Poor-prognosis Nonseminomatous Germ Cell Research Articles

707P Paclitaxel, ifosfamide and cisplatin (TIP) in patients (pts) with poor prognosis nonseminomatous germ cell tumor (NSGCT) with unfavourable serum tumor markers (STM) decline: A phase II study

707P Paclitaxel, ifosfamide and cisplatin (TIP) in patients (pts) with poor prognosis nonseminomatous germ cell tumor (NSGCT) with unfavourable serum tumor markers (STM) decline: A phase II study

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%.

Adaptation of chemotherapy to the decline tumor markers in patients with poor prognosis nonseminomatous germ cell tumors:Real-world French experience.

385 Background: Personalized chemotherapy based on tumor marker decline is the new standard in poor prognosis germ-cell tumor in Europe since 2014 (GETUG 13, Lancet, Fizazi et al). The purpose of this study was to analyze the reproducibility of the princeps study in patients not selected in clinical routine between 2014 and 2018. Methods: Patients (pts) were eligible if they had at least one criteria of IGCCCG classification for poor prognosis group. They had to be treated according the study terms of GETUG 13 study and did not received prior treatment. They had to received 1 BEP (Bleomycin, Etoposide, Cisplatin). Tumor markers (HCG and AFP) were dosed between day 18 and 21. Then, they received 3 additional BEP if they had favorable tumor marker decline or intensive chemotherapy if they had unfavorable decline. Results: This retrospective study included 104 patients in 14 french centers treated between 2013 and 2018: 22,1 % (n = 23) in the favorable group (Fav), 77,9 % (n = 81) in the unfavorable group (Unfav). Thirty-two pts had PS ≥ 2. In Unfav, there were more pts with HCG &gt; 50 000 UI/L (44,2 % vs 13 %, p = 0,0067), neutrophil-to-lymphocyt ratio was also higher (median 6,4 vs 4,5, p = 0,0199). At cycle 1, all pts received BEP in Fav and 87,5 % (n = 70) in Unfav. After chemotherapy and surgery, 65,2 % in Fav and 41,3 % in Unfav obtained complete response. At 30 months (median follow-up), Fav-OS was 80,5 % (IC95% 55,8 – 92,2) and Unfav-OS was 64,4 % (IC95% 52 – 74,4). At 30 months, rates were 69,6 % (IC95% 46,6 -84,2) and 63.5 % (IC95% 51,9 – 73) respectively. In GETUG 13 study, 3-years OS was 84 % in Fav and 73 % on Unfav; 3-years PFS was 70 % and 59 % respectively. Seven pts died because of toxicity in Unfav (No one in Fav). Neuropathy, anemia and thrombopenia were more frequent in Unfav. Salvage high-dose chemotherapy with stem-cell transplant was required in 4 (66,7 %) pts in Fav and 8 (36,4 %) pts in Unfav. Conclusions: This study showed a reproducibility of the princeps study in terms of PFS and OS. Toxicity seemed more important in real world. For the congress, results will be reported with 50 additional pts.

Prognostic significance of an early decline in serum alpha-fetoprotein during chemotherapy for ovarian yolk sac tumors

BackgroundThe ovarian yolk sac tumor (OYST) is a very rare malignancy arising in young women. Our objective was to determine whether an early decline in serum alpha-fetoprotein (AFP) during chemotherapy has a prognostic impact. MethodsThis retrospective study is based on prospectively recorded OYST cases at Gustave Roussy (Cancer Treatment Center). Survival curves were estimated using the Kaplan-Meier method. The serum AFP decline was calculated with the formula previously developed and validated in male patients with poor prognosis non-seminomatous germ cell tumors. Univariate and multivariate analyses were performed using the log-rank test and logistic regression, respectively. ResultsData on AFP were available to calculate an early AFP decline in 57 patients. All patients had undergone surgery followed by chemotherapy. The 5-year overall survival (OS) and event-free survival (EFS) rates were 86% (95% CI: 74%–93%) and 84% (95% CI: 73%–91%), respectively. The disease stage, presence of ascites at presentation, use of the BEP regimen, serum AFP half-life and an early AFP decline were significantly predictive factors for OS and EFS in the univariate analysis. The OS rate was 100% and 49% (95% CI: 26%–72%) in patients with a favorable AFP decline and in those with an unfavorable decline, respectively (p<0.001). In the multivariate analysis, only the presence of ascites at diagnosis (RR=7.3, p=0.03) and an unfavorable early AFP decline (RR=16.9, p<0.01) were significant negative predictive factors for OS. ConclusionsAn early AFP decline during chemotherapy is an independent prognostic factor in patients with OYSTs. Conflict of interest statementNo conflict of interest

