Survival of stage III non-seminoma testis cancer patients versus simulated controls, according to race/ethnicity.

BACKGROUND: It is unknown whether 5-year overall survival (OS) differs and to what extent between the American Joint Committee on Cancer stage III non-seminoma testicular germ cell tumor (NS-TGCT) patients and simulated age-matched male population-based controls, according to race/ethnicity groups. METHODS: We identified newly diagnosed (2004-2014) stage III NS-TGCT patients within the Surveillance Epidemiology and End Results database 2004-2019. For each case, we simulated an age-matched male control (Monte Carlo simulation), relying on Social Security Administration (SSA) Life Tables with 5 years of follow-up. We compared OS rates between stage III NS-TGCT patients and simulated age-matched male population-based controls, according to race/ethnicity groups (Caucasian, Hispanic, Asian/Pacific Islander and African American). Both, cancer-specific mortality (CSM) and other-cause mortality (OCM) were computed. RESULTS: Of 2054 stage III NS-TGCT patients, 60% were Caucasians versus 33% Hispanics versus 4% Asians/Pacific Islanders versus 3% African Americans. The 5-year OS difference between stage III NS-TGCT patients versus simulated age-matched male population-based controls was highest in Asians/Pacific Islanders (64 vs. 99%, Δ = 35%), followed by African Americans (66 vs. 97%, Δ = 31%), Hispanics (72 vs. 99%, Δ = 27%), and Caucasians (76 vs. 98%, Δ = 22%). The 5-year CSM rate was highest in Asians/Pacific Islanders (32%), followed by African Americans (26%), Hispanics (25%), and Caucasians (20%). The 5-year OCM rate was highest in African Americans (8%), followed by Caucasians (4%), Asians/Pacific Islanders (4%), and Hispanics (2%). CONCLUSION: Relative to SSA Life Tables, the highest 5-year OS disadvantage applied to stage III NS-TGCT Asian/Pacific Islander race/ethnicity group, followed by African American, Hispanic and Caucasian, in that order.

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.

Unilateral Post-Chemotherapy Robot-Assisted Retroperitoneal Lymph Node Dissection for Stage II Non-Seminomatous Germ Cell Tumors: Sexual and Reproductive Outcomes.

We aimed to report sexual and reproductive outcomes following post-chemotherapy robot-assisted retroperitoneal unilateral lymph node dissection (PC-rRPLND) for non-seminomatous germ cell tumors (NSGCTs) at a high-volume cancer center. We collected records regarding sexual and reproductive outcomes of patients undergoing unilateral PC-rRPLND for stage II NSGCTs from January 2018 to November 2021. Preoperative and postoperative (at 12 months) ejaculatory function as well as erectile function, based on the International Index of Erectile Function-5 (IIEF-5) and Erection Hardness Score (EHS), were assessed. Only patients with a pre-operative IIEF-5 of ≥22 and EHS of ≥3 were included in this analysis. Overall, 22 patients undergoing unilateral PC-rRPLND met the inclusion criteria. Of these, seven (31.8%) patients presented an andrological disorder of any type after PC-rRPLND. Specifically, retrograde ejaculation was present in three (13.6%) patients and hypospermia was present in one (4.5%) patient. Moreover, three (13.6%) patients yielded erectile dysfunction (IIEF-5 < 22 and/or EHS < 3). Lastly, two (9.1%) succeeded in naturally conceiving a child after PC-rRPLND. Retrograde ejaculation is confirmed to be one of the most common complications of PC-rRPLND. Moreover, a non-negligible number of patients experience erectile dysfunction.

A Rare Case of Paratesticular Sarcoma: A Case Report.

Paratesticular rhabdomyosarcoma (PRMS) is a rare and aggressive soft tissue tumour that can mimic testicular sarcoma on initial imaging studies, leading to diagnostic ambiguity and treatment delays. In this case report, we present the case of a 45-year-old male who came to our department and was evaluated under ultrasound imaging along with colour Doppler. The patient underwent further examination under a multi-slice CT machine, which provided additional information, and finally underwent a 1.5T MRI scan. After a provisional diagnosis was made, the patient underwent surgery, and the specimen was sent for histopathology and relevant immunohistopathological markers. This case underscores the diagnostic challenges posed by PRMS and emphasizes the need for a multidisciplinary approach involving radiologists, oncologists, and surgeons for timely diagnosis and optimal management. We discuss the clinical implications, imaging characteristics, differential diagnosis, and therapeutic considerations for PRMS to guide clinicians in similar diagnostic dilemmas.

