A Retrospective Analysis of 83 Patients with Testicular Mass Who Underwent Testis-Sparing Surgery: The Eurasian Uro-oncology Association Multicenter Study.

INTRODUCTION: Herein, we analyzed the histopathological, oncological and functional outcomes of testis-sparing surgery (TSS) in patients with distinct risk for testicular cancer. METHODS: This is a multicenter retrospective study on consecutive patients who underwent TSS. Patients were categorized in high- or low-risk testicular germ cell tumor (TGCT) according to the presence/absence of features compatible with testicular dysgenesis syndrome. Histology was categorized per size and risk groups. RESULTS: TSS was performed in 83 patients (86 tumors) of them, 27 in the high-risk group. Fifty-nine patients had a non-tumoral contralateral testis present. Sixty masses and 26 masses were benign and TGCTs, respectively. No statistical differences were observed in mean age (30.9 ± 10.32 years), pathological tumor size (14.67 ± 6.7 mm) between risk groups or between benign and malignant tumors (p = 0.608). When categorized per risk groups, 22 (73.3%) and 4 (7.1%) of the TSS specimens were malignant in the high- and low-risk patient groups, respectively. Univariate analysis showed that the only independent variable significantly related to malignant outcome was previous history of TGCT. During a mean follow-up of 25.5 ± 22.7 months, no patient developed systemic disease. Local recurrence was detected in 5 patients and received radical orchiectomy. Postoperative testosterone levels remained normal in 88% of those patients with normal preoperative level. No erectile dysfunction was reported in patients with benign lesions. CONCLUSION: TSS is a safe and feasible approach with adequate cancer control, and preservation of sexual function is possible in 2/3 of patients harboring malignancy. Incidence of TGCT varies extremely between patients at high and low risk for TGCT requiring a careful consideration and counseling.

A Machine Learning Algorithm for Predicting the Risk of Developing to M1b Stage of Patients With Germ Cell Testicular Cancer.

Objective: Distant metastasis other than non-regional lymph nodes and lung (i.e., M1b stage) significantly contributes to the poor survival prognosis of patients with germ cell testicular cancer (GCTC). The aim of this study was to develop a machine learning (ML) algorithm model to predict the risk of patients with GCTC developing the M1b stage, which can be used to assist in early intervention of patients. Methods: The clinical and pathological data of patients with GCTC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Combing the patient's characteristic variables, we applied six machine learning (ML) algorithms to develop the predictive models, including logistic regression(LR), eXtreme Gradient Boosting (XGBoost), light Gradient Boosting Machine (lightGBM), random forest (RF), multilayer perceptron (MLP), and k-nearest neighbor (kNN). Model performances were evaluated by 10-fold cross-receiver operating characteristic (ROC) curves, which calculated the area under the curve (AUC) of models for predictive accuracy. A total of 54 patients from our own center (October 2006 to June 2021) were collected as the external validation cohort. Results: A total of 4,323 patients eligible for inclusion were screened for enrollment from the SEER database, of which 178 (4.12%) developing M1b stage. Multivariate logistic regression showed that lymph node dissection (LND), T stage, N stage, lung metastases, and distant lymph node metastases were the independent predictors of developing M1b stage risk. The models based on both the XGBoost and RF algorithms showed stable and efficient prediction performance in the training and external validation groups. Conclusion: S-stage is not an independent factor for predicting the risk of developing the M1b stage of patients with GCTC. The ML models based on both XGBoost and RF algorithms have high predictive effectiveness and may be used to predict the risk of developing the M1b stage of patients with GCTC, which is of promising value in clinical decision-making. Models still need to be tested with a larger sample of real-world data.

Impact of differing methodologies for serum miRNA-371a-3p assessment in stage I testicular germ cell cancer recurrence.

Introduction: Current evidence shows that serum miR-371a-3p can identify disease recurrence in testicular germ cell tumour (TGCT) patients and correlates with tumour load. Despite convincing evidence showing the advantages of including miR-371a-3p testing to complement and overcome the classical serum tumour markers limitations, the successful introduction of a serum miRNA based test into clinical practice has been impeded by a lack of consensus regarding optimal methodologies and lack of a universal protocol and thresholds. Herein, we investigate two quantitative real-time PCR (qRT-PCR) based pipelines in detecting disease recurrence in stage I TGCT patients under active surveillance, and compare the sensitivity and specificity for each method. Methods: Sequential serum samples collected from 33 stage I TGCT patients undergoing active surveillance were analysed for miR-371a-3p via qRT-PCR with and without an amplification step included. Results: Using a pre-amplified protocol, all known recurrences were detected via elevated miR-371a-3p expression, while without pre-amplification, we failed to detect recurrence in 3/10 known recurrence patients. For pre-amplified analysis, sensitivity and specificity was 90% and 94.4% respectively. Without amplification, sensitivity dropped to 60%, but exhibited 100% specificity. Discussion: We conclude that incorporating pre-amplification increases sensitivity of miR-371a-3p detection, but produces more false positive results. The ideal protocol for quantification of miR-371a-3p still needs to be determined. TGCT patients undergoing active surveillance may benefit from serum miR-371a-3p quantification with earlier detection of recurrences compared to current standard methods. However, larger cross-institutional studies where samples are processed and data is analysed in a standardised manner are required prior to its routine clinical implementation.

