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Aim: A risk-adapted strategy for metastatic seminoma may further refine the necessary burden of chemotherapy while sparing futile treatment for early recognized good responders. The objective of this proof-of-principle study was to evaluate the association of an early metabolic response to PEB and the dimensional response at the end of treatment. Methods: Patients (pts) with newly-diagnosed seminoma and who were candidate to PEB were staged at baseline by computed tomography (CT), PET and serum tumor markers (STM). Then, restaging with PET after 2 cycles of PEB (PET2), and with CT after treatment (3-4 cycles [CT3-4]) were provided. One (greatest) target lesion was chosen to evaluate metabolic/dimensional changes in each case. The primary endpoint was the association between PET2 (EORTC criteria) and CT3-4 response. Secondary endpoints were progression-free survival (PFS) and ability to detect visceral metastases. An analysis after the initial 35 pts was planned. Results: In the time-frame 06/2010-11/2013, 35 pts have been enrolled in this single-site study. Two pts had CSIIA, 12 CSIIB, 13 CSIIC, and 8 CSIII. 3 had an intermediate prognosis because of liver (1) and bone (2) disease. These two were recognized by PET while having a bone-negative CT scan. 4 had a retroperitoneal and 1 a mediastinal primary. All pts had a PET-positive target disease (retroperitoneal in 33 and mediastinal in 2). After 2 cycles of PEB, 25 pts (71.4%) had a metabolic complete response (CR), 10 a partial response (PR). 10 pts had a CR at CT3-4. PET2-negative pts had a significantly smaller residual disease at CT3-4 scan (median 1.2 cm [IQR: 2.8-6] vs 4 cm [IQR: 1-1.9], p Conclusions: PET2 early identified pts having the greatest response to chemotherapy and who finally reached the cut off for observation only ( Disclosure: All authors have declared no conflicts of interest.

Aim: Outcomes of first-line treatment (Tx) for patients (pts) with metastatic poor prognosis GCT are still suboptimal in literature. However, the low incidence of disease and the increasing effectiveness of salvage therapy are issues against further clinical research in the field. We conducted a retrospective study to evaluate the impact of Tx period on prognosis of pts referred to our tertiary cancer center. Methods: A retrospective analysis was conducted on pts receiving at least first-line chemotherapy (CT) at our center. Distribution of frequencies of clinical characteristics were evaluated in the periods 1000 IU/ml, HCG > 1000 IU/l. All tests and confidence intervals were two-sided and set at p = 0.05 level of significance. Results: Between the years 1982 and 2013, 168 pts have been identified. Median age was 27 yrs (IQR: 22-34). No clinical factor had significantly different distribution over time, only LBB metastases trended to higher frequency from 1997 onwards (27.5% Conclusions: In this single-center series of poor prognosis GCT we could not demonstrate an effect on Tx period on survival. The slight differences in PFS on UVA are likely due to modest discrepancies in distribution of clinical variables (LBB). The global picture is that of a stable and very high cure-rate. Based on these results, attempts to improve the outcome exclusively in this field should be discouraged. Results are biased by their retrospective quality. Disclosure: All authors have declared no conflicts of interest.

Background: Transitional cell carcinoma (TCC) is the most common histology accounting for 90% of cases, and the remaining 10% are represented by pure divergent histologies (non-TCCs) such as small cell and squamous cell carcinoma, adenocarcinoma, and micropapillary variant. All non-TCCs are associated with features of aggressiveness such as advanced tumor stage, high risk of recurrence and cancer specific mortality compare to TCC. No standard of care for non-TCCs has been established. The primary objective will be to determine the activity of the combination of paclitaxel, ifosfamide, and cisplatin (TIP) (or carboplatin) in patients with non-TCCs. Secondary objectives will include safety and survival. Trial design: 66 pts with locally advanced (i.e. T3b-4 ± N+) or metastatic non-TCCs will receive paclitaxel 175 mg/m2 on day 1, and ifosfamide 1200 mg/ m2 + cisplatin 25 mg/ m2 on days 1-3 (or carboplatin AUC 4.5 on day 1) every 21 days for 6 cycles. Further eligibility requirements will include ECOG-PS ≤ 1 and no prior systemic therapy, except for relapse after >6 months of perioperative treatment. Carboplatin will be administered instead of cisplatin for patients who will be judged as cisplatin-ineligible (Galsky MD, Lancet Oncol 2011). Patients will be staged and evaluated every 2 cycles with computed tomography (CT) and positron emission tomography (PET)/CT scans. The primary endpoint is progression-free survival (PFS). Simon's Optimal 2-stage design is applied. The null hypothesis that the PFS rate at 6 months is ≤ 40% will be tested against a one-sided alternative that the 6-month PFS rate is ≥ 57%. Based on a nominal power of 80% and alpha (one-sided) of 5%, in the first stage 19 patients will be accrued. If there will be ≤ 8 progression-free patients at 6 months, the study will be stopped. Otherwise 47 additional patients will be accrued for a total of 66. The null hypothesis will be rejected if ≥ 33 patients will be progression free at 6 months. This design yields a type I error rate of 4.9% and power of 80.3% when the PFS rate at 6 months is 57%. At present, one patient has been enrolled and is under treatment. The trial is sponsored by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano Italy (EudraCT registry number 2014-000043-32). Disclosure: All authors have declared no conflicts of interest.

