Normal Serum Tumor Markers Research Articles

Complex treatment of residual metastatic germ cell cancer: A single center experience

BackgroundTesticular cancer is the most common solid malignancy among men aged 15–35. Radical orchiectomy and platinum-based chemotherapy (BEP) are curative in the majority of patients, including advanced, metastatic cases. According to current urooncology guidelines all non-seminoma patients harbouring post-chemotherapy residual masses of ≥ 1 cm should undergo salvage retroperitoneal lymph node dissection (RPLND). However, only 10% of residual tumors contain viable disease. ObjectiveTo assess patient outcomes and complications considering different treatment regimens and clinical characteristics. Materials and methodsIn a retrospective cross-sectional study patients (n=127) who underwent postchemotherapy RPLND between 2007 and 2023 at our referral center were evaluated. The patients received systemic treatment at various oncology centers. The number of BEP cycles received were occasionally different from standard. Only patients with normal postchemotherapy serum tumor markers and primary testicular or extragonadal germ cell neoplasms were included. Treatment groups were established according to the number of BEP cycles received, and the extent of RPLND (bilateral or modified template). Treatment outcomes and complications were assessed. ResultsStandard 3–4 courses of BEP were received by 100 (78,7%) patients, while 11 (8,7%) patients underwent less, and 16 (12,6%) more courses than standard. On histopathologic evaluation viable germ cell tumor, teratoma, and necrosis/fibrosis was present in 26 (20,5%), 67 (52,7%) and 34 (26,8%) of specimen, respectively. In the 5–6 BEP series subgroup high rate of viable disease (37,5%) was found and significantly more nephrectomies were performed, than other chemotherapy subgroups. Extratesticular GCT, viable disease in residual mass or progression after RPLND indicated lower survival. Mild (Clavien-Dindo I-II) or no postoperative complications were reported in 93,7% of cases. ConclusionsThe study suggests no significant benefit from exceeding 3–4 courses of BEP. Timely salvage RPLND should be performed in high volume centers for optimal treatment outcomes with acceptable complication rates. Adherence to the Heidenreich criteria is advisable where practical.

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.

Prognostic Factor Risk Groups for Clinical Stage I Seminoma: An Individual Patient Data Analysis by the European Association of Urology Testicular Cancer Guidelines Panel and Guidelines Office

BackgroundThe relapse rate in patients with clinical stage I (CSI) seminomatous germ cell tumor of the testis (SGCTT) who were undergoing surveillance after radical orchidectomy is 4–30%, depending on tumor size and rete testis invasion (RTI). However, the level of evidence supporting the use of both risk factors in clinical decision-making is low. ObjectiveWe aimed to identify the most important prognostic factors for relapse in CSI SGCTT patients. Design, setting, and participantsIndividual patient data for 1016 CSI SGCTT patients diagnosed between 1994 and 2019 with normal postorchidectomy serum tumor marker levels and undergoing surveillance were collected from nine institutions. Outcome measurements and statistical analysisMultivariable Cox proportional hazard regression models were fit to identify the most important prognostic factors. The primary endpoint was the time to first relapse by imaging and/or markers. Relapse probabilities were estimated by the Kaplan-Meier method. Results and limitationsAfter a median follow-up of 7.7 yr, 149 (14.7%) patients had relapsed. Categorical tumor size (≤2, >2–5, and >5 cm), presence of RTI, and lymphovascular invasion were used to form three risk groups: low (56.4%), intermediate (41.3%), and high (2.3%) risks with 5-yr cumulative relapse probabilities of 8%, 20%, and 44%, respectively. The model outperformed the currently used model with tumor size ≤4 versus >4 cm and presence of RTI (Harrell’s C index 0.65 vs 0.61). The low- and intermediate-risk groups were validated successfully in an independent cohort of 285 patients. ConclusionsThe risk of relapse after radical orchidectomy in CSI SGCTT patients under surveillance is low. We propose a new risk stratification model that outperformed the current model and identified a small subgroup with a high risk of relapse. Patient summaryThe risk of relapse after radical orchidectomy in patients with clinical stage I seminomatous germ cell tumor of the testis is low. We propose a new risk stratification model that outperformed the current model and identified a small subgroup with a high risk of relapse.