A population-based validation of the IGCCCG Update Consortium for survival in metastatic non-seminoma testis cancer.

BACKGROUND: In 2021, the International Germ Cell Cancer Collaborative Group (IGCCCG) Update Consortium reported improved overall survival (OS) rates in a modern cohort of metastatic non-seminoma testis cancer patients within each of the IGCCCG prognosis groups (96% in good vs. 89% in intermediate vs. 67% in poor), compared to the previous IGCCCG publication (92% in good vs. 80% in intermediate vs. 48% in poor). We hypothesized that a similar survival improvement may apply to a contemporary North-American population-based cohort of non-seminoma testis cancer patients. PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (2010-2018) was used. Kaplan-Meier plots and multivariable Cox regression models tested the effect of IGCCCG prognosis groups on overall mortality (OM). RESULTS: Of 1672 surgically treated metastatic non-seminoma patients, 778 (47%) exhibited good vs. 251 (15%) intermediate vs. 643 (38%) poor prognosis. In the overall cohort, five-year OS rate was 94% for good prognosis vs. 87% for intermediate prognosis vs. 65% for poor prognosis. In multivariable Cox regression models predicting OM, intermediate (Hazard ratio [HR] 2.4, 95% confidence interval [CI] 1.4-3.9, P < 0.001) and poor prognosis group (HR 6.6, 95% CI 1.0-1.0, P < 0.001) were independent predictors of higher OM, relative to good prognosis group. CONCLUSIONS: The survival improvement reported by the IGCCCG Update Consortium is also operational in non-seminoma testis cancer patients within the most contemporary SEER database. This observation indicates that the survival improvement is not only applicable to centres of excellence, but also applies to other institutions at large.

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.

Predictive and prognostic biomarkers in urological tumours.

Advancements in cutting-edge molecular profiling techniques, such as next-generation sequencing and bioinformatic analytic tools, have allowed researchers to examine tumour biology in detail and stratify patients based on factors linked with clinical outcome and response to therapy. This manuscript highlights the most relevant prognostic and predictive biomarkers in kidney, bladder, prostate and testicular cancers with recognised impact in clinical practice. In bladder and prostate cancer, new genetic acquisitions concerning the biology of tumours have modified the therapeutic scenario and led to the approval of target directed therapies, increasing the quality of patient care. Thus, it has become of paramount importance to choose adequate molecular tests, i.e., FGFR screening for urothelial cancer and BRCA1-2 alterations for prostate cancer, to guide the treatment plan for patients. While no tissue or blood-based biomarkers are currently used in routine clinical practice for renal cell carcinoma and testicular cancers, the field is quickly expanding. In kidney tumours, gene expression signatures might be the key to identify patients who will respond better to immunotherapy or anti-angiogenic drugs. In testicular germ cell tumours, the use of microRNA has outperformed conventional serum biomarkers in the diagnosis of primary tumours, prediction of chemoresistance, follow-up monitoring, and relapse prediction.

Retroperitoneal Lymph Node Dissection in Clinical Stage IIA/B Metastatic Seminoma: Results of the COlogne Trial of Retroperitoneal Lymphadenectomy In Metastatic Seminoma (COTRIMS).