4547 Background: Knowledge of the expression of molecular drivers and potentially druggable targets may enhance prognostic classification of metastatic UC. We aimed at assessing the expression of m...

e15529 Background: Patients (pts) with GCT who fail to be cured following multiple chemotherapy (CT) courses (± high-dose CT) have an extremely poor prognosis and long-term remissions are anecdotal. Pazopanib (PZP) is a potent and selective, orally available, TKI of VEGFR1, 2, and 3, PDGFRα, PDGFRβ, and cKit. We updated the initial results of the ongoing open-label, single-group, phase 2 study which is sponsored by INT Milano. Methods: Patients failing at least 2 platinum-based CT (including high-dose CT) received PZP 800 mg/day orally until disease progression (PD) or evidence of unacceptable toxicity/side effects. All pts underwent measurement of serum tumor markers (STM), a computed tomography and a FDG-PET after 1 month and q2 months thereafter. In a Simon’s 2-stage design, the primary endpoint is 3-month progression-free survival (PFS). In stage 1, 18 evaluable patients will be accrued. If ≥ 3 pts will be progression-free at 3 months, enrolment will be extended to the 2ndstage. Results: From 06 to 12...

4561 Background: Patients (pts) with GCT who fail to be cured following multiple chemotherapy (CT) courses (including high-dose CT) have an extremely poor prognosis. EMA/CO regimen has shown efficacy in high-risk gestational trophoblastic tumors. Since 1992 we introduced this regimen for human chorionic gonadotropin (HCG)-producing refractory GCT. Methods: We retrieved data of adult male pts who received methotrexate (MTX) 100 mg/m2 followed by MTX 200 mg/m2 over 12h d1, etoposide 100 mg/m2 and dactinomycin 0.5 mg mg/m2 d1-2, folinic acid 15 mg orally every 6h d2-3, followed by cyclophosphamide 600 mg/m2 plus vincristine 1 mg/m2 d8, every 21 days. Treatment was continued until marker normalization. Pts had a HCG+ GCT and had failed at least 2 CT regimens. Multivariable analysis (MVA) was undertaken to analyze candidate prognostic factors. ITT analysis was applied. Results: From 02/92 to 05/13, 41 pts were treated in 3rd (20, 49%) or >3rd line (21, 51%). 36 (88%) had a mixed GCT, 2 a pure seminoma and 3 a ...

341 Background: A risk-adapted treatment for TCC may guide new trial designs for early-recognized unresponsive patients (pts). We aimed to prospectively identify early fluorodeoxyglucose (FDG)-PET/CT as a predictor of response and outcome. Methods: Pts with newly-diagnosed advanced/metastatic TCC receiving first-line chemotherapy underwent CT and FDG-PET/CT at baseline, a restaging with PET/CT after 2 cycles only (PET2), and a CT (± FDG-PET/CT) at the end of treatment and during follow up. The endpoints were PET2 metabolic response, RECIST response, progression-free (PFS) and overall survival (OS). Univariable (UVA) and multivariable (MVA) Cox models were fitted. Prespecified variables were presence of visceral metastases, nodal or soft tissue disease, and PET2 response. Results: In the time-frame 05/2010-10/2012, 31 pts with ECOG-PS 0 received a modified MVAC regimen according to Institutional protocol, every 3 weeks. After 2 cycles of MVAC, 6 patients (19.3%) had a complete (CR) and 17 (54.8%) a partial metabolic response (PR) (74% total responders; 95% CI, 55.4-88.1%), 4 had stable disease (SD), 4 progressed. Metabolic response (CR + PR) was associated with final CT response (p=0.007 at Fisher exact test). Metabolic CR was followed by a RECIST CR in all but one cases and metabolic progression at PET2 corresponded to a RECIST PD in all four patients and they all switched to second line chemotherapy. Median follow up was 18 months (IQR: 10-47). Those with metabolic response had a median (95% CI) PFS of 8 (7-11) months compared to 3 (2-5) months of patients without response (p=0.024). PET2 responders had a significant benefit in 8-month PFS (p

