Nonseminomatous Germ Cell Tumor Patients Research Articles

Bone Metastases in Non-Seminomatous Germ Cell Tumors: A 20-Year Retrospective Analysis.

Background: Non-seminomatous germ cell tumors (NSGCTs) represent a rare yet the most prevalent malignancy among young men. Bone metastases (BMs) are exceedingly uncommon in this neoplasm, and available data regarding the initial disease presentation, survival outcomes, and prognostic significance of BMs are limited. Methods: We conducted a retrospective analysis of 40 NSGCT patients with BMs treated between 2001 and 2021 in our tertiary care center. The cohort was stratified into synchronous (n = 29) and metachronous (n = 11) groups based on the presence of BM at diagnosis or only at relapse, respectively. We assessed overall survival (OS), progression-free survival (PFS), disease presentation, and treatments. Results: After a median follow-up of 93 months, the 5-year PFS and OS rates were 37.6% and 53.9% in the synchronous group and 18.2% and 36.4% in the metachronous group, respectively. At the initial diagnosis, most patients were classified into the IGCCCG poor prognostic group (n = 34, 85%). BMs were mostly asymptomatic (n = 23, 57.5%), involved the spine (n = 37, 92.5%), and could become visible only after disease response (n = 4, 10%). A pathological examination of resected bone lesions after first-line treatment revealed necrosis (n = 5, 71.4%), teratoma, or seminoma (both n = 1, 14.3%). At first relapse, eight patients in the synchronous group did not experience bone recurrence, while eight patients experienced recurrence at the initial affected bone site. Conclusions: In NSGCT patients, BMs often present asymptomatically and may initially be unnoticed. However, these patients may have a poorer prognosis compared to those in the IGCCCG poor prognostic group. Further studies including control groups are needed to assess the independent prognostic significance of BMs.

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

AimsTo 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 methodsUsing 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. ResultsAmong 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). ConclusionTeratoma 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.

Utility of circulating tumor DNA (ctDNA) as a predictive biomarker for disease monitoring in patients with non-seminomatous germ-cell tumor (NSGCT).

500 Background: Serum tumor markers (STM) are currently utilized in the management of testicular NSGCT. However, STMs are normal in a substantial proportion of patients with NSGCT (up to 40%) and can be falsely elevated in certain other clinical conditions. Therefore, a highly sensitive and specific biomarker for NSGCT can be helpful for disease monitoring with diagnostic and therapeutic implications. Herein, we test the clinical utility of ctDNA to predict patient outcomes and monitor treatment response in stage II-III NSGCT. Methods: A total of 106 plasma samples were collected from a cohort of 25 Stage II-III NSGCT patients post-orchiectomy with a median age of 29 years (IQR: 26.8-38.8) and a median follow-up of 10 months (IQR: 7.2-17.5). Longitudinal ctDNA testing was performed using a personalized, tumor-informed ctDNA assay (Signatera bespoke mPCR-NGS assay). ctDNA results were analyzed and evaluated for their correlation with clinical outcomes (event-free survival [EFS]) during surveillance after first-line therapy (retroperitoneal lymph node dissection [RPLND] or chemotherapy) or after salvage chemotherapy. EFS is described as the interval from orchiectomy to the date of recurrence or evidence of residual/persistent disease after the completion of RPLND or chemotherapy. Results: Of 25 patients, 28% (7/25) had stage II and 72% (18/25) had stage III disease. Five patients with stage II disease underwent RPLND, and all tested positive for ctDNA prior to RPLND. Of the 18 patients with stage III disease, 83.3% (15/18) tested ctDNA positive pre-chemotherapy. For patients who completed 1st line treatment with RPLND or chemotherapy and had ctDNA testing post-completion of therapy, none of the patients who tested negative for ctDNA experienced relapse (recurrence rate: 0%, 0/6) compared to a recurrence rate of 30.8% (4/13) in patients who had normal STM levels. The detection of ctDNA was associated with a significantly shorter EFS (HR=11.4, 95%Cl 1.09-1537, p=0.041) while elevated STM results were not (HR=2.14, 95%Cl 0.51-8.94, p=0.298). ctDNA-positivity remained strongly associated with poor EFS (HR=12.98, 95%CI 1.17-1869, p=0.035) when adjusted for STM status. For patients who progressed after 1st line therapy and were treated with salvage chemotherapy, no events were seen in those who were ctDNA negative after therapy (0/6) compared with an event rate of 25% (2/8) in patients with normal STMs. Conclusions: Personalized monitoring of ctDNA seems predictive for recurrence in patients with NSGCT. To the best of our knowledge, this is one of the first reports presenting the clinical implications of ctDNA monitoring in this patient population. Our findings suggest that ctDNA monitoring may help optimize clinical decision-making, however, larger prospective studies are needed to validate the findings of this study.

