Current role of PSMA-PET imaging in the clinical management of prostate cancer.

Despite the developments of the last few years, metastatic castration-resistant prostate cancer (PC) remains a deadly disease. Until recently, almost all guidelines recommended magnetic resonance imaging (MRI) or computed tomography (CT) for the initial staging and local/systematic recurrence. Positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA) at the present stage, emerged as a promising diagnostic imaging tool for PC. PSMA PET/CT alone or in combination with multiparametric magnetic resonance imaging (mpMRI) can improve the detection of clinically significant PC, especially for Prostate Imaging Reporting & Data System (PI-RADS) = 3 lesions. In addition, PSMA PET/CT is more accurate than CT and bone scan for intermediate to high-risk disease at the initial staging. Contrariwise, a negative PET is not useful for surgeons to avoid a pelvic nodal dissection. PET-PSMA imaging is appropriate for prostate-specific antigen (PSA) persistence or PSA rise from undetectable level after radical prostatectomy or for PSA rise above nadir after definitive radiotherapy. Also, it is recommended for patients fit for curative salvage treatment. It should be noted that in patients, candidates for radionuclide therapy with Lutetium-177 (117Lu), a PSMA strong expression from PET/CT at baseline is considered necessary. This review summarizes the evolution of PSMA PET/CT and its current role in the management of PC.

JQ1 inhibits tumour growth in combination with cisplatin and suppresses JAK/STAT signalling pathway in ovarian cancer.

BACKGROUND: Overexpression of c-Myc is commonly seen in human ovarian cancers, and this could be a potentially novel therapeutic target for this disease. JQ1, a selective small-molecule BET (Bromodomain and extraterminal domain family) bromodomain (BRDs) inhibitor, has been found to suppress tumour progression in several cancer cell types. RESULTS: Using a panel of ovarian cancer cell lines and primary cell cultures from human ovarian cancer ascites, we demonstrated that JQ1 significantly suppressed cell proliferation and induced apoptosis in an ovarian cancer cell by targeting BRD4 and c-Μyc. In addition, JQ1 sensitized ovarian cancer cells to cisplatin, the most commonly used chemotherapeutic agent in ovarian cancer. Importantly, this effect was observed in ovarian cells, which exhibited resistance to cisplatin alone. Finally, we show that JQ1 interacts with the JAK-STAT signalling pathway, a pathway important in supporting ovarian cancer cell survival by suppressing or inducing genes involved in cell survival and apoptosis, respectively. CONCLUSION: Our data, taken together, suggest that JQ1 is an attractive antitumour candidate for further investigation in the treatment of ovarian cancer, as it associates with cell proliferation, apoptosis, and alterations in the JAK-STAT signalling pathway, especially in patients with a platinum-resistant profile or in patients with relapsed disease.

EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer-An International Collaborative Multistakeholder Effort†: Under the Auspices of the EAU-ESMO Guidelines Committees.

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach. PATIENT SUMMARY: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.

Patterns of practice and pharmacoeconomic analysis of the management of patients with metastatic renal cell carcinoma (mRCC) in Greece--the CRISIS study. A retrospective analysis by the Hellenic Genitourinary Cancer Group (HGUCG).

Background:Metastatic RCC (mRCC) treatment has been revolutionized with 11 approved targeted agents. We report patterns of practice, outcomes and pharmacoeconomic analyses after the introduction of targeted therapy. Patients and methods: CRISIS was a retrospective multicenter study of mRCCpatients who received targeted therapy . Results were related to the start of 1st-line therapy, with a cut off at 1 January 2011 in order to depict the impact of increased availability of effective options. Results: 164 patients, were included. 70.1% and 44.5% received 2nd and 3rd-line therapy, respectively. More patients were treated in 2nd-line after 1 January 2011. After a median follow-up of 55.1 months, median progression-free (PFS) and overall survival (OS) were 10.7 (95% confidence intervals [CI]: 8.3-13.7), 7.3 (95% CI: 5.1-8.6), 5.8 (95% CI: 3.8-7.8) and 34 (95% CI: 28.5-39.8), 22.4 (95% CI: 16-32.1), 18.3 (95% CI: 12.4-26.4) months for first, second and third line, respectively. Efficacy of sunitinib and pazopanib in 1st-line were similar. The mean total cost/patient was 35,012.2 Euros (standard deviation [SD]: 28,971.5). Conclusions: Our study confirms previous real-world data suggesting that continuing advances in the treatment of mRCC produce favorable outcomes in everyday practice. Pharmacoeconomic analyses are important for cost-effective utilization of emerging novel therapies.

