Addition Of Neoadjuvant Chemotherapy Research Articles

Characteristics, Treatment and Outcomes of Patients with Primary Urethral Cancer: A Multi-Center Review over Two Decades

<h3>Purpose/Objective(s)</h3> Primary urethral cancer is an uncommon and aggressive malignancy that accounts for less than 1% of all genitourinary malignancies. Due to its rarity, no prospective trials exist to formally guide treatment. Current approaches are informed by retrospective series and extrapolation from other genitourinary cancers. In this study, we sought to characterize the management trajectory of consecutive patients with urethral cancer in our hospital system over the past 2 decades. <h3>Materials/Methods</h3> The medical records of all adult patients who had received treatment for urethral cancer between January 2000 and December 2021 within a multi-center academic hospital system were queried. Baseline clinicopathologic features, treatment details, and progression were recorded and stratified by histology. Survival analysis was performed using multivariable Cox proportional hazards regression. <h3>Results</h3> There were 37 females and 31 males with urethral cancer included in this analysis, of whom 45 (66%) presented with at least stage III disease. Median age at diagnosis was 69 years (IQR 59–74) and median follow-up was 24 months (IQR 7–48). The most common histologies consisted of squamous cell carcinoma (SCC, 29%), urothelial carcinoma (UC, 28%), and adenocarcinoma (AC, 28%). Compared to all other histologies, SCCs were more likely to present in the distal urethra (85% vs. 35%, <i>P</i><0.001) and with regional nodal involvement (50% vs. 19%, <i>P</i>=0.020), while UCs were more often diagnosed in males (74% vs. 35%, <i>P</i>=0.011). ACs tended to feature larger primary tumors with more frequent indication for exenteration in resectable settings (41% vs. 12%, <i>P</i>=0.041). Receipt of any neoadjuvant therapy (N=11), rather than any adjuvant therapy (N=14) or surgery alone (N=26), was associated with a trend toward longer distant recurrence-free survival among patients who underwent curative-intent resection (median not reached vs. 72 months, HR 0.22, 95% CI 0.04–1.10, <i>P</i>=0.065) after adjustment for age, sex, and stage. Among patients who received curative-intent external beam radiation (N=27), additional high-dose rate (HDR) brachytherapy (N=10) conferred superior locoregional control (median 48 vs. 19 months, HR 0.21, 95% CI 0.05–0.91, <i>P</i>=0.038). Urethral stricture requiring operative dilation was noted in 3 patients, of whom 2 had received HDR brachytherapy. <h3>Conclusion</h3> Urethral cancer is an uncommon malignancy with sparse evidence to guide treatment, especially for rarer histologies including neuroendocrine carcinoma, sarcoma, and mucosal melanoma. While further prospective studies are warranted, the addition of neoadjuvant chemotherapy and/or radiotherapy prior to surgery, as well as HDR brachytherapy following external beam radiation, may be considered in the multi-disciplinary management of urethral cancer.

Oncologic and survival outcomes in elderly patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy and total mesorectal excision.

The efficacy of the addition of neoadjuvant chemotherapy to neoadjuvant chemoradiotherapy and total mesorectal excision for locally advanced rectal cancer in elderly patients has not been established. A total of 3096 locally advanced rectal cancer patients who received neoadjuvant chemotherapy, along with neoadjuvant chemoradiotherapy and total mesorectal excision, with or without adjuvant chemotherapy, between January 2010 and December 2018, were studied retrospectively. Patients were divided into elderly (>75years) and younger (≤75years) groups, and propensity score matching was used to balance a potentially confounding clinical bias. Overall survival, cancer-specific survival, disease-free survival, distant metastasis-free survival and local recurrence-free survival rates for the two groups were compared. Hazard ratios (HR) with 95% confidence intervals (CI) for different clinicopathological variables were calculated to determine predictors of 3-year overall survival. Mean follow-up was 39.0 (range, 5-140) months. The overall 3-year overall survival, cancer-specific survival, disease-free survival, distant metastasis-free survival and locoregional relapse-free survival rates were 86.1, 87.6, 80.0, 82.4 and 95.4%, respectively. Only 3-year overall survival rates differed significantly between the elderly (77.2%) and younger (88.9%) groups (P=0.01). Cancer-specific survival, disease-free survival, distant metastasis-free survival and locoregional relapse-free survival rates did not differ significantly between the two groups. Significant negative independent prognostic factors for 3-year overall survival were age>75years (HR=2.016, 95% CI 1.157-23.511, P=0.01) and high pathologic TNM stage (yp stage III, P<0.001). For elderly locally advanced rectal cancer patients who have good health and performance status, the addition of neoadjuvant chemotherapy to neoadjuvant chemoradiotherapy and total mesorectal excision can result in disease-related survival rates and oncological outcomes similar to those experienced by younger patients. The decision to use this treatment approach in elderly patients should not be based solely on chronological age.

