Surveillance after Complete Response to First-Line Chemotherapy in Patients with Metastatic Nonseminomatous Germ Cell Tumor.

PURPOSE: The optimal management of patients with metastatic germ cell tumors who achieve a complete response (CR) after first-line chemotherapy remains unsettled. This study reports long-term outcomes of patients with metastatic germ cell tumor managed with surveillance after achieving a CR to first-line chemotherapy. MATERIALS AND METHODS: Patients with metastatic nonseminomatous germ cell tumor treated at Indiana University between 1990 and 2017 who achieved a CR after first-line chemotherapy and were monitored with surveillance were retrospectively analyzed. CR was defined as normalization of tumor markers AFP and hCG, and no residual mass >1 cm in long axis. Kaplan-Meier methods were used to analyze progression-free survival (PFS) and overall survival (OS). RESULTS: Three hundred sixty-seven patients achieved a CR and were managed with surveillance. After a median followup of 4.97 years, 34 patients had disease progression. At most recent followup, 346 (94%) patients were alive with no evidence of disease, 10 patients (2.7%) died of their disease, 5 (1.4%) died of other causes and 6 (1.6%) were lost to followup. The estimated 2-year PFS was 91% (95% CI: 87%-94%) and 2-year OS was 98% (95% CI: 96%-99%). The estimated 2-year PFS by International Germ Cell Cancer Collaborative Group risk category was 92% for good vs 90% for intermediate vs 87% for poor risk (p=0.15), and the estimated 2-year OS was 99% for good vs 96% for intermediate vs 93% for poor risk disease (p=0.001). CONCLUSIONS: Patients with metastatic nonseminomatous germ cell tumor who achieve a CR after first-line chemotherapy can be observed. Most patients who relapse can be salvaged with surgery and/or chemotherapy.

Percentage of Teratoma in Orchiectomy and Risk of Retroperitoneal Teratoma at the Time of Postchemotherapy Retroperitoneal Lymph Node Dissection in Germ Cell Tumors.

PURPOSE: Presence of teratoma in the orchiectomy and residual retroperitoneal mass size are known predictors of finding teratoma during postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). We sought to determine if the percentage of teratoma in the orchiectomy specimen could better stratify the risk of teratoma in the retroperitoneum. MATERIALS AND METHODS: The Indiana University Testis Cancer Database was reviewed to identify patients who underwent PC-RPLND for nonseminomatous germ cell tumors from 2010 to 2018. A logistic regression model was fit to predict the presence of retroperitoneal teratoma using teratoma and yolk sac tumor in the orchiectomy, residual mass size and log transformed values of prechemotherapy alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin. The study cohort was split into 60% training and 40% validation sets using 200 bootstraps. A predictive nomogram was developed for predicting teratoma in the retroperitoneum. RESULTS: A total of 422 men were included. Presence of teratoma in the orchiectomy (OR 1.02, p <0.001), residual mass size (OR 1.16, p <0.001) and log transformed prechemotherapy AFP (OR 1.12, p=0.002) were predictive factors for having teratoma in the retroperitoneum. The C-statistic using this model demonstrated a predictive ability of 0.77. Training set C-statistic was 0.78 compared to 0.75 for the validation set. A nomogram was developed to aid in clinical utility. CONCLUSIONS: The model better predicts patients at higher risk for teratoma in the retroperitoneum following chemotherapy, which can aid in a more informed referral for surgical resection.

Management of patients with metastatic teratoma with malignant somatic transformation.

PURPOSE OF REVIEW: The purpose of this review is to examine the historical context alongside contemporary studies in order to provide the most current recommendations for the management of patients with metastatic teratoma with malignant somatic transformation (MST). RECENT FINDINGS: The main themes in the recent literature covered herein include prognostic features, the management of early-stage disease, recommended chemotherapeutic and surgical strategies as well as recognized patterns of late relapse. SUMMARY: Recent literature, combined with a significant contribution from historical studies, suggests that while MST is uncommon, its aggressive nature coupled with its resistance with traditional germ cell tumor chemotherapies makes it very difficult to manage. The key message is that surgery is recommended in all resectable MST from primary retroperitoneal lymph node dissection for clinical stage I, to radical removal of disease after chemotherapy and when chemotherapy fails. In advanced cases with documented spread of the transformed histologic subtype, systemic therapies targeted to the identified tumor type should be considered.