305 Background: The small, yet significant, survival advantage with neoadjuvant chemotherapy in MIBC needs to be improved. A rationale exists for inhibiting the RAF/MEK/ERK pathway and investigating S-CG combination in an ongoing open-label, single-group, phase II trial. Methods: Patients (pts) with T2-4N0 MIBC received 4 cycles of cisplatin 70 mg/m2 on day 1 and gemcitabine 1000 mg/m2 on day 1 and 8, every 3 weeks. Sorafenib 400 mg q12h was administered daily from day 1 to cystectomy. An optimal 2-stage Simon’s design is applied. 6 pathologic complete responses (pT0, primary endpoint) should be observed in the first stage before moving to full enrollment of 45 cases. Residual carcinoma in situ with no evidence of invasive tumor was considered as pT0. Intention-to-treat analysis was applied. Biomarker and circulating tumor cell (CTC) analysis is ongoing. Results: 23 pts were enrolled from 04/11 to 07/13. Thus far, 21 completed the treatment and are evaluable. Median age was 61yrs (IQR: 54-66). 11 had T2, 9 T3, and one a T4 disease. 6 pts had hydronephrosis at presentation. 19 pts underwent radical cystectomy. Eight pts (38.1%, 95% CI: 18.1-61.6%) had a pT0 and 2 pts a pT

376 Background: Patients (pts) with germ cell tumors (GCT) who fail to be cured following multiple chemotherapy (CT) courses (± high-dose CT) have an extremely poor prognosis and long-term remissions are anecdotal. Pazopanib (PZP) is a potent and selective, orally available, TKI of VEGFR1, 2, and 3, PDGFRα, PDGFRβ, and cKit. Here we report the initial results of the ongoing open-label, single-group, phase II study which is sponsored by INT Milano (ClinicalTrials.gov NCT01743482). Methods: Pts with refractory GCT received pazopanib 800 mg/day orally until disease progression or evidence of unacceptable toxicity/side effects. Eligibility requirements included failure of at least two platinum-based CT, including high-dose CT. All pts underwent measurement of serum tumor markers (STM), a computed tomography and a FDG-PET after one month of treatment and q2 months thereafter. Results: From May 2013 to July 2013, five pts were enrolled, three in fourth, and two in fifth-line. Median age was 39 (IQR: 33 to 48). Three out of five had failed high-dose chemotherapy (HDCT), two had an extragonadal primary, all pts had at least one elevated STM at baseline, the sole parameter in one patient, two had liver metastases, four pts had a retroperitoneal relapse. Four had elevation of alfafetoprotein (AFP), one of human choriogonadotropin (HCG). Four were nonseminomas, one a pure seminoma. After the first month of treatment, four out of five pts had a decrease in marker levels, one patient had disease progression (PD). Two of the responding pts had a necrotic evolution of disease at computed tomography corresponding to a RECIST and metabolic (PET/CT) progression, two had a stable disease. Two-month follow up is available for three out of four responders: one interrupted PZP for toxicity and had a marker PD, another an increase to baseline levels and the last one a further reduction (pure seminoma, one out of five confirmed response at two months). There were two cases of hepatic toxicities (one G2 and one G3-4 with dose interruption). Conclusions: PZP is endowed with preliminary activity in extensively pretreated patients with GCT. The unique availability of STM in interpreting densitometric and metabolic response might provide insights into response assessment of solid tumors under antiangiogenic therapy. Clinical trial information: NCT01743482.