Single agent high-dose ifosfamide in refractory or relapsed osteosarcoma.

e22006 Background: Osteosarcoma (OS) is the most common primary malignant neoplasm of the bone in children and adolescents, typically occurring in the metaphysis of long bones. Historically, patients were treated with surgical resection, but the addition of neoadjuvant chemotherapy over the last 50 years has greatly improved prognosis, with survival rates increasing from 20% to almost 70% for non-metastatic tumors. However, prognosis remains poor for patients with refractory or recurrent disease, and Ifosfamide containing regimens are the standard 2nd line chemotherapy. Ifosfamide has been utilized in various combinations with other chemotherapeutic agents including methotrexate, cisplatin and epirubicin with variable reported results. Alternatively, it has been used as a single agent at an escalated dose of 12-14 gm/m2 with improved response. However, high dose Ifosfamide (HDI) is associated with nephrotoxicity. We aim to evaluate our institution’s experience with single agent HDI in terms of both outcome and safety. Methods: This is a single institutional retrospective study conducted at the Children’s Hospital of Michigan. All pediatric patients up to age 21 years with refractory or relapsed osteosarcoma who received at least 2 cycles of HDI therapy after MAP over the course of 20 years were included. Progression free and event free survival were calculated. Nephrotoxicity was documented as per common terminology criteria for adverse events (CTCAE) v.50 grading. Results: A total of 46 charts were screened, 19 patients were found to have recurrent or refractory OS. 3 patients were only treated surgically. 16 patients received 2nd line chemotherapy with/without surgical resection. 13 patients received single agent HDI and were included in our analysis. The mean age at diagnosis was 13.78, with 6 recurrent and 7 refractory patients. Patients received an average of 5 cycles of HDI. At end of therapy, objective response rate was 46% and disease control rate was 61%. 5 patients in our analysis had reported nephrotoxicity, with 3 patients having transient grade 1 elevations in creatinine that improved while remaining on chemotherapy. 2 patients developed persistent grade I elevation of creatinine, both developed this nephrotoxicity after being off therapy for more than 1 year. Nephrotoxicity was associated with higher number of cycles of HDI, with these patients receiving at least 4 cycles. At this point of follow up, 3 patients are alive without evidence of disease at least 2 years after completion of chemotherapy. Conclusions: Our experience is consistent with prior reports that HDI is efficacious as single agent therapy for patients with osteosarcoma that is refractory or recurrent with acceptable nephrotoxicity. In our experience, nephrotoxicity occasionally developed months after the cessation of therapy. As such, long term follow up of survivors is necessary.