Treatment and Clinical Outcomes of Patients with Teratoma with Somatic-Type Malignant Transformation: An International Collaboration.

PURPOSE: We assessed prognostic factors, treatments and outcomes in patients with teratoma with malignant transformation, a rare occurrence among germ cell tumors. MATERIALS AND METHODS: Data on patients diagnosed with teratoma with malignant transformation between June 1981 and August 2014 were collected across 5 referral centers. Chemotherapy was dichotomized as based on germ cell tumor or teratoma with malignant transformation. Cox analyses were done to evaluate prognostic factors of overall survival, the primary end point. Each factor was evaluated in a univariable model. Forward stepwise selection was used to construct an optimal model. RESULTS: Among 320 patients the tumor primary site was gonadal in 287 (89.7%), retroperitoneal in 17 (5.3%) and mediastinal in 16 (5%). Teratoma with malignant transformation and germ cell tumor were diagnosed concurrently in 130 patients (40.6%). A total of 49 patients (16.8%) initially presented with clinical stage I. The remaining patients were at good (123 or 42.3%), intermediate (42 or 14.4%) and poor (77 or 26.5%) risk for metastasis according to IGCCCG (International Germ Cell Cancer Collaborative Group). First line chemotherapy was given for germ cell tumor in 159 patients (49.7%), chemotherapy for teratoma with malignant transformation was performed in 14 (4.4%) and only surgery was done in 147 (45.9%). Median followup was 25.1 months (IQR 5.4-63.8). Five-year overall survival was 83.4% (95% CI 61.3 to 93.5) in patients with clinical stage I and it was also worse than expected in those with metastasis. On multivariable analyses nonprimitive neuroectodermal tumor histology (overall p = 0.004), gonadal primary tumor (p = 0.005) and fewer prior chemotherapy regimens (p <0.001) were independent predictors of better overall survival. Chemotherapy was not independently prognostic. CONCLUSIONS: Less heavily pretreated teratoma with malignant transformation with a gonadal primary tumor and nonprimitive neuroectodermal tumor histology appears to be associated with longer overall survival. Generally, teratoma with malignant transformation had a worse prognosis than germ cell tumor. Uncertainties persist regarding optimal chemotherapy.

Neoadjuvant chemotherapy in urothelial bladder cancer: impact of regimen and variant histology.

AIM: We compared the efficacy of methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) versus gemcitabine/cisplatin in urothelial cancer and neoadjuvant chemotherapy (NACT) efficacy in variant histology (VH). MATERIALS & METHODS: Radical cystectomy patients were retrospectively compared with those who received NACT. Factors associated with survival, pathologic complete response (pCR) and downstaging (pDS) were evaluated in multivariable models. RESULTS: 9% of radical cystectomy patients (84/919) received NACT, with improved survival, pCR and pDS on both regimens. MVAC lead to higher pDS without an increase in pCR. On multivariable analysis, there was a nonsignificant increase in pDS with MVAC. NACT conferred similar responses in squamous and glandular differentiation VH. CONCLUSION: NACT was associated with improved survival, pCR and pDS. Furthermore, responses to NACT were not dependent on presence of VH.

Outcomes of postchemotherapy retroperitoneal lymph node dissection following high-dose chemotherapy with stem cell transplantation.