Critical elements of pediatric testicular germ cell tumors surgery

Children, adolescents and young adults with testicular germ cell tumors require appropriate surgical care to insure excellent outcomes. This article presents the most critical elements, and their basis in evidence, for surgery in this population. Specifically, the importance of inguinal radical orchiectomy for malignant tumors, partial orchiectomy for prepubertal tumors and normal serum tumor markers, and the appropriate use of post-chemotherapy retroperitoneal lymph node dissection in those with residual retroperitoneal masses.

European Association of Urology (EAU) Testicular Cancer Guidelines Panel: A new prognostic factor risk group classification for patients with clinical stage 1 seminoma in active surveillance.

410 Background: Between 4%- 30% of patients with clinical stage 1 (CS I) seminoma testis (ST) in active surveillance (AS) relapse depending on pathological risk factors tumor size (TS) and rete testis invasion (RTI). The level of evidence supporting these pathological risk factors in clinical decision-making is low due to heterogeneous study design and reporting and the difficulty to analyze patient subgroups according to combination of these factors. The objectives of the present study were to identify the most important pathological prognostic factors predicting relapse in CS I seminoma patients with normal post-orchidectomy serum tumor marker (STM) levels in AS and to construct risk-groups for guiding treatment decision-making and follow-up. Methods: Individual patient data from 1016 CS I-ST patients diagnosed between February 1994 and January 2019 in AS were collected from 9 institutions. Central pathology review was not routinely performed in all institutions; therefore, pagetoid and stromal RTI were not differentiated explicitly in most cases. Assessing patient age, pre-orchidectomy STM b-human chorionic gonadotropin and lactate dehydrogenase, pathological TS, RTI, lympho-vascular invasion (LVI), multi-focality, and GCNIS, multivariable Cox proportional hazards regression models were fit to identify the most important prognostic factors for the time to first relapse by imaging and/or markers (primary endpoint). Probabilities of relapse were estimated using Kaplan-Meier curves. Results: After median follow-up of 7.7 years, 149 (14.7%) patients relapsed, 104 identified by imaging alone, 44 by imaging with elevated STMs and 1 by elevated STMs alone. Excluding 18 patients with unknown LVI from the multivariable analyses, TS (≤ 2 cm, between 2 and 5 cm, > 5 cm), presence of RTI and presence of LVI were used to form three risk groups: very low, low and high-risk (Table). Five-years probability of relapse varied from 8% in the very low risk-group to 44% in the high risk-group. The new model outperformed the current model with TS < 4cm vs ≥ 4 and RTI (Harrell's C index 0.65 vs 0.61) and identifies a subgroup of patients with a higher risk of relapse. Conclusions: The new risk-group stratification for CS I -ST patients in AS outperforms the histopathological model based on TS and RTI. It will serve to better inform patients on the risk of relapse during follow-up after orchidectomy but requires an independent validation. [Table: see text]

Growing Teratoma Syndrome-A Clinicoradiological Series.