Nephroureterectomy vs. segmental ureterectomy of clinically localized, high-grade, urothelial carcinoma of the ureter: Practice patterns and outcomes

BackgroundNephroureterectomy (NU) remains the gold-standard for upper-tract urothelial carcinoma (UTUC). However, nephron-sparing management (NSM), specifically segmental ureterectomy (SU) for urothelial tumors distal to the renal pelvis may offer decreased risk of renal insufficiency and equivalent cancer control. ObjectivesTo identify patient-specific and facility-related factors that are associated with the selection of SU vs. NU for patients with clinically localized, high-grade, ureteral UTUC. Design, setting, participantsWe searched the National Cancer Database between 2004 and 2015 for patients with high-grade, clinically localized, primary ureteral UTUC managed by either NU or SU. Outcome measurements and statistical analysisUnivariate and multivariate analysis was performed to assess patient, disease-specific, facility and treatment-related factors associated with SU vs. NU. Since surgical approach was only indexed after 2010, separate multivariable logistic regressions were performed including and excluding surgical approach in order to capture patients treated between 2004 and 2009. Survival analysis utilized Kaplan-Meier methods and Cox proportional hazards regression. Results and limitationsMultivariate analysis including surgical approach demonstrated that among other factors, higher clinical stage (P = 0.034), larger tumor size (P < 0.001), the addition of neoadjuvant chemotherapy (P = 0.002), and the utilization of minimally invasive surgery (P < 0.05) decreased the likelihood of patients receiving SU. In this same cohort, institutions with larger facility volumes (P = 0.038) and performing intraoperative lymph node dissection (P < 0.001) were associated with a higher probability of SU. Excluding surgical approach, once again more advanced clinical stage (P = 0.005), larger tumor size (P < 0.001), and neoadjuvant chemotherapy (P = 0.003) decreased the probability of patients receiving SU, while increasing age (P = 0.049) and intraoperative lymph node dissection (P < 0.001) were more closely associated with SU compared to NU. No differences were noted in pathological T stage (P > 0.05), 30-day readmission (P = 0.7), 30-day mortality (P = 0.09), and 90-day mortality (P = 0.157) on multivariate analysis between SU and NU. Additionally, no significant differences were seen in median overall survival between patients receiving SU or NU (53 vs. 50 months; P = 0.143). ConclusionsComparable outcomes suggest segmental ureterectomy for high-grade ureteral UTUC is appropriate in well-selected patients. Practice patterns appear consistent with guideline recommendations (decreased tumor size and lower clinical stage favor SU), but treatment disparities may exist based on a multitude of patient, pathologic- and facility-related factors. Improved dissemination of knowledge regarding practice patterns and outcomes of SU for UTUC of the ureter has the potential to improve delivery of NSM in appropriate patients. Patient summaryIn this study, we examined factors associated with different surgical procedures for cancer of the ureter. We found that smaller tumor sizes, a less advanced clinical stage, intraoperative lymph dissection higher facility volumes tended to favor kidney-sparing treatment, while survival outcomes appear comparable to renal extirpation.

Neoadjuvant or Adjuvant Chemotherapy Plus Concurrent CRT Versus Concurrent CRT Alone in the Treatment of Nasopharyngeal Carcinoma: A Study Based on EBV DNA

The goal of this study was to explore the value of adding neoadjuvant chemotherapy (NACT) or adjuvant chemotherapy (ACT) to concurrent chemoradiotherapy (CCRT) in patients with nasopharyngeal carcinoma (NPC) with different risks of treatment failure. A total of 2,263 eligible patients with stage III-IVb NPC treated with CCRT ± NACT or ACT were included in this retrospective study. Distant metastasis-free survival (DMFS), overall survival, and progression-free survival were calculated using the Kaplan-Meier method and differences were compared using the log-rank test. Patients in the low-risk group (stage N0-1 disease and Epstein-Barr virus [EBV] DNA <4,000 copies/mL) who received NACT followed by CCRT achieved significantly better 5-year DMFS than those treated with CCRT alone (96.2% vs 91.3%; P= .008). Multivariate analyses also demonstrated that additional NACT was the only independent prognostic factor for DMFS (hazard ratio, 0.42; 95% CI, 0.22-0.80; P=.009). In both the intermediate-risk group (stage N0-1 disease and EBV DNA ≥4,000 copies/mL and stage N2-3 disease and EBV DNA <4,000 copies/mL) and the high-risk group (stage N2-3 disease and EBV DNA ≥4,000 copies/mL), comparison of NACT or ACT + CCRT versus CCRT alone indicated no significantly better survival for all end points. The addition of NACT to CCRT could reduce distant failure in patients with low risk of treatment failure.