BACKGROUND: Characterizing the role of postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) after high-dose chemotherapy (HDCT) has been limited by small sample sizes. This study reports on survival after HDCT with stem cell support and PC-RPLND as well as histologic findings in the retroperitoneum. METHODS: The prospectively maintained testicular cancer database of Indiana University was queried for patients receiving HDCT with stem cell transplantation before PC-RPLND. The cause and date of death were obtained through patient chart review and contact with referring physicians. The Kaplan-Meier method was used to evaluate overall survival (OS). The log-rank test was used for tests of significance. A multivariate, backward, stepwise Cox regression model was built to evaluate predictors of overall mortality. RESULTS: A total of 92 patients were included in the study. In the entire cohort, the retroperitoneal (RP) histology findings at the time of PC-RPLND were necrosis (26%), teratoma (34%), and cancer (38%). Sixty-six patients (72%) harbored either a teratoma or active cancer in the RP specimen at PC-RPLND. The median follow-up for the entire cohort was 80.6 months. A total of 28 patients (30%) died during follow-up. The 5-year OS rate of the entire cohort was 70%. The most significant predictor of death was PC-RPLND performed in the desperation setting with elevated markers. CONCLUSIONS: Despite these patients being heavily pretreated with multiple cycles of chemotherapy, including HDCT, approximately three-fourths were found to have a teratoma and/or active cancer in the retroperitoneum. This underscores the importance of PC-RPLND for rendering patients free of disease and providing a potential for cure.

The impact of bleomycin on retroperitoneal histology at post-chemotherapy retroperitoneal lymph node dissection of good risk germ cell tumors.

PURPOSE: Induction chemotherapy for International Germ Cell Cancer Collaborative Group (IGCCCG) good risk metastatic testicular cancer includes 3 cycles of bleomycin, etoposide and cisplatin (BEP x3) or 4 cycles of etoposide and cisplatin (EP x4). We examine differences in active cancer in the retroperitoneum between patients receiving BEP x3 compared to EP x4. MATERIALS AND METHODS: The Indiana University Testis Cancer database was queried to identify IGCCCG good risk patients who received BEP x3 or EP x4 induction chemotherapy before retroperitoneal lymph node dissection. The primary outcome of interest was retroperitoneal histology. The association between the use of bleomycin in the induction regimen with active cancer in the retroperitoneal specimen was tested using a propensity score adjusted analysis. RESULTS: A total of 179 men (79%) received BEP x3 while 47 (21%) received EP x4. Median age of the bleomycin, etoposide and cisplatin group was 27 years (range 15 to 50) vs 30 years (range 18 to 71) in the etoposide and cisplatin group. The incidence of active cancer in the retroperitoneal specimen at post-chemotherapy retroperitoneal lymph node dissection was significantly higher in the EP x4 group compared to the BEP x3 group (31.9% vs 7.8%, p <0.01). This significant difference in the bleomycin, etoposide and cisplatin vs etoposide and cisplatin groups remained in the propensity adjusted analysis (22.9% vs 7.8%, p=0.015). CONCLUSIONS: There was a higher incidence of active cancer in the retroperitoneal specimen in good risk patients who received 4 cycles of induction etoposide and cisplatin chemotherapy compared to 3 cycles of bleomycin, etoposide and cisplatin in this retrospective analysis. The overall burden of treatment may be higher for men receiving EP x4 for induction chemotherapy.

The changing reality of urothelial bladder cancer: should non-squamous variant histology be managed as a distinct clinical entity?

OBJECTIVES: To assess the effect of non-squamous differentiation (non-SQD) variant histology on survival in muscle-invasive bladder urothelial cancer (UC). PATIENTS AND METHODS: A cohort of 411 radical cystectomy (RC) cases performed with curative intent for muscle-invasive primary UC was identified between 2008 and June 2013. Survival analysis was evaluated using Kaplan-Meier methodology comparing non-variant (NV) + SQD histology to non-SQD variant histology (non-SQD variants). Multivariable cox proportional hazards regression assessed all-cause and disease-specific mortality. RESULTS: Of the 411 RC cases, 77 (19%) had non-SQD variant histology. The median overall survival (OS) for non-SQD variant histology was 28 months, whereas the NV+SQD group had not reached the median OS at 74 months (log-rank test P < 0.001). After adjusting for sex, age, pathological stage, and any systemic chemotherapy, patients with non-SQD variant histology at RC had a 1.57-times increased adjusted risk of all-cause mortality (P = 0.027) and 1.69-times increased risk of disease-specific mortality (P = 0.030) compared with NV+SQD patients. CONCLUSIONS: While SQD behaves similarly to NV, non-SQD variant histology portends worse OS and disease-specific survival regardless of neoadjuvant or adjuvant chemotherapy and pathological stage. Non-SQD variants of UC could perhaps be considered a distinct clinical entity in UC with goals for developing new treatment algorithms through novel clinical trials.