Risk of residual cancer after complete response following first-line chemotherapy in men with metastatic non-seminomatous germ cell tumour and International Germ Cell Cancer Cooperative Group intermediate/poor prognosis: A multi-institutional retrospective cohort study

IntroductionCurrent guidelines recommend surveillance in metastatic non-seminomatous germ cell tumour patients treated with first-line-chemotherapy and a complete clinical response (normalisation of serum tumour markers and residual masses <1 cm). However, this recommendation is based on a series including patients with good prognosis according to International Germ Cell Cancer Cooperative Group prognostic group (IGCCCG-PG). The aim of this study was to analyse the proportion of residual teratoma and survival among patients with intermediate/poor IGCCCG-PG and a complete clinical response after first-line-chemotherapy. Material & methodsThis is a retrospective study of men with intermediate/poor IGCCCG-PG, who had a complete clinical response after first-line chemotherapy. Patients were either followed by surveillance or treated with post-chemotherapy retroperitoneal lymph node dissection (pcRPLND). ResultsBetween 2009 and 2018, 143 men with intermediate (n = 83) or poor (n = 60) IGCCCG-PG were treated at 11 international centres. Among 33 patients treated with pcRPLND, the specimen showed teratoma and viable cancer in 16 (48%) and 4 (12%). During a median a 7-year follow-up, 20/110 (18%) patients managed with surveillance relapsed, of whom seven (6%) had a retroperitoneal-only relapse versus 2/33 patients managed with pcRPLND relapsed. No difference was observed regarding overall survival (OS) among men treated with pcRPLND or surveillance (5-year OS, 93% and 89%, p-value = 0.35). The median time-to-recurrence among men on surveillance was 1.3 years (range: 0.3–9.1), and the most common sites of relapses included retroperitoneum (11%), chest (5%), and bones (4%). ConclusionsWhile most men with intermediate/poor IGCCCG-PG harbour teratoma/cancer in the retroperitoneum despite a complete response to first-line-chemotherapy, only 6% managed with surveillance relapsed in the retroperitoneum. There was no significant difference in OS between the two groups.

Improved survival of poor-risk non-seminomatous germ cell tumor patients: real-world data from a single institute in Japan.

The International Germ Cell Cancer Collaborative Group Update Consortium showed the improved survival of patients with a non-seminomatous germ cell tumor. We updated the survival data of the non-seminomatous germ cell tumor patients treated at our hospital. We analyzed the outcomes of 138 patients treated in 1981-2018. We compared the survival of the patients treated in the early (1981-99) and later (2000-18) periods and determined the groups' progression-free survival and overall survival using the Kaplan-Meier method. We used a web-based application of the International Germ Cell Cancer Collaborative Group Update model to calculate each patient's predicted 3-year progression-free survival. The 5-year progression-free survival rates of the good, intermediate and poor prognosis groups were 91, 83 and 64%, and their 5-year overall survival rates were 97, 89 and 82%, respectively. There were no significant differences in the progression-free survival or overall survival of the good and intermediate prognosis groups by treatment year. The 5-year progression-free survival of the poor prognosis group was almost identical in both treatment year (60 and 65%, respectively). By contrast, the 5-year overall survival in the later period (85%) was higher than that in the early period (70%). The median-predicted 3-year progression-free survival rates of the good, intermediate and poor prognosis groups were 92, 83 and 51% (P<0.01), respectively. The concordance index for the good, intermediate and poor prognosis groups were 0.56, 0.79 and 0.67, respectively. The survival of our poor prognosis non-seminomatous germ cell tumor patients improved over time. The 5-year overall survival of patients treated in 2000-18 reached 85%.

Role of Lactate Dehydrogenase in Identifying Relapse for Patients With Stage I Testicular Cancer on Surveillance.