Factors associated with degree of tumour response to neo-adjuvant radiotherapy in rectal cancer and subsequent corresponding outcomes

BackgroundTumour response to neo-adjuvant radiotherapy for rectal cancer varies significantly between patients, as classified by Tumour Regression Grade (TRG 0–3), with 0 equating to pathological complete response (pCR) and 3 denoting minimal/no response. pCR is associated with significantly better local recurrence rates and survival, but is achieved in only 20–30% of patients. The literature contains limited data reporting factors predictive of tumour response and corresponding outcomes according to degree of regression. MethodsAll patients with rectal cancer who received neo-adjuvant radiotherapy, entered into the National Cancer Database (NCDB) in 2009–2013, were included. Data were analysed on procedure performed, tumour details, pathological findings, chemo-radiotherapy regimens, patient demographics, outcomes and survival. Multivariate regression analysis was used to identify factors independently associated with pCR. ResultsOf 13,742 patients, 32.4% achieved pCR/TRG0 (4452). Factors associated with pCR (vs. TRG3) included adenocarcinoma rather than mucinous adenocarcinoma histology; well/moderately differentiated grade; lower clinical tumour (cT1, cT2, cT3) and nodal (N0 and N1) stage, and the addition of neo-adjuvant chemotherapy. Elevated CEA levels were associated with TRG3. pCR patients had higher rates of local excision, shorter mean length of stay and lower unplanned readmission rates, than TRG3. R0 resection rates and overall survival were significantly higher in all grades of regression, compared to TRG3 (p < 0.0001). ConclusionTumour regression correlates with outcomes. Identifying factors predictive of response may facilitate higher pCR rates, the tailoring of therapy, and improve outcomes.

Neoadjuvant chemotherapy plus concomitant chemoradiation versus concomitant chemoradiation for locoregionally advanced nasopharyngeal carcinoma: A systematic review and meta-analysis of comparative studies.

e17552 Background: To determine if addition of neoadjuvant chemotherapy (NACT) to concomitant chemoradiation (CCRT) for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) improves overall survival. Methods: We searched MEDLINE for eligible studies comparing NACT plus CCRT versus (vs) CCRT alone for locoregionally advanced NPC. We assessed the methodological quality of the included studies using the MERGE criteria. We performed the meta-analysis with random effects model using Revman 5.3 to estimate the pooled hazard ratios (HR), confidence intervals (CI), P values (P) and I squared statistic (I2). The primary outcome was overall survival (OS); secondary outcomes include progression-free survival (PFS) and adverse events (AE). We used the GRADE approach to appraise the quality of evidence from randomized trials. Results: We found four randomized and five retrospective comparative studies including 2178 patients with low to moderate risk of bias in their methodologic quality. Pooled estimates from both randomized and retrospective studies demonstrated a benefit in PFS (HR 0.78, 95% CI 0.66 to 0.93, P = 0.006, I2 = 0%) and OS (HR 0.77, 95% CI 0.61 to 0.96, P = 0.02, I2 = 0%) with NACT. In the randomized trials, there was moderate quality evidence that NACT improved PFS significantly (HR 0.73, 95% CI 0.57 to 0.93, P = 0.01, I2 = 0%); trend towards OS benefit (HR 0.76, 95% CI 0.56 to 1.03, P = 0.08, I2= 0%) and was associated with more frequent AE. There were no significant differences in the results between the randomized and retrospective comparative studies (PFS HR 0.73 vs 0.82, interaction P (IP) = 0.58; OS HR 0.76 vs 0.78, IP = 0.93). Conclusions: Neoadjuvant chemotherapy delays disease progression substantially and may improve survival for locoregionally advanced nasopharyngeal carcinoma. There were no divergent results between randomized and retrospective comparative studies. Future trials should test more effective and/or better tolerated agents during the neoadjuvant therapy phase.

Minimally Invasive Ivor Lewis Esophagectomy

The two main types of esