646 Background: Serum tumor markers (STM) are used in the management of patients with testicular cancer. However, a proportion have normal STM even with cancer present. Circulating tumor DNA (ctDNA) has shown promise in for detection of persistent disease. We sought to determine the utility of ctDNA for predicting retroperitoneal histology by comparing patients’ retroperitoneal lymph node dissection (RPLND) histology with their pre-operative ctDNA status. Methods: Patients undergoing primary (P-RPLND) or post-chemotherapy (PC-RPLND) from March 2023 to January 2024 had prospectively collected plasma ctDNA assay (Signatera, Natera Inc.) The association between ctDNA and RPLND histology was assessed. Sensitivity (SN), specificity (SP), and positive (PPV) and negative predictive values (NPV) were calculated for ctDNA to detect active cancer or teratoma alone in the RPLND histology. Results: Forty-six patients undergoing RPLND had pre-operative ctDNA collection with a median age of 33.5 (IQR:27-38.8). Plasma was collected on average, 8.6 days pre-operatively. Twenty (43.5%) patients underwent P-RPLND and 26 (56.5%) patients underwent PC-RPLND. ctDNA was positive in 23 (50%) patients. Two patients underwent P-RPLND for stage I disease and both had (-) ctDNA and histology. Eighteen patients underwent P-RPLND for stage II disease. Of these, 16 had active cancer, 1 had pure teratoma, and 1 had negative histology. ctDNA was positive in 15 of these patients all of which were found to have either teratoma or active cancer on pathology. Of the 3 patients with (-) ctDNA, 1 had negative histology, 1 had mixed, teratoma and seminoma, and 1 had pure seminoma. There were 26 patients who had ctDNA drawn prior to PC-RPLND. Of these, 4 had active cancer, 16 had pure teratoma, and 6 had necrosis on final RPLND histology. ctDNA was positive in 8 patients all of whom had either teratoma or active cancer on histology. Of the 18 PC-RPLND patients with a (-) ctDNA test, 1 had active cancer, 11 had teratoma, and 6 had necrosis. There were no false positive tests in the entire cohort. The SN, SP, PPV, and NPV were 85%, 77%, 74%, 87%, respectively for predicting active cancer. These numbers vary by primary or PC-RPLND patients (Table). Conclusions: To our knowledge, this is the first study evaluating test characteristics of ctDNA results in relation to RPLND histology. These findings suggest that ctDNA may be a useful adjunctive screening tool to predict active cancer or teratoma in the RP. Test characteristics of ctDNA stratified by primary or post-chemotherapy RPLND. Sensitivity Specificity PPV NPV P-RPLND GCT and/or Teratoma 88% 100% 100% 60% GCT only 88% 75% 93% 60% Teratoma only 100% 26% 7% 100% PC-RPLND GCT and/or teratoma 40% 100% 100% 33% GCT only 75% 77% 38% 94% Teratoma only 31% 70% 63% 39%
The purpose of this review is to present a comprehensive and updated review of the literature and summary of the indications, risks and outcomes related to salvage, desperation and late relapse surgery for advanced testicular cancer. After completing a thorough review of the current literature, this review has attempted to provide an overview of the indications for salvage, desperation and late relapse retroperitoneal lymph node dissection (RPLND) followed by a summary of the histopathologic and clinical outcomes regarding each. Recent literature, combined with a significant contribution from historical studies suggest that while testicular cancer is a relatively uncommon malignancy overall, it represents the most common solid organ malignancy for young men. Although a significant number of men are cured with a combination of first-line treatments, the remaining men are a diverse and often challenging cohort who require the benefit of expertise to improve their outcomes. The role of surgical strategies in the salvage, desperation and late relapse settings is unquestionable, although the most important question remains who will benefit. This often requires a multi-disciplinary approach at centers specializing in this disease process in order to recognize who should get surgery, what surgery to do and how to minimize the potential morbidity associated with the operation.
157 Background: Men who are found to have positive LN at the time of RP are at risk for worse prognosis and outcomes. Our purpose is to determine whether RT after RP has a greater survival benefit than ADT alone or surgery alone in these men. Methods: This study cohort consisted of men who had RP at the University of California, San Francisco. Men with positive pelvic LN were stratified by type of adjuvant therapy: ADT, RT with or without ADT, or RP only. T-test and chi-square were used to compare clinical and pathologic characteristics. Biochemical recurrence-free, metastatic recurrence-free, and disease-specific survival were assessed with the Kaplan-Meier method, log-rank test, and Cox proportional hazards regression. Biochemical recurrence was defined as two consecutive prostate-specific antigen values >=0.2ng/mL. Results: Of the 1,600 men had pelvic LN dissection at time of RP, 105 had positive LN. Mean age was 61 (SD 7). Median number of LN dissected was 14 (IQR 10-21) for pN1 patients versus nine (5 to 15) for pN0, p<0.01. Median percentage of positive LN was 11% (IQR 7-17). Men with positive LN had higher clinical risk and worse pathologic grade, positive margin rates, and T-stage compared to men without positive LN, all p<0.01. Recurrence-free survival was 55% for pN1 versus 81% for pN1 at 5 years, log-rank p<0.01. Following positive LN dissection at RP, 29 men received ADT monotherapy, 43 men received RT (+/- ADT), and 33 had not yet undergone treatment after RP during a median follow up of 28 months (IQR 6 to 70). Rates of seminal vesicle invasion by treatment group were 52% for ADT, 65% for RT (+/- ADT), and 35% for RP only, p=0.03. Men who underwent ADT alone, RT (+/- ADT), and RP only had few outcome events to date and similar rates of MFS (97% versus 93% versus 92%, p=0.76) and DSS (96% vs. 100% vs. 100%, p=0.32) at 3 years. Cox regression adjusted for surgical CAPRA score also showed that MFS and DSS did not differ between ADT alone, RT (+/- ADT), and RP only groups. Conclusions: Men with positive LN at the time of RP have aggressive clinical and pathologic features. Nevertheless, metastatic recurrence-free and prostate cancer-specific survival rates 3 years after surgery remain good. Although no additional survival benefit to post-RP RT was seen in this cohort of men with limited follow up, further follow up is ongoing.