EAU Guidelines on testicular cancer: 2011 update

ContextOn behalf of the European Association of Urology (EAU), guidelines for the diagnosis, therapy, and follow-up of testicular cancer were established. ObjectiveThis article is a short version of the EAU testicular cancer guidelines and summarises the main conclusions from the guidelines on the management of testicular cancer. Evidence acquisitionGuidelines were compiled by a multidisciplinary guidelines working group. A systematic review was carried out using Medline and Embase, also taking Cochrane evidence and data from the European Germ Cell Cancer Consensus Group into consideration. A panel of experts weighted the references, and a level of evidence and grade of recommendation were assigned. ResultsThere is a paucity of literature especially regarding longer term follow-up, and results from a number of ongoing trials are awaited. The choice of treatment centre is of the utmost importance, and treatment in reference centres within clinical trials, especially for poor-prognosis nonseminomatous germ cell tumours (NSGCTs), provides better outcomes. For patients with clinical stage I seminoma, based on recently published data on long-term toxicity, adjuvant radiotherapy is no longer recommended as first-line adjuvant treatment. The TNM classification 2009 is recommended. ConclusionsThese guidelines contain information for the standardised management of patients with testicular cancer based on the latest scientific insights. Cure rates are generally excellent, but because testicular cancer mainly affects men in their third or fourth decade of life, treatment effects on fertility require careful counselling of patients, and treatment must be tailored taking individual circumstances and patient preferences into account. Take home messageAlthough testicular cancer has excellent cure rates, the choice of treatment centre is of the utmost importance. Expert centres achieve better results for both early stage testicular cancer (lower relapse rates) and overall survival (higher stages within clinical trials). For patients with clinical stage I seminoma, adjuvant radiotherapy is no longer recommended as first-line adjuvant treatment.

Guía clínica sobre el cáncer de testículo de la EAU: actualización de 2011

ContextOn behalf of the European Association of Urology (EAU), guidelines for the diagnosis, therapy, and follow-up of testicular cancer were established. ObjectiveThis article is a short version of the EAU testicular cancer guidelines and summarises the main conclusions from the guidelines on the management of testicular cancer. Evidence acquisitionGuidelines were compiled by a multidisciplinary guidelines working group. A systematic review was carried out using Medline and Embase, also taking Cochrane evidence and data from the European Germ Cell Cancer Consensus Group into consideration. A panel of experts weighted the references, and a level of evidence and grade of recommendation were assigned. ResultsThere is a paucity of literature especially regarding longer term follow-up, and results from a number of ongoing trials are awaited. The choice of treatment centre is of the utmost importance, and treatment in reference centres within clinical trials, especially for poor-prognosis nonseminomatous germ cell tumours, provides better outcomes. For patients with clinical stage I seminoma, based on recently published data on long-term toxicity, adjuvant radiotherapy is no longer recommended as first-line adjuvant treatment. The TNM classification 2009 is recommended. ConclusionsThese guidelines contain information for the standardised management of patients with testicular cancer based on the latest scientific insights. Cure rates are generally excellent, but because testicular cancer mainly affects men in their third or fourth decade of life, treatment effects on fertility require careful counselling of patients, and treatment must be tailored taking individual circumstances and patient preferences into account. Take Home MessageAlthough testicular cancer has excellent cure rates, the choice of treatment centre is of the utmost importance. Expert centres achieve better results for both early stage testicular cancer (lower relapse rates) and overall survival (higher stages within clinical trials). For patients with clinical stage I seminoma, adjuvant radiotherapy is no longer recommended as first-line adjuvant treatment.