BACKGROUND: Radiation therapy and systemic chemotherapy are recommended treatment options in marker-negative clinical stage (CS) IIA/B seminoma. Despite high cure rates of 82-94%, both therapeutic options are associated with significant long-term toxicities. OBJECTIVE: To evaluate the feasibility, oncological efficacy, and treatment-associated morbidity of primary nerve-sparing retroperitoneal lymph node dissection (nsRPLND) in CS IIA/B seminoma. DESIGN, SETTING, AND PARTICIPANTS: A prospective, single-arm, clinical phase 2 trial including CS IIA/B seminoma patients was conducted. INTERVENTION: Primary nerve-sparing retroperitoneal lymphadenectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Relapse-free and overall survival, surgery-associated complications according to the Clavien-Dindo classification, and Kaplan-Meier methods for survival calculation were assessed. RESULTS AND LIMITATIONS: Thirty patients at a mean age of 39.1 (34-52) yr with marker-negative CS IIA and IIB seminomas were recruited. The median follow-up was 22 (8-30) mo. Nineteen (63%) and 11 (36%) patients were diagnosed with stages IIA and B, respectively, at the time of primary diagnosis. Fourteen (47%) and 16 (53%) patients were diagnosed with CS IIA and IIB, respectively, at the time of nsRPLND. Twenty-seven and three patients underwent open and robot-assisted nsRPLND, respectively. The median operating room time was 125 (115-145) min, median blood loss was <150 ml, and median time of hospitalization was 4.5 (3-9) d. Four (13%) patients experienced Clavien-Dindo grade 3a complications. Lymph node histology revealed seminoma in 25 (80%) patients; two and three patients demonstrated embryonal carcinoma and benign disease, respectively. Sixteen patients underwent a serum analysis of miR371 preoperatively, which predicted metastatic disease in 12/13 and benign histology in 3/3 patients. Three of 30 (10%) patients developed an outfield relapse 4, 6, and 9 mo postoperatively and were salvaged by systemic chemotherapy. Limitations are the low patient number and length of follow-up. CONCLUSIONS: The nsRPLND approach results in a high cure rate at midterm follow-up and is associated with a low frequency of treatment-associated morbidities, making this approach a feasible alternative to radiation therapy or systemic chemotherapy. PATIENT SUMMARY: The standard treatment of clinical stage IIA/B seminomas is radiation therapy or chemotherapy, which results in a significantly increased frequency of long-term toxicity and secondary neoplasms. In this trial, we demonstrate that nerve-sparing retroperitoneal lymph node dissection is a feasible therapeutic approach with low morbidity and high oncological efficacy.

Sperm DNA methylation dynamics after chemotherapy: a longitudinal study of a patient with testicular germ cell tumor treatment.

BACKGROUND: An important issue for young men affected by testicular germ cell tumor (TGCT) is how TGCT and its treatment will affect, transiently or permanently, their future reproductive health. Previous studies have reported that xenobiotics can induce changes on human sperm epigenome and have the potential to promote epigenetic alterations in the offspring. OBJECTIVES: Here, we report the first longitudinal DNA methylation profiling of frozen sperm from a TGCT patient before and up to 2 years after a bleomycin, etoposide, and cisplatin (BEP) chemotherapy. MATERIALS AND METHODS: A TGCT was diagnosed in a 30-year-old patient. A cryopreservation of spermatozoa was proposed before adjuvant BEP treatment. Semen samples were collected before and after chemotherapy at 6, 9, 12, and 24 months. The DNA methylation status was determined by RRBS to detect DNA differentially methylated regions (DMRs). RESULTS: The analysis revealed that among the 74 DMRs showing modified methylation status 6 months after therapy, 17 remained altered 24 months after treatment. We next associated DMRs with differentially methylated genes (DMGs), which were subsequently intersected with loci known to be important or expressed during early development. DISCUSSION AND CONCLUSION: The consequences of the cancer treatment on the sperm epigenome during the recovery periods are topical issues of increasing significance as epigenetic modifications to the paternal genome may have deleterious effects on the offspring. The altered methylated status of these DMGs important for early development might modify their expression pattern and thus affect their function during key stages of embryogenesis, potentially leading to developmental disorders or miscarriages.

Incidence and Survival of Testicular Cancers in a Province in Northern Italy and Their Association with Second Tumors.

This study investigated the incidence, mortality, and 5-year survival rates of testicular cancers diagnosed in a northern Italian province, which were eventually associated with previous or subsequent extratesticular neoplasms. Cases from 1996 to 2020 were examined by age and histotype (seminoma vs. non-seminoma). The standardized incidence rate was calculated using the European population, and the annual percent change (APC) was reported. The five-year relative survival was estimated using the Pohar Perme method. The association with the second neoplasm was also evaluated. In our study, 385 patients with testicular cancer were included, most of whom were aged between 30 and 40 years. The non-seminoma and seminoma groups accounted for 44% and 18% of younger adults, respectively. The incidence rate increased during the study period (APC 1.6*); however, it increased in seminomas (APC 2.3*) but not in non-seminomas (APC -0.1). Conversely, the mortality rate remained constantly low either overall or in each of the two groups. The overall 5-year survival rate of testicular cancer patients was 95% (99% and 88% for seminomas and non-seminomas, respectively). Primary extratesticular tumors were documented in 37 cases, 18 after and 19 before the testicular cancer diagnosis. Our study confirms that the increased incidence and excellent survival rate are the prerogative of seminomas.