Three-tiered nodal classification system for bladder cancer: a new proposal.

AIM: To evaluate a three-tiered prognostic stratification using one, two to five and >five positive lymph nodes (LNs) and this nodal staging system performs across different pelvic LN dissection (PLND) templates and adjuvant chemotherapy status. METHODS: We evaluated 244 patients with positive LN urothelial cancer who underwent radical cystectomy and PLND between 2000 and 2011. Survival analyses utilizing the Kaplan-Meier method and log rank test were performed. Median follow-up was 55.3 months (range: 0.4-141). Multivariable Cox proportional hazards models were built to evaluate the prognostic stratification. RESULTS: Extended PLND template was performed on 152 (62.3%) patients and standard on 92 (37.7%). The median number of LNs resected was 14 in the standard group vs 22 in the extended group (p < 0.01) and positive LNs was 2 vs 3 (p = 0.09), respectively. Stratification in patients with: one positive LN, two to five positive LNs or >five positive LNs lead to 5-year recurrence-free survival of: 48.6, 34.5 and 15.9% for each group, while the 5-year overall survival was: 43.0, 22.1 and 11.3%, respectively. Stratification in the three groups was also verified irrespective of PLND template and adjuvant chemotherapy. Two multivariable models confirmed the findings when controlling for demographic features and known pathologic risk factors. CONCLUSION: Three-tiered nodal classification system using the number of metastatic LNs (one, two to five and >five) stratifies patients with lymphatic disease into distinct prognostic groups.

Differentiating reconstructive techniques in partial nephrectomy: a propensity score analysis.

INTRODUCTION: To assess whether volumetric measurements can differentiate functional changes between reconstructive techniques after partial nephrectomy. MATERIALS AND METHODS: One hundred and fifty-six patients undergoing partial nephrectomy for a single renal mass were retrospectively studied between 2008 and 2012. Computed tomography scans were available for volume calculations on 56 (18 non-renorrhaphy and 38 renorrhaphy). Institutional review board approval was obtained. The primary outcome was %volume loss in the operated kidney, which was calculated from three-dimensional reconstructions using a semiautomatic segmentation algorithm. Multivariable regression and propensity score analysis was performed. RESULTS: Volumetric analysis detected a difference in mean %volume loss between two-layer reconstruction (cortical renorrhaphy and base-layer) and base-layer only (15.6% versus 3.8%, p < 0.001). The mean %glomerular filtration rate (GFR) loss was also greater in the two-layer group (8.9% versus 2.4%, p = 0.03). Demographics were similar between groups except the two-layer group was older, had more males, and increased ischemia time. On multivariable regression the presence of two-layer closure (ß = -15.2%, p < 0.001) and tumor diameter (ß = -7.4, p = 0.004) were significant predictors of %volume loss while ischemia time (p = 0.88) was not. Two-layer closure remained a predictor on propensity-adjusted analysis (ß = -14.3, p = 0.004). The base-layer only group had two (5.3%) urine leaks and two (5.3%) bleeding complications. The two-layer group had two (1.7%) urine leaks and three (2.5%) bleeding complications (p = 0.23, 0.41). CONCLUSIONS: Volume loss calculated from CT scans can be used to monitor postoperative renal function. Techniques for renal reconstruction and tumor diameter are associated with volume and functional loss after partial nephrectomy and should be controlled for in future studies.

Reoperative retroperitoneal lymph node dissection for metastatic germ cell tumors: analysis of local recurrence and predictors of survival.