Context Growing teratoma syndrome (GTS) is a rare entity seen following chemotherapy for metastatic nonseminomatous germ cell tumors, characterized by increase in size of the metastatic deposits, with normal serum tumor markers. Aims In this article, we aim to describe the various clinicoradiological presentations of GTS treated at our center. Design All patients who satisfied the GTS criteria from 2001 to 2019 were included. Characteristic imaging appearances along with sites of primary lesion and metastatic disease, stage and risk stratification at diagnosis, details of chemotherapy, details of surgical treatment and histopathology, levels of tumor markers, serum β-human chorionic gonadotropin, lactate dehydrogenase, and alpha fetoprotein levels at baseline and at the end of all chemotherapy were analyzed. Results The significant radiological findings observed were an increase in the fat and cystic components and appearance of coarse calcifications within the lesions. Majority of the cases were male patients (87.5%) with testicular primaries and GTS transformation in nodal metastases being the most common occurrence (75%). All eight cases (100%) showed an increase in size and cystic component, whereas four out of eight cases (50%) had presence of internal septations and internal calcification. Conclusion Early recognition of this entity and clinical decision making through serial radiological imaging are of utmost importance as these growing deposits are resistant to chemotherapy and radiotherapy, with complete surgical excision being the only curative and definitive treatment option.

Clinical and surgical outcome differences on the basis of pathology category in cervical neuroblastic tumors

Background: Cervical neuroblastic tumors (NTs) are rare but less aggressive cancer with an above-average survival rate. Little has been published regarding the management and surgical outcomes of patients with cervical NTs based on pathology category. This study compared and identified the preoperative characteristics of cervical NTs in different pathology categories and evaluated the outcomes of patients undergoing surgical resection. Materials and methods: Upon the institutional review board's approval, a retrospective chart review was performed at Beijing Children's Hospital from April 2013 to August 2020. Demographics of patients, imaging data, lab test results, operation details and outcomes were recorded and analyzed. Results: Of 32 cervical NTs, 24(80%) were classified as neuroblastoma (NB) /ganglioneuroblastoma-nodular (GNBn) and 8(20%) as ganglioneuroblastoma-intermixed (GNBi)/ ganglioneuroma (GN). Patients with GNBi/GN were older than those with NB/GNBn (44.5 months (IQR 16–81) vs 9 months (IQR 1–47); P = 0.001). GNBi/GN patients presented more frequently with stage 1 disease compared with NB/GNBn patients (100% vs. 29.2%, P = 0.001), less frequently with tumor-related symptoms (0% vs. 70.8%, P = 0.001), artery encased tumor (0% vs. 41.7%, P = 0.035), and surgical complications (25% vs. 70.8%, P = 0.038). GNBi/GN patients were also less likely to show elevated neuron specific enolase (NSE) (12.5% vs. 79.2%, P = 0.002). Conclusions: Cervical NB/GNBn and GNBi/GN patients had distinct characteristic clinical presentations and surgical outcomes. For children with features suggestive of benign disease (older age, asymptomatic, normal serum tumor markers) and no artery image-defined risk factors (IDRFs), upfront resection can be considered.

Prognostic significance of raised serum tumor markers (STM) after 2 cycles of chemotherapy in men with intermediate- and poor-risk non-seminomatous testicular germ cell tumors (NSGCT) treated at a single-centre in India.

