Advanced Germ Cell Tumors Research Articles

Characteristics and outcomes among patients with delayed orchidectomy for advanced germ cell tumours.

Characteristics and outcomes among patients with delayed orchidectomy for advanced germ cell tumours.

Longitudinal circulating tumor DNA monitoring for detection of molecular residual disease in patients with advanced germ cell tumors.

e17022 Background: Germ cell malignancies, commonly manifesting as testicular cancer, is one of the most common malignancies in men 15 to 45 years of age, with the incidence doubling over the past 40 years. When identified promptly and treated with a multidisciplinary approach, germ cell tumors have an excellent prognosis with cure rate >90% and 5-year survival rate >95%. Treatment involves radical orchiectomy for diagnostic and therapeutic purposes. Further management includes active surveillance, adjuvant chemotherapy, retroperitoneal lymph node dissection (RLND), and radiation therapy. While AFP, B-HCG, and LDH are good biomarkers, they are not sensitive or specific for detecting molecular residual disease (MRD). B-HCG is detected in <30% of individuals with seminoma and B-HCG and AFP are detected in 50–60% of patients with non-seminomatous tumors. We describe the use of circulating tumor DNA (ctDNA) for detection of MRD in advanced germ cell malignancy, especially when baseline biomarkers are negative. Methods: This is a retrospective analysis of 20 patients with testicular cancer treated at Rush University Medical Center who monitored closely for MRD. Signatera (Natera Inc.), a personalized tumor-informed ctDNA assay, was utilized for detection and quantification of ctDNA in patients’ plasma samples, measured at MRD (1-12 weeks post-orchiectomy) and regular intervals thereafter, regardless of treatment modality. Event free survival (EFS) was determined, defined as the period from radical orchiectomy to date of radiographic progression of disease. Results: There was a total of 20 patients (35% seminoma, 65% non-seminoma) with 2 of the patients having extragonadal disease. The mean age was 32.2 years old with IQR (28-36). Post operatively, 20% underwent RLND, 10% were on surveillance, 53% received post-orchiectomy chemotherapy, 6.7% of patients underwent autologous stem cell transplant. The median follow up time is 1.14 years. Two patients had positive ctDNA despite negative baseline traditional biomarkers. There were 23.3% (7/30) of patients that had evidence of radiographic progression. Of the patients with progression, serial ctDNA monitoring had high rates of concordance (85%, 6/7) of ctDNA positivity with biomarker positivity and radiographic progression. Conclusions: Overall, ctDNA correlated with, and sometimes even preceded, traditional biomarkers and radiographic findings of disease progression. The ctDNA positivity of 2 patients in this cohort despite negative baseline AFP, B-HCG, and LDH, highlights the sensitivity and specificity of ctDNA for MRD compared to more traditional biomarkers. Serial monitoring of ctDNA offers valuable insights into germ cell tumor disease status, including presence of MRD, and there is a need for prospective studies to guide treatment escalation and de-escalation in germ cell tumors.

Survival outcomes of postchemotherapy retroperitoneal lymph node dissection for nonseminomatous germ cell tumors: A retrospective cohort study from a single tertiary center in South India.

Chemotherapy, postchemotherapy retroperitoneal lymph node dissection (pcRPLND), and metastasectomy remain the standard of care for the management of advanced nonseminomatous germ cell tumor (NSGCT). We retrospectively studied 73 patients who had pcRPLND at a single tertiary-care center (2003-2022). Surgical and clinicopathological features and oncological outcomes are presented. The mean age was 28.27 years (15-48). Three-fourths had Stage III disease at diagnosis. International Germ Cell Cancer Collaborative Group risk stratification was 54.54% and 21.21% in intermediate risk, and poor risk, respectively. Sixty-two patients had Standard, 7 had Salvage and 4 underwent Desperation pcRPLND. Eleven patients (15.06%) required adjunctive procedures. Thirteen patients (17.8%) had ≥ class 3 Clavien-Dindo complications and postoperative mortality occurred in 5 (6.8%) patients. The histopathologies (HPE) of the pcRPLNDs were necrosis, teratoma, and viable tumor in 39.7%, 45.2%, and 15.1%, respectively. Seven patients underwent metastasectomy. An 85% size reduction in the size of RPLN predicted necrosis. There was 71.4% concordance between pcRPLND and metastasectomy HPEs. The median follow-up was 26.72 months (inter-quartile range - 13.25-47.84). The 2-year recurrence-free survival (RFS) rate was 93% (95% confidence interval [CI]-83%-97%) and the overall survival (OS) rate was 90% (95% CI-80%-95%). This is the largest series of pcRPLND for NSGCT in India to our knowledge. Although most of the cohort belonged to stage III, an RFS and OS rate of >90% at 2 years was achieved. We believe that successful management of postchemotherapy residual masses in NSGCT is contingent on the availability of multidisciplinary expertise and is therefore best done at tertiary-care referral centers.

