Pembrolizumab (pembro) is approved for the II-line in mUC. In PEANUT trial (NCT03464734) we investigated the efficacy of the combination of pembro plus nab-paclitaxel after chemotherapy (CT) failure. Herein, a long-term follow-up (FUP) update and a post-hoc analysis are presented. In an open-label, single-arm, phase 2 trial pts with mUC after failure of ≤2 platinum-based CT were enrolled. Pts received 200 mg pembro on D1, and 125 mg/m2 nab-paclitaxel on D1 and D8, every 3 weeks, until disease progression (PD) or unacceptable toxicity. The primary endpoint was the progression-free survival (PFS). As of April 1, 2023, 11/70 (15.7%) pts enrolled are in CR after a median FUP of 45.5 mo (95% CI, 42.3 – 49.8). 5/70 (7.1%) completed 2-yrs of treatment. Median OS was 11.7 mo (95% CI, 8.27 – 17.2) and median PFS was 5.1 mo (95% CI, 4.1 – 7.37). The ORR was 47.1%. For CR or PR pts, median OS was 28.4 mo (95% CI, 16.2 – NA). OS rate was 19 (27.1%) at 46 mo. Treatment was discontinued due to toxicity in 12/70 (17.4%) pts: in 9/70 only nab-paclitaxel, in 3/70 both. After PD, 22/70 (32.4%) patients underwent further therapies. Levels of hemoglobin (HR 0.88; 95% CI, 0.76 – 1; p value 0.095) and NLR at baseline (HR 1.2; 95% CI, 1.1 – 1.3; p value 0.0032), discontinuation due to toxicity (HR 0.34; 95% CI, 0.14 – 0.79; p value 0.012) and subsequent therapy (HR 2.4; 95% CI, 1.3 – 4.4; p value 0.0033) appear to have a statistically significant impact in PFS. Instead, the primary (bladder vs UTUC) (HR 2.3; 95% CI, 1.1 – 4.7; p value 0.027), liver metastases (HR 2.4; 95% CI, 1.3 – 4.2; p value 0.0032), NLR at baseline (HR 1.2; 95% CI, 1.1 – 1.3; p value 0.0014) and discontinuation due to toxicity (HR 0.38; 95% CI, 0.16 – 0.89; p value 0.026) seem to have a greater influence on OS. After nearly 4 years, the combination of pembrolizumab and nab-paclitaxel maintained clinically meaningful efficacy in pts with mUC that progressed after platinum-based CT. OS data and post-hoc analyzes are consistent with what has been published in the literature in this disease setting.

Background: Pembrolizumab is a new standard of care for patients with platinum-treated, metastatic urothelial carcinoma (UC). Nab-paclitaxel is active in advanced UC. In the PEANUT study (NCT03464734) we investigated their combination in advanced UC. Patients and methods: PEANUT was an open-label, single-arm, phase II trial that included patients who had failed one or two chemotherapy regimens, including platinum chemotherapy. Biomarker analyses focused on programmed cell -death ligand-1 combined positive score (CPS) and comprehensive genomic profiling on tumor samples and circulating tumor DNA. Patients received 200 mg pembrolizumab on day 1 (D1), and 125 mg/m(2) nab-paclitaxel on D1 and D8, every 3 weeks, until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) according to RECIST (v1.1). The assumption was to detect an improvement in the median PFS from <= 3.0 months (H0) to >= 5.0 months (H1). Results: Between January 2019 and January 2020, the PEANUT study enrolled 70 patients: 24% had failed two prior systemic therapies; 31% had an Eastern Cooperative Oncology Group (ECOG) performance status of 1; and 28.6% had liver metastases. After a median follow-up of 9.8 months, 40 patients have relapsed (57.1%). The median PFS was 5.9 months [95% confidence interval (CI) 3.1-11.5]. The confirmed objective response rate (ORR) was 38.6% (95% CI 27-51) with 17 partial responses and 10 complete responses (14.3%). The median duration of response was not reached. Five patients (7.1% ) had ongoing responses lasting >12 months. The most common any-grade treatment-related adverse events included alopecia (71.4%), neutropenia (32.9% ), and peripheral neuropathy (34.3%). Neither tumor mutational burden nor CPS was significantly associated with PFS at univariable analyses. The single-arm design of the trial was the major limitation. Conclusions: Pembrolizumab combined with nab-paclitaxel, as secondand third-line chemoimmunotherapy for metastatic UC, showed a favorable safety profile, durable PFS, and a clinically meaningful ORR in these preliminary analyses. This combination warrants additional randomized studies in earlier disease stages.