Development and validation of prognostic nomogram for germ cell testicular cancer patients.

The purpose of our study was to establish a reliable and practical nomogram based on significant clinical factors to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with germ cell testicular cancer (GCTC). Patients diagnosed with GCTC between 2004 and 2015 were obtained from the SEER database. Nomograms were constructed using the R software to predict the OS and CSS probabilities and the constructed nomograms were validated and calibrated. A total of 22,165 GCTC patients were enrolled in the study, including the training cohort (15,515 patients) and the validation cohort (6,650 patients). In the training cohort, multivariate Cox regression showed that age, race, AJCC stage, SEER stage and surgery were independent prognostic factors for OS, while age, race, AJCC stage, TM stage, SEER stage and radiotherapy were independent prognostic factors for CSS. Based on the above Cox regression results, we constructed prognostic nomograms of OS and CSS in GCTC patients and found that the OS nomograms had higher C-index and AUC compared to TNM stage in the training and validation cohorts. In addition, in the training and external validation cohorts, the calibration curves showed a good consistency between the predicted and actual 3-, 5- and 10-year OS and CSS rates of the nomogram. The current prognostic nomogram can provide a personalized risk assessment for the survival of GCTC patients.

Is testicular microlithiasis a really innocent condition? Its effects on oncological outcomes of germ cell testicular cancer: An observational study. / ¿Son las microlitiasis testicular realmente un síntoma sin transcendencia? Sus efectos en los resultados oncológicos en el cáncer de testículo: estudio observacional.

OBJECTIVES: Although it is a well known condition that presence of testicular microlithiasis (TM) with the co-occurrence of specific risk factors such as historyof previous germ cell testicular cancer (GCTC), infertility, undescended testes or atrophic testes have high risks for GCTC development, TM is still a controversial topic. Its effects on oncological outcomes have still not been investigated in detail. In this study, we aimed to evaluate whether the presence of TM has an effect on GCTC prognosis and oncological outcomes. METHODS: Seventy five patients among 93 patients who underwent radical orchidectomy between January 2010 and February 2016 were selected and divided into two groups. Group I consisted of 51 patients without TM. Group II consisted of 24 patients with TM. Each groups were compared in terms of demographic datas, prognostic risk factors, complete blood count parameters and oncological outcomes. RESULTS: During the median follow-up of 58 (1-106) months, a significantly higher local recurrence rate (54.2% vs. 3.9%, p<0.001) distant metastasis rate (58.3% vs. 5.9%, p<0.001) and lower cancer-specific survival rate (45.8% vs. 94.1%, p<0.001) were observed in patients with TM. In this group, the duration of recurrence-free survival (47.65±9.45 vs.101.96±2.80 months, p<0.001), metstais-free survival (49.50±8.88 vs. 100.00±3.36 months, p<0.001) and cancer-specific survival (54.37±8.76  vs. 100.19±3.25 months, p<0.001) were also statisticaly lower. In multivariate analysis, ß-hCG, LDH, neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio and the presence of undescended testis were found as independent predictive factors for local recurrence, distant metastasis and cancer-specific survival. Red blood cell distribution width and the presence of testicular microlithiasis were found to be independent predictive factors for local recurrence. CONCLUSION: According to our results, bilateral TM was associated with higher rates of local recurrence, distant metastasis and cancer spesific mortality in presenceof risk factors, regardless of classic or limited microlithiasis.