Impact of the Number of Cycles of Platinum Based First Line Chemotherapy for Advanced Urothelial Carcinoma.

PURPOSE: We evaluated the impact of the number of cycles of platinum based, first line chemotherapy (fewer than 6 cycles vs the conventional 6 cycles or more) on the survival of patients with metastatic urothelial carcinoma. MATERIALS AND METHODS: We used the RISC (Retrospective International Study of Invasive/Advanced Cancer of the Urothelium) database. The association of the number of cycles of chemotherapy with overall survival was investigated by Cox multiple regression analysis after controlling for recognized prognostic factors. We excluded patients who received fewer than 3 or more than 9 platinum chemotherapy cycles to reduce confounding factors. The primary analysis was a comparison of overall survival for 3 to 5 vs 6 to 9 cycles using 6-month landmark analysis when 281 death events were observed. RESULTS: Of the 1,020 patients in the RISC 472 received cisplatin or carboplatin, of whom 338 and 134, respectively, were evaluable. A total of 157 patients received 3 to 5 cycles (median 4) and 315 received 6 to 9 cycles (median 6). There was no significant difference in overall survival between 3 to 5 and 6 to 9 cycles (HR 1.02, 95% CI 0.78-1.33, p = 0.91). No significant interactions were observed for the type of platinum (p = 0.09) and completed planned chemotherapy (p = 0.56). The limitations of a hypothesis generating, retrospective analysis applied. CONCLUSIONS: Four cycles of platinum based, first line chemotherapy appeared adequate and did not significantly compromise the survival of patients with advanced urothelial carcinoma. The omission of excessive cycles may avoid unnecessary cumulative toxicity and facilitate a better transition to second line therapy and investigational switch maintenance therapy strategies. These results require prospective validation but they may impact practice in select patients.

Current Clinical Practice Guidelines for the Treatment of Renal Cell Carcinoma: A Systematic Review and Critical Evaluation.

The landscape of local and systemic therapy of renal cell carcinoma (RCC) is rapidly changing. The increase in the incidental finding of small renal tumors has increased the application of nephron-sparing procedures, while ten novel agents targeting the vascular endothelial growth factor (VEGF) or the mammalian target of rapamycin pathways, or inhibiting the interaction of the programmed death 1 receptor with its ligand, have been approved since 2006 and have dramatically improved the prognosis of metastatic RCC (mRCC). These rapid developments have resulted in continuous changes in the respective Clinical Practice Guidelines/Expert Recommendations. We conducted a systematic review of the existing guidelines in MEDLINE according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement, aiming to identify areas of agreement and discrepancy among them and to evaluate the underlying reasons for such discrepancies. Data synthesis identified selection criteria for nonsurgical approaches in renal masses; the role of modern laparoscopic techniques in the context of partial nephrectomy; selection criteria for cytoreductive nephrectomy and metastasectomy in mRCC; systemic therapy of metastatic non-clear-cell renal cancers; and optimal sequence of available agents in mRCC relapsed after anti-VEGF therapy as the major areas of uncertainty. Agreement or uncertainty was not always correlated with the availability of data from phase III randomized controlled trials. Our review suggests that the combination of systematic review and critical evaluation can define practices of wide applicability and areas for future research by identifying areas of agreement and uncertainty among existing guidelines. IMPLICATIONS FOR PRACTICE: Currently, there is uncertainity on the role of surgery in MRCC and on the choice of available guidelines in relapsed RCC. The best practice is individualization of targeted therapies. Systematic review of guidelines can help to identify unmet medical needs and areas of future research.

Obesity and Outcomes in Patients with Metastatic Urothelial Carcinoma.