•In the PURE-01 study, multiparametric magnetic resonance imaging (mpMRI) of the bladder was used to stage and evaluate the response to pembrolizumab, before radical cystectomy.•Assessments of mpMRI sequence were externally reviewed, showing preliminary but promising reproducibility.•We proposed an mpMRI-based definition of complete response predicting the pathological complete response to pembrolizumab that was externally replicated.

BACKGROUND:Patients with predominant variant histology (VH) of bladder tumors, defined as involving >50 % of the tumor specimens, are typically excluded from clinical trials, and for these patients, the efficacy of standard chemotherapy is limited. OBJECTIVE:To evaluate the activity of preoperative pembrolizumab in patients with muscle-invasive bladder carcinoma (MIBC) and VH, enrolled in PURE-01 study (NCT02736266). DESIGN, SETTING, AND PARTICIPANTS:In the open-label, single-arm, phase 2 PURE-01 study, three courses of 200 mg pembrolizumab preceding radical cystectomy (RC) were administered in T2-4aN0M0 MIBC patients. The amended study design included patients with predominant VH. INTERVENTION:Neoadjuvant pembrolizumab and RC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Pathological complete response (pT0) in intention-to-treat population was the primary endpoint. Biomarker analyses included programmed cell-death ligand-1 (PD-L1) expression using the combined positive score (CPS; Dako 22C3 antibody) and comprehensive genomic profiling (FoundationOne assay). Multivariable logistic regression analyses (MVAs) evaluated the histological category (predominant VH vs nonpredominant VH vs pure urothelial carcinoma), tumor mutational burden (TMB) and CPS in association with the pathological response. RESULTS AND LIMITATIONS:From February 2017 to June 2019, 114 patients were enrolled; 34 (30%) of them presented with VH, including 19 (17%) with predominant VH. In total, the pT0 rate was 37% (95% confidence interval [CI]: 28-46) and the pT ≤ 1 rate was 55% (95% CI: 46-65). The majority of predominant VH patients presented with squamous-cell carcinoma (SCC; N = 7), and six of seven (86%) had downstaging to pT ≤ 1, with one pT0; two of three lymphoepithelioma-like (LEL) variants had a pT0 response. None of the remaining nine predominant VHs had a response. On MVA, TMB and CPS were associated with both the pT0 and the pT ≤ 1 response, regardless of tumor histology. CONCLUSIONS:The updated PURE-01 results confirm the activity of neoadjuvant pembrolizumab in MIBC. Patients with SCC and LEL features may be suitable for neoadjuvant immunotherapy trials. CPS and TMB are the key response predictors irrespective of the histological subtypes. PATIENT SUMMARY:In the PURE-01 study, we have preliminarily evaluated the activity of neoadjuvant pembrolizumab in patients with predominant variant histology (VH). Of these patients, those harboring squamous-cell carcinoma or a lymphoepithelioma-like variant feature had major, although preliminary, pathological responses compared with those with other predominant VHs. Expression of programmed cell-death ligand-1 and tumor mutational burden may predict the pathological response to pembrolizumab, and provide a rationale for selecting patients according to these features instead of the histological bladder cancer subtypes.

