CSM after stratification for stage (I vs. II vs. III) and adjustment for prognosis groups in stage III. RESULTS: In all 13,515 non-seminoma patients, CSM in non-Caucasians was invariably higher than in Caucasians. In stage-specific analyses, race/ethnicity represented an independent predictor of CSM in Hispanics in stage I (HR 1.8, p = 0.004), stage II (HR 2.2, p = 0.007) and stage III (HR 1.4, p < 0.001); in African-Americans in stage I (HR 3.2; p = 0.007) and stage III (HR 1.5; p = 0.042); and in Asians in only stage III (HR 1.6, p = 0.01). CONCLUSIONS: In general, CSM is higher in non-Caucasian non-seminoma patients. However, the CSM increase differs according to non-Caucasian race/ethnicity groups. Specifically, higher CSM applies to all stages of non-seminoma in Hispanics, to stages I and III in African-Americans and only to stage III in Asians. These differences are important for individual patient management, as well as for design of prospective trials.

The Histopathological Spectrum of Scrotal Lesions in a Tertiary Care Hospital: A Cross-Sectional Study.

BACKGROUND: The incidence and clinical presentation of testicular and paratesticular lesions are variable. A preoperative diagnosis is often difficult with only a clinical examination. The diagnosis of testicular lesions is mainly based on histological investigation, despite advances in imaging and tumor marker testing. This study aimed to document the histopathological spectrum of scrotal lesions, including testicular and paratesticular lesions. AIM: The study aimed to research the histopathological spectrum of scrotal lesions. SETTINGS AND DESIGN: This was a cross-sectional study conducted at NKP Salve Institute of Medical Sciences & Research Centre and Lata Mangeshkar Hospital, a tertiary care hospital in Nagpur, India. MATERIALS AND METHODS: Following the institutional ethics committee's approval, a two-year cross-sectional study was carried out in the tertiary care hospital. Seventy operated scrotal specimens sent for histopathological examination were included in the study. The clinical details and investigations of the patients, as well as the gross and histopathological findings of all the specimens, were studied carefully. STATISTICAL ANALYSIS: The clinical details and gross and histopathological findings were noted in a proforma, entered in a Microsoft Excel sheet (Microsoft Corp., Redmond, WA), and verified. The data were presented in a tabular form using tablets, pie charts, and bar diagrams. The collected data were analyzed and presented in percentages and frequencies. RESULTS: The present study evaluated the histopathological spectrum of scrotal lesions in 70 operated scrotal masses. The mean age of the participants in the study was 46.55 ± 18.69 years, with the youngest patient at four years and the oldest being 88 years of age. Sixty-six (80%) of the 70 cases were of non-neoplastic lesions, while 14 (20%) were of neoplastic lesions. Testicular atrophy (16 cases) was the most common non-neoplastic lesion. The most frequent neoplastic lesion in the present study was a seminoma (seven cases). CONCLUSION: This study strongly recommends routine histopathological examination of all scrotal specimens for the detection of various testicular and paratesticular lesions, as well as neoplasms. Histopathology not only provides a tissue diagnosis in scrotal disorders, but it also adds to understanding etiopathogenesis and can aid in the development of future treatment options.

Cumulative incidences of hypogonadism, hypertension, and dyslipidaemia in patients with stage I seminoma treated with a risk-adapted strategy: a Spanish single-centre retrospective analysis.

PURPOSE: To describe the incidences of hypogonadism, hypertension, and dyslipidaemia in patients with stage 1 seminoma (S1S) testicular cancer (TC) treated with a risk-adapted strategy. METHODS: A retrospective analysis from 2000 to 2020 was conducted. Active surveillance (AS), carboplatin one cycle, and carboplatin two cycles were offered according to risk factors. Cumulative incidences and relapse-free survival (RFS) were estimated. RESULTS: Of the 145 patients, 8 (5.4%) were excluded due to bilateral TC or hypogonadism at diagnosis. Median follow-up time was 8.2 years. Eighty-four, 30, and 33 patients were treated with AS, carboplatin one cycle, and carboplatin two cycles, respectively. In the overall population, the 5-year and 10-year cumulative incidences were 1.6% and 5.3% for hypogonadism; 2.0% and 8.6% for hypertension; and 12.4% and 25.1% for dyslipidaemia. No statistically significant differences were found in the incidences among the three adjuvant strategies. Five-year and 10-year RFS were 85.9% and 83.3% for AS; 92.4% and 84.0% for carboplatin one cycle; and 96.7% at both times for carboplatin two cycles. CONCLUSION: There were no statistically differences in cumulative incidences of hypogonadism, hypertension, and dyslipidaemia in S1S patients treated with a risk-adapted strategy.

Radiation Therapy for Stage IIA/B Seminoma: Modeling Secondary Cancer Risk for Protons and VMAT versus 3D Photons.

Radiation therapy (RT) is an effective treatment for stage IIA and select stage IIB seminomas. However, given the long life expectancy of seminoma patients, there are concerns about the risk of secondary cancers from RT. This study assessed differences in secondary cancer risk for stage II seminoma patients following proton pencil-beam scanning (PBS) and photon VMAT, compared to 3D conformal photon RT. Ten seminoma patients, five with a IIA staging who received 30 GyRBE and five with a IIB staging who received 36 GyRBE, had three RT plans generated. Doses to organs at risk (OAR) were evaluated, and secondary cancer risks were calculated as the Excess Absolute Risk (EAR) and Lifetime Attributable Risk (LAR). PBS reduced the mean OAR dose by 60% on average compared to 3D, and reduced the EAR and LAR for all OAR, with the greatest reductions seen for the bowel, liver, and stomach. VMAT reduced high doses but increased the low-dose bath, leading to an increased EAR and LAR for some OAR. PBS provided superior dosimetric sparing of OAR compared to 3D and VMAT in stage II seminoma cases, with models demonstrating that this may reduce secondary cancer risk. Therefore, proton therapy shows the potential to reduce acute and late side effects of RT for this population.