Thrombosis Rates and Genetic Thrombophilia Risk Among Patients With Advanced Germ Cell Tumors Treated With Chemotherapy

IntroductionMen with advanced germ cell tumors (GCT) treated with chemotherapy are at high risk of venous thromboembolism (VTE). Predictors of VTE may identify patients who would benefit from prophylactic anticoagulation. Patients and MethodsMen with advanced GCT (Stage IS, II, III) treated with chemotherapy were identified at 2 centers. High genomic risk was defined from a 5 single nucleotide polymorphism (SNP) germline panel. Logistic regression was used to evaluate the impact of genomic risk on VTE within 6 months of chemotherapy initiation. Orthogonal Projection to Latent Structures Discriminant Analysis (OPLS-DA) was used to build models to predict VTE based on clinical variables and an 86 SNP panel. ResultsThis 123-patient cohort experienced a VTE rate of 26% with an incidence of high genomic risk of 21%. Men with high genomic risk did not have a significantly higher VTE rate (31%, 8/26) than men with low genomic risk (25%, 24/97), unadjusted OR 1.4 (95% CI 0.5-3.5, P = .54). Incorporation of clinical variables (Khorana score, N3 status and elevated LDH) resulted in adjusted OR 2.1 (95% CI 0.7-6.5, P = .18). A combined model using clinical variables and 86 SNPs performed similarly (AUC 0.77) compared to clinical variables alone (AUC 0.72). ConclusionsA previously established 5-SNP panel was not associated with VTE among patients with GCT receiving chemotherapy. However, multivariable models based on clinical variables alone warrant further validation to inform prophylactic anticoagulation strategies.

High Dose Chemotherapy With Autologous Stem Cell Transplant for Patients With Advanced Germ Cell Tumors: Real-World Evidence From a Tertiary Cancer Center in Brazil

BackgroundHigh-dose chemotherapy followed by stem cell transplant (HDCT) is potentially curative for patients with refractory germ cell tumors (rGCT). There is scarce real-world data supporting its implementation in low- and middle-income countries. We described the experience of our tertiary cancer center in Sao Paulo, Brazil. MethodsWe identified male patients ≥18 years-old with rGCT referred to HDCT after board discussion. Clinical data, including delays in HDCT protocol, were extracted from medical records, and survival outcomes were estimated using the Kaplan-Meier method. The log-rank test and Cox proportional hazard were used to determine effects on overall survival (OS). ResultsFrom January 2013 to January 2023, 34 patients were referred and considered eligible to receive 2 cycles of HDCT. Most patients had primary testicular tumors (82%), nonseminomatous histology (88%), and poor International Germ Cell Collaborative Group (IGCCCG) (79%). Twenty-three patients received HDCT (1 cycle, n = 8; 2 cycles, n = 15). Main reasons for not receiving any HDCT were death due to progressive disease (n = 1), performance deterioration (n = 7), and failure of stem cell mobilization (n = 3). OS at 2 years was 36.7% for the eligible population, 56.1% for patients who underwent at least 1 HDCT, and 77.1% for those who had ≥2 cycles. The 2-year OS rate for patients not given HDCT was 0%. All patients had delays in protocol, and poor-risk patients had longer intervals from referral to protocol initiation (0.7 vs. 1.8 month, P < .01). ConclusionOutcomes of patients who received ≥1 HDCT were encouraging; however, only 15 from 34 eligible patients were able to receive the planned 2 cycles of HDCT. Further strategies to minimize treatment delays in low- and middle-income countries are needed.