Background Interim results from APACHE (NCT03081923) have been presented, with the monotherapy arm stopped for futility (Necchi, Eur Urol 2018). Updated results with the expanded combination therapy cohort are presented. Methods Apache is an open-label, randomized, 3-stage, phase 2 study. Pts who have failed ≥2 chemotherapy (CT) regimens received Durva, 1.5 gr q4w, x 13 cycles (arm A) or Durva plus with Treme, 75 mg q4w, x 4 cycles, followed by Durva alone x total 13 cycles (arm B). The primary endpoint is the modified objective response-rate (mORR=RECIST 1.1 complete or partial response [PR] or stable disease [SD]+STM reduction >10%). H0: mORR rate ≤10%, H1: mORR ≥25% (α and β = 10%). The total sample size of 120 pts is split into 3 stages: in stage 1, each arm is terminated whenever no response is observed in 11 pts/arm. In stage 2, 29 additional pts/arm are enrolled. Biomarker analyses include: PD-L1 expression on immune cells (Ventana SP142) and comprehensive genomic profiling (CGP) with FoundationOne assay. Results From 02/17-11/18, 29 pts were enrolled (11 arm A and 18 arm B). 22 had gonadal and 7 extragonadal GCT, 19 had received >/=3 prior CT regimens. Median tumour mutational burden (TMB) was 4 mutations (mut)/mb, 1 pt showed microsatellite instability in arm A. 10 pts (34.5%) experienced any-Grade AEs, without differences between arms. In the expanded arm B, 2 responses (11.1%, 1 RECIST-PR in seminoma and 1 SD with STM reduction in nonseminoma) and 2 SD were observed. PD occurred regardless of PD-L1 expression and TMB. After median follow-up of 16.3 months, 12-month OS in arm A was 30% (95%CI: 7.2-57.7) and in arm B was 29.6% (95%CI: 10.2-52.2). Further CT post-PD was administered in 8 pts (27.6%), but was mostly ineffective (7/8 SD/PD). Conclusions Despite objective responses were rare with IO, long-term OS results are encouraging in very highly pre-treated GCT pts, suggesting a role for maintenance approach in earlier setting (2nd-line CT), and privileging Durva+Treme due to more responses. Conventional IO biomarkers did not allow for patient selection, and further research is warranted. Clinical trial identification NCT03081923. Legal entity responsible for the study AstraZeneca. Funding AstraZeneca. Disclosure S.M. Ali: Full / Part-time employment: Foundation Medicine. J. Chung: Full / Part-time employment: Foundation Medicine. J.S. Ross: Full / Part-time employment: Foundation Medicine. A. Necchi: Honoraria (institution), Advisory / Consultancy: Merck; Honoraria (institution), Advisory / Consultancy: AstraZeneca; Honoraria (institution), Advisory / Consultancy, Spouse / Financial dependant: Bayer; Advisory / Consultancy: BMS; Advisory / Consultancy: Clovis; Honoraria (institution), Advisory / Consultancy: Janssen; Honoraria (institution), Advisory / Consultancy: Roche. All other authors have declared no conflicts of interest.

Background The PURE01 study (NCT02736266) evaluates preoperative pembrolizumab before radical cystectomy (RC). Here, the possibility to predict the pathologic complete response (pT0) after neoadjuvant immunotherapy could have paradigm-shifting implications for the management of patients with MIBC. Methods The reported analyses include comprehensive genomic profiling with FoundationONE CDx assay and programmed cell-death-ligand-1 (PD-L1) combined positive score (CPS, Dako 22C3 antibody) on baseline TURB samples. Multivariable logistic regression analyses (MVA) evaluated clinical T-stage and biomarkers (tumor mutational burden [TMB], and CPS) in association with pT0 response. Multivariable-derived coefficients were used to develop a novel risk calculator. Decision-curve analysis was used to evaluate the net benefit of the predictive model. Results From 02/2017 to 06/2019, 112 patients with full biomarker data were enrolled. At MVA, only CPS showed a significant association with pT0 (p = 0.005). Increasing TMB and CPS values featured a linear association with logistic pT0 probabilities (p = 0.02 and p = 0.004). Very high TMB values, associated with a predicted probability of pT0 > = 55%, were independent from CPS contribution. The coefficients of the predictive model were used to develop a risk calculator. The c-index of the model was 0.77. At decision-curve analysis, the net-benefit of the model was higher than the “treat-all” option from more than 10% threshold probabilities. Conclusion We presented the first biomarker-based risk stratification tool that can be used to recommend use of neoadjuvant pembrolizumab in those patients who have equal or greater chances to achieve a pT0 status compared to the literature on neoadjuvant chemotherapy or to RC alone, depending on cisplatin eligibility. Clinical trial identification PURE01 study (NCT02736266). Legal entity responsible for the study The authors. Funding Merck & Co., Inc., Kenilworth, NJ, USA; Associazione Italiana per la Ricerca sul Cancro (AIRC). Disclosure R. Madison: Shareholder / Stockholder / Stock options, Full / Part-time employment, employee and stock owner of Foundation Medicine Inc: Foundation Medicine Inc. M. Colecchia: Speaker Bureau / Expert testimony: Roche Diagnostics. S.M. Ali: Full / Part-time employment: Foundation Medicine. J.H. Chung: Full / Part-time employment: Foundation Medicine. J. Ross: Leadership role, Research grant / Funding (institution), Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. A. Salonia: Speaker Bureau / Expert testimony: Astellas Pharma; Travel / Accommodation / Expenses: Konpharma. A. Briganti: Advisory / Consultancy: Astellas Pharma; Advisory / Consultancy: Hanssen-Cilag; Advisory / Consultancy: OPKO Health; Advisory / Consultancy: MDxHealth; Advisory / Consultancy: Ferring; Research grant / Funding (institution): Novartis. A. Necchi: Advisory / Consultancy: Merck, Incyte, AstraZeneca, Roche, Rainier Therapeutics, Clovis Oncology, Bristol-Myers Squibb, Bayer, Basilea Pharmaceutica; Research grant / Funding (institution): AstraZeneca, Ipsen, Merck and Incyte; Spouse / Financial dependant: Bayer. All other authors have declared no conflicts of interest.