Paclitaxel + BEP (T-BEP) Regimen as Induction Chemotherapy in Poor Prognosis Patients With Nonseminomatous Germ Cell Tumors: A Phase II Study

To evaluate paclitaxel, bleomycin, etoposide, and cisplatin (T-BEP) in patients with poor-prognosis nonseminomatous germ cell tumor (NSGCT). Paclitaxel is an active treatment of nonseminomatous germ cell tumors. The present study was an open-label, single-center, Phase II study. Chemotherapy-naive patients received T-BEP (paclitaxel 175 mg/m2 [day 2], cisplatin 20 mg/m2 [days 1-5], etoposide 100 mg/m2 [days 1-5], bleomycin 30 IU [days 1, 3, and 5]), and granulocyte colony-stimulating factor 300 μg (days 6-10). The number of cycles (range 4-6) was dependent on the normalization of tumor markers. Secondary resection was planned for patients with tumor marker-negative partial remission. Assessments included radiologic response, tumor markers, and safety. The primary endpoint was progression-free survival (PFS) 1 year after chemotherapy. Of 51 patients, 49 completed chemotherapy and were evaluable for response: 12 (25%) had a complete response, 29 (59%) were marker-negative (tumor marker normalization) and 3 (6%) were marker-positive (tumor marker decrease for ≥1 month) incomplete responders, and 5 (10%) had progressive disease. A total of 37 patients underwent secondary resection. After the treatment of 27 patients, an unplanned analysis showed inappropriate toxicity at cycle 1 (grade 3-4 infection [6 patients] resulting in 2 toxic deaths), which led to treatment modification (BEP [cycle 1], T-BEP [subsequent cycles]), with no further toxic deaths observed. Grade 3-4 adverse events included neutropenia (71%), febrile neutropenia (33%), and infection (14%). During the first year after chemotherapy, 1 patient was lost to follow-up, and 21 patients relapsed. The PFS rate at 1 year after chemotherapy was 58% (29 of 50 patients). T-BEP did not improve PFS in patients with poor-prognosis NSGCT. The administration of T-BEP from cycle 1 resulted in excessive toxicity but was administered safely from cycle 2.

Kinetics of tumor marker decline as an independent prognostic factor in patients with relapsed metastatic germ-cell tumors.

Early serum tumor marker decline (STMD) during chemotherapy was shown to predict survival in patients with poor prognosis non-seminomatous germ cell tumors (GCT) in the first line. The aim of the study was to assess the prognostic value of STMD in relapsed GCT;s patients. From January 1995 to December 2007, all patients treated for GCT s with salvage therapy at the National Cancer Institute of Slovakia were identified from the tumor registry database and screened retrospectively for serum AFP and betaHCG level at the time of relapse. STMD rate was calculated for each patient and each tumor marker with an abnormal marker value at baseline and each tumor marker M (HCG or AFP) using only two values: the baseline value (M0) and the value obtained after one cycle of chemotherapy (day 21 value; M1). The decline rate was calculated using a logarithmic transformation, and it was expressed as a theoretical number of weeks necessary to normalization that was called predicted time to normalization. Decline rates were classified into "favorable" or "unfavorable". Totally, 75 patients were identified, 39 had favourable (group A) and 36 unfavorable (group B) STMD. The 2-year and 5-year PFS rates were 61% and 58% for group A and 17% and 7% group B (p<0.00001). Of all the baseline characteristics that were included in the Cox model, STMD was the most important predictor of PFS and OS. We suggest that STMD is strong independent prognostic factor in GCT patients treated with salvage chemotherapy. Prospective studies of different approaches in this patient's population based on STMD are warranted.

Early predicted time to normalization of tumor markers predicts outcome in poor-prognosis nonseminomatous germ cell tumors: Fizazi K, Culine S, Kramar A, Amato RJ, Bouzy J, Chen I, Droz J-P, Logothetis CJ, Genito-Urinary Group of the French Federation of Cancer Centers, Paris, France.

Purpose The prognostic relevance of the rate of decline of serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) during the first 3 weeks of chemotherapy for nonseminomatous germ cell tumors (NSGCT) was studied in the context of the International Germ Cell Cancer Collaborative Group (IGCCCG) classification. Patients and methods Data from 653 patients prospectively recruited in clinical trials were studied. Tumor markers were obtained before chemotherapy and 3 weeks later. Decline rates were calculated using a logarithmic formula and expressed as a predicted time to normalization (TTN). A favorable TTN was defined when both AFP and HCG had a favorable decline rate, including cases with normal values. Results The median follow-up was 50 months (range, 2 to 151 months). Tumor decline rate expressed as a predicted TTN was associated with both progression-free survival (PFS; P P P = .01) and OS (hazard ratio = 4.6; P = .002) in patients from the IGCCCG poor-prognosis group in multivariate analysis. Conclusion Early predicted time to tumor marker normalization is an independent prognostic factor in patients with poor-prognosis NSGCT and may be a useful tool in the therapeutic management of these patients.