P188 - Influence of prognostic group classification of advanced male germ cell tumor on treatment outcomes

P188 - Influence of prognostic group classification of advanced male germ cell tumor on treatment outcomes

Predictors of the development of febrile neutropenia in chemotherapy for advanced germ cell tumors.

To identify the predictive factors for the development of febrile neutropenia (FN) in the course of chemotherapy for patients with germ cell tumors. From January 2005 to December 2018, 80 patients were treated with induction chemotherapy for advanced germ cell tumors at Kanagawa Cancer Center Hospital, Japan. Of these, we retrospectively analyzed 267 cycles of chemotherapy. The incidence of FN was used as the objective variable. As predictive factors, we analyzed age, international germ cell consensus classification (IGCCC), laboratory data at the start of chemotherapy in each cycle, length of the largest metastatic lesion, number of cycles, and prophylactic use of granulocyte colony stimulating factor (G-CSF). We finally analyzed 267 cycles in 78 patients. The median age was 36 years (15-64). There was a total of 267 cycles. FN occurred in 40 cycles (15%) in 31 patients (40%). The first cycle was accompanied by a significantly higher FN than the subsequent cycles (p < 0.001). The univariate analysis identified age ≧36 years (p = 0.001), creatinine clearance (CCr) <70 (p < 0.001), serum albumin <3.3 (p = 0.002), maximum tumor diameter ≧60 mm (p = 0.036), and first cycle as significant risk factors. The multivariate analysis identified age, CCr, and first cycle as independent predictive factors of FN development. We identified older age, renal dysfunction, and first cycle of chemotherapy as predictive factors for FN. No statistically significant difference was shown in the usage of prophylactic G-CSF. Special attention should be given to FN in patients with high-risk factors.

UP56 - Influence of prognostic group classification of advanced male germ cell tumor on treatment outcomes

UP56 - Influence of prognostic group classification of advanced male germ cell tumor on treatment outcomes

The genomic and transcriptomic landscapes of chemotherapy naïve vs post-chemotherapy germ cell tumors.

5007 Background: Cisplatin resistance occurs in up to 30% of patients with advanced germ cell tumors (GCTs). Despite effective salvage treatment regimen, there is a 50% risk of cancer-specific death. Previously, we identified molecular features, including TP53 mutations and MDM2 amplification, associated with cisplatin resistance (Bagrodia, 2016). Herein, we evaluate the genomic and transcriptomic landscapes of chemotherapy naïve vs post-chemotherapy GCT’s to uncover genetic factors that might drive cisplatin resistance. Methods: GCTs (N = 138) were tested at Caris Life Sciences (Phoenix, AZ) with next-generation sequencing of DNA (592-gene or whole exome) and RNA (whole transcriptome). Prevalence was calculated for pathogenic SNVs/indels and copy number amplifications (CNA≥6 copies). Primary (N = 65) and metastatic (N = 73) sites were defined based on the biopsy site. A specialized genitourinary pathologist blindly reviewed selected H&amp;E-stained slides and designated tumors as chemotherapy naïve (N = 66) or post-chemotherapy (N = 17) based on treatment related changes. Differentially regulated pathways were assessed by gene set enrichment analysis (GSEA). Transcriptomic signatures predictive of response to immunotherapy (T cell-inflamed) and platinum sensitivity (PSS, high score suggests increased platinum sensitivity) were applied. Mann-Whitney U and χ² tests were applied, with P-values adjusted for multiple comparisons. Results: Primary and metastatic GCT had slight differences between putative drivers of platinum therapy resistance: KIT (15% vs 1), TP53 (10% vs 17), KRAS (13% vs 9) mutations and MDM2 CNA (4% vs 3), all p &gt; 0.05. When comparing post-chemo vs chemo naïve GCTs, no significant differences in the genomic landscape were observed (p &gt; 0.05). Chemo naïve tumors were shown to be enriched for gene sets associated with KRAS signaling and epithelial-to-mesenchymal transition. Additionally, they trended towards a higher proportion of T cell-inflamed tumors as compared to post-chemo samples (32% vs 18, p = 0.36). The average PSS for chemo naïve was slightly higher than post-chemo (CN: 0.07 Arbitrary Units (AU), N = 62 vs PC: -1.82, N =16, p = .52). Chemo naïve tumors with TP53, KRAS, or KIT mutation or MDM2 CNA had a lower PSS (-4.16 AU, N= 18) than tumors with none of those alterations (2.17, N = 38), p = 0.05. Finally, chemo naïve tumors with MDM2 CNA (N=2, -16.26 AU) had the lowest PSS followed by tumors with mutations in TP53 (N=6, -2.04), KIT (N = 2, -1.77) and KRAS (N=9, -1.05) (mutations were mutually exclusive except for a concurrent KRAS and TP53 mutation). Conclusions: This study provides evidence that chemo naïve GCTs with mutations in TP53, KRAS, KIT or MDM2 CNA have higher expression of genes associated with resistance to platinum-based chemotherapy. These findings contribute to a better understanding of the molecular characteristics of GCTs and may inform prognosis and treatment.