5036 Background: Testicular GCT is a rare malignancy, with excellent outcomes. However, approximately one-fourth of intermediate risk and half of the patients with poor risk disease succumb to recurrent GCT. We looked at the prognostic significance of raised serum tumor markers after 2 cycles of chemotherapy in patients with poor risk GCT. Methods: This is a chart-review based retrospective analysis of patients with intermediate and poor risk NSGCT diagnosed and treated at a tertiary care centre in New Delhi, India from 2015-2021. Risk categories were defined as per the International Germ Cell Cancer Collaborative Group. Multivariable Cox regression models were constructed to analyse the prognostic impact of normal STM at the end of second cycle of chemotherapy on overall survival (OS) and relapse free survival (RFS), while adjusted for measured confounders. Results: A total of 312 patients were identified with testicular NSGCT, of whom 109 were intermediate (n = 48, 44%) and poor risk (n = 61, 56%). The median age at diagnosis was 27 (interquartile range, 21-34) years. ECOG PS of patients was 0-1 in 51% and 2-4 in 49%, and poor risk patients were more likely to have a poor ECOG PS at diagnosis (70% vs 30%, P < 0.001). First-line chemotherapy was BEP in 86% patients and VIP in the remaining 14%, and surgery for residual disease was performed in 22%. Overall, 35% patients had normal STM after 2 cycles of chemotherapy, and patients with intermediate risk were likely to achieve normal STM at this time-point (50% vs 23%). At a median follow-up of 62 months, the 5-year RFS rate was 62% (poor risk 52% and intermediate risk 78%), and OS rate was 68% (58% and 80%, respectively). Men with normal STM after 2 cycles chemotherapy had a better RFS (hazard ratio [HR], 0.70; 95% confidence interval 0.48-0.81; P < 0.001) and OS (HR,0.82; 95% CI 0.61-0.99; P = 0.04). After adjusting for risk category, and ECOG PS in a multivariable Cox regression model, patients with normal STM at the end of 2 cycles of chemo continued to have better outcomes (adjusted HR for RFS, 0.78; 95% CI, 0.77-0.89; P = 0.03, and adjusted HR for OS, 0.92; 95% CI,0.81-0.99; P = 0.05). Intermediate risk NSGCT and good ECOG PS also predicted better RFS and OS. Conclusions: Patients with NSGCT whose STMs do not normalize after 2 cycles of chemotherapy have worse RFS and OS compared to those with normal STM at this time-point. Further clinical trials will be needed to study the role of escalation or switch of chemotherapy in this subset of population.

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.

Prognostic Significance of Preoperative Tumor Markers in Pseudomyxoma Peritonei from Low-Grade Appendiceal Mucinous Neoplasm: a Study from the US HIPEC Collaborative

BackgroundTumor markers are commonly utilized in the diagnostic evaluation, treatment decision making, and surveillance of appendiceal tumors. In this study, we aimed to determine the prognostic significance of elevated preoperative tumor markers in patients with pseudomyxoma peritonei secondary to low-grade appendiceal mucinous neoplasm who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. MethodsUsing a multi-institutional database, eligible patients with measured preoperative tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), or cancer antigen 125 (CA-125)] were identified. Univariate and multivariate Cox-proportional hazards regression analysis assessed relationships between normal and elevated serum tumor markers with progression-free and overall survival in the context of multiple clinicopathologic variables. ResultszTwo hundred and sixty-four patients met criteria. CEA was the most commonly measured tumor marker (97%). Patients who had any elevated tumor marker had a higher peritoneal carcinomatosis index (PCI) as compared to those with normal range markers. Elevated CEA and CA 19-9 levels were individually associated with longer inpatient length of stay, requirement for intraoperative transfusion, and incomplete cytoreduction. Utilization of neoadjuvant chemotherapy, increased PCI score, elevated CA 19-9 (p = 0.007), and CA-125 levels (p = 0.01) were predictive of decreased progression-free survival on univariate analysis. However, in a multivariate model, only elevated PCI was a statistically significant predictor of progression-free survival. ConclusionElevated preoperative tumor markers indicate a higher burden of disease but are not independently associated with survival in this retrospective multi-institutional cohort. Further prospective studies are needed to clarify the utility of these markers in this patient population.

Efficacy of TIP (paclitaxel, ifosfamide and cisplatin) as salvage chemotherapy for relapsed germ cell cancer patients stratified by the modified International Prognostic Factors Study Group (IPFSG) score: The Northern Ireland (NI) Experience.