Early predicted time to normalization of tumor markers predicts outcome in poor-prognosis nonseminomatous germ cell tumors.

The prognostic relevance of the rate of decline of serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) during the first 3 weeks of chemotherapy for nonseminomatous germ cell tumors (NSGCT) was studied in the context of the International Germ Cell Cancer Collaborative Group (IGCCCG) classification. Data from 653 patients prospectively recruited in clinical trials were studied. Tumor markers were obtained before chemotherapy and 3 weeks later. Decline rates were calculated using a logarithmic formula and expressed as a predicted time to normalization (TTN). A favorable TTN was defined when both AFP and HCG had a favorable decline rate, including cases with normal values. The median follow-up was 50 months (range, 2 to 151 months). Tumor decline rate expressed as a predicted TTN was associated with both progression-free survival (PFS; P <.0001) and overall survival (OS; P <.0001). The 4-year PFS rates were 64% and 38% in patients from the poor-prognosis group who had a favorable and an unfavorable TTN, respectively. The 4-year OS rates were 83% and 58%, respectively. This effect was independent from the initial tumor marker values, the primary tumor site, and the presence of nonpulmonary visceral metastases: tumor marker decline rate remained a strong predictor for both PFS (hazard ratio = 2.5; P =.01) and OS (hazard ratio = 4.6; P =.002) in patients from the IGCCCG poor-prognosis group in multivariate analysis. Early predicted time to tumor marker normalization is an independent prognostic factor in patients with poor-prognosis NSGCT and may be a useful tool in the therapeutic management of these patients.

Intensive Induction Chemotherapy With CBOP/BEP in Patients With Poor Prognosis Germ Cell Tumors

Despite a high cure rate in patients with testicular cancer, there remain patients in the poor prognosis group who have a less favorable outcome. Intensive induction chemotherapy using a regimen consisting of carboplatin, bleomycin, vincristine, and cisplatin, followed by bleomycin, etoposide, and cisplatin (CBOP/BEP), developed at the Royal Marsden Hospital, is designed to overcome the rapid proliferation seen in germ cell tumors. This study assesses the outcome of patients with poor-prognosis nonseminomatous germ cell tumors (NSGCT) treated with CBOP/BEP. Patients with NSGCT from three centers, classified as poor prognosis according to International Germ Cell Classification Consensus Group criteria, were treated with CBOP/BEP regimen during the period from 1989 to 2000. Data on treatment toxicity, relapse-free survival (RFS), and overall survival (OS) were collected prospectively on a hospital database. Fifty-four male patients with poor prognosis NSGCT were treated with CBOP/BEP. The RFS at 3 and 5 years for all patients was 83.2% (95% confidence interval [CI], 68.8% to 91.3%). After a median follow-up of 4 years, the OS of the 54 patients was 91.5% (95% CI, 78.6% to 96.8%) at 3 years and 87.6% (95% CI, 71.3% to 94.9%) at 5 years. Three-year OS in patients with a primary mediastinal germ cell tumor was 77.1% (95% CI, 34.5% to 93.9%) compared with 95.4% (95% CI, 82.8% to 98.8%) in patients with a testicular primary tumor (P =.24). The results reported here compare favorably with the historical results of alternative regimens used in the management of poor-prognosis NSGCT. We suggest a phase III trial to confirm our findings.

New approaches to the management of poor prognosis non-seminomatous germ cell tumours

New approaches to the management of poor prognosis non-seminomatous germ cell tumours

New approaches to the management of poor prognosis non-seminomatous germ cell tumours.

While most patients with disseminated non-seminomatous germ cell tumours (NSGCT) are cured by treatment with cisplatinum-based chemotherapy, a subset die from refractory or relapsing disease. Poor prognostic factors at diagnosis include bulky disease, visceral involvement, high serum marker levels and an inadequate rate of fall in these markers in response to treatment. There are a number of approaches to poorer risk patients. One is to use conventional induction chemotherapy followed by second-line salvage regimens in those who fail induction. Results with this approach have been disappointing. A second approach is to use more intensive induction regimens, in some cases with growth factor support; whether these are superior to standard treatment has yet to be established by randomised studies. A third approach, based on the chemotherapy-dose responsiveness of NSGCT, consists of the administration of very high dose chemotherapy followed by haematological rescue with autologous marrow to patients failing initial therapy. Review of autograft studies suggest that durable remissions can be obtained in most patients with responsive disease, but not if the disease is chemotherapy-refractory. A new approach may be elective early autografting in patients identified at diagnosis to have very poor prognosis disease.

BOP/VIP - A new platinum-intensive chemotherapy regimen for poor prognosis germ cell tumours

Ninety-one patients with poor prognosis non-seminomatous germ cell tumours (NSGCT) were treated with an initial intensive chemotherapy schedule. Suitable patients fulfilled one or more of the following criteria: lymph node metastases greater than 10 cm diameter; liver, brain or bone metastases; serum HCG level greater than 50,000 IU/L; and extragonadal primary tumours. Treatment consisted of 3 cycles of bleomycin, vincristine and cisplatin (BOP) administered at 10 day intervals, followed by 3 cycles of etoposide, ifosfamide and cisplatin (VIP) at 21 day intervals. A total of 64 patients (70%) achieved a complete remission. This comprised 46 patients who received BOP/VIP only, and 18 patients who received additional chemotherapy after BOP/VIP. Of these 64 patients, 51 underwent complete surgical resection of residual masses, including 11 in whom there was evidence of teratoma with cellular atypia or non-germ cell cancer in the resected tissue. A further 9 patients had persisting unresected radiological masses in the presence of marker complete remission. The overall response rate was 80%. Currently 57 patients (63%) remain alive and free from disease progression. The median follow-up period is 90 weeks (range 24-206 weeks), with a 2 yr actuarial progression-free survival of 66% (95% c.i. 55-77%). Major toxicity was myelosuppression, occurring during the VIP arm of therapy, with a median nadir WBC of 1.1 x 10(9)/L and median platelet count of 51 x 10(9)/L. Other toxicity included peripheral neuropathy (WHO Grade 2 and 3 in 22%). We conclude that treatment results with the BOP/VIP schedule in this poor prognosis patient group are at least comparable with other schedules, and toxicity is manageable.(ABSTRACT TRUNCATED AT 250 WORDS)

Management of Patients with Poor-Prognosis Nonseminomatous Germ Cell Cancer

The treatment and outcome of 57 patients with poor-prognosis metastatic nonseminomatous germ cell cancer were reviewed. The patients were treated between 1980 and 1986. Poor-prognosis patients were characterized by the presence of at least one of the following findings: (1) retroperitoneal tumor mass greater than 10 cm; (2) greater than 3 lung metastases, the largest being greater than 2 cm; (3) extrapulmonary, extralymphatic, metastases; and (4) extragonadal primary tumor. The intended treatment consisted of cisplatin-based combination chemotherapy followed by secondary surgery. From 1980 to 1983 a modified Einhorn regimen was used (cisplatin 100 mg/m2 per cycle; CVB). In case of unacceptable vinblastine toxicity, this drug was substituted by VP-16 (500 mg per m2 per cycle; BEP20). From October 1983 the intention was to replace at least 3 of the CVB/BEP20 cycles by BEP60 cycles (days 1-3: cisplatin 60 mg/m2, days 1-3: VP-16 120 mg/m2; days 1, 5, 15: bleomycin 30 mg). There were 33 patients in the CVB/BEP20 group and 24 patients in the BEP60 group. Two patients of the CVB/BEP20 group and 6 patients of the BEP60 group were not evaluable for response, but are included in the survival analysis. The reasons for exclusion from response evaluation were that these patients could not receive the intended chemotherapy in appropriate doses due to severely reduced pretreatment general condition or due to early death. Fourteen patients with multiple lung metastases but no other poor-prognosis criteria had a 93% survival indicating that they did not represent poor-prognosis germ cell cancer. After excluding these 14 patients, the 4-year survival was 58% for 19 CVB/BEP20 patients and 72% for BEP60 patients. This difference did not reach the level of statistical significance in this limited series. The introduction of high-dose cisplatin had thus not led to clearly superior treatment results as compared to CVB/BEP20.