Background: ICIs can overcome immune-suppression and activate effective immune responses against cancer cells. Therapy with ICIs have led to a clinically-meaningful extension in overall survival across several solid tumors, being endowed with long term disease control-rate in a part of responding patients (pts). However, an acceleration of the tumor growth rate (TGR) during ICI, defined as hyperprogressive disease (HPD), has been reported in 9-29% of pts. Mechanisms underlying HPD are unknown, yet murine double minute 2 (MDM2) family amplification was found in some of these pts. Methods: We retrospectively identified a series of 334 pts with miscellaneous advanced solid tumors treated with anti-PD1/PD-L1-containing ICI (mono or combo therapy) at our Institution. Inclusion criteria included imaging assessment at 3 timepoints: during reference period (from 3 months to 2 weeks before ICI baseline scan), before ICI therapy start (baseline scan, performed within 28 days) and during ICI treatment. Patients were considered HPD if they showed progressive disease (PD) by RECIST 1.1 at first radiological evaluation and a ≥ 2-fold increase of the TGR during ICI therapy compared to reference period. FISH analysis to evaluate MDM2 family genes amplification was performed in HPD cases whose paraffin embedded tumor material was available. Results: 73 cases were initially excluded from our analysis due to lack of tumor assessment during ICI. Of the remaining pts, 109 reported PD at first evaluation. Of them, only 45 were suitable for the analyses, having all requested radiological examinations available. Seven cases met HPD criteria: 3,5% of evaluable pts (7/197) and 6.4% of all the PD. No correlation with histology, age, serum biomarkers and type of ICI was found. FISH test for MDM2 family has been performed on 3 cases: one case showed amplification MDM4 gene (mean of signals > 8); other cases showed only increased MDM4 ratio score of unknown significance. Conclusions: Despite the limits of a retrospective analysis and small numbers, in our series HPD is a rare but clinically relevant event. The role of MDM2 family alteration as predictive biomarker is promising and deserves more investigations. Prospective studies including genomic and biological analysis are warranted. Legal entity responsible for the study: Elena Farè. Funding: Has not received any funding. Disclosure: F.G.M. de Braud: Advisor: BMS, Ignyta, MSD, Novartis, Pfizer, Amgen, Roche, Merck Serono, Servier. All other authors have declared no conflicts of interest.