328 Background: Second-line chemotherapy (CT) of advanced GCT is vividly debated and no standard of care has been established. Since 1985 we introduced the modified PEI combination with the aim to reduce toxicity while maintaining efficacy over the original regimen. Methods: We retrieved data of pts who received ifosfamide at 2.5 gr/m2 (with mesna) on days 1-2, etoposide and cisplatin at 100 mg/m2 and 33 mg/m2, respectively, on days 3-5 every 21 days for a maximum of 4 cycles, followed by surgery of residuals. Multivariable analysis (MVA) was undertaken for pre-specified variables and IGCCCG-2 score was analysed as a continuous covariate. ITT analysis was applied. Results: From 02/85 to 01/12, 189 pts failing cisplatin, bleomycin, and vinblastine (PVB, N=25) or etoposide (PEB, N=164) were treated. 87% had a gonadal primary, 50.3% were MSKCC poor risk, 74.7% were IGCCCG-2 intermediate-to-very high risk, 21.8% had liver, bone or brain (LBB) mets, 16.7% were late relapses. 35 pts (18.5%) had a complete response (CR), 68 (35.9%) a marker normalization (PRm-) (major response-rate: 54.4%). 41/68 PRm- were rendered disease-free (total NED-rate: 40.2%). After a median follow-up of 122.1 mos (IQR 71.4-232), median (95%CI) PFS was 7.2 mos (6.2-9.5) and median OS was 21.7 mos (16.7-69.5). 2yr PFS was 34.3% (28.1-41.9) and 5yr OS was 42.1% (35.3-50.2). Mediastinal primary (HR 3.06, 95%CI, 1.68-5.58), LBB mets (HR 2.02, 95%CI, 1.30-3.16), and AFP>1000 ng/mL (HR 2.78, 95%CI, 1.51-5.14) were negative prognostic factors for OS at MVA while no effect was seen according to IGCCCG-2 category. 70.3% of grade 3-4 neutropenia (25% febrile neutropenia), 48.1% thrombocytopenia, 21.1% anemia, 3% neurotoxicity, and no severe renal toxicity were recored. 81 pts (78% before 2000) had a dose reduction of ≥1 drug for ≥1 cycle. No discontinuations for toxicity occurred. Conclusions: Dose-modified Italian PEI showed activity comparable with the best ones achievable by conventional-dose CT (CDCT) in an unselected patient population, and a favorable toxicity profile. Results are among the most robust available for a CDCT, and should be considered as an appropriate benchmark to be compared with high-dose CT.

284 Background: MVAC and cisplatin-gemcitabine (CG) are the established standard of care for untreated patients (pts) with locally advanced-metastatic UC. CG is the preferred choice in most cases due to the better toxicity profile. Modifying MVAC by reducing side-effects may have the potential to improve efficacy. Methods: Data relative to unresectable T/N+/M+ pts entering sequential single-institution trials were collected. Chronologically, these changes to classic MVAC were provided: deletion of day 22 and administration of 25 mg/m2CDDP d2-5 (modified MVAC [mMVAC]); deletion of day 22 only, and deletion of days 15 and 22 in a 3-week schedule (simplified [s]MVAC1 and 2). 4-6 cycles were provided. Multivariable analysis was undertaken for recognized clinical variables. ITT analysis was applied. Results: From 09/86 to 04/12, 157 pts were treated (25 mMVAC, 72 sMVAC1, 60 sMVAC2). 84% had a bladder primary, 70% had distant metastases, 53% and 36% had nodal and visceral mets, respectively. 43.9% had a Bajorin score 1-2. 65.8% attained a complete (19.1%) or partial response (46.7%), 24.3% a stable disease, with no difference among regimens. After a median follow up of 87 mos (IQR 37-161), median (95% CI) PFS was 10.2 mos (8.4-10.8) and median OS was 19.5 mos (16.3-24.1). 2yr (95% CI) PFS and 5yr OS were 30.9% (23.8-40.1) and 25.3% (18.8-34.1). Responses were mainly seen in nodal mets (OR: 2.48, 95%CI, 1.12-5.54). Presence of visceral (HR: 2.42, 95%CI, 1.37-4.30), nodal mets (HR: 1.70, 95%CI, 1.07-2.69) and mMVAC regimen (HR: 1.73, 95%CI, 1.02-2.92) were negative prognostic factors for OS. G3-4 toxicities were similar among regimens and were 36% neutropenia, 14% thrombocytopenia, 12% anemia, 10% mucositis, and 4% renal toxicity. 2 pts died for toxicity. Conclusions: Simplifying MVAC schedule may result in improved activity and efficacy while reducing toxicity. Though retrospective, the combined results of MVAC modification would claim a benefit over either classic/dose-dense MVAC or CG in terms of efficacy and safety. A reappraisal of the upfront management of advanced/metastatic UC is warranted.

329 Background: CD30 is invariably expressed by untreated EC thus lending support to a rationale for a targeted approach. However, preliminary reports claimed an effect of chemotherapy (CT)-induced downmodulation of CD30 that might affect the potential use in relapsing disease. We aimed at evaluating the persistence of CD30-positivity in post-CT residuals. Methods: We retrieved paraffin-embedded post-CT samples yielding non-teratoma viable cells after ≥ 1 CDDP-based CT from the institutional surgical series. EC component was required and assessed by morphology and Oct-3/4 staining. The entire set was re-stained for CD30 and assessed by 2 pathologists blinded to study purpose. CD30-positivity was defined as a >80% membranous staining with a diffuse moderate-to-strong intensity. Clinical data included site of tumor primary, histology, CT regimen, and type of surgery. Results: From 12/1990 to 09/2012, a total of 246 cases with pure EC or mixed GCT residuals were treated. 49 (EC: 16; mixed GCT: 33) had both complete data and suitable tissue for study purposes. 40 pts had retroperitoneal or mediastinal nodes, 12 pts had lung metastases, 4 had either liver, bone or brain mets. 35/49 cases (70%) preserved CD30 positivity. 20/35 (57%) pts had residual disease after 1stline CT, 15/35 (43%) after multiple CTs (median 3.5, range 2-5). 2 pts (6%) had undergone high-dose CT and 4/35 (11%) were late relapses. 32/35 pts (91%) had gonadal primary, 1 had a retroperitoneal and another a mediastinal primary. The median survival of 35 CD30-positive patients was 16 mos (IQR 3.3-22.9) while it was 48.5 mos (IQR 21.7-72.6) for the 14 CD30-negative patients (p=0.0297 at Gehan-Breslow-Wilcoxon test). 5-year overall survival of CD30-positive and negative patients was 35.7% (95% CI: 18.2-53.6) and 49.7% (95% CI: 19.7-74.0), respectively. Conclusions: Our results on selected relapsing pts suggest that EC retained CD30 even in the far salvage setting, thus confirming to be a reliable target for treatment. A trend towards a poorer prognosis and shorter survival characterized CD30+ cases. A phase 2 study with the antibody-drug conjugate Brentuximab vedotin is currently in plan for GCT.

Aims and BackgroundNeoadjuvant systemic chemotherapy in infiltrating transitional cell carcinoma of the bladder has proved to be effective and to provide a pathologic complete response in about 30% of patients. No survival benefit has yet been proved.MethodsWe analyzed the outcome of 75 patients with advanced bladder cancer (stages T2-T4 N+/N0 M0) treated from 1985 to 1993 at two institutions in the same geographic area with 2 or 3 cycles of neoadjuvant CMV (cisplatin, methotrexate and vinblastine) chemotherapy plus cystectomy. Transurethral resection of the tumor was expressly avoided in order to keep the tumor intact as a marker lesion to evaluate response to chemotherapy.ResultsAt the time of analysis, the median follow-up of 67 assessable patients was 51.5±3.9 (SE) months. Forty-six patients (69%) had clinical evidence of extravesical spread of the bladder tumor and 6 of lymph node metastases at presentation. After cystectomy, a pathologic complete response (pT0, pN0) was achieved in only 6 cases (9%) and a pathologic partial response in 32 patients (48%). The overall 5-year survival rate of all patients was 61 ±6%. Those patients who had a major response to chemotherapy (pCR + pPR) had a 5-year disease-free survival rate of 74%, which was statistically higher (P=0.0021) than the 44% for the remaining nonresponding patients (pNR). Overall, 43% of the patients with stage T2-T3a disease achieved tumor downstaging (CR, 5%; PR, 38%) compared with 63% of the patients with T3b-T4 (CR, 11%; PR, 52%), although there was no significant difference in 5-year survival curves between the two groups.ConclusionsA pathologic complete response was achieved in less than 10% of the cases without a preoperative tumor resection. Unfortunately, most of the responses were only partial. Even though the study appears to suggest a survival advantage for those patients who achieved a downstaging, CMV chemotherapy had a limited curative potential in most of the patients. It seems unlikely that determinant proof will be obtained that neoadjuvant chemotherapy may improve survival over a nontreatment control arm. The intrinsic chemoresistance or the suboptimal response to chemotherapy of bladder cancer remains the most adverse prognostic factor.

168 Background: Abiraterone acetate (AA) is an inhibitor of extragonadal androgen biosynthesis that prolongs overall survival in CRPC patients who have received a chemotherapy including docetaxel. The most common adverse events related to AA therapy were fluid retention, hypertension, hypokaliemia and cardiac disorders. No safety data are available in patients with concomitant cardiac disease. Methods: Metastatic CRPC patients were enrolled in this prospective study if they were also suffering from a concomitant controlled cardiovascular disease. AA 1000 mg per day and prednisone 5 mg bid were administered orally until grade 3-4 adverse events (AE) or disease progression. The primary endpoint was the safety profile while the secondary endpoints were progression-free survival and PSA response. Results: From April to September 2011, 33 CRPC patients with concomitant cardiovascular disorders have been treated with AA. Main patients characteristics were: median age 71 years (range 57–81); baseline mean PSA value 40 ng/ml (6.32-995); the most common sites of disease were bone (27 pts, 81%), lung (11 pts, 33%) and liver (5 pts, 15%). All patients were previously challenged with at least 2 lines of hormone therapy and 1 chemotherapy regimen including docetaxel. The most common pre-existing cardiac disorders were hypertension 22 (66%), arrhythmias 4 (12%), cardiac ischemia 3 (9%) and conduction irregularity 2 (4%). Additionally 9 patients (27%) had metabolic disorders including dislipidemy and hyperglicemia. AA was feasible without inducing grade 3-4 AE nor treatment modification. The most common grade 1-2 AE were asthenia (27%), hypertension (18%) and fluid retention (28%). After a median time of treatment of 4 months (range 2–7 months) no dose modifications due to toxicity were required. No efficacy data are still available. Conclusions: Treatment with AA was feasible and well tolerated also in patients suffering from cardiac comorbidities and risk factors for cardiovascular disease.

341 Background: Rescue of patients (pts) who fail to be cured following 2–3 chemotherapy (CT) combinations ± high dose CT (HDCT) or who are cisplatin-refractory is still an unmet need. The identification of novel active agents/combinations is a priority. Methods: We reviewed the characteristics of consecutive pts who received TPG combination at our Institution for relapse/progression after 2 or 3 previous platinum-based CT lines. Treatment consisted of the administration of paclitaxel 80 mg/m2 IV, cisplatin 50 mg/m2 IV and gemcitabine 800 mg/m2 IV on days 1 and 8 q3w. Program provided up to 8 administrations of TPG followed by surgery of all resectable masses. Paraffin slides of all cases with residual viable cancer after TPG were retrieved: CD30 staining and somatic mutation analysis by Sequenom OncoCarta Panel v.1.0 were planned. Results: From 04/1999 to 07/2011, 74 pts have been treated with TPG, 64 in 3rd and 10 pts in 4th line. Median age was 32 (20–55), median number of prior CDDP cycles was 7 (4–10), 10 pts (13%) had already received HDCT, 4 pts had primary mediastinal GCT, 42 (57%) were CDDP-refractory/abs refractory, 25 pts (34%) had either liver, bone or brain metastases before TPG. 40% developed G3-4 hematologic and 2 pts G3 renal toxicity, none of them being dose-limiting. No treatment delays have been observed. Median number of administrations was 7 (1–10). 8 complete responses (CR), 28 partial responses with normal markers (PRm-) and 13 incomplete response/stable disease have been recorded, for a major response rate (CR+PRm-) of 49%. 34 pts (46%) underwent post-CT surgery which was radical in 15 cases (44%) and led to 7 pathologic CR. 3-, 6- and 12-month PFS was 68% (95% CI 55–76%), 31% (21–42) and 20% (12–30), respectively. 1-yr PFS after HDCT only was 24% (4–53). 12- and 24-month OS was 46% (34–57) and 26% (16–37), respectively. Median PFS and OS were 5 (1–104) and 12 mos (1–116). Conclusions: TPG combination rates first among salvage therapies for refractory GCT, even after failure of HDCT. Benchmark survival endpoints for trials on new agents/combinations have been set. Results of the biomarker analysis will be available in Feb 2012 and may help to corroborate a window of opportunity for targeted agents in GCT.

Renal cell carcinoma accounts for 80% of all kidney cancers -worldwide; the tumor staging at diagnosis ranges from small, low-stage tumors to more advanced neoplasms [1-5]. The survival rate has increased in recent years: nowadays, patients with localized disease have a 5-year survival >80% but in those with distant metastatic RCC, 5-year survival is

4639 Background: Treatment of patients (pts) with advanced penile SCC is very often unsuccessful. Single agents or combination therapies (Rx) combined with surgery achieved unsatisfactory results. ...

396 Background: Carcinoma of Bellini collecting ducts (CDC) is very uncommon but it is one of the most aggressive urological entities. For this tumor, originating from the epithelium of Bellini ducts in the distal tubule and preferentially occurring in young populations, no standard effective therapy has been so far established. Results of previous clinical experiences with chemo- or immunotherapy have been disappointing. We report our experience in 7 cases of CDC treated with targeted therapies. Methods: From December 2004 to May 2010, 333 patients with advanced renal cell carcinoma have been treated with targeted therapies at Istituto Nazionale Tumori of Milan. From the global database analysis, seven cases with histological subtype of CDC have been identified. All patients had advanced disease and received a targeted therapy as first-line treatment. Six of them underwent previous nephrectomy, all had nodal involvement, and three had two or more sites of disease including lung, liver, and adrenal glands. Four patients received sorafenib as first-line treatment, two sunitinib, and one temsirolimus. After sorafenib failure, two patients received a second-line treatment consisting of both sunitinib and temsirolimus. Results: Five patients developed early progression of disease with a very short 4-month survival. One patient had a long term partial response of 33 months with sorafenib, he underwent second-line sunitinib and had no progression for further 10 months. The last patient reached a progression-free survival of 6 months with temsirolimus; when progressed, he achieved a disease control for further 9 months during sunitinib therapy. Both patients are alive after 50 and 15 months of treatment, respectively. The most common adverse events, low or moderate in severity, consisted of fatigue, hand-foot skin reaction, diarrhea, hypertension, and anemia. Conclusions: Prognosis of advanced CDC remains unfavorable. New target agents may be active in this disease and need further prospective phase II studies. [Table: see text]

A biologic profile including proliferative.activity, evaluated as H-3-thymidine labeling index (H-3-dT LI), DNA ploidy, p53 tumor-suppressor gene and P-glycoprotein (P-170), as an expression of the multidrug resistance gene, was defined for 50 primary transitional cell carcinomas of the bladder. H-3-dT LI was evaluated by autoradiography on histologic sections after incubation of fresh tumor biopsies with H-3-thymidine. Ploidy was defined by flow cytometric analysis of DNA content on nuclei suspensions obtained from frozen material. Expression of p53 protein and P-170 glycoprotein was detected by immunohistochemistry using the PAb1801 and C219 monoclonal antibody respectively, on sections from paraffin-embedded tumor biopsies. Invasive tumors showed a higher median H-3-dT LI (12.7% vs 4.2%) and a higher frequency of aneuploidy (73% vs 43%) and more frequently expressed p53 (82% vs 36%) than superficial tumors. Further analysis showed that proliferative activity was higher in invasive than in superficial cancers only in p53-positive or aneuploid tumors and not in p53-negative or diploid tumors. Moreover, proliferative activity and p53 overexpression, but not ploidy, were directly related to histologic grading and tumor stage. Generally, P-170 was not significantly related to any biologic or clinico-pathologic factor. Kinetic and phenotypic biologic markers are differently related to clinico-pathologic factors. A panel of biologic features can be easily evaluated on small transurethral biopsies at diagnosis, during endocavitary treatment or follow-up in bladder cancer patients.

5084 Background: Primary RPLND is our choice for clinical stage I (CSI) NSGCTs. Open RPLND (O-RPLND) has been our standard policy since 1985, while laparoscopic RPLND (L-RPLND) has been introduced since the late-1990s. Methods: Between June 2003-March 2008, 150 consecutive CSI NSGCT patients (pts) have been submitted to O-RPLND (n = 91) or L-RPLND (n = 59). Pts with high risk disease (vascular invasion/embryonal carcinoma > 90% in the primary tumor) were more frequently offered O-RPLND, while pts with low risk disease (none of the 2 above) were usually considered for L-RPLND. We reviewed our data focusing on: complications, operating time (OT), hospital stay (HS), number of removed nodes, occurrence of nodal metastases as well as of metastasis during follow-up and global need of chemotherapy (CT). Results: O-RPLND (91). 59/91 (64.8%) were high-risk patients. Median OT was 140 min (IQR 110–150). Five (5.5%) complications occurred: 4 lymphorrea and 1 hemorrhage. Median HS was 6 days (IQR 5–7). Nodal metastases were found in 24 (26.4%) pts. Median number of removed nodes was 20 (IQR 14–25). L-RPLND (59). 54/59 (91.2%) were low-risk patients. Median OT was 210 min (IQR 180–240). Ten (16.9%) complications occurred: 5 required conversions to open procedure due to intraoperative bleeding (4) or technical impossibility to conclude the procedure (1). Median HS was 4 days (IQR 4–5). Nodal metastases were found in 5 (8.5%) pts: 2 of them received immediate adjuvant CT. Median number of removed nodes was 14 (IQR 11–20). OT and HS were significantly better in O-RPLND and L-RPLND series, respectively (p.0001 at Mann Whitney test). After a median follow-up of 15.1 months (1–52), distant metastases were observed in 10 (0.7%) pts: 7/91 (7.7%) following O-RPLND and 1/59 (1.7%) following L-RPLND. CT was administered to 7 (7.7%) pts following O-RPLND and to 3 (5.1%) pts following L-RPLND. Conclusions: In this large case-series, no excess of recurrences but a higher rate of complications were recorded in L-RPLND pts. O-RPLND had a significant better OT while HS was shorter in L-RPLND series. Both procedures are still being applied: pts are currently offered one of the 2 modalities after counseling. No significant financial relationships to disclose.

16036 Background: Patients (pts) who fail to be cured following 2 lines at least of cisplatin-based chemotherapy (CT), high-dose CT (HD-CT) or both fare badly. Nonetheless a combination with paclit...

A study on 81 patients who underwent partail cystectomy for bladder cancer is presented. The low postoperative mortality (2.46%) and the high 5-year survival (72%) show that this type of surgery is effective and without major complications. Thirty-eight patients were treated with endovesical thiotepa (OTT); the remaining 41 patients were untreated after surgery. Results showed that survival and number of relapses were similar in the two groups. This fact seems to prove that chemotherapy with OTT is not essential after segmental cystectomy. To explain this assertion, several hypotheses are presented.

This is a report on a case of 2 concurrent neoplasms of different histology within the same kidney: a renal cell carcinoma and a transitional cell carcinoma of the renal pelvis in a patient affected by chronic renal failure due to abuse of phenacetin. There was also a transitional cell carcinoma of the urinary bladder.

A clinical study was made of 21 patients (13 men and eight women) who had undergone anterior resection of the rectum for cancer at the National Tumour Institute of Milan between April 1984 and April 1985. After surgery, 13 patients (including three men with benign prostatic hypertrophy) showed voiding dysfunctions (hesitancy, dysuria, and weak stream) and bladder areflexia. Two of them also had positive Lapides' tests. An early rehabilitative treatment was started after surgery and the entire group was thoroughly reexamined one year later. Only the two patients with positive Lapides' tests still had bladder areflexia with residual urine greater than 100 ml. One of them also had a urinary tract infection. None of them showed decreased renal function.

A total of 44 patients with infiltrating, locally advanced bladder cancer (stages T 3a-b, T 4a-b and N+/N0) were treated with the systemic chemotherapy regimen of cisplatin, methotrexate and vinblastine (CMV) in the neoadjuvant setting, of whom 39 were evaluable for response. After planned radical cystectomy and 2 to 3 cycles of chemotherapy no tumor was found on the pathological specimen of 4 patients (10%), the tumor was downstaged in 19 (49%) and no change was observed in 16 (41%).Toxicity included leukopenia in 29 patients (66%), 1 of whom died of granulocytopenic sepsis, nausea and vomiting in 39 (89%) and mild to moderate mucositis in 18 (41%). Median followup is 12 months with a range of 6 to 39 months. Of 32 patients followed for longer than 6 months 6 (19%) experienced progression or recurrence of disease. We conclude that preoperative CMV chemotherapy is effective in inducing downstaging of the tumor, although systemic toxicity limits its use to cautiously selected patients.

373 Background: Mediastinal GCTs and PMNSGCTs poorly benefit from CT and half of patients (pts) still die for disease. Enhancing the risk stratification may result in tailoring a personalized treatment strategy since diagnosis. Methods: Between 1985 and 2012, 87 pts with PM-GCT were treated at our center. Of them, pure seminomatous histology was excluded. Cox proportional hazards regression analysis was conducted to examine the prognostic impact of these candidate factors on overall survival (OS): type of 1st-line CT (high [HDCT] vs conventional dose [CDCT]), post-CT surgery, type of baseline elevated serum tumor marker (STM), presence of lung or liver-bone-brain metastases (LBB), STM response (still elevated vs normal or normalized), and histology (viable cancer [VC] vs necrosis/teratoma [NT]). OS curves were compared by Kaplan Meier method with the log-rank test. Results: The study included 68 cases with PMNSGCT. Median age was 28.5 yrs (IQR: 23-35). 12 pts (17.7%) presented with mediastinal syndrome, 23 (33.8%) had lung and 7 (10.3%) LBB metastases. 12 pts received upfront HDCT and 45 pts (66.2%) underwent post-CT surgery. The final model of poor prognostic factors included no surgery (HR: 8.74, 95%CI, 1.77-43.01), surgery + VC (HR: 6.97, 95%CI, 1.46-33.30), and lung metastases (HR: 2.92, 95%CI, 0.99-8.64). The model demonstrated moderate discriminatory ability for OS (c-statistic=0.68). A risk stratification model based on the combination of these factors and accounting for a 50% five-year survival cutoff identified 2 groups (poor prognosis, N=28 vs good prognosis, N=26) with distinct overall survival curves (p

Sacral chordoma is one of the rarest tumors of the central nervous system (less than 1 % of the entire group). Mictional disorders are among the most frequent symptoms and are caused by the extrinsic compression brought to bear on the cauda equina and by surgical demolition of the sacrum. Seven patients who had undergone sacral resection for chordoma, starting from S2, were followed for at least one year. It was observed that mictional disorders were often early symptoms signalling the presence of chordoma. Several patients were affected by a complete bladder denervation (infrasacral lesion) after surgery. Early rehabilitative treatment given after surgery for one year restored normal bladder functions in all the patients whose bladder denervation seemed to be not total (negative Lapides’ test). Even when a complete infrasacral lesion of the bladder has been ascertained, early rehabilitative treatment may well prevent serious renal damage.