Testicular cancer: new developments, molecular pathology, and current research keynote.

Germ cell tumors (GCTs) are now considered a curable cancer, with a > 95% cure rate in all patients and about 90% cure rate in patients with metastatic disease. The success of physicians in curing the disease is underpinned by multidisciplinary advances. Of relevance in this regard are the nowadays-applied homogeneous terminology based on pathologically better characterized testicular neoplasms and the development of a widely used risk stratification model for metastatic disease introduced by the International Germ Cell Cancer Collaborative Group in 1997 and updated in 2021. Non-pulmonary visceral metastases, high levels of the serum tumor markers alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG), and primary mediastinal non-seminoma are currently identified as determinants of poor prognosis. In addition, the presence of distinct microRNA profiles between seminomas and non-seminoma GCTs has opened up important perspectives in terms of noninvasive biomarkers that can be used in diagnosis and treatment monitoring.

Evaluation of a miRNA-371a-3p Assay for Predicting Final Histopathology in Patients Undergoing Primary Nerve-sparing Retroperitoneal Lymphadenectomy for Stage IIA/B Seminoma or Nonseminoma.

Patients with marker-negative clinical stage IIA/B seminoma or nonseminoma represent a therapeutic challenge, as 20-30% might harbor nonmalignant histologies. MicroRNA 371a-3p (miR371) may represent a biomarker with diagnostic and predictive properties in testicular germ cell tumors (TGCTs). We evaluated the predictive accuracy of this biomarker in identifying the presence or absence of lymph node metastases (LNMs) in clinical stage IIA/B TGCT. In a cohort of 24 consecutive patients with marker-negative clinical stage IIA/B TGCT (n = 15 seminoma, n = 9 nonseminoma) serum miR371 was assessed 1 d before nerve-sparing retroperitoneal lymphadenectomy. Histology revealed metastatic TGCT in 22/24 patients (91.7%), with positive miR371a findings for 20 of these 22 patients with metastases (90.9%). Histology revealed no malignancy in one patient and lymphoma in another, both of whom had negative miR371a findings. One additional patient with pure teratoma and one with a microscopic seminomatous LNM had false-negative miR371a findings. The miR371 assay had sensitivity of 90.9% and specificity of 50%. The positive predictive value was 100.0% and the negative predictive value was 75.0%. According to the data available, miR371a represents a highly reliable, personalized tumor marker for predicting the presence of low-volume retroperitoneal LNMs in marker-negative TGCT. miR371 has potential for inclusion in the diagnostic armamentarium for men with equivocal lymph nodes to facilitate avoidance of unnecessary treatment and the associated toxicity. PATIENT SUMMARY: Our study demonstrates that blood tests for the biomarker miR371 are highly reliable in predicting the presence of lymph node metastases in patients with stage IIA/B testicular cancer. For patients with equivocal findings, use of this test may help in avoiding unnecessary treatment.

Molecular characterization of the CXCR4 / CXCR7 axis in germ cell tumors and its targetability using nanobody-drug-conjugates.

Being stimulated by the chemokine CXCL12, the CXCR4 / CXCR7 cascade is involved in tumor proliferation, migration, and metastasis. The interaction between CXCL12, secreted by cells from the microenvironment, and its receptors is complex and has been ascribed to promote chemotherapy resistance. However, the role of this signaling axis and its targetability in germ cell tumors (GCT) is not fully understood. Thus, this study investigated the therapeutic efficacy of a nanobody-drug-conjugate targeting CXCR4 (CXCR4-NDC) and functionally characterized this signaling pathway in GCT using small molecule inhibitors and nanobodies. As shown by diminished cell viability, enhanced apoptosis induction, and detection of mitotic catastrophes, we confirmed the cytotoxic efficacy of the CXCR4-NDC in CXCR4+-GCT cells (i.e. seminoma and yolk-sac tumor), while non-malignant CXCR4--fibroblasts, remained largely unaffected. Stimulation of CXCR4+ / CXCR7+-GCT cells with CXCL12 resulted in an enhanced proliferative and migratory capacity, while this effect could be reverted using CXCR4 inhibitors or a CXCR7-nanobody. Molecularly, the CXCR4 / CXCR7-signaling cascade could be activated independently of MAPK (ERK1 / 2)-phosphorylation. Although, in CXCR4- / CXCR7--embryonal carcinoma cells, CXCR7-expression was re-induced upon inhibition of ERK1 / 2-signaling. This study identified a nanobody-drug-conjugate targeting CXCR4 as a putative therapeutic option for GCT, i.e. seminoma and yolk-sac tumors. Furthermore, this study shed light on the functional role of the CXCR4 / CXCR7 / CXCL12-signaling cascade in GCT, demonstrating an important influence on proliferation and migration.

The effect of diagnosis delay in testis cancer on tumor size, tumor stage and tumor markers.

INTRODUCTION: In testicular cancer, the positive effect of early diagnosis on survival has been known for many years. In this study, we aimed to determine the diagnostic features of testicular cancer patients, to examine the effect of duration of diagnosis delay (DD) on tumor size, tumor stage, and serum tumor markers, and to reveal the possible benefits of early diagnosis. METHODS: A total of 71 patients who underwent inguinal orchiectomy due to suspicion of testicular cancer and whose pathology was found to be the germ cell tumor were included in the study. The relationship between the duration of diagnosis delay and tumor size, level of tumor markers, TNM stage, presence of LAP, and presence of metastasis were examined. RESULTS: Seminoma was detected in 39 (54.9%) patients and non-seminoma tumor was detected in 32 (45.1%) patients. In the correlation analysis between the markers, a significant and positive correlation was found between DD and radiological tumor size, pathological tumor size, retroperitoneal LAP detection rate, LDH and AFP levels, and N stage (respectively; r=0.345 p=0.003, r=0.324 p=0.006, r=0.244 p=0.041, r=0.286 p=0.015, r=0.244 p=0.040, r=0.238 p=0.046). It was determined that a 1-day increase in DD caused an increase of 0.431mm in the pathological size of the tumor. CONCLUSION: Duration of diagnosis delay is an issue that still keeps its importance for testicular tumors. Delay in diagnosis not only leads to an increase in tumor size but also negatively affects tumor stage and prognostic factors.

Dose comparison of robustly optimized intensity modulated proton therapy (IMPT) vs IMRT and VMAT photon plans for testicular seminoma.

BACKGROUND: Patients with stage II seminoma have traditionally been treated with photons to the retroperitoneal and iliac space, which leads to a substantial dose bath to abdominal and pelvic organs at risk (OAR). As these patients are young and with excellent prognosis, reducing dose to OAR and thereby the risk of secondary cancer is of utmost importance. We compared IMPT to opposing IMRT fields and VMAT, assessing dose to OAR and both overall and organ-specific secondary cancer risk. MATERIAL AND METHODS: A comparative treatment planning study was conducted on planning CT-scans from ten patients with stage II seminoma, treated with photons to a 'dog-leg' field with doses ranging from 20 to 25 Gy and a 10 Gy sequential boost to the metastatic lymph node(s). Photon plans were either 3-4 field IMRT (Eclipse) or 1-2 arc VMAT (Pinnacle). Proton plans used robust (5 mm; 3.5%) IMPT (Eclipse), multi field optimization with 3 posterior fields supplemented by 2 anterior fields at the level of the iliac vessels. Thirty plans were generated. Mean doses to OARs were compared for IMRT vs IMPT and VMAT vs IMPT. The risk of secondary cancer was calculated according to the model described by Schneider, using excess absolute risk (EAR, per 10,000 persons per year) for body outline, stomach, duodenum, pancreas, bowel, bladder and spinal cord. RESULTS: Mean doses to all OARs were significantly lower with IMPT except similar kidney (IMRT) and spinal cord (VMAT) doses. The relative EAR for body outline was 0.59 for IMPT/IMRT (p < .05) and 0.33 for IMPT/VMAT (p < .05). Organ specific secondary cancer risk was also lower for IMPT except for pancreas and duodenum. CONCLUSION: Proton therapy reduced radiation dose to OAR compared to both IMRT and VMAT plans, and potentially reduce the risk of secondary cancer both overall and for most OAR.