Tumor markers alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase assume a key role in the management of testicular germ cell tumors. While alpha-fetoprotein and human chorionic gonadotropin have modest sensitivity and specificity for germ cell tumors, lactate dehydrogenase has weak sensitivity and specificity. We explored the utility of lactate dehydrogenase in identifying relapse among stage I seminomatous and nonseminomatous germ cell tumors on surveillance. Patients with a history of stage I testicular germ cell tumors were identified from a prospectively maintained database at the Princess Margaret Cancer Centre from December 1980 to May 2021 and surveyed according to established institutional algorithm guidelines. The utility of lactate dehydrogenase elevation to independently detect germ cell tumor relapse was examined. Among 1,014 seminoma and 676 nonseminomatous germ cell tumor patients, 176 and 176 patients relapsed with a median time to relapse of 13.6 and 8.9 months, respectively. Imaging alone was the most common mode of relapse detection in 144 and 74 of seminoma and nonseminomatous germ cell tumor patients, respectively. Lactate dehydrogenase was elevated in 49 cases of seminoma and 38 cases of nonseminomatous germ cell tumors at relapse, but was never the sole relapse indicator. Among 350 seminoma and 311 nonseminomatous germ cell tumor patients who never relapsed, 210 and 233, respectively, had at least 1 elevated lactate dehydrogenase value. Lactate dehydrogenase alone did not independently contribute to early relapse detection in stage I seminoma or nonseminomatous germ cell tumor. Elevated lactate dehydrogenase values were documented in a high proportion of nonrelapsing seminoma and nonseminomatous germ cell tumor cases.

Clinical characteristics of testicular non-seminomatous germ cell tumor from West China: a 10-year experience.

Clinical characteristics of testicular non-seminomatous germ cell tumor from West China: a 10-year experience.

Craniocaudal nodal length (CCNL) as a risk-factor for relapse in stage I non-seminomatous germ cell tumors (NSGCT).

e17011 Background: Lymphovascular invasion and embryonal carcinoma predominant (ECP) subtype are the only consistent factors predictive of relapse on active surveillance (AS) in Stage I NSGCT. Current practice guidelines define stage I disease by axial dimensions only, despite routine coronal reformations of axial CT images permitting CCNL measurement. CCNL was previously reported to be associated with increased risk of relapse in stage I NSGCT, independent of other risk factors (Howard et al, 2014). We sought to validate this finding through time-to-event (TTE) analyses in a larger, independent cohort. Methods: Patients with NSGCT who had undergone orchiectomy between 2/1/10 and 10/31/2017 and had baseline CT imaging performed within 90 days of orchiectomy were included. CCNL was measured using the largest lymph node by axial dimensions, with nodal morphological descriptors recorded. Median CCNL (17mm) was rounded to the nearest 5mm (15mm) and dichotomized into &lt;15mm or &gt; 15mm, deemed the most clinically translatable landmark. TTE was a composite of either relapse on AS, a positive primary retroperitoneal lymph node dissection (PRPLND), or relapse after negative PRPLND. TTE was estimated using Kaplan-Meier method, with time calculated from date of orchiectomy to date of event or censoring at last follow-up. Results: 134 stage I NSGCT patients were included, 64 (48%) with stage IA and 70 (52%) with stage IB. Median age at diagnosis was 30 years (range 18 to 34). ECP histology was seen in 82 (61%) patients. Median CCNL was 17mm (range 5 to 34) and 71 patients (53%) had a CCNL &gt; 15mm. Presence of fatty hilum and suspicious morphology were observed in 86 (66%) and 11 patients (8%) respectively. CCNL did not differ by stage at diagnosis (Wilcoxon p = 0.26) or ECP histology (Wilcoxon p = 0.95). PRPLND was performed in 7 of 64 stage IA (11%) and 45 of 70 stage IB (64%) patients. Twenty-six patients relapsed on AS, 9 had positive PRPLND histology and 3 with a negative PRPLND later relapsed. All 38 events occurred in the first year after orchiectomy except for relapse on AS in three stage IA patients at 1.2, 2.8 and 4.0 years. Median follow-up time is 5.0 years (range 1.5 months to 10 years). The one-year event-free rate was 72.7% (95% CI: 64.0, 79.6). TTE differed significantly by stage at diagnosis and did not differ significantly by ECP histology, CCNL (&gt; 15mm versus ≤15mm), presence of fatty hilum, or presence of suspicious morphology (all p &gt; 0.05). In a stratified analysis, event rate did not differ by CCNL &gt; 15mm versus ≤15mm within stage IA or IB patients (p = 0.58 and 0.60, respectively). Conclusions: Using TTE analyses in a larger, contemporary patient cohort, CCLN was not associated with increased risk of relapse in stage I NSGCT and does not lend support to its addition to staging or risk prediction models. The association between CCNL and relapse risk in stage I seminoma is currently being analyzed.

Management of residual nonretroperitoneal disease in nonseminomatous germ-cell tumors (NSGCT).