Germline thrombophilia gene alterations and thrombosis rates among patients with advanced germ cell tumors treated with chemotherapy.

e17023 Background: Men with advanced germ cell tumors (GCT) treated with cisplatin-based chemotherapy are at high risk of venous thromboembolism (VTE). Validated predictors of VTE would allow development of targeted prophylactic anticoagulation strategies in this population. We hypothesized that a high genomic risk score from a previously identified panel of germline single nucleotide polymorphisms (SNPs) in thrombophilia genes would be associated with an increased risk of VTE within 6 months of chemotherapy initiation for GCT. Methods: Men with stage IIA or higher GCT who received 3-4 cycles of cisplatin-based chemotherapy were identified at two centers with available tissue for germline sequencing. High genomic risk was defined as having 4 or more risk alleles from an established 5 SNP germline panel composed of ABO (rs8176719), F5 (rs6025), F2 (rs1799963), FGG (rs2066865), and F11 (rs2036914). Univariable and multivariable logistic regression were used to evaluate the impact of genomic risk on VTE incidence within six months of chemotherapy initiation. Results: 123 patients were identified with 72% having non-seminoma histology and 28% categorized as IGCCCG intermediate or poor risk. The VTE rate was 26% (32/123), and the incidence of high genomic risk was 21% (26/123). Men with high genomic risk did not have a significantly higher VTE rate (31%, 8/26) than men with low genomic risk (25%, 24/97), unadjusted OR 1.4 (95% CI 0.5 – 3.5, p = 0.54). A multivariable model identified Khorana score, N3 status and elevated LDH as predictors for VTE (Table). The association between high genomic risk and VTE strengthened when adjusting for clinical variables, but remained non-significant, adjusted OR 2.1 (95% CI 0.7 – 6.5, p = 0.18). The optimal threshold to define high genomic risk in this cohort was 3 or more risk alleles, adjusted OR 2.5 (95% CI 0.9 – 6.8, p = 0.08). ABO (non-O blood type) was the only individual SNP significantly associated with VTE (p &lt; 0.01). Conclusions: In this multi-institutional cohort, a previously established germline thrombophilia panel was not clearly associated with increased VTE risk among patients with GCT receiving chemotherapy. Khorana score, elevated LDH, clinical nodal stage, and non-O blood type were the strongest predictors of VTE. Exploratory analysis of the association between VTE risk and 76 additional SNPs is ongoing. Prospective studies of prophylactic anticoagulation are warranted in high-risk patients with advanced GCT undergoing chemotherapy.[Table: see text]

High-dose chemotherapy with autologous stem cell transplant (HDCT) for patients (pts) with advanced germ-cell tumors (aGCT): Real-world evidence from a tertiary cancer center in Brazil.