The environment and male reproductive system: the potential role and underlying mechanisms of cadmium in testis cancer.

Cadmium is a known human carcinogen, and has been shown to profoundly affect male reproductive function, at multiple levels, by exerting both endocrine and non-endocrine actions. Nevertheless, the potential role of cadmium in the etiology of testis cancer has been scantly investigated in humans, and, currently, available epidemiological observational studies are insufficient to draw definitive conclusions in this regard. On the contrary, experimental studies in laboratory animals demonstrated that cadmium is a strong inducer of testis tumors, mostly represented by benign Leydig cell adenoma; moreover, malignant transformation was also reported in few animals, following cadmium treatment. Early experimental studies in animals proposed an endocrine-dependent mechanism of cadmium-induced testis tumorigenesis; however, more recent findings from cell-free assays, in vitro studies, and short-term in vivo studies, highlighted that cadmium might also contribute to testis tumor development by early occurring endocrine-independent mechanisms, which include aberrant gene expression within the testis, and genotoxic effects, and take place well before the timing of testis tumorigenesis. These endocrine-independent mechanisms, however, have not been directly investigated on testis tumor samples retrieved from affected, cadmium-treated animals so far. The present review focuses on the relationship between cadmium exposure and testis cancer, by reporting the few epidemiological observational human studies available, and by providing animal-based experimental evidences of cadmium implication in the pathogenesis and progression of testis tumor. Moreover, the relevance of experimental animal studies to human cadmium exposure and the translational potential of experimental findings will be extensively discussed, by critically addressing strengths and weaknesses of available data.

The long non-coding RNA transcript, LOC100130460 (CAND1.11) gene, encodes a novel protein highly expressed in cancer cells and tumor human testis tissues.

BACKGROUND: Testis-specific genes encoding for long non-coding RNA (lncRNA) have been detected in several cancers; many produce proteins with restricted or aberrant expression patterns in normal or cancer tissues. OBJECTIVE: To characterize new lncRNA involved in normal and/or pathological differentiation of testicular cells. METHODS: Using bioinformatics analysis, we found that lncRNA LOC100130460 (CAND1.11) is expressed in normal and tumor testis; its expression was assessed in several human cell lines by qRT-PCR. CAND1.11 protein, produced by a single nucleotide mutation, was studied by western blot and immunofluorescence analysis on normal, classic seminoma, and Leydig cell tumor testicular tissues. RESULTS: CAND1.11 gene is primate-specific; its expression was low in SH-SY5Y cells and increased when differentiated with retinoic acid treatment. CAND1.11 expression in PC3 cells was higher than in PNT2 cells. CAND1.11 protein is present in the human testis and overexpressed in testicular cancer tissues. CONCLUSIONS: This report is one of the few providing evidence that a lncRNA produces a protein expressed in normal human tissues and overexpressed in several testicular cancers, suggesting its involvement in regulating cell proliferation and differentiation. Although further studies are needed to validate the results, our data indicate that CAND1.11 could be a potential new prognostic biomarker to use in proliferation and cancer.

Differences in future life expectancy of testicular germ-cell tumor patients vs. age-matched male population-based controls.