5034 Background: The management of NSGCT patients (pts) with post-chemotherapy residual non-retroperitoneal disease (RP) remains unsettled. Decisions for surveillance vs surgical resection are commonly steered by pathology from retroperitoneal lymph node dissection (RPLND). Data is limited in pts who do not require RPLND (normal or normalized RP post-chemo). Methods: The prospectively maintained Indiana University testicular cancer database was queried for pts with metastatic NSGCT who completed first-line chemotherapy and had residual extra-RP disease without residual RP disease. Pts with post-chemo non-RP surgical resection were included. Results: 134 pts met eligibility. Median age at diagnosis was 28.6 (range, 16.2-51.5). Primary tumor predominant histology was embryonal (35.1%), mixed (25.4%), seminoma (2.2%), yolk sac (9.7%), choriocarcinoma (15.7%), teratoma (11.2%). 76 pts (56.7%) had teratoma in the primary tumor. Metastatic sites at diagnosis were RP (15.7%), mediastinal LN (8.2%), lung (28.4%), liver (11.2%), bone (6.7%), brain (21.6%). Those with RP mets at diagnosis had normalization of RP nodes after chemo. IGCCCG risk was good in 57, intermediate in 21, and poor in 56 pts. Median pre-chemo AFP was 66 (0.9-467,000). hCG was 960.5 (0.5-1,300,000). First-line chemo was BEPX4 in 68, BEPx3 in 29, EPX4 in 10, VIPX4 in 9, and other in 18 pts. All pts had surgical resection of non-RP disease. None had RPLND. 84 pts had lung nodule resection, 16 had mediastinal LN, 8 had cervical LN, 5 had liver, 6 had bone, and 20 had brain met resection. Of the 76 pts with teratomatous elements in the orchiectomy, 41 (53.9%) had teratoma and 24 (31.6%) had non-teratoma GCT in post-chemo non-RP surgical specimens. Of the 58 pts without teratoma in the orchiectomy, 9 (15.5%) had teratoma and 34 (58.6%) had non-teratoma GCT in the non-RP surgical resection specimens. Teratoma in the orchiectomy was a predictor of non-RP teratoma (Fisher’s exact test P&lt;0.0001). Conclusions: The presence of teratoma in orchiectomy predicts teratoma in residual post-chemo non-RP disease in pts who do not undergo RPLND. The absence of teratoma in orchiectomy should not preclude resection of residual non-RP disease given a subset of patients had persistent GCT. [Table: see text]

Survival of nonseminomatous germ cell tumors in pediatric patients and young adults - A stage group stratified analysis.

Testicular germ cell tumors, particularly nonseminomatous germ cell tumors (NSGCT), comprise the most common solid malignancy in male children and younger adults. While these patients experience excellent survival outcomes, few studies have characterized their survival by age. Thus, we aimed to characterize the relative survival of NSGCT by age, stratifying patients by stage group. Using the Surveillance Epidemiology and End Results (SEER) database, we divided patients with NSGCT into pediatric patients and adolescents (<19 years), young adults (19-30 years), and older adults (>30 years). Survival analysis, using Cox proportional hazards models and Kaplan Meier curves, described overall and cancer-specific survival (CSS) of each age category for Stage I-III NSGCT by stage group. A total of 14,786 patients met inclusion criteria and comprised the age groups <19 years (N=1,287), 19 to 30 years (N=7,729), and >30 years (N=5,770). Stage group distribution at presentation was similar between each group. Survival analysis demonstrated no differences in cancer-specific survival (CSS) among Stage I or II NSGCT. However, among Stage III tumors, multivariable models noted worse CSS in patients >30 years (HR=3.35 (95%CI: 1.45-7.73), P=0.005) and those 19-30 years (HR=2.28 (95%CI: 0.99-5.21), P=0.053) compared to pediatric and adolescent patients. Younger NSGCT patients experience excellent oncologic outcomes compared to their older counterparts. These survival differences by age group are largely driven by differential survival among Stage III neoplasms. Furthermore, our report lends additional evidence that age is an important prognostic factor in advanced NSGCT, including pediatric and adolescent patients.

Tumor Marker Decline in Predicting Treatment Outcome among Poor-Risk Testicular Germ Cell Tumors-A Tertiary Cancer Center Data.

Lakshmi Haridas K.Introduction Testicular germ cell tumors are rare in India. Despite the advances in chemotherapy, poor-risk testicular nonseminomatous germ cell tumors (NSGCT) remain as a clinical challenge. Various prognostic factors have been described in this rare disease. The Indian data in this regard is scarce. Our study is the first attempt to assess the tumor marker decline with respect to treatment outcome in poor-risk NSGCT in Indian patients. Materials and Methods This retrospective study was done among newly diagnosed poor-risk NSGCT, treated at genitourinary clinic, at our tertiary cancer center during the period 2017 to 2019. The prognostic significance of tumor marker decline in them was correlated with 2-year progression-free survival (PFS) and 2-year overall survival (OS). Statistical Methods The association between two variables were assessed using chi-squared/Fischer's exact test. The PFS and OS were estimated using Kaplan-Meier method and the significance difference between survival curves was tested using log rank test. The risk for survival was estimated using cox regression analysis. A p -value of <0.05 was considered as significant. Results Out of 11 eligible patients, four (36%) had favorable tumor marker decline and seven (64%) had unfavorable decline. The 2-year PFS among favorable and unfavorable decline group were 66.7 and 42.9%, respectively ( p -0.358), and the 2-year OS was 66.7 and 71.4%, respectively ( p -0.974). Teratoma was not found to be a significant factor in our study. Tumors with only beta human chorionic gonadotropin (βHCG) elevation were observed to have good outcome. Postchemotherapy unresectable residual disease showed a significant trend toward inferior survival, the 2-year PFS was 38 versus 100% ( p -0.188) and the 2-year OS was 62.5 versus 100% ( p -0.334) in patients with and without unresectable residual disease, respectively. Conclusion Majority of our poor-risk NSGCT patients had unfavorable tumor marker decline and progressive events. However, the survival difference was not significant, given the small sample size. Tumors with only βHCG elevation were observed to have good outcome. Postchemotherapy unresectable residual disease showed a significant trend toward inferior survival.

Survival Outcomes of Patients With Mediastinal Germ Cell Tumors: Experience of a Cancer Center in South America.

PurposeMediastinal germ cell tumors (GCT) are rare neoplasms associated with poor survival prognosis. Due to their low incidence, limited information is available about this disease in South America. The objective of this study is to report the clinical characteristics and outcomes of patients with mediastinal GCT in a cancer center in Colombia.Materials and MethodsWe conducted a retrospective analysis of patients with mediastinal GCT treated at the National Cancer Institute at Bogota (Colombia) between 2008 and 2020. Survival curves were presented using the Kaplan–Meier method. Chi-square and Cox proportional hazard model tests were used for data analysis.ResultsSixty-one patients were included in the study. Of them, 60 were male and 51 (83.6%) of whom had non-seminomatous germ cell tumors (NSGCT). Twenty-nine patients (47.5%) presented with superior vena cava syndrome, and 18 (29.5%) patients had extrapulmonary metastatic involvement. The three-year overall survival (OS) of NSGCT patients was 26%. The 3-year OS of NSGCT patients who underwent surgical resection of residual mediastinal mass after chemotherapy was 59%. Non-surgical management after first-line chemotherapy was associated with a worse survival prognosis in NSGCT patients (p = 0.002). Ten patients with mediastinal seminomatous germ cell tumors (SCGT) achieved a 3-year OS of 100%.ConclusionMediastinal NSGCT had poor outcomes. Surgery of the residual mass after first-line chemotherapy seems to improve the outcome of NSGCT patients. Advanced disease at presentation may reflect inadequate access to reference cancer centers in Colombia and potentially explain poor survival outcomes in this cohort. On the other hand, mediastinal SCGT is a biologically different disease; most patients will achieve disease remission and long-term survival with first-line chemotherapy.

The absence of spermatogenesis in radical orchiectomy specimen is associated with advanced-stage nonseminomatous testicular cancer.

To assess if clinical, pathological, and spermatogenesis factors are associated with clinical staging in patients with testicular germ cell tumors. We retrospectively reviewed the pathology reports and slides from 267 men who underwent radical orchiectomy for testicular cancer at our institution during 1998-2019. Histologic slides were reviewed and the presence of mature spermatozoa was documented. Clinical, laboratory and radiographic characteristics were recorded. Logistic regression analyses were used to identify factors associated with advanced disease stage at diagnosis. Of 267 male patients, 115 (43%) patients had testicular non-seminomatous germ cell tumors (NSGCT) and 152 (57%) seminomatous germ cell tumors (SGCT). Among NSGCT patients, those presenting with metastatic disease had a higher proportion of predominant (>50%) embryonal carcinoma (64% vs. 43%, respectively, P = 0.03), and lymphovascular invasion (45.8% vs. 26.6%, respectively, P = 0.03) than non-metastatic patients. Spermatogenesis was observed in 56/65 (86.2%) and 36/49 (73.5%) of non-metastatic and metastatic NSGCT patients, respectively (P = 0.09). On semen analysis, severe oligospermia (<5 million/ml) was more common in metastatic than in non-metastatic NSGCT (26.5% vs. 8.3%, respectively, P = 0.04). On multivariate analysis, predominant embryonal carcinoma and lack of spermatogenesis in pathological specimens were associated with metastatic disease. The absence of spermatogenesis and a high proportion of embryonal carcinoma was associated with advanced disease in patients with NSGCT. Whether it may also translate as a predictor of oncologic outcome needs further evaluation.

Post-chemotherapy modified template retroperitoneal lymph node dissection in patients with nonseminomatous germ cell tumours.

Although a full bilateral template RPLND is thought to be the standard of care for the management of postchemotherapy retroperitoneal residual masses for nonseminomatous germ cell tumors (NSGCT), in the past decade modified templates have become increasingly popular. In this study, we aimed to present our oncological and perioperative outcomes of consecutive seventeen NSGCT patients who underwent a modified template unilateral PC-RPLND for retroperitoneal residual disease. We retrospectively evaluated the medical records of 17 consecutive NSGCT patients who underwent modified template unilateral PC-RPLND in our university hospital between 2017 and 2020. All patients had normal serum tumour markers with residual disease in the retroperitoneum. Surgical characteristics including the size of the retroperitoneal residual mass, residual tumor pathology, removed lymph nodes, positive percentage of removed lymph nodes, accompanying operations, complications, mean operation time and hospital stay, and long-term results including survival and antegrade ejaculation were evaluated. Eleven patients underwent left and six right-sided surgery. Median residual lymph node diameter was 41mm. Median hospitalisation time was 3.5 days. Median follow-up time was 10.5 months. Necrosis/fibrosis was seen in 6 patients, and teratoma in 11 patients. No viable tumour was seen. No patients died in the follow-up period. None of the patients relapsed during follow-up. Ten/seventeen patients had antegrade ejaculation. Modified template unilateral PC-RPLND leads to very good oncological outcomes with decreased perioperative morbidity as well as better antegrade ejaculation rates. Low volume retroperitoneal disease seems to fit this procedure best.

Outcome of testicular non-seminomatous germ cell tumours: report from a tertiary cancer centre in eastern India.

Non-seminomatous germ cell tumour (NSGCT) is a rare but highly curable malignancy. The literature on the management and outcomes of NSGCT is scarce from India. Here, we report the demography and treatment outcomes of NSGCT treated at our centre. This is a retrospective analysis of testicular and retroperitoneal NSGCT patients treated from March 2011 to December 2019. Patients were staged appropriately with imaging, pre- and post-operative tumour marker. Patients received stage adjusted adjuvant treatment after high inguinal orchiectomy. Patients with advanced disease were risk stratified as per International Germ Cell Cancer Collaborative Group (IGCCCG) classification. A total of 100 patients were treated with a median age of 28 years (Range: 18–51). Primary site was testis in 92 and retroperitoneum in 8 patients. Testicular violation was present in 17 (18%) patients. The stage of the disease was I in 32, II in 19 and III in 49 patients, respectively. IGCCCG risk groups were good in 29 (46%), intermediate in 13 (21%) and poor in 21 (33%) patients. Eleven patients (24%) underwent retroperitoneal lymph node dissection amongst 45 with post-chemotherapy residual disease. After a median follow-up of 26.6 months (range: 2.2–100.7), 3-year event-free survival and overall survival (OS) were 70.7% ± 5.6% and 78.2% ± 5.4%, respectively. S3 tumour marker (p = 0.01) and non-pulmonary visceral metastasis (p < 0.001) emerged as independent poor prognostic factors for OS in multivariate analysis. To conclude, testicular NSGCT has very high cure rate. Two-third patients present with advanced disease and one-third of them had poor risk disease. S3 tumour marker and non-pulmonary visceral metastasis are poor risk factors for OS.

Surveillance of postchemotherapy subcentimeter residual retroperitoneal mass in metastatic nonseminomatous germ cell tumor: Does how you measure matter?

BackgroundApproximately 70% to 80% of patients with metastatic nonseminomatous germ cell tumor (NSGCT) treated with cisplatin-based chemotherapy achieve a complete response, defined as normalization of serum tumor markers and either no residual retroperitoneal mass (RRM) or an RRM <1.0 cm. While there is universal agreement that patients with an RRM ≥1.0 cm should undergo retroperitoneal lymph node dissection (RPLND), many institutions including ours recommend surveillance for patients who achieve a complete response. However, studies have not defined which axis of the RRM should be considered when deciding between surveillance and RPLND. Patients and MethodsGood-risk metastatic NSGCT patients treated with cisplatin-based chemotherapy who achieved a complete response and underwent surveillance were identified using our institution's electronic medical records. A post-hoc review was performed by a blinded radiologist. The RRM dimensions in the transaxial short axis (TSA), transaxial long axis (TLA), and craniocaudal axis (CCA) were recorded. Differences in the frequency of recurrence between groups with an RRM <1.0 cm and ≥1.0 cm in the TLA and CCA were assessed using the Fisher exact test. ResultsThirty-nine patients who met study criteria were included. At a median follow-up of 63.8 months, 2 patients (5.1%) recurred. Both were successfully treated with salvage chemotherapy and RPLND. Thirteen (33%) and 27 (69%) patients had an RRM ≥1.0 cm in the TLA and CCA, respectively. There were no statistically significant differences in the risk of recurrence between patients with an RRM <1.0 cm and ≥1.0 cm in the TLA (P = 0.54) or CCA (P = 0.53). ConclusionsSurveillance is an effective strategy in good-risk NSGCT patients with a postchemotherapy RRM <1.0 cm in the TSA. Our study suggests referencing the TSA and not the TLA or CCA may avoid unnecessary postchemotherapy RPLNDs.