5028 Background: Salvage therapy for relapsed or refractory germ cell tumours (GCTs) after first-line treatment (1LT) failure remain controversial. The ongoing TIGER trial aims to compare conventional-dose chemotherapy (CDCT) using TIP with high-dose chemotherapy (HDCT) and to validate a modified version of the IPFSG stratification system as a secondary objective. We retrospectively analysed data from patients treated with TIP at our institution and stratified by the modified IPFSG (mIPFSG) groupings, correlating this with clinical outcomes. Methods: Data from all GCT patients who received TIP in NI between 2005 and 2014 was collected. Patients were scored using known IPFSG factors including progression-free interval (0-1), metastasis site (0-3), response to 1LT (0-2), primary tumour site (0-3), HCG (0-1), AFP (0-2), and histology (-1 to 0), and categorised into the modified strata. Descriptive and inferential statistics using SPSS compared survival measure outcomes and the favourable response rate (FRR) i.e the proportion of patients achieving either a complete response or partial response with normal serum tumour markers, according to mIPFSG group. Results: Thirty patients were identified, all of whom received 4 cycles of TIP. The median age was 37 years (range 17-57), 28 patients were non-seminoma histology with 2 patients seminoma. The cohort comprised predominantly of patients with more adverse mIPFSG features and the FRR of the group was 30%, with a median progression-free survival (PFS) of 9 months and 2-year overall survival (OS) of 50%. Clinical outcomes differed by mIPFSG score as shown below. Conclusions: Our study shows TIP efficacy comparable to published data, and to our knowledge is the first to show correlation between clinical outcomes with the regimen and the new mIPFSG model. The differences in outcomes to CDCT using TIP across risk groups in real world practice shows potential for a stratified approach to patient selection for salvage therapy, as is under investigation by the TIGER study.[Table: see text]

Pre-orchiectomy serum tumor markers as a predictor of recurrence in stage I germ cell tumors.

389 Background: Organ confined (stage IA/IB) testicular cancer has a high cure rate regardless of initial treatment modality, making it important to weigh the toxicities of treatment against potential benefits. While many clinicians routinely obtain serum tumor markers (STMs) prior to radical orchiectomy, their role in predicting recurrence in stage IA and IB testicular cancer has not been studied. Methods: A multi-institutional database of stage I testicular cancer patients diagnosed between 2006 and 2018 was created. Univariate and multivariate regression models were created to understand which factors predict recurrence. Recurrence analyses using Kaplan-Meier curves for elevated and normal pre-orchiectomy STMs were also generated. Results: 150 patients met the study criteria, of whom 16 (11%) relapsed (Table). 9 (56%) patients with recurrence had elevated pre-orchiectomy STMs, and 7 (44%) had normal pre-orchiectomy STMs. Similarly, 75 patients (56%) without relapse had elevated pre-orchiectomy STMs. Of 9 patients with elevated pre-orchiectomy STMs, 6 (67%) had normal STMs at recurrence; of 7 with normal pre-orchiectomy STMs, 4 patients (57%) had elevated STMs at recurrence. On Kaplan-Meier analysis, no association between level of pre-orchiectomy STMs and recurrence free survival was observed. Conclusions: Pre-orchiectomy STMs were not independently associated with recurrence in stage I testis cancer. Interestingly, there was also no association between positivity of pre-orchiectomy STMs and whether or not STMs were elevated at recurrence. These findings support the continued use of standard-of-care imaging and STMs in surveillance of stage IA/IB testicular cancer patients regardless of pre-orchiectomy STMs. [Table: see text]

Elevated carbohydrate antigen 125 post-operation as a prognostic marker in gastric cancer patients with stage II-III.

BackgroundGastric cancer is one of the high occurrence cancers among gastrointestinal tumor. Further research should be carried out to find more prognostic factors, screening patients with poor prognosis, who need stronger treatment.MethodsThe clinicopathologic characteristic, the levels of tumor markers and survival of 105 patients who underwent gastrectomy with a D2 lymph node dissection in Zhejiang Cancer Hospital were collected and analyzed.ResultsIn the 105 patients, there were 71 males, and the median age was 56 years (range, 21–83 years). In 105 patients, 77 patients were diagnosed with non-cardia cancer, 84.8% patients were diagnosed of poorly differentiated adenocarcinoma, more than half of the patients were diagnosed of T3–4, and 92 patients had lymph node metastasis, while the clinical stage III patients were accounted for 85%. Seventy point five percent patients were Borrmann III type. The median OS of the patients with increased preoperative serum CEA, CA125, CA19-9, AFP and combined were shorter than those patients with normal serum tumor markers, but without statistical significance (P=0.350, P=0.498, P=0.240, P=0.578 and P=0.219). The OS of patients with elevated levels of CEA, CA19-9, and AFP after operation were shorter than patients with decreased ones without statistical significance (P=0.321, P=0.118 and P=0.424). Elevated CA125 after operation was shorter than patients with decreased ones significantly (P<0.005).ConclusionsElevated of CA125 after operation was associated with poor OS in stage II–III GC patients.