BACKGROUND: It is unknown whether five-year overall survival (OS) differs and to what extent between testicular germ-cell tumor (TGCT) patients and age-matched male population-based controls. MATERIALS: We identified newly diagnosed (2004-2014) TGCT patients within Surveillance Epidemiology and End Results database 2004-2019. We compared OS between non-seminoma (NS-TGCT) and seminoma (S-TGCT) patients relative to age-matched male population-based controls based on Social Security Administration Life-Tables. Smoothed cumulative incidence plots displayed cancer-specific mortality (CSM) vs. other-cause mortality (OCM). RESULTS: Of all 20,935 TGCT patients, 43% had NS-TGCT and 57% had S-TGCT. Of NS-TGCT patients, 63% were stage I vs. 16% stage II vs. 21% stage III. Of S-TGCT patients, 86% were stage I vs. 8% were stage II vs. 6% stage III. Five-year OS differences between NS-TGCT patients vs age-matched male population-based controls were 97 vs. 99% (Δ = 2%) for stage I, 96 vs. 99% (Δ = 3%) for stage II, 76 vs 98% (Δ = 22%) for stage III. Five-year OS differences between S-TGCT patients vs age-matched male population-based controls were 97 vs. 98% (Δ = 1%) for stage I, 95 vs. 97% (Δ = 2%) for stage II, 87 vs. 98% (Δ = 11%) for stage III. OCM rates ranged from 1 to 3% in NS-TGCT patients and from 2 to 4% in S-TGCT patients. CONCLUSION: The OS difference between NS-TGCT patients vs. age-matched male population-based controls was invariably higher across all stages (2-22%) than for S-TGCT patients (1-11%). Reassuringly, OCM rates were marginal in stage I and stage II patients. Conversely, higher OCM rates were recorded in stage III patients.

Conditional survival of stage III non-seminoma testis cancer patients.

PURPOSE: In many primaries other than non-seminoma testis cancer, the risk of death due to cancer decreases with increasing disease-free interval duration after initial diagnosis and treatment. This effect is known as conditional survival and is relatively unexplored in stage III non-seminoma patients, where it may matter most in clinical decision-making. We examined the effect of disease-free interval duration on overall survival in stage III non-seminoma patients. MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results Database (2004-2018), stage III non-seminoma patients were identified. Multivariable Cox regression analyses and conditional survival models were applied. RESULTS: Of 2,092 surgically treated stage III non-seminoma patients, 385 (18%) exhibited good vs. 558 (27%) intermediate vs. 1,149 (55%) poor prognosis. In multivariable Cox regression models, poor prognosis group independently predicted overall mortality (HR 3.3, P < 0.001). In conditional survival analyses based on 36 months' disease-free interval duration, 5-year overall survival estimates were as follows: good prognosis patients 96 vs. 89% at initial diagnosis without accounting for disease-free interval duration (Δ=+7); intermediate prognosis patients 94 vs. 85% at initial diagnosis without accounting for disease-free interval duration (Δ=+9); poor prognosis patients 94 vs. 65% at initial diagnosis without accounting for disease-free interval duration (Δ=+29). CONCLUSIONS: Conditional survival estimates based on 36 months' disease-free interval duration provide a more accurate and more optimistic outlook for stage III non-seminoma patients than predictions defined at initial diagnosis, without accounting for disease-free interval duration.

Male infertility and urological tumors: Pathogenesis and therapeutical implications.

Most genitourinary tract cancers have a negative impact on male fertility. Although testicular cancers have the worst impact, other tumors such as prostate, bladder, and penis are diagnosed early and treated in relatively younger patients in which couple fertility can be an important concern. The purpose of this review is to highlight both the pathogenetic mechanisms of damage to male fertility in the context of the main urological cancers and the methods of preserving male fertility in an oncological setting, in light of the most recent scientific evidence. A systematic review of available literature was carried out on the main scientific search engines, such as PubMed, Clinicaltrials.Gov, and Google scholar. Three hundred twenty-five relevant articles on this subject were identified, 98 of which were selected being the most relevant to the purpose of this review. There is a strong evidence in literature that all of the genitourinary oncological therapies have a deep negative impact on male fertility: orchiectomy, partial orchiectomy, retroperitoneal lymphadenectomy (RPLND), radical cystectomy, prostatectomy, penectomy, as well as radiotherapy, chemotherapy, and hormonal androgen suppression. Preservation of fertility is possible and includes cryopreservation, hormonal manipulation with GnRH analogs before chemotherapy, androgen replacement. Germ cell auto transplantation is an intriguing strategy with future perspectives. Careful evaluation of male fertility must be a key point before treating genitourinary tumors, taking into account patients' age and couples' perspectives. Informed consent should provide adequate information to the patient about the current state of his fertility and about the balance between risks and benefits in oncological terms. Standard approaches to genitourinary tumors should include a multidisciplinary team with urologists, oncologists, radiotherapists, psycho-sexologists, andrologists, gynecologists, and reproductive endocrinologists.