Background: Obesity has been associated with worse outcomes in patients with clinically localized urothelial cancer. However, this impact has not been evaluated in metastatic disease. Objective: To assess the impact of obesity on outcomes of patients with metastatic urothelial cancer. Methods: Data from 537 patients were aggregated from eight phase II and phase III clinical trials investigating first-line cisplatin-based combination therapy in metastatic urothelial cancer. Chemotherapy regimen, adverse events, treatment response, and survival outcomes were compared across body mass index (BMI) and body surface area (BSA) categories. Results: BMI was classified according to WHO criteria (<18.5 underweight, 18.5-24.99 normal weight, 25-29.99 overweight, >30 obese). BSA was classified as either below or greater than or equal to (average for this cohort (1.87 m2 for males and 1.66 m2 for females). There was no significant difference in number of chemotherapy cycles, adverse events, and response rate or survival outcomes (overall and progression-free) across BMI and BSA categories. There was no significant difference in adverse events across BMI categories, but the incidences of embolic events and renal failure were higher in patients with an average or higher BSA than those with a lower than average BSA (6.6% vs. 3.1% for renal failure p = 0.06; 5.9% vs. 2.7% for renal failure, p = 0.07). There was no significant difference in response rate or survival outcomes (overall and progression-free) amongst BMI and BSA categories. Conclusions: Obese patients with metastatic urothelial cancer on cisplatin-based therapies have similar response rates, survival outcomes, and tolerability of cisplatin-based therapy to non-obese patients.

A Cytokine Cocktail Augments the Efficacy of Adoptive NK-92 Cell Therapy Against Mouse Xenografts of Human Cancer.

BACKGROUND/AIM: Peripheral blood mononuclear cells (PBMCs) activated with immobilized monoclonal antibody against cluster of differentiation 3 (CD3) secrete cytokines in their culture supernatant (termed ACD3S). We examined the antitumor efficacy of ACD3S-activated NK-92 cells in vitro and in vivo. MATERIALS AND METHODS: Interleukin (IL) 2-depleted NK-92 cells were reactivated with ACD3S, analyzed for their phenotype and tested for cytotoxicity, and perforin and interferon γ (IFNγ) production. Severe combined immunodeficient (SCID) mice xenografted with human melanoma and breast cancer cells were treated with ACD3S-activated NK-92 cells and tumor growth was monitored. RESULTS: Brief activation of IL2-depleted NK-92 cells with ACD3S fully restored their in vitro cytotoxicity towards tumor cells. ACD3S-activated NK-92 cells were phenotypically similar to standard NK-92 cells, but exhibited prolonged cytotoxicity and produced higher levels of IFNγ. When adoptively transferred to tumor-bearing SCID mice, these cells retarded the growth of melanoma and breast tumors. CONCLUSION: Stimulation of NK-92 cells with ACD3S may be useful in clinical cancer therapy, as an alternative method for ex vivo natural killer cell activation.

Outcome of patients with nonmetastatic muscle-invasive bladder cancer not undergoing cystectomy after treatment with noncisplatin-based chemotherapy and/or radiotherapy: a retrospective analysis.

Transurethral resection of bladder tumor (TURBT), radiotherapy, chemotherapy, or combinations can be used in patients with muscle-invasive bladder cancer (MIBC) not undergoing cystectomy. Nevertheless, unfitness for cystectomy is frequently associated with unfitness for other therapeutic modalities. We report the outcome of patients with MIBC who did not undergo cystectomy and did not receive cisplatin-based chemotherapy. Selection criteria for the study were nonmetastatic MIBC, no cystectomy, no cisplatin-based chemotherapy. Chemotherapy and/or radiotherapy should have been used aside from TURBT. Forty-nine patients (median age 79), managed between April 2001 and January 2012, were included in this analysis. Median Charlson Comorbidity Index was 5, while 76% were unfit for cisplatin. Treatment included radiotherapy (n = 7), carboplatin-based chemotherapy (n = 25), carboplatin-based chemotherapy followed by radiotherapy (n = 10), and radiochemotherapy (n = 7). Five-year event-free rate was 26% (standard error [SE] = 7) for overall survival, 23% (SE = 7) for progression-free survival, and 30 (SE = 8) for cancer-specific survival (CSS). Patients who were treated with combination of radiotherapy and chemotherapy had significantly longer CSS compared to those treated with radiotherapy or chemotherapy only (5-year CSS rate: 16% [SE 8] vs. 63% [SE 15], P = 0.053). Unfit-for-cystectomy patients frequently receive suboptimal nonsurgical treatment. Their outcome was poor. Combining chemotherapy with radiotherapy produced better outcomes and should be prospectively evaluated.