414 Background: HDCT is a potentially curative treatment for pts with aGCT after conventional-dose chemotherapy (CDC). There is scarce evidence of outcomes from aGCT pts treated with HDCT in low and middle-income countries. Methods: We reviewed our institutional database to identify pts with progressive aGCT referred for HDCT following tumor boards. Medical charts were analyzed to extract clinical data. Log-rank was used to compare survival estimates and Cox proportional hazard to determine effects on overall survival (OS). Exploratory correlation and survival trend analysis used synthetic minority oversampling and Spearman’s rho estimated correlations. Results: From 1/2013 to 8/2022, 35 aGCT pts were referred for HDCT. Median age was 28 years (IQR 25-30). Most pts had testicular primary (84%), non-seminoma histology (87%), 1 prior treatment line (62%), poor-risk by IGCCCG (78%), and intermediate to very high-risk by IPFSG (45%). Of these, 32 pts were deemed eligible after initial evaluation, 25 had mobilization chemotherapy, and 21 received ≥1 cycle of HDCT. Reasons for treatment non-fulfillment included progressive disease and/or performance deterioration due to toxicity. HDCT regimen varied, with most pts receiving TI-CE (62%). Most pts had delays ≥1 month (85%) and ≥2 months (52%) in the scheduled treatment. The 1-year and 2-year OS rates were 42% and 38% in the eligible population, while 70% and 62% among those who had ≥ 1 cycle HDCT. No risk factors correlated with OS in the univariate analysis (Table). Exploratory analysis of oversampled pts treated with ≥1 cycle of HDCT showed correlation of poor IGCCCG (p&lt;0.01) and IPFSG (p=0.03) with OS. Time to mobilization (TTM) was larger in poor-risk IGCCCG pts (0.4 vs. 1.7 months, p&lt;0.01). Four deaths were attributed to HDCT. Conclusions: HDCT was feasible at our tertiary center in Brazil, despite some treatment-related deaths. For pts who had at least 1 HDCT cycle, survival outcomes were similar to the established literature. Significant delays in protocol were noted and correlated with prognostic group risk. [Table: see text]

Successful surgical management of massive hemoretroperitoneum caused by spontaneous rupture of retroperitoneal lymph node metastases in a patient with advanced mixed germ cell tumor: a COVID-19 pandemic-related surgical challenge

BackgroundSpontaneous rapture of a germ cell tumor (GCT) metastases causing massive hemoretroperitoneum in a patient without choriocarcinoma component who has not received previous systemic chemotherapy is an exceedingly rare event. In such a devastating case scenario, a high index of clinical suspicion for early diagnosis and appropriate management is crucial.Case presentationWe report on a 25-year-old male patient with a 4-month history of orchiectomy for testicular GCT (tGCT), who presented in the emergency department with acute abdomen and hemodynamic instability. Urgent computed tomography scan depicted a retroperitoneal mass measuring approximately 13 × 11.4 × 15 cm and massive intraperitoneal hemorrhage. Hemoperitoneum caused by spontaneous rapture of the metastatic retroperitoneal mass was suspected. COVID-19 pandemic-related deviation from the oncologic surveillance standards combined with COVID-19-related patient’s emotional distress and self-neglect had led to loss of opportunity for appropriate adjuvant chemotherapy, obviously leading to the development of this devastating complication. An emergency, surgical exploration was decided. The bleeding mass was adequately exposed following a Cattell–Braasch maneuver and active bleeding was controlled by a challenging resection of approximately 80% of the lymph node mass volume. Pathological evaluation of the specimen revealed teratoma with low volume of yolk sac tumor component and extensive necrosis, findings compatible with the patient’s history. Postoperative recovery was uneventful, followed by early start of adjuvant chemotherapy. Two years after the operation the patient is doing well with no evidence of recurrent disease.ConclusionsMassive hemoperitoneum is a devastating event that exceedingly rarely can complicate the clinical course of patients with advanced tGCT. Emergency surgical intervention is usually necessary however, sound judgement and careful surgical techniques are required for a positive and uneventful outcome. During COVID-19 pandemic, first-line medical personnel push their limits further not only to ensure health care services standards but also, to manage unpredictable, life-threatening cancer-related complications, associated with COVID-19-related deviation from appropriate oncologic surveillance and care.

Study of neoadjuvant chemotherapy in advanced malignant ovarian germ cell tumors at a tertiary center in western India.

To study clinical characters and outcomes in patients of malignant ovarian germ cell tumor (MOGCT) undergoing surgery following neoadjuvant chemotherapy (NACT). Retrospective study of patients undergoing surgery following NACT for MOGCT at our institute. Platinum based chemotherapy was given in all patients in NACT. Between March 2013 and February 2023, 30 patients had surgery after NACT. Patient's median age was 22 years (range, 12 to 35 years) and median follow up 42months (range, 6 to 132 months). Majority had endodermal sinus tumor (n=12), dysgerminoma (n=9) and mixed GCT (n=7). All had either International Federation of Gynecology and Obstetrics (FIGO) stage 3 (n=19) or FIGO stage 4 disease (n=11). Complete response to NACT seen in 5 patients and 23 patients had partial response. Fertility sparing surgery in 18 patients and complete surgery in 12 patients. Suboptimal surgery was seen in 4 patients. Currently, 20 of 30 patients are alive and disease free, 3 lost for follow up and 7 patients had progression after adjuvant therapy. Five patients had mortality-4 with progression and 1 with bleomycin toxicity. Fifteen of 17 eligible patients have resumed menstruation and one had successful pregnancy. Prognostic factors noted in study are stage, optimal surgery and viable tumor in histopathology. Dysgerminoma had better outcome than other histology. NACT may be a reasonable option in patients with extensive unresectable disease or in whom fertility sparing is not possible or in the poor general condition. Fertility sparing surgery can be attempted post neoadjuvant chemotherapy without adversely affecting prognosis.

First cytogenomic characterization of murine testis tumor cell line MLTC-1

The cell line MLTC-1 was established in 1982 as a transplantable Leydig cell tumor from a C57BL/6 mouse. The cell line has already been applied in &amp;gt;100 studies: still, the only information about its genetic content is given in the first description: MLTC-1 initially had a polyploid karyotype. Here, a molecular karyotyping and multicolor banding-based molecular cytogenetic study was done to provide the first chromosomal/ (molecular) cytogenetic characterization of MLTC-1. A hexaploid karyotype with 72 to 105 chromosomes was hereby characterized. Besides polyploidy, unbalanced two- and three-way translocations, dicentrics and one neocentric derivative were identified. Also, no Y-chromosome could be detected in this clearly male derived cell line. Overall, a completely unbalanced genome is present in MLTC-1 with ~20 regions being subject to copy number losses or gains. After translating these imbalances into the human genome in a standardized way, a 40% match of imbalances with human Leydig cell tumors was evident; however, about the same rate of concordance was detectable for human spermatocytic seminomas and non-seminomas as well as testicular germ cell tumor. Accordingly, MLTC-1 is better suited as an advanced testicular germ cell tumor model in general, rather than specifically for human Leydig cell tumors.

Multimodal treatment of testicular cancer: chemotherapy, surgery or radiotherapy?

Metastatic testicular germ cell tumors patients require histology- and stage-appropriate therapy to achieve optimal therapeutic outcomes. This work focuses on the interdisciplinary presentation of current recommendations for the treatment of metastatic germ cell tumor patients. The interdisciplinary recommendations were formulated based on the German S3guideline and supplemented by recent literature. Using astage-specific and guideline-based treatment approach, interdisciplinary cooperation between urology, oncology, and radiotherapy is mandatory to successfully achieve ahigh rate of cure and, in the case of complex advanced tumors, also the most effective therapy possible. The question of optimal treatment approaches for seminoma in cSIIA/B remains particularly challenging. Since treatment of advanced or multiple relapsed germ cell tumor patients remains complex, patients should be referred for an online second opinion ( https://urologie.ekonsil.org ).

Need for organ preservation in postchemotherapy retroperitoneal lymph node dissection (PC-RPLND).

5031 Background: The aim ofPC-RPLND for advanced nonseminomatous germ cell tumors is to resect all remaining metastatic tissue. So far, the resection of adjacent visceral or vascular organs is also commonly performed to achieve complete resection of the residual mass. To determine the possibility of more organ preservation, we aimed to analyze the pathohistology of patients with adjunctive surgery as the frequency of metastatic involvement in those organs with teratoma or vital cancer is currently unknown. Methods: We reviewed a cohort of 1204 patients who underwent PC-RPLND between 2008 and 2021 as a 2-center study and identified 242 (20.1%) cases of adjunctive surgery during PC-RPLND. We analysed the pathohistological presence of germ cell tumor elements in the resected organs: viable tumor (V), teratoma (T) or necrosis / fibrosis (N). Surgery associated complications were reported according to the Clavien-Dindo classification. Outcomes of subgroups were compared by using log-rank test. Results: V, T and N were present in 54 (22%), 94 (39%) and 94 (39%) of all patients with adjunct resected organs. In 242 patients, 325 adjunct organs were resected with 66 (27.3%) of these patients receiving a resection of multiple organs. The kidney was the most often resected organ (n = 77; V: 29% T: 39% N: 32%), followed by V. Cava (n = 67; V: 25% T: 36%, N: 39%) and partial liver resections (n = 50; V: 16%, T: 30%, N: 54%). Postoperative complications occurred in 30% of which 22% were Clavien grade III-V, showing no significant differences between V, T and N; p = 0.093. 27% of all patients suffered from a relapse during a median follow-up of 22 months [0-180]. Patients with T or V in the resected specimens had a significantly reduced 5-year RFS compared to patients with only N (39%, 81%, p &lt; 0.001). Conclusions: This study shows tremendous need for more organ preservation as 40% of all resections of adjunct organs are oncologically unnecessary due to the presence of N only in the pathological specimens. Therefore, in case of doubt, we should increase intraoperative frozen section to avoid oncologically unnecessary adjunctive surgeries, especially nephrectomies and vascular resections. Additionally, serological or image-based means for a more accurate presurgical workup are required to spare patients with N from PC-RPLND in general.

Structure of residual metastases in patients with advanced testicular non-seminomatous germ cell tumors and incomplete serological and radiological response to chemotherapy

Objective: to analyze histological structure and identify predictors of detecting malignant non-seminoma in residual tumor masses obtained from patients with testicular non-seminomatous germ cell tumors (TNSGCTs) who had not achieved complete serological and radiological response to chemotherapy (CT).Materials and methods. This study included 96 out of 703 patients with TNSGCTs (13.7 %) operated on in N.N. Blokhin National Medical Research Center of Oncology. The inclusion criteria were as follows: verified advanced TNSGCT, elevated levels of alpha-fetoprotein and/or chorionic gonadotropin at the moment of CT initiation, at least 3 completed courses of first-line or second-line platinum-based CT, residual tumor foci after CT visualized with radiological methods, alpha-fetoprotein &gt;7.29 IU/mL or chorionic gonadotropin &gt;5 mIU/mL 3 weeks after the initiation of the last CT course, and surgery after CT. Histological examination of the primary tumors demonstrated that they contained elements of seminoma (n = 14; 14.6 %), teratoma (n = 29; 30.2 %), choriocarcinoma in (n = 23; 23.9 %), embryonal carcinoma (n = 45; 46.9 %), and yolk sac (n = 18; 18.8 %). All study participants received first-line CT; 58 of them (60.4 %) also received second-line CT. All patients underwent surgery after CT, including retroperitoneal lymph node dissection (RPLND) (n = 96; 100 %) and excision of extra-retroperitoneal lesions (n = 8; 8.3 %).Results. Histological examination of excised retroperitoneal masses showed that they contained areas of necrosis and fibrosis (n = 25; 26.0 %), teratoma (n = 29; 30.2 %), and viable malignant non-seminoma (n = 42; 43.8 %). There was a strong positive correlation between the existence of residual malignant non-seminomatous components in retroperitoneal masses and presence of choriocarcinoma (r = 0.300; р = 0.004), as well as the absence of embryonal carcinoma in the primary tumor (r = –0.300; р = 0.004), invasion of retroperitoneal metastases into major vessels and/or adjacent organs (r = 0.243; р = 0.017), and second-line CT prior to RPLND (r = 0.413; р &lt;0.0001). Patients having ≥3 risk factors were significantly more likely to have residual malignant non-seminoma in retroperitoneal masses than patients who had 0–2 risk factors (73.5 % vs 27.3 %; р &lt;0.0001). Excised residual extra-retroperitoneal masses contained areas of necrosis and fibrosis (n = 3; 37.5 %), teratoma (n = 1; 12.5 %), and malignant non-seminoma (n = 4; 62.5 %). Concordant structure of retroperitoneal and extra-retroperitoneal lesions was observed in 4 patients (50.0 %).Conclusion. Malignant non-seminomas were detected in 43.8 % of retroperitoneal and 62.5 % of extra-retroperitoneal residual tumorsremoved after CT in patients with advanced TNSGCTs and incomplete serological and radiological response. Discordant structure of metastases at different locations was observed in 50 % of patients. Our finding can be used to select candidates for surgical excision of residual tumors among these patients.