PURPOSE: While reoperative retroperitoneal lymph node dissection results in durable long-term survival, outcomes are comparatively worse than in patients who undergo initial adequate resection. We identified predictors of cancer specific survival and correlated technical aspects of initial resection to local recurrence in patients treated with repeat retroperitoneal lymph node dissection. MATERIALS AND METHODS: We reviewed subsequent data on 203 patients treated with reoperation for recurrent retroperitoneal germ cell tumor after initial retroperitoneal lymph node dissection with local relapse. We used multivariate Cox proportion hazard models for cancer specific survival and multivariate logistic regression for local recurrence. RESULTS: The only 2 factors associated with local recurrence at lymph node dissection were incomplete lumbar vessel division at initial resection (p<0.01) and teratoma histology in the reoperative pathology specimen (p=0.01). Median followup was 73 months. Initial survival analysis including preoperative variables indicated that active cancer at initial operation (p=0.04), increased serum tumor markers (p=0.02), M1b stage (p<0.01) and salvage chemotherapy (p=0.01) were independent predictors of worse cancer specific survival. After introducing the final pathological data from reoperation into the final multivariate model only active cancer at reoperation (p<0.01), M1b stage (p=0.01) and salvage chemotherapy before reoperation (p=0.02) retained the association with worse oncologic outcomes. CONCLUSIONS: Tumor biology and inadequate surgical technique (incomplete lumbar ligation) are associated with local recurrence after initial retroperitoneal lymph node dissection. Decreased cancer specific survival is expected in this population, mostly driven by active cancer in the final pathology specimen.

Management of germ cell tumors with somatic type malignancy: pathological features, prognostic factors and survival outcomes.

PURPOSE: Germ cell tumors with somatic type malignancy are rare, occurring in approximately 2.7% to 8.6% of germ cell tumor cases. Prognostic factors and optimal management remain poorly defined. MATERIALS AND METHODS: The Indiana University testis cancer database was queried from 1979 to 2011 for patients demonstrating germ cell tumor with somatic type malignancy at orchiectomy or subsequent resection. Patients with transformation to primitive neuroectodermal tumor only were excluded from study due to distinct management. Chart review, pathological review and survival analysis were performed. RESULTS: A total of 121 patients met the study inclusion criteria. The most common somatic type malignancy histologies were sarcoma (59), carcinoma (31) and sarcomatoid yolk sac tumor (17). Of these patients 32 demonstrated somatic type malignancy at germ cell tumor diagnosis. For those with delayed identification, median time from germ cell tumor to somatic type malignancy diagnosis was 33 months. This interval was longest for carcinomas (108 months). At a median followup of 71 months, 5-year cancer specific survival was 64%. Predictors of poorer cancer specific survival included somatic type malignancy diagnosed at late relapse (p = 0.017), referral to Indiana University for reoperative retroperitoneal lymph node dissection (p = 0.026) and grade (p = 0.026). None of these factors maintained prognostic significance on multivariate analysis. Somatic type malignancy histology subtype, stage, risk category and number of resections were not predictive of cancer specific survival. CONCLUSIONS: Germ cell tumor with somatic type malignancy is associated with poorer cancer specific survival than traditional germ cell tumor. Established prognostic factors for germ cell tumor lose predictive value in the setting of somatic type malignancy. Aggressive and serial resections are often necessary to optimize cancer specific survival. Tumor grade is an important prognostic factor in sarcomas and sarcomatoid yolk sac tumors.

Survival analysis of pure seminoma at post-chemotherapy retroperitoneal lymph node dissection.

PURPOSE: Viable seminoma encountered at post-chemotherapy retroperitoneal lymph node dissection for pure testicular seminoma is rare due to the chemosensitivity of this germ cell tumor. In this study we define the natural history of viable seminoma at post-chemotherapy retroperitoneal lymph node dissection. MATERIALS AND METHODS: The Indiana University testis cancer database was queried from 1988 to 2011 to identify all patients with primary testicular or retroperitoneal pure seminoma and who were found to have pure seminoma at post-chemotherapy retroperitoneal lymph node dissection. Clinical characteristics were reviewed and survival analysis was performed. RESULTS: A total of 36 patients met the study inclusion criteria. All patients received standard first line cisplatin based chemotherapy and 17 received salvage chemotherapy. The decision to proceed to retroperitoneal lymph node dissection was based on enlarging retroperitoneal mass and/or positron emission positivity in the majority of cases. Seven patients had undergone previous retroperitoneal lymph node dissection. Additional surgical procedures were required in 19 patients to achieve a complete resection. The 5-year cancer specific survival rate was 54%. However, only 9 of 36 patients remained continuously free of disease and of these patients 4 received adjuvant chemotherapy. Mean time from post-chemotherapy retroperitoneal lymph node dissection to death was 6.9 months. Second line chemotherapy, reoperative retroperitoneal lymph node dissection and earlier era of treatment were associated with poorer cancer specific survival. CONCLUSIONS: A total of 36 patients with pure seminoma were found to have viable pure seminoma at post-chemotherapy retroperitoneal lymph node dissection. While 5-year cancer specific survival was 54%, these surgeries are technically demanding and only a minority of patients achieves a durable cure from surgery alone.

Clinical and pathological features predictive of nephrectomy at post-chemotherapy retroperitoneal lymph node dissection.

PURPOSE: We determined the clinical and pathological features associated with nephrectomy at post-chemotherapy retroperitoneal lymph node dissection. MATERIALS AND METHODS: We retrospectively reviewed the testis cancer database from 1980 to 2007 to identify all patients treated with post-chemotherapy retroperitoneal lymph node dissection. Patients with pure seminoma and nongerm cell histology were excluded from study. A total of 1,807 patients were identified, of whom 17 without recorded mass size were excluded from further study. Pathological and clinical variables were assessed by bivariate analysis. Multivariate logistic regression was used to determine predictors of nephrectomy at post-chemotherapy retroperitoneal lymph node dissection. RESULTS: The overall incidence of nephrectomy at post-chemotherapy retroperitoneal lymph node dissection was 14.8% (265 of 1,790 cases). The incidence of nephrectomy was 17.0%, 18.9%, 13.6% and 8.0% in 1980 to 1988 (group 1), 1989 to 1997 (group 2), 1998 to 2002 (group 3) and 2002 to 2007 (group 4) (p = 0.0001). The nephrectomy rate for tumors less than 2, 2 to 5, 5 to 10 and greater than 10 cm was 6.0%, 5.8%, 13.9% and 31.9%, respectively (p = 0.0001). The incidence of nephrectomy based on retroperitoneal histology was 10.3% for fibrosis, 14.5% for teratoma and 20.4% for cancer (p = 0.0001). The strongest predictor of nephrectomy at post-chemotherapy retroperitoneal lymph node dissection was retroperitoneal mass size greater than 10 cm (OR 9.30, 95% CI 3.8-22.7). CONCLUSIONS: The incidence of nephrectomy at post-chemotherapy retroperitoneal lymph node dissection has decreased in the last 3 decades. A higher incidence was observed in patients with larger volume tumors, those who received salvage chemotherapy, those with a left primary testicular tumor and those with increased markers at post-chemotherapy surgery.

Incidence, histology and management of intraluminal thrombus at post-chemotherapy retroperitoneal lymph node dissection.

PURPOSE: We determined the incidence, histology and management of intraluminal thrombus in a large group of patients treated with post-chemotherapy retroperitoneal lymph node dissection. MATERIALS AND METHODS: We queried the testicular cancer database at our institution from January 1990 to June 2010. Tumor resection en bloc with major vascular structures and/or thrombectomy at post-chemotherapy retroperitoneal lymph node dissection was done in 240 patients, of whom 89 had a total of 98 intraluminal thrombi involving major vasculature. RESULTS: The site of the 98 thrombi was the inferior vena cava (72), aorta (1) and renal vein (20). Management of the 72 vena caval thrombi included cavectomy (36), partial cavectomy (9) and thrombectomy (27). For the 20 renal vein thrombi management included nephrectomy (18) and thrombectomy (2). The single aortic thrombus was managed by aortic resection and replacement. Pathological evaluation revealed bland thrombi in 31 cases, necrosis in 23, teratoma in 28, active germ cell cancer in 12 and sarcoma in 4. In 40 patients a total of 71 additional procedures were required, including nephrectomy in 32, liver resection in 6, bowel resection in 7, thoracotomy in 6, vertebral resection in 3, orchiectomy in 11, and duodenal repair, ureteroureterotomy, stent removal, cholecystectomy, appendectomy and paraspinal tumor removal in 1 each. There were 17 Clavien III or worse complications in a total of 11 patients, including 2 deaths. Average estimated blood loss was 1,165 ml (range 200 to 7,000) and average hospital stay was 9.3 days (range 2 to 70). CONCLUSIONS: The incidence of intraluminal thrombus at post-chemotherapy retroperitoneal lymph node dissection is 5.8%. Cancer pathology was observed in 44.9% of cases. Surgeons who perform post-chemotherapy retroperitoneal lymph node dissection should be well versed in vascular techniques with respect to the major vasculature.

Late Relapse of Germ Cell Tumors After Prior Chemotherapy or Surgery-only.

BACKGROUND: Late relapse (LR) of germ cell tumor (GCT) is defined as relapsed disease >2 years from initial treatment. LR remains a challenge both for optimal screening methods and management. We report the method of detection, treatments received, and outcomes in patients with chemotherapy-exposed vs chemotherapy-naïve LR GCT. PATIENTS AND METHODS: The Indiana University testicular cancer database was queried identifying 131 patients with LR GCT evaluated at Indiana University from January 2000 to January 2019. Method of detection of LR was recorded along with site, treatment received, and survival outcomes. The cohort was divided into 4 groups according to seminoma versus non-seminoma GCT (NSGCT) and chemotherapy-exposed vs chemotherapy-naïve LR. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and compared using the log-rank test. Medians with 95% confidence intervals were also calculated along with the 2-year probabilities. RESULTS: Median age at LR was 38.3 (range, 19.3-56.8). Chemotherapy-exposed accounted for 75 (57%) and chemotherapy-naïve for 56 (43%) of cases. The 2-year OS comparing chemotherapy-exposed versus chemotherapy-naïve was 78.2% versus 100% (P = .0003). For the 72 chemo-exposed NSGCT LR pts, 2-year PFS based on treatment: surgery vs chemotherapy versus surgery + chemotherapy was 67.1% versus 0% versus 47.1% (P < 0.0001). Fifty-nine percent of chemotherapy-exposed LR had elevation of alpha fetoprotein (AFP) at LR diagnosis. CONCLUSION: GCT pts require lifetime follow-up with annual physical exam and tumor markers. Surgical resection, when feasible, remains the preferred treatment for chemotherapy-exposed LR. Chemotherapy-exposed LR has worse outcomes compared to chemotherapy-naïve LR patients.

Primary Retroperitoneal Lymph Node Dissection for Stage II Seminoma: Is Surgery the New Path Forward?

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.

Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for seminoma: Limitations of surgical intervention after first-line chemotherapy.

PURPOSE: Patients with relapsed seminoma after first-line chemotherapy can be treated with salvage chemotherapy or postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). Based on prior experience, surgical management can have worse efficacy and increased morbidity compared to nonseminomatous germ cell tumor. Our aim was to characterize the surgical efficacy and difficulty in highly selected patients with residual disease after first-line chemotherapy. MATERIALS AND METHODS: The Indiana University testis cancer database was queried to identify men who underwent PC-RPLND for seminoma between January 2011 and December 2021. Included patients underwent first-line chemotherapy and had evidence of retroperitoneal disease progression. RESULTS: We identified 889 patients that underwent PC-RPLND, of which only 14 patients were operated on for seminoma. One patient was excluded for lack of follow-up. Out of 13 patients, only 3 patients were disease free with surgery only. Median follow up time was 29.9 months (interquartile ranges : 22.6-53.7). Two patients died of disease. The remaining 8 patients were treated successfully with salvage chemotherapy. During PC-RPLND, 4 patients required nephrectomy, 1 patient required an aortic graft, 2 patients required a partial ureterectomy, and 3 patients required partial or complete caval resection. CONCLUSION: The decision between salvage chemotherapy and PC-RPLND as second-line therapy can be challenging. Salvage chemotherapy is effective but is associated with short and long-term morbidity. Surgical efficacy in this setting seems to be limited, but careful selection of patients may lead to surgical success without affecting the ability to receive any systemic salvage therapies if necessary or causing life-threating morbidity.