Utilization of Systemic Chemotherapy in Advanced Urothelial Cancer: A Retrospective Collaborative Study by the Hellenic Genitourinary Cancer Group (HGUCG).

BACKGROUND: Advanced urothelial cancer (AUCa) is associated with poor long-term survival. Two major concerns are related to nonexposure to cisplatin-based chemotherapy and poor outcome after relapse. Our purpose was to record patterns of practice in AUCa in Greece, focusing on first-line treatment and management of relapsed disease. METHODS: Patients with AUCa treated from 2011 to 2013 were included in the analysis. Fitness for cisplatin was assessed by recently established criteria. RESULTS: Of 327 patients treated with first-line chemotherapy, 179 (55%) did not receive cisplatin. Criteria for unfitness for cisplatin were: Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥ 2, 21%; creatinine clearance ≤ 60 mL/min, 55%; hearing impairment, 8%; neuropathy, 1%; and cardiac failure, 5%. Forty-six patients (27%) did not fulfill any criterion for unfitness for cisplatin. The main reasons for these deviations were comorbidities (28%) and advanced age (32%). Seventy-four (68%) of 109 patients who experienced a relapse received second-line chemotherapy. The most frequent reason for not offering second-line chemotherapy was poor PS or limited life expectancy (66%). CONCLUSION: In line with international data, approximately 50% of Greek patients with AUCa do not receive cisplatin-based chemotherapy, although 27% of them were suitable for such treatment. In addition, about one third of patients with relapse did not receive second-line chemotherapy because of poor PS or short life expectancy. Enforcing criteria for fitness for cisplatin and earlier diagnosis of relapse represent 2 targets for improvement in current treatment practice for AUCa.

Epothilones in epithelial ovarian, fallopian tube, or primary peritoneal cancer: a systematic review.

Ovarian cancer is the most lethal gynecologic malignancy; consequently, there is a need for effective therapies. Epothilones are microtubule-stabilizing agents that inhibit cell growth. Currently, patupilone and its four synthetic derivatives ixabepilone, BMS-310705, sagopilone, 20-desmethyl-20-methylsulfanyl epothilone B and epothilone D, as well as its derivative KOS-1584, are under clinical evaluation. This is the first systematic review conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines that synthesizes all available data emerging from trials and evaluates the efficacy and safety of epothilones in epithelial ovarian, primary fallopian tube, and primary peritoneal cancer. Despite the fact that epothilones have proven active in taxane-resistant settings in preclinical models, it is not yet clear from Phase II/III studies reviewed here that their clinical activity is superior to that of taxanes. Nevertheless, responses to epothilones have been observed in platinum-refractory/resistant ovarian cancer patients. Moreover, despite the shared mechanism of action of epothilones, their clinical profile seems clearly different, with diarrhea being the most common dose-limiting toxicity encountered with patupilone, whereas neutropenia and sensory neuropathy are the most common toxic effects observed with the other epothilones. In any case, randomized trials comparing epothilones with standard treatments seem warranted to define further the role of these agents, whereas biomarker analysis might further optimize patient selection.

HER2 as a target in invasive urothelial carcinoma.