Primary Management of Non-Seminomatous Germ Cell Brain Metastases with Stereotactic Radiosurgery: A Case Series

Non-seminomatous germ cell tumors (NSGCT) are a clinically rare entity, mainly occurring in otherwise healthy young men. While standard of care for brain metastases has shifted to stereotactic radiosurgery (SRS) for many histologies, in NSGCT patients with brain metastases, it remains whole brain radiation therapy (WBRT). Radiation-induced neurocognitive deficits have been documented in patients with NSGCT brain metastases treated with WBRT. This is further complicated by the fact that these patients typically receive neuro-toxic high dose chemotherapy. There remain no published reports evaluating the efficacy of SRS as the primary treatment of NSGCT brain metastases. We hypothesize that SRS is a feasible alternative to WBRT for the treatment of NSGCT metastases to the brain. The available records of patients with various non-seminomatous germ cell tumor histologies treated between 2011 and 2018 at a single institution were retrospectively reviewed. All of the 26 male patients received initial gamma knife or Linac based radiosurgery without WBRT. Five of the patients underwent SRS to a post-surgical resection cavity. Nearly 75% of patients received adjuvant tandem stem cell transplant with high dose chemotherapy. The median follow-up of the cohort was 42 months (range 17-107 months) with a median age of 27 years old (range, 17-56) and a mean of 3 (range, 1-14) lesions treated. At the time of SRS, patients had received a median of 5 prior lines of chemotherapy, with a median of 3 disease relapses. The 1-year OS was 73% with a median survival of 23 months. Only one treated lesion was observed with local progression, resulting in a 2-year LC rate of 99% (this recurrence was salvaged successfully with repeat SRS). Only one neurologically related death occurred, leading to a neuro-specific EFS rate of 96%. A total of 23% of patients experienced distant brain recurrence at a median time of 2.7 months, which resulted in a 1-year distant brain control of 77%. Of the 6 patients with distant failure, 4 were successfully salvaged with repeat SRS treatment without additional relapse on follow-up imaging. Only one patient received salvage WBRT 19 months post initial SRS, leading to a 2-year WBRT free survival of 96%. Radiosurgical management of brain metastases has demonstrated feasibility in the management of several cancer histologies, but this has yet to be determined for NSGCTs. Brain metastases from NSGCTs are often limited in number, and mainly affect young men with good functional status. Avoidance of WBRT in patients receiving adjuvant high dose chemotherapy may provide control of intracranial disease with the goal of preserving neurocognitive function in these young patients. Our preliminary results suggest that SRS may safely replace WBRT as an initial treatment of choice in patients with NSGCT brain metastases receiving adjuvant high dose chemotherapy.

Long-term Surveillance of Patients with Complete Response Following Chemotherapy for Metastatic Nonseminomatous Germ Cell Tumor

BackgroundThere is controversy regarding the management of patients with normal markers and residual masses (≤1 cm) after chemotherapy for nonseminomatous germ cell tumors (NSGCTs). ObjectiveTo determine long-term outcomes of a surveillance strategy in such patients. Design, setting, and participantsA retrospective review of our multidisciplinary testicular cancer database was performed. All patients who underwent primary chemotherapy for metastatic NSGCTs were identified between 1981 and 2016. A complete response (CR) was defined as normalization of serum tumor markers and a ≤1 cm residual mass in the largest axial dimension following chemotherapy. All such patients were surveilled. Outcome measurements and statistical analysisOutcome variables of interest were time to death, time to cancer-specific survival, and time to relapse. Overall survival and relapse-free survival were calculated using the Kaplan-Meier method, and the cumulative incidence of cause-specific survival rates was calculated using competing risk analysis. The impact of risk group and chemotherapy regimen on relapse-free survival was assessed using log-rank test. Results and limitationsDuring the study period, 1429 metastatic germ cell tumor patients were treated with primary chemotherapy. CR was achieved in 191 (18.5%) NSGCT patients. The median age at diagnosis was 27.4 yr, with a median follow-up of 81.1 mo. The majority had American Joint Committee on Cancer stage II at diagnosis (I: 23.8%; II: 49.2%; III: 27%) and International Germ Cell Cancer Collaborative Group good-risk disease (good: 78%; intermediate: 17.8%; poor: 4.2%). Of the 191 patients with a CR, 175 (91.6%) never relapsed and remain disease free. Sixteen (8.4%) patients relapsed after a median of 11.3 mo (range 1–332 mo), with over half (nine patients; 4.7%) relapsing in the retroperitoneum only and salvaged successfully with postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) alone. Of these nine patients, only two (1%) had viable disease in the PC-RPLND specimen. The remaining seven patients had relapses outside the retroperitoneum and received salvage chemotherapy ± postchemotherapy resection. Overall, nine (4.7%) patients have died, but only four (2.1%) from testis cancer. ConclusionsOur data, the largest series to date, confirm that surveillance is safe and effective for men who achieve a CR following chemotherapy for metastatic NSGCTs. Patient summarySurveillance is a safe strategy for patients who achieve a complete response following chemotherapy for metastatic testis cancer.

Management of Metastatic Pure Teratoma in Chemotherapy Naive Patients With Testicular Primaries.

Patients diagnosed with stage II nonseminomatous germ cell tumors (NSGCT) often receive chemotherapy as primary treatment which exposes patients to immediate and long-term risks of chemotherapy. These risks can be avoided by proceeding to primary retroperitoneal lymph node dissection (RPLND) when a high suspicion of pure metastatic teratoma in the retroperitoneum (RP) exists. We propose that all stage II NSGCT patients with pure testicular teratoma, normal serum tumor markers, and with RP cystic metastases on imaging can safely be treated with primary RPLND. We identified 14 patients found to have 100% teratoma in orchiectomy specimens, negative serum tumor markers, and with metastatic cystic RP disease. Disease recurrence was also evaluated to establish efficacy of treatment. All 14 patients were chemotherapy naive and found to have pure metastatic teratoma. All patients were IGCCCG good risk with stage IIA (21.4%), IIB (35.7%), and IIC (42.9%) disease. Median RP mass size was 4.9 cm (1.8 to 24 cm). All patients underwent a RPLND finding 100% teratoma in the RP. Median follow-up was 6.9 years. One patient (7.1%) who received a right modified template RPLND relapsed in the left RP 10.2 years later who underwent treatment and has been disease free for over 5.5 years. Primary surgical treatment in this cohort of pure metastatic teratoma resulted in good clinical outcomes and the ability to avoid unnecessary induction chemotherapy. It is important that contrary to previous suppositions, patients with pure teratoma of the testis can independently metastasize with teratoma only, without metastatic carcinoma.

Validation of the two best models to predict “benign” pathohistology in patients with advanced nonseminomatous germ cell tumors (NSGCT) undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND).

389 Background: The aim of our study is to validate and evaluate the two currently best performing prediction models (Vergouwe and Leao) for final pathohistology in NSGCT patients undergoing PC-RPLND and we introduce a new radiomics approach. Methods: We performed a retrospective analysis including 496 patients who underwent a PC-RPLND between 2008 and 2018 to validate the two prediction models using published formulas and thresholds. ROC were plotted and AUC was calculated. We determined the optimal cut point and used bootstrapping (1,000 replications) to estimate its variability. For radiomics, lymph nodes of 80 patients were identified on CT images, semiautomatically segmented with 93 radiographic features (pyRadiomics package). A linear support vector machine algorithm was applied to analyze reproducible radiomics features. A continuous reduction of features analyzed was performed using Random Forest algorithms and ROC analysis. Results: In our validation cohort, the Vergouwe model had a significantly better AUC compared to Leao model (0.749 [CI 0.706-0.792] vs. 0.689 [0.642-0.736], p=0.004) to predict benign histology. At a threshold of &gt; 70% for the probability of benign disease, the Leao model would have avoided PC-RPLND in 8.6% with benign disease with an error rate of 5.6% for viable tumor. The Vergouwe model would avoid PC-RPLND in 23.4% with benign disease with an error rate of 12.7% for viable tumor/teratoma. Of the 93 radiomic features analyzed, 51 features were reproducible. Applying the trained algorithm on the training dataset resulted in an accuracy of 0.96 (93% sensitivity, 100% specificity, 100% PPV), on an independent validation cohort the accuracy was 0.81 (88% sensitivity, 72% specificity, 78% PPV). Conclusions: According to our data, the discriminatory accuracy of both models is not sufficient to safely select patients for surveillance strategy instead of PC-RPLND. The radiomics model is promising but needs prospective validation. Further studies including new biomarkers are needed to optimize the accuracy of potential prediction models.