OBJETIVO: Aunque es bien conocida la presencia de microlitiasis testiculares con el desarrollo de cáncer testicular, la infertilidad, teste no descendido o atrofia testicular, aun es un tema controvertido. Los efectos en los resultados oncológicos no han sido estudiados en detalle. En este estudio, nuestro objetivo ha sido evaluar la presencia de microlitiasis en los resultados oncológicos del cáncer de testículo.MÉTODOS: Un total de 75 pacientes fueron incluidosen el análisis de un total de 93 pacientes que recibieron una orquiectomía radical entre enero 2010 y febrero 2016. Los pacientes se dividieron en 2 grupos: I- consta de 51 pacientes sin microlitiasis, II consta de 24 pacientes con microlitiasis. Ambos grupos fueron comparados en términos de variables demográficas, factores de riesgo, analítica sanguínea y resultados oncológicos. RESULTADOS: La mediana de seguimiento fue de 59 meses (1-106). Se observó un incremento significativo de la recurrencia local (54,2% vs. 3,9%, p<0,001), metástasis a distancia (58,3% vs. 5,9%, p<0,001) y bajada de la supervivencia cáncer especifica (45,8% vs. 94,1%, p<0,001) en pacientes con microlitiasis. En este grupo, la duración de la superviviencia libre de recurrencia (47,65±9,45 vs.101,96±2,80 meses,p<0,001), supervivencia libre de metástasis (49,50±8,88 vs. 100,00±3,36 meses, p<0,001) y supervivencia cáncer especifica (54,37±8,76 vs.100,19±3,25 meses, p <0,001) fueron también menores. Al estudio multivariado, ß-hCG, LDH, neutrophil/lymphocyte ratio, monocyte/lymphocyte y la presencia de testes no descendido fueron factores independientes predictores de recurrencia local, metástasis a distancia y supervivencia cáncer-especifica. La distribución de los hematíes y la presencia de microlitiasis fueron factores independientes de recurrencia local. CONCLUSIONES: Las microlitiasis bilaterales se asocian a mayor tasa de recurrencia local, metástasis a distancia y supervivencia cáncer especifica, independientemente de su tamaño.

Cisplatin-Based Therapy and CINV: Optimal Antiemetics During Germ Cell Testicular Cancer Treatment

BACKGROUND: Cisplatin-based chemotherapy regimens are the backbone of chemotherapy for germ cell testicular cancer. Cisplatin is administered for five days, causing an overlap of acute and delayed chemotherapy-induced nausea and vomiting (CINV). Although CINV is widely researched, studies involving multiday chemotherapy regimens are limited. OBJECTIVES: This article synthesizes the research in antiemetics used in multiday cisplatin-based chemotherapy regimens and provides recommendations to optimize antiemetic therapy. METHODS: A literature review was conducted for articles examining antiemetics in multiday cisplatin-based chemotherapy regimens. Results were synthesized, and findings were applied to existing antiemetic strategies. FINDINGS: Although an optimal regimen has not been identified, patients receiving multiday cisplatin chemotherapy should have an antiemetic administered on each day of chemotherapy and two to three days after chemotherapy. Antiemetics should include an NK1 antagonist, 5-HT3 receptor antagonist, and dexamethasone.

A New Model to Predict Benign Histology in Residual Retroperitoneal Masses After Chemotherapy in Nonseminoma.

BACKGROUND: Postchemotherapy retroperitoneal lymph node dissection (pcRPLND) is indicated in testicular cancer patients with normalised or plateaued serum tumour markers and residual retroperitoneal lesions >1cm. Challenges remain in predicting postchemotherapy residual mass (pcRM) histology, which may lead to unnecessary surgery. OBJECTIVE: To develop an accurate model to predict pcRM histology in patients with nonseminomatous germ cell tumours (NSGCTs). DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of 335 patients undergoing pcRPLND for metastatic NSGCTs to develop a model to predict benign histology in retroperitoneal pcRM. Our model was compared with others and externally validated. INTERVENTION: Chemotherapy and pcRPLND. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable logistic regression to evaluate the presence of benign histology, and fractional polynomials to allow for a nonlinear association between continuous variables and the outcome. The final Princess Margaret model (PMM) was selected based on the number of variables used, reliability, and discriminative capacity to predict benign pcRM. RESULTS AND LIMITATIONS: PMM included the presence of teratoma in the orchiectomy, prechemotherapy α-fetoprotein, prechemotherapy mass size, and change in mass size during chemotherapy. Model specificity was 99.3%. Compared with Vergouwe et al's model, PMM had significantly better accuracy (C statistic 0.843 vs 0.783). PMM appropriately identified a larger number of patients for whom pcRPLND can safely be avoided (13.9% vs 0%). Validated in external cohorts, the model retained high discrimination (C statistic 0.88 and 0.80). Larger and prospective studies are needed to further validate this model. CONCLUSIONS: Our clinical model, externally validated, showed improved discriminative ability in predicting pcRM histology when compared with other models. The higher accuracy and reduced number of variables make this a novel and appealing model to use for patient counselling and treatment strategies. PATIENT SUMMARY: Princess Margaret model accurately predicted postchemotherapy benign histology. These results might have clinical impact by avoiding unnecessary retroperitoneal lymph node dissection and consequently changing the paradigm of advanced testicular cancer treatment.