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.

The relationship of neutrophil to lymphocyte ratio with testicular cancer.

ABSTRACTPurpose:To assess the relationship between testicular germ cell tumors (TGCT) and neutrophil to lymphocyte ratio (NLR) and to determine whether this ratio can be used as a serum tumor marker.Material and Methods:Sixty-one patients with testicular germ cell tumors were included into the study. Patients were grouped as localized and non-localized. Histologically patients were categorized as seminoma and nonseminomatous germ cell tumors. Complete blood cell count was measured the day before surgery and at the postoperative 1st month. Preoperative and postoperative mean NLR values were compared.Results:Thirty-six patients (59%) had seminomas and 25 patients (41%) had nonseminomatous testicular cancer. Forty-five patients (73.8%) had localized and 16 patients (26.2%) had non-localized testicular cancer. There was a statistically significant difference between preoperative and postoperative mean NLR of the localized patients (p=0.001) but no such difference was detected for non-localized patients (p=0.576). Nineteen patients with localized seminomas had normal preoperative serum tumor markers. There was a significant difference between preoperative and postoperative mean NLR in this group of patients (p=0.010). Twenty-six patients with localized tumors had preoperative increased serum tumor markers which normalized after orchiectomy. Mean NLR of these patients significantly decreased from 3.10±2.13 to 1.62±0.59 postoperatively (p=0.010).Conclusions:NLR appears to be a useful marker for TGCT. It is successful in predicting localized and non-localized disease in early postoperative period.

Multiple Paratesticular Fibrous Pseudotumors in an Adult Patient: Case Report

Abstract- Paratesticular fibrous pseudotumors (PFP) are relatively rare benign spindle cell tumors. These tumors usually are originated from testicularis tunics and grow into the epididymis and spermatic cord. PFP is a consequent of a reactive proliferation of inflammatory tissue. We report a case of PFP with simultaneous multiple tunica albuginea and tunica vaginalis lesions. A 33-year-old man presented with painless right scrotal lump, normal serum tumor markers, and one centimeter paratesticular mass in ultra-sonography that underwent testis-sparing surgery due to a benign microscopic appearance in frozen section evaluation. Testis sparing surgery can be considered as the preferred management because of the lack of obvious evidence of potential malignancy in this tumor

Prognostic value of serum tumor marker (STM) rate of decline during high-dose chemotherapy (HDCT) and peripheral-blood stem-cell transplant (PBSCT) for relapsed germ-cell tumors (rGCT).