PURPOSE On the basis of National Comprehensive Cancer Network guidelines, clinical stage (CS) II seminoma is treated with radiotherapy or chemotherapy. Primary retroperitoneal lymph node dissection (RPLND) demonstrated recent success as first-line therapy for RP-only disease. Our aim was to confirm surgical efficacy and evaluate recurrences after primary RPLND for CS IIA/IIB seminoma to determine if various clinical factors could predict recurrences. PATIENTS AND METHODS Patients who underwent primary RPLND for seminoma from 2014 to 2021 were identified. All patients had at least 6 months of follow-up. Nineteen patients were part of a clinical trial. Patients receiving adjuvant chemotherapy were excluded from Kaplan-Meier recurrence-free survival (RFS) analysis. RESULTS We identified 67 patients who underwent RPLND for RP-only seminoma. One patient had pN0 disease. Median follow-up time after RPLND was 22.4 months (interquartile range, 12.3-36.1 months) and 11 patients were found to have a recurrence. The 2-year RFS for RPLND-only patients without adjuvant chemotherapy was 80.2%. Patients who developed RP disease for a period > 12 months had the lowest chance of recurrence, with a 2-year RFS of 92.2%. Seven initial CS II patients were on surveillance for 3-12 months before surgery and no patients experienced recurrence. Pathologic nodal stage and high-risk factors such as tumor size > 4 cm or rete testis invasion of the orchiectomy specimen did not affect recurrence. CONCLUSION CS II seminoma can be treated with surgery to avoid rigors of chemotherapy or radiotherapy. Patients with delayed development of CS II disease (> 12 months) had the best surgical results. Patients may present with borderline CS II disease, and careful surveillance may avoid overtreatment. Further study on patient selection and extent of dissection remains uncertain and warrants further investigation.
388 Background: Understanding the genetic alterations in patients with relapsed/refractory GCT (rrGCT) could delineate the pathogenesis of cisplatin resistance. Our study uses CGP to characterize genomic alterations (GA) in refractory GCT and correlate with clinical outcomes. Methods: 432 patients with rrGCT were seen at Indiana University between Jan 2016 to Sep 2019 of whom 52 patients underwent CGP using a hybrid-capture based commercial assay to evaluate all classes of GA. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and reported as mutations/Mb and microsatellite instability (MSI) was determined on 114 loci. PDL1 expression was determined by IHC (DAKO 22C3 antibody). Results: All patients relapsed after first-line cisplatin-based combination chemotherapy. Median age at diagnosis was 33 (range 15-68). Primary site of GCT was testicular in 85% and mediastinum in 8%. 6 patients had pure seminoma and 46 had non-seminoma. Platinum refractory disease, defined as serologic or radiographic progression within 4 weeks of first-line chemotherapy comprised 23% of patients. The primary tumor was used for sequencing in 6 cases (12%) and non-primary tumor metastatic site (lymph node, lung, liver, brain, omentum) in 46 cases (88%). The most common GA in the entire cohort were FGF6 (27%), FGF23 (27%), KDM5A (27%), CCND2 (27%), KRAS (18%), TP53 (14%), KIT (8%), APC (8%), ZNF217 (6%), MUTYH (6%), AURKA (6%), NRAS (6%), EGFR (6%), CTNNB1 (6%), GNAS (6%). Most common alterations for testicular primary tumors were FGF6, FGF23, KDM5A, CCND2, KRAS, TP53, KIT. For non-testicular primary GCT, most common GA were APC, TP53, EGFR. Most common GA for non-seminoma were FGF6, FGF23, KDM5A, CCND2, KRAS, TP53, APC. Most common GA for pure seminoma was KIT. Potentially targetable genomic alterations were found in 17 patients (33%). 10 of 17 patients (59%) tested had PDL1 score ≥1% and 3 patients had PDL1 ≥50%. Median TMB was 3.5 mutations/MB. There were 4 patients (8%) with TMB ≥ 10 mutations/Mb and 2 patients (4%) with TMB ≥ 20 mutations/Mb. 1 of 48 patients (2%) evaluated for MSI had MSI-High status. Isochromosome 12p was detected in the majority of samples where it was tested. Outcomes with GA-directed therapy will be presented at the conference. Conclusions: CGP can reveal potential therapeutic targets in patients with rrGCT including EGFR, ERBB3, KIT, and MET. Consistent with reported clinical trials in rrGCT, biomarkers predicting response to immune checkpoint blockade are uncommon with most patients having low TMB, absence of MSI-H status, and low expression of PDL1.