Molecular genetic evidence supporting the neoplastic nature of fibrous stroma in testicular teratoma.

Testicular teratoma typically consists of heterogeneous mixtures of diverse epithelial and stromal components. The biological nature and genetic characteristics of the fibrous stroma of testicular teratomas have not been thoroughly investigated. Chromosome 12p abnormalities are the hallmark genetic alterations of germ cell tumors. We studied chromosome 12p abnormalities in the fibrous stroma and other components of pure testicular teratomas from 32 patients using interphase fluorescence in situ hybridization. Overall, 72% (23/32) of pure testicular teratomas had chromosome 12p abnormalities. Isochromosome 12p or 12p overrepresentation independent of isochromosome 12p was detected in the fibrous stroma in 53% (17/32) and 41% (13/32) of cases, respectively. Among the 17 cases positive for isochromosome 12p, 8 (47%) also had 12p overrepresentation. In 31% (10/32) cases, the fibrous stroma showed neither 12p overrepresentation nor isochromosome 12p. Isochromosome 12p and 12p overrepresentation were identified, respectively, in the gastrointestinal-type epithelium of 14/23 (61%) and 15/23 (65%) cases; in the respiratory-type epithelium of 41% (7/17) and 41% (7/17) cases; in the squamous epithelium of 62% (8/13) and 54% (7/13) cases; and in the cartilage of 63% (5/8) and 38% (3/8) cases. Concordant chromosomal 12p abnormalities were observed between the fibrous stroma and epithelial elements of testicular teratomas. Our results indicate that the fibrous stroma of testicular teratomas frequently has genetic abnormalities similar to those of the epithelial components. Concordant chromosome 12p alterations between the fibrous stroma and epithelial elements provide further evidence that both epithelial and fibrous components of teratoma are derived from a common progenitor.

Primary Retroperitoneal Lymph Node Dissection for Patients With Pathologic Stage II Nonseminomatous Germ Cell Tumor-N1, N2, and N3 Disease: Is Adjuvant Chemotherapy Necessary?

PURPOSE: According to National Comprehensive Cancer Network guidelines, adjuvant chemotherapy (AC) has been advocated after primary retroperitoneal lymph node dissection (RPLND) to reduce the risk of relapse in pathologic nodal (pN) stage pN2 or pN3, whereas surveillance is preferred for pN1. We sought to explore the oncologic efficacy of primary RPLND alone for pathologic stage II in nonseminomatous germ cell tumors (NSGCTs) to reduce overtreatment with chemotherapy. METHODS: Patients with pathologic stage II NSGCT after primary RPLND between 2007 and 2017 were identified. Patients were excluded for elevated preoperative serum tumor markers, receipt of AC, or if pure teratoma or primitive neuroectodermal tumor elements were found in the retroperitoneal pathology. RESULTS: We identified 117 patients with active NSGCT in the retroperitoneum after primary RPLND. We excluded seven patients who lacked meaningful follow-up and 13 patients who received AC. There were 97 patients treated with RPLND alone: 41 pN1, 46 pN2, and 10 pN3. In total, 77 of 97 patients had not recurred after a median follow-up time of 52 months. The 2-year recurrence-free survival (RFS) was 80.3%, and the 5-year RFS was 79%. No differences in RFS were noted among nodal stage-pN1, pN2, and pN3-on Kaplan-Meier analysis. Lymphovascular invasion in the orchiectomy specimen, a high-risk pathologic feature, was also predictive of recurrence after primary RPLND. All 20 patients who recurred were treated with first-line chemotherapy and remained continuously disease free. CONCLUSION: Most men with pathologic stage II disease treated with surgery alone in our series never experienced a recurrence. We did not observe a difference in recurrences between patients with pN1 and pN2. The recommendation for AC for pN2 disease may be overtreatment in most patients.