e16044 Background: Rate of STM decline is prognostic in patients (pts) with metastatic GCT receiving first-line chemotherapy. We investigated the prognostic value of STM decline in pts with rGCT treated with HDCT and PBSCT. Methods: 444 consecutive pts with rGCT were treated with HDCT and PBSCT at Indiana University between 2004-2018. All pts were planned for 2 consecutive HDCT courses. Pts with elevated STM (AFP &gt; 25 and/or hCG &gt; 4.9) were included in this analysis. Slope and half-life (T1/2) were calculated for weekly AFP and hCG values during HDCT starting with peak value during days 1-7 to avoid interference from lysis. T1/2 AFP≤7 days and hCG≤3 days were categorized as satisfactory (SAT); normalization within 7 days was also considered SAT regardless of T1/2. Pts with elevated AFP and hCG must have adequate decline in both to be SAT. Progression-free (PFS) and overall survival (OS) were compared for SAT vs unsatisfactory (UNSAT) using log-rank test and analyzed using Kaplan-Meier methods. Results: 2-yr PFS for pts with elevated STM at initiation of HDCT (N = 335) was inferior to pts with normal STM (N = 109) [49% vs. 89%; p &lt; 0.001]. Among the 335 pts with elevated STM, 300 had non-seminoma and 35 had seminoma. Median age was 31 (range, 17-58). Primary site: testis (285), mediastinum (25), and retroperitoneum/other (25). Metastatic sites included retroperitoneum (267), lung (226), liver (81), brain (76), and bone (21). At initiation of HDCT, 73 pts had elevated AFP only, 215 had elevated hCG only, and 47 had elevated both AFP and hCG. Median AFP 9 (1-21,347) and hCG 115 (1-178,140). 307 pts (92%) completed 2 planned cycles of HDCT. Overall, 45/335 pts had SAT decline (13 for AFP; 29 for hCG; 3 for both). Pts with SAT STM decline had superior outcomes compared to UNSAT: 2-yr PFS 71% vs 46% (p = 0.004) and 2-yr OS 77% vs 52% (p = 0.004). When evaluating each STM separately, SAT decline in hCG had superior outcomes vs UNSAT: 2-yr PFS 76% vs 47% (p = 0.002). There was statistically non-significant difference in outcomes for AFP: 2-yr PFS 50% vs 43% (p = 0.55). Conclusions: SAT rate of STM decline predicts superior outcomes in pts with rGCT undergoing HDCT and PBSCT. Although UNSAT STM decline does not preclude long-term remissions, these pts are at higher risk of relapse and death.

Appropriateness for testis-sparing surgery based on the testicular tumor size in a pediatric and adolescent population

In children, most small testicular tumors are benign, and testicular-sparing surgery (TSS) is a viable treatment option. The objective of this study is to assess for correlation between the tumor size and final pathologic diagnoses appropriate for TSS for pediatric and adolescent patients with an intratesticular mass and negative serum tumor markers (STMs). A retrospective review of 24 patients (aged 0-18 years) who underwent radical or partial orchiectomy between 2003 and 2015. Patients with unifocal, unilateral intratesticular tumors and negative STMs were included. Tumors with benign and non-germ cell histology were considered appropriate for TSS, and active germ cell tumor elements on final histology were categorized as inappropriate for TSS. Baseline characteristics, tumor size, and frozen section results were evaluated for association, for the entire cohort and then for a subset of pubertal and postpubertal patients (defined as ≥10 years old). Patients with testicular tumor pathology inappropriate for TSS were significantly older (median age 17.1 years, P=0.03). A 2-cm size cutoff did not accurately predict pathology for the entire cohort, or for just pubertal and postpubertal patients (P=0.132, P=0.154, respectively). Frozen section and final pathology demonstrated good agreement (κ=0.826, P<0.001) as did pre-operative and final pathologic size measurement (κ=0.703, P<0.001). Frozen section analysis did not miss a TSS inappropriate pathology. The present data refute the finding in adults that a 2-cm cutoff accurately predicts pathology in pediatric patients with an intratesticular mass and normal STMs. These data suggest that TSS should still be offered, regardless of the tumor size alone, but frozen section appears to more accurately predict pathology than the tumor size, and its use should, thus, be emphasized. There are several limitations of this study to mention. First, this is a retrospective review of a small cohort of patients with a rare clinical scenario, which necessitated the combination of pediatric and adolescent patients. The study did not evaluate oncologic outcomes. In children with an intratesticular tumor and normal STMs, a tumor size cutoff of 2cm does not appear to accurately predict the final pathology. However, the data presented support the continued use intra-operative frozen section analysis in both children and adolescents undergoing TSS.