Standard versus high-dose chemotherapy in mediastinal germ cell tumors: a narrative review.

The aim of this review is to analyze feasibility and toxicities of high-dose chemotherapy (HDCT) in comparison to standard dose chemotherapy (SDCT) in patients affected by mediastinal germ cell tumors (MGCTs), discussing factors that may affect therapeutic choices, such as: management of residual disease, early response predictors for chemotherapeutic efficacy and determinants of chemotherapeutic resistance. In this review, we discuss the main clinical experiences with HDCT and SDCT in germ cell tumor (GCT) patients specifically in those affected by MGCT. MGCTs represent a very small subset characterized by a poor prognosis, despite improvements in their clinical management and in understanding their biology. From early 1970s, HDCT has become an alternative to SDCT for both first-line and salvage therapeutic settings in advanced GCT patients. Several HDCT schedules-either cisplatin or carboplatin-based-have been tested so far, both in clinical randomized trial and in single-center experiences, with divergent results in terms of clinical outcomes and tolerability. Moreover, the majority of these studies included, but were not exclusively designed for, advanced MGCT patients, making difficult to infer data for this specific subset. an extended review of literature through PubMed was conducted using the keywords "mediastinal germinal cell tumors", "standard dose chemotherapy" and "high dose chemotherapy". HDCT regimens could not be considered to date a standard option as first-line therapy in advanced MGCT patients, whilst they could be an alternative to SDCT regimens in relapsed tumors after proper patient selection.

Peritoneal carcinosis in male germ cell tumor patients: a registry study compiled by the German Testicular Cancer Study Group (GTCSG)

PurposeTo report on the clinical characteristics, outcome, and frequency of peritoneal carcinosis (PC) in patients with advanced germ cell tumors (GCT), a multicenter registry analysis was carried out.MethodsA multicenter registry analysis was conducted by the German Testicular Cancer Study Group (GTCSG) with international collaborators. Data was collected and analyzed retrospectively. Patients were eligible for inclusion if PC was diagnosed either by radiologic or histopathologic finding during the course of disease. Descriptive and explorative statistical analysis was carried out with cancer-specific survival (CSS) as primary study endpoint.ResultsCollaborators from ten GCT expert centers identified 28 GCT (0.77%) patients with PC after screening approximately 3767 GCT patient files and one case was contributed from a cancer registry request. Patients were diagnosed from 1997 to 2019 at a median age of 37 years (interquartile range, 13). Two patients (7%) presented with stage I and 27 patients (93%) with synchronous metastatic disease at first diagnosis. The primary histology was seminoma in seven (27%) and non-seminoma in 21 patients (72%). PC was detected after a median of 15.3 months from primary diagnosis (range 0–177) and two consecutive treatment lines (range 0–5), respectively. The median CSS from the time of detection of PC was 10.5 months (95%Confidence Interval 0.47–1.30) associated with an overall 2-year CSS rate of 30%.ConclusionPC represents a rare tumor manifestation in GCT patients and was primarily associated with the occurrence of advanced cisplatin-refractory disease conferring to a dismal prognosis.

High dose chemotherapy followed by autologous hematopoietic stem cell transplantation for advanced germ cell tumors: State of the art and a single-center experience.

Evidence for the choice of second line, standard vs high dose chemotherapy, (SDCT, HDCT) for patients with relapsed germ cell tumors (GCTs) comes mainly from retrospective studies. relevant literature was reviewed, considering as endpoints both survival and long term quality of life (QoL). Patients with metastatic GCT progressing after first-line treatment at our Institution were retrospectively evaluated. HDCT seems to achieve a higher rate of long-term remissions. QoL data for this group of patients are lacking. Our experience on 29 patients was in line with these results. Two-year OS for the 18 patients treated with one or two HDCT/PBSCT procedures was 47.5 %, while 2-year PFS was 44 %. For the 11 receiving SDCT 2-year OS was 36.4 %, and 2-year PFS was 32.7 %. HDCT/PBSCT confirmed to be effective in treating patients with relapsed GCT, but prospective studies are needed.