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The administration of adjuvant chemotherapy for patients with penile squamous cell carcinoma (PSCC) with high-risk features is controversial. In 21 patients who had received adjuvant taxane, cisplatin, and 5-fluorouracil, the expression of p53 in the tumor-positive lymph nodes was the only factor that showed a trend toward poorer survival endpoints. If confirmed, these findings could help in selecting the best candidates for adjuvant chemotherapy. Background: Little is known about the outcomes and prognostic factors of adjuvant chemotherapy for locally advanced penile squamous cell carcinoma after regional lymphadenectomy (LAD). Patients and Methods: We retrospectively reviewed the data from 21 patients who had received taxane, cisplatin, and 5-fluorouracil (TPF, every 3 weeks) in the adjuvant setting at our center. Univariable and multivariable Cox regression analyses were undertaken for disease-free (DFS) and overall survival (OS) of TPF. Results: The patients had received TPF from July 2004 to July 2012 after inguinal (n = 6) or inguinal plus pelvic LAD (n = 15), and the median follow-up was 52 months. Thirteen (61.9%) had pelvic and 5 (23.8%) bilateral inguinal nodal metastases. The median time from LAD to the start of TPF was 5.4 weeks (interquartile range [IQR], 4.1-7.3 weeks). Metastatic tumor tissue from 11 of 19 evaluable patients (57.9%) showed positive immunohistochemistry staining for p53. Univariably, only the expression of p53 showed a trend toward poorer DFS (hazard ratio [HR], 4.14; 95% confidence interval [CI], 0.87-19.68; P = .074) and OS (HR, 4.54; 95% CI, 0.95-21.56; P = .056). The same results were obtained multivariably for DFS (HR, 3.76; 95% CI, 0.78-17.96; P = .096) and OS (HR, 4.29; 95% CI, 0.89-20.57; P = .067). The median DFS was 8.9 months (IQR, 5.9-22.7 months) for p53-expressing patients versus not estimable for non p53-expressing patients (P = .051) and the median OS was 17.2 months (IQR, 12.8-22.7 months) and not estimable, respectively (P = .037). Conclusion: In patients who had received adjuvant TPF for node-positive penile squamous cell carcinoma, p53 IHC expression seemed to be associated with a poorer outcome, and further study is warranted in larger data sets to confirm these findings. This information might be useful to improve the prognostic allocation. (C) 2016 Elsevier Inc. All rights reserved.

564 Background: Despite the overall high cure-rate for patients (pts) with CSI seminoma (sem) regardless of the intervention used, huge discrepancy exists in the number of CT scans that are proposed to pts during FUP period, mainly during active surveillance (AS). The impact of such discrepancy in diagnosing pts with a high-risk relapse was assessed in published literature with a meta-analysis (MA). Methods: We searched for arms of studies of AS or active treatment (AT, adjuvant chemotherapy and radiotherapy) in pts with CSI sem. Meta-analytic techniques were used to pool and compare study level data of AS and AT groups and to study the impact of the number of CT scans (as a continuous variable) during FUP upon the % of pts with CSIII or with IGCCCG intermediate (int) prognosis sem at relapse. Results: 22 studies were analyzed (33 arms, n = 11025 pts). 39.6% had a high-risk sem, 38.8% (n = 4274) underwent AS vs 61.2% (n = 6751) AT. The number of CT scans ≤2y ranged 4-8, and 0-7 for AS and AT groups. Overall, 922 pts experienced a relapse (651 in AS and 271 in AT arms), 73.9%

Neoadjuvant systemic cisplatin, methotrexate and vinblastine chemotherapy has been used in the treatment of 69 patients with advanced bladder cancer (stages T2-T4 N+/N0 M0). Sixty patients were evaluable for response at a median follow-up of 48 months. Preoperative resection of the tumor was purposely avoided in order to keep a marker lesion. After planned radical cystectomy, pathological complete responses (pCRs) and partial responses (pPRs) were documented in 5 (8.3%) and 29 cases (43.4%), respectively. These patients had a 5-year disease-free survival rate of 80%, which was statistically superior (p = 0.0013) to 35% for the remaining nonresponding patients. One patient (20%) with a pCR died of systemic disease after 14 months, while the remaining 4 patients (80%) are alive and free of disease after a median follow-up of 57 months. A higher percentage of pCRs and pPRs was observed in the group of patients with stage T3b-T4 tumor (pCR 11%, pPR 63%) in contrast to the patients with stage T2-T3a disease (pCR 4.5%, pPR 45.5%), even if no significant difference in the 5-year survival rate was observed between the 2 groups. Patients with a G2 tumor before chemotherapy survived longer (5-year survival rate of 78%) than those with G3 disease (5-year survival rate of 61%), but no significant difference was achieved.