Conventional Tumor Markers in Cerebralspinal Fluid in Patients with Elevated Serum Tumor Markers and without Central Nervous System Malignant Diseases.

Objective To explore the diffusion pattern of tumor markers (TM) from serum to cerebrospinal fluid (CSF) via the blood-brain barrier in patients with elevated serum tumor markers (TM).Methods Inpatients receiving lumbar puncture during hospitalization in our center from January 1, 2013 to December 31, 2015 were divided into study group (n=181) and control group (n=251). The study group consisted of patients with elevated serum TMs but without malignant central nervous system diseases. The control group consisted of patients with normal serum TM levels and without malignant diseases. TMs measured in the study group included elevated serum alpha-fetoprotein (AFP) (n=0), carcinoembryonic antigen (CEA) (n=26), carcinomic antigen(CA)125 (n=39), CA15- 3 (n=3),CA19- 9 (n=19), CA724 (n=47), CYFRA21- 1 (n=49), and SCC (n=17).Levels of TMs in the CSF of study group was compared with that of control group.Results Median CEA (U=0.00,P=0.00),CA19- 9 (U=0.00,P=0.00),CA15- 3 (U=0.00,P=0.04),SCC (U=0.00,P=0.00),CA125 (U=0.00,P=0.00),CA72- 4 (U=3.00,P=0.00)),and CYFRA21- 1 (U=0.00,P=0.00) in CSF were significantly lower than the corresponding serum TM levels in the study group.There was no significant difference between study group and control group for the CSF level of CEA (U=3091.00,P=0.18),CA19- 9 (U=1897.00,P=0.14), CA15- 3 (U=373.50,P=0.91)and SCC (U=1925.50,P=0.76). CSF CA125 (U=2188.00,P=0.00) and CA724 (U=1279.00,P=0.00) levels in the study group were lower than those in control group. CSF level of CYFRA21- 1 (U=1826.50,P=0.00) in study group was higher than that in control group;however, it was still lower than the upper limit of reference value. Conclusion In patients with elevated serum CEA, CA19- 9, CA15- 3, SCC, CA125, and CA72- 4 levels, transblood-brain-barrier diffusion of TMs from serum to CSF is highly unlikely.

Inflammation-based prognostic system predicts postoperative survival of esophageal carcinoma patients with normal preoperative serum carcinoembryonic antigen and squamous cell carcinoma antigen levels.

BackgroundThe Glasgow Prognostic Score (GPS) is an established inflammation-based system that is used to predict the prognosis for several types of malignancies. In this retrospective study, we assessed the postoperative survival of 725 patients with non-metastatic esophageal squamous cell carcinoma who had normal preoperative serum tumor marker levels according to the GPS.MethodsAmong 1394 patients who underwent esophagectomy between August 2006 and December 2010, 725 with normal preoperative serum levels of carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag) were enrolled. All demographic, pathologic, and survival data were analyzed retrospectively. Uni- and multivariate analyses were performed to evaluate the relationship with overall survival. The Kaplan–Meier analysis and log-rank tests were used to compare the survival curves between patients with GPS 0 (group A) and 1 or 2 (group B).ResultsPatients in group A exhibited significantly better 3- and 5-year cancer-specific survival (CSS) rates (0.780 and 0.759, respectively) than those in group B (0.624 and 0.605, respectively). Multivariate Cox regression analysis revealed that age, tumor length, pathological tumor-node-metastasis (pTNM) stage, venous invasion, lymph node metastasis, serum albumin and C-reactive protein levels, and GPS were associated with postoperative survival of these patients. Further multivariate analysis confirmed that GPS was an independent prognostic factor. The Kaplan–Meier analysis and log-rank tests demonstrated a significant difference in CSS between groups A and B (P = 0.001).ConclusionsGPS may be a valuable prognostic indicator for esophageal cancer patients with normal preoperative CEA and SCC-Ag serum levels.