We evaluated primary tumors from two cohorts, Spain (N = 111) and Greece (N = 102), for patients who were treated with platinum-based chemotherapy. Patients were tested for HER2 status (IHC score of 3+ or FISH ratio of ≥ 2.2) by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), DNA copy number, mRNA expression, and mutation status in patients with metastatic urothelial carcinoma (UC), and its impact on survival. ERBB2 mutation was determined by hotspot sequencing. mRNA expression was assessed using NanoString counting. Association of overall survival (OS) and HER2 status was assessed by a Cox regression model. NIH-3T3 cells containing HER2 V777L were assessed for growth, invasion, and HER2 kinase activation. In all, 22% of Spanish and 4% of Greek cohorts had 3+ HER2 staining by IHC. FISH amplification was identified in 20% of Spanish and 4% of Greek cohorts. Kappa coefficient between FISH and IHC was 0.47. HER2 status was not associated with OS in univariate (Spanish P = 0.34; Greek P = 0.11) or multivariate (Spanish P = 0.49; Greek P = 0.12) analysis. HER2-positive tumors expressed higher levels of HER2 mRNA than HER2-negative tumors (P < 0.001). HER2 mutations (V777L and L755S) were identified in two (2%) patients. In vitro analysis of V777L results in transformation of NIH-3T3 cells, leading to increased growth, invasion on soft agar, and HER2 kinase constitutive activation. In summary, HER2 overexpression or amplification in the primary tumor did not predict OS in patients with metastatic UC. HER2 positivity rates can differ between different populations. Further trials in genomically screened patients are needed to assess HER2-targeted therapies in UC.

Profile of trebananib (AMG386) and its potential in the treatment of ovarian cancer.

Angiogenesis has been implicated in ovarian cancer pathogenesis. Bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, has recently been incorporated in ovarian cancer treatment in combination with chemotherapy both in a frontline setting and in disease recurrence. However, resistance eventually develops and treatment with bevacizumab is associated with increased risk for toxicities such as thromboembolic and hemorrhagic events, gastrointestinal perforation, and impaired wound healing, suggesting the need for new therapeutic approaches. Targeting of the angiopoietins/Tie2 pathway has gained accumulating interest during the last few years as a strategy to overcome bevacizumab resistance and toxicities. Trebananib is a first-in-class peptibody that inhibits angiopoietin 1 and 2 interaction with their receptor Tie2. The molecular profile of this agent, the preclinical data, and clinical studies demonstrating its efficacy in ovarian cancer are discussed in this review.

Prognostic significance of cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma treated with first-line sunitinib: a European multiinstitutional study.

INTRODUCTION/BACKGROUND: The aim of this study was to evaluate the prognostic role of CN in patients with mRCC and synchronous metastases treated with the VEGF receptor TKI, sunitinib. PATIENTS AND METHODS: Patients with a diagnosis of metastases before, at the time of, or within 3 months from the diagnosis of renal cell carcinoma (RCC) and first-line treatment with sunitinib were included. Baseline characteristics were correlated with overall survival (OS) according to hazard ratios estimated from univariate Cox proportional hazards models. Significant factors were then included in a multivariate Cox proportional hazards model. RESULTS: One hundred eighty-six patients treated between January 2006 and March 2012 were selected. Thirty-six (19%) had not undergone CN. CN was offered to younger patients with better prognoses. Patients who underwent CN lived significantly longer than patients without CN (median OS, 23.9 [95% confidence interval (CI), 20.8-28.8] vs. 9 [95% CI, 4-16.4] months; P < .001). Multivariate analysis showed that CN had an independent prognostic significance. No specific subgroup benefiting from CN was identified. CONCLUSION: CN was an independent favorable prognostic factor in patients with synchronous metastases from RCC, treated with sunitinib. Information regarding the selection of mRCC patients likely to benefit from CN might be derived by ongoing phase III trials.

FGFR3 expression in primary and metastatic urothelial carcinoma of the bladder.

While fibroblast growth factor receptor 3 (FGFR3) is frequently mutated or overexpressed in nonmuscle-invasive urothelial carcinoma (UC), the prevalence of FGFR3 protein expression and mutation remains unknown in muscle-invasive disease. FGFR3 protein and mRNA expression, mutational status, and copy number variation were retrospectively analyzed in 231 patients with formalin-fixed paraffin-embedded primary UCs, 33 metastases, and 14 paired primary and metastatic tumors using the following methods: immunohistochemistry, NanoString nCounterTM, OncoMap or Affymetrix OncoScanTM array, and Gain and Loss of Analysis of DNA and Genomic Identification of Significant Targets in Cancer software. FGFR3 immunohistochemistry staining was present in 29% of primary UCs and 49% of metastases and did not impact overall survival (P = 0.89, primary tumors; P = 0.78, metastases). FGFR3 mutations were observed in 2% of primary tumors and 9% of metastases. Mutant tumors expressed higher levels of FGFR3 mRNA than wild-type tumors (P < 0.001). FGFR3 copy number gain and loss were rare events in primary and metastatic tumors (0.8% each; 3.0% and 12.3%, respectively). FGFR3 immunohistochemistry staining is present in one third of primary muscle-invasive UCs and half of metastases, while FGFR3 mutations and copy number changes are relatively uncommon.