Background: Immunotherapy with immune checkpoint inhibitors (ICIs) is modifying the standard of care for several solid tumours. Nevertheless, the results in terms of efficacy are still limited to a minority of patients even if the percentage of response differed among tumours type. The evaluation of response with ICI has been improved by the definition of new immune-related Response Criteria (irRC) that identified pseudo-progression followed by delayed tumour shrinkage in up to 10% of patients treated with anti CTLA-4 or anti PD1/PDL-1 agents. Afterward, hyper-progression (HP) after ICI administration has been recently reported but a mechanicistic explanation of the relationship with the ICI administration has not yet clearly identified. For this presentation, the obvious difficulty is to distinguish between resistance and consequent progression due to the tumour biology and a truly progression primed by ICI treatment. Methods: A total of 132 patients with solid tumors treated from 2014 to 2017 with antiPD1 (n = 15), anti PDL1 (n = 47), antiPD1 plus antiCTLA4 (n = 41) or plus antiGITR (n = 14), or IDO inhibitor (n = 6) or antiOX40 (n = 2), and bifunctional anti PDL1/antiTGFbeta monoclonal antibody (n = 7) in phase I/II trial at Istituto Nazionale Tumori were retrospectively evaluated for their tumor growth rate (TGR) before treatment and upon treatment. We defined the HP as: 1. progression at first restaging on ICI; 2. increase in tumor size >50%; 3. >2-fold increase in TGR, as reported by Champiat et coll. Results: Of 132 patients analyzed, 34 patients stopped the treatment before the first tumor evaluation (21 for clinical progression and 13 for drug-related adverse events), 42 patients exhibited disease progression at the first RECIST evaluation. Based on the criteria for the definition of HP, we excluded 14 pts without a previous imaging, 4 pts without target lesions and only 3 out of 24 pts (ovarian, gastric and squamous lung cancers) can be defined as HP (2.3%). Conclusions: In our experience, the occurrence of HP is limited to a small amount of patients treated with ICI in early phase clinical trials. In our analysis most of the patients have been treated with combo of ICIs, which could be a possible explanation for the lower incidence of HP as compared to what is reported. Nevertheless, the most important bias of underestimation for the evaluation of truly HP can be due to the very stringent criteria used for their definition that exclude patients with progression of non-target lesions and patients with early clinical progressions. As matter of fact, early clinical progression related to tumor biology and not to treatment is a major issue and the criteria reported by Champiat are not adequate to assess HP in patients receiving ICIs as first line of treatment, where we should probably concentrate our effort to investigate HP. Despite the fact that prospective trials are necessary to obtain more accurate data about the true incidence of HP and its etiology, we are evaluating a wider number of cases from disease treated in clinical trials and/or with standard of care to assess if incidence is related to histology. Legal entity responsible for the study: Fondazione IRCCS Istituto Nazionale Tumori Milano Funding: Has not received any funding Disclosure: F. de Braud: Advisor for BMS, Ignyta, MSD, Novartis, Pfizer, Amgen, Roche, Merck Serono, Servier. All other authors have declared no conflicts of interest.

Background:Bone metastases (BM) are rare in germ cell tumor (GCT) patients. Systematic data on risk factors, treatment and outcome are largely lacking. Patients and methods:A database created by an international consortium including 123 GCT patients with BM at primary diagnosis was retrospectively analysed. Survival estimates were calculated by the method of Kaplan-Meier and compared by log-rank testing. Cox regression analysis was applied for risk factor analyses. Results:In our cohort of patients, BM at primary diagnosis more often affected multiple sites (61%) and BM as the only metastatic site were scarce (9%). Histology was non-seminoma in 77% and seminoma in 23% of patients. After a median follow-up of 18 months (range, 0-228), estimated median PFS and OS were 21 (range, 0-225) and 98 months (95%CI, 36-160), respective 2-year PFS and OS rates were 34% and 45%. Negative prognosticators in univariate analysis were a mediastinal primary (PFS; HR 1.92; 95%CI, 1.05-3.50; OS; HR 2.16; 95%CI, 1.14-4.09) and the presence of liver and/or brain metastases (PFS; HR 1.89; 95%CI, 1.13-3.17; OS; HR 1.91; 95%CI, 0.024) Seminomatous histology was the strongest predictor for favorable PFS (multivariate Cox regression; HR, 0.32; P=0.011) with respective 2-year PFS and OS rates of 68% and 75% compared with 24% and 36% for non-seminoma patients. Conclusions:Outcome of GCT patients with primary metastatic bone disease is particularly poor in non-seminoma patients, even worse than the expected outcomes of the general IGCCCG 'poor prognosis' group. This series does not indicate that mutlimodal treatment improves the prognosis over stage-adapted chemotherapy alone, however, the statistical power of these results is limited due to low patient numbers in each specific subgroup.