We conducted an analysis of immunohistochemical expression of multiple biomarkers in patients with metastatic (M) urothelial carcinoma (UC), including their prognostic effect in the setting of first-line chemotherapy. Expression of vascular endothelial growth factor receptor (VEGFR)-3 and platelet-derived growth factor receptor (PDGFR)-alpha were associated with a divergent prognostic meaning. Present data do not support the use of immunohistochemistry (IHC) to select patients for clinical trials and highlight the hurdles of targeting angiogenesis in this field. Background: Knowledge of the expression of molecular drivers and potentially druggable targets might enhance prognostic classification of M UC. Materials and Methods: We analyzed archival tissue from patients with UC who underwent first-line chemotherapy for locally advanced (LA) and M disease between the years 2000 and 2013. The following biomarkers were evaluated using IHC: excision repair cross complementation (ERCC) group 1 (ERCC1), epidermal growth factor receptor (EGFR), HER2, VEGFR-3, PDGFR alpha, p53, and p63. Expression of ERCC1, EGFR, and HER2 was dichotomized as positive (2+, 3+) or negative (

There is no clear indication for postchemotherapy surgery in patients with metastatic urothelial cancer (UC). We analyzed the contribution of postchemotherapy lymphadenectomy on survival in patients treated at our center. Twenty-eight patients were identified and results compared with those of a nonsurgically treated cohort. Surgery and response to chemotherapy were prognostic for progression-free (PFS) and overall survival (OS). If confirmed, results might have implications in daily practice and clinical trials. Background: The contribution of postchemotherapy pelvic (PLND) or retroperitoneal lymphadenectomy (RPLND) on survival in patients with advanced and metastatic UC is still unclear. Patients and Methods: Between September 1986 and May 2012, 157 patients with locally advanced or metastatic UC received first-line chemotherapy consisting of mMVAC (modified methotrexate, vinblastine, doxorubicin, and cisplatin), according to our policy. Patients with subdiaphragmatic nodal disease and/or local recurrence only and who experienced at least stable disease (SD) were selected. Fifty-nine patients were identified, 28 of whom underwent surgery, 31 started consolidation chemotherapy with or without radiotherapy or observation. The prognostic effect of candidate factors on survival was evaluated using Cox proportional hazard regression models. Results: A total of 14 PLND and 14 RPLND patients were identified after they had achieved a complete response (CR; n = 7) or a partial response (PR) and SD (n = 21). Median follow-up was 88 months (interquartile range, 24-211 months). Median PFS was 18 (95% confidence interval [CI], 11-not estimated) and 11 (95% CI, 5-19) months, respectively, in favor of the surgical cohort and curves were statistically different (log-rank test, P = .009). In multivariate analysis, postchemotherapy surgery was significantly prognostic for PFS and OS and response to chemotherapy (PR and SD vs. CR) was prognostic for PFS and trended to significance for OS. A model including these 2 factors showed bootstrap-corrected Harrel C statistics for PFS and OS of 0.65 and 0.68, respectively. Conclusion: In well selected patients with UC like those who achieved a clinical benefit with chemotherapy and had nodal metastatic disease, there was a survival advantage in removal of disease residuals.

Primary mediastinal nonseminomatous germ cell tumors comprise a heterogeneous series of neoplasms characterized by limited chemosensitivity and a poor prognosis. We analyzed a large series of patients from our tertiary cancer center, including pre- and postsurgical variables, with the aim to provide a prognostic model that might be suitable for clinical use. The variables identified in the prognostic model were surgical removal of residuals after first-line chemotherapy, histological response, and the presence of lung metastases. Their joint analysis defined distinct overall survival (OS) curves. Background: Primary mediastinal germ cell tumors (PMGCTs) poorly benefit from chemotherapy and half of patients die because of disease progression. Enhancing the risk stratification might result in tailoring a more personalized treatment strategy from the time of diagnosis. Patients and Methods: Between the years 1985 and 2012, 86 patients with PMGCT were treated at our center. Cox proportional hazards regression analysis was conducted in the population of nonseminomas to examine the prognostic effect of candidate factors on progression-free and OS. OS curves were compared using the Kaplan-Meier method and the log-rank test. Results: Mean age was 29.8 years (range, 15-63 years). Twenty-five patients (29.1%) had lung and 8 (9.3%) liver, bone, or brain metastases. Twelve patients (13.9%) received upfront high-dose chemotherapy and 45 patients (52.3%) underwent surgery after chemotherapy. Cox analyses included 61 evaluable primary mediastinal nonseminomatous germ cell tumors (PMNSGCTs). The final model of factors indicating a poor prognosis included the combination of surgery and histological response (overall P = .011) and lung metastases (hazard ratio, 3.03; 95% confidence interval, 1.12-8.15; P = .028). The model showed a bootstrap-corrected Harrel c-statistic for OS of 0.66. A risk stratification model based on the combination of these factors and accounting for a 50% 5-year survival cutoff identified 2 groups (poor prognosis, n = 33 vs. good prognosis, n = 28) with distinct OS curves (P < .001). Preoperative serum tumor marker level was not associated with the final histology (P = .853, chi(2) test). Results were limited by small numbers. Conclusion: Patients with PMNSGCT included 2 subpopulations with distinct prognosis, and therapeutic improvements are needed for patients with poor-risk features.

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.

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