Gynecologic oncology patients in the surgical high dependency unit: an analysis of indications.

PURPOSE: The establishment of high dependency units (HDUs) has been an undoubted advance in the management of patients undergoing major oncological procedures. The aim of this study was to examine the impact of various preoperative and perioperative patients' characteristics on the prolonged HDU stay. METHODS: We conducted a retrospective study including all gynecologic oncology patients who underwent surgical management and were admitted postoperatively to our hospitals' HDU from 2006 to 2010. RESULTS: A total of 1,014 patients were transferred to the HDU and divided into two groups according to the length of HDU stay. Group A consisted of 840 (82.8 %) patients who stayed in the HDU for ≤24 h and Group B included 174 (17.2 %) patients who remained in the HDU under close observation for >24 h. Older age was the only preoperative characteristic that remained significantly associated with HDU prolonged stay. In addition, three intraoperative factors such as use of invasive hemodynamic monitoring, bowel resection and estimated blood loss were proved to be independently associated with prolonged HDU stay. CONCLUSION: Certain characteristics could identify those patients who are more likely to benefit most from HDU admission.

Posttreatment prognostic nomogram for patients with metastatic urothelial cancer completing first-line cisplatin-based chemotherapy.

BACKGROUND: Models to predict the outcome of patients with metastatic urothelial cancer (UC), based on pretreatment variables, have previously been developed. However, patients often request "updated" prognostic estimates based upon their response to treatment. PATIENTS AND METHODS: Data were pooled from 317 patients enrolled in 8 trials evaluating first-line cisplatin-based chemotherapy in metastatic UC. Variables were combined in the Cox proportional hazards model to produce a nomogram to predict survival from the end of treatment. The nomogram was validated externally using data from a phase III trial. RESULTS: The median survival from end of treatment was 10.65 months (95% confidence interval; 9.20-13.24); 69% of patients had died. Baseline and posttreatment variables were evaluated. Baseline performance status, baseline number of visceral metastatic sites, baseline white blood counts, and response to treatment were included in the final model. The nomogram achieved a bootstrap-corrected concordance index of 0.68. Upon external validation, the nomogram achieved a concordance index of 0.67. CONCLUSIONS: A model derived from pretreatment and posttreatment variables was constructed to predict survival from the completion of first-line chemotherapy in patients with metastatic UC. This model may be useful for patient counseling and for stratification of trials exploring "maintenance" therapy.

Cisplatin-based combination chemotherapy in septuagenarians with metastatic urothelial cancer.

PURPOSE: Cisplatin-based chemotherapy is standard first-line treatment for metastatic urothelial carcinoma. However, cisplatin is frequently avoided in elderly patients due to concerns regarding toxicities. We analyzed the efficacy, and tolerability, of cisplatin-based chemotherapy in elderly patients. METHODS: Individual patient data were pooled from 8 phase II and III trials evaluating cisplatin-based first-line chemotherapy in patients with metastatic urothelial carcinoma. Adverse events, treatment delivery, response proportions, and survival outcomes were compared between patients aged<70 vs. ≥ 70 years. RESULTS: Of the 543 patients included, 162 patients (30%) were ≥ 70 years old. The majority (93%) of elderly patients were aged 70 to 79 years. There was no significant difference in the proportions of patients experiencing Grade 3 to 4 renal failure, febrile neutropenia, or treatment-related death between younger and older patient cohorts. The median survival of the patients ≥ 70 years was 12.1 months compared to 12.8 months for patients<70 years (P = 0.91). There was no significant difference in survival between age groups when controlling for baseline performance status or the presence of visceral metastases or both. CONCLUSIONS: Fit septuagenarians, with adequate renal function, tolerate cisplatin-based chemotherapy similarly to their younger counterparts and achieve comparable clinical outcomes.