BACKGROUND In the late 1990s, the use of high-dose chemotherapy (HDCT) and stem-cell rescue held promise for patients with advanced and poor prognosis germ-cell tumors (GCT). We started a randomized phase II trial to assess the efficacy of sequential HDCT compared with cisplatin, etoposide, and bleomycin (PEB). PATIENTS AND METHODS Patients were randomly assigned to receive four cycles of PEB every 3 weeks or two cycles of PEB followed by a high-dose sequence (HDS) comprising HD-cyclophosphamide (7.0 g/m(2)), 2 courses of cisplatin and HD-etoposide (2.4 g/m(2)) with stem-cell support, and a single course of HD-carboplatin [area under the curve (AUC) 27 mg/ml × min] with autologous stem-cell transplant. Postchemotherapy surgery was planned on responding residual disease in both arms. The primary end point was progression-free survival (PFS). The study was designed to detect a 30% improvement of 5-year PFS (from 40% to 70%), with 80% power and two-sided α at 5%. RESULTS From December 1996 to March 2007, 85 patients were randomized: 43 in PEB and 42 in HDS arm. Median follow-up was 114.2 months [interquartile range (IQR): 87.7-165.8]. Complete or partial response with normal markers (PRm-) were obtained in 28 (65.1%) and 29 (69.1%) patients, respectively. Five-year PFS was 55.8% [95% confidence interval (CI) 42.8-72.8] and 54.8% (95% CI 41.6%-72.1%) in PEB and HDS arm, respectively (log-rank test P = 0.726). Five-year overall survival was 62.8% (95% CI 49.9-79.0) and 59.3% (95% CI 46.1-76.3). One toxic death (PEB arm) was recorded. CONCLUSIONS The study failed to meet the primary end point. Furthermore, survival estimates of conventional-dose chemotherapy higher than expected should be accounted for and will likely limit further improvements in the first-line setting. CLINICALTRIALS.GOV: NCT02161692.

BACKGROUND:Outcomes of radiotherapy (RT) compared with chemotherapy (CT) remain poorly defined for clinical stage (CS) IIA and IIB seminoma. We aimed to evaluate the current role of the two treatment modalities in this setting of testicular seminoma.PATIENTS AND METHODS:A systematic review and meta-analysis (MA) was carried out to identify all evaluable studies. Search was limited to studies published after 1990 and included the Medline, Embase databases, and abstracts from ASCO (GU), ESMO, AUA, and ASTRO meetings up to April 2014. Sensitivity analyses were applied including the following: CSIIA and CSIIB, paraortic + iliac RT only in both stages, RT dose (≥30 versus <30 Gy), and PEB/EP regimens only.RESULTS:Thirteen studies have been selected for MA on relapse outcome. No randomized trials compared RT and CT. There were 4 prospective and 9 retrospective studies, with a total of 607 patients receiving RT and 283 patients CT. The pooled relapse rate (RR) was similar between the RT [0.11, 95% confidence interval (CI) 0.08-0.14, P for heterogeneity = 0.096, I(2) = 38%] and CT groups (0.08, 95% CI 0.01-0.15, P for heterogeneity <0.001, I(2) = 82.5%). However, in the sensitivity analysis, the pooled RR for RT in CSIIB was 0.12 (95% CI 0.06-0.17) while it was 0.05 (95% CI 0-0.11) for CT. Long-term side-effects and incidence of second cancers were more frequently reported following RT. The overall incidence of nontesticular second malignancies was 0.04 (95% CI 0.01-0.02) in the RT group and 0.02 (95% CI 0.003-0.04) in the CT group.CONCLUSIONS:Although RT and CT appeared to be equal options in CSIIA and IIB seminoma, a trend in favor of CT for a lower incidence of side-effects and RR in CSIIB was found. This evidence is limited by the retrospective quality of studies and their small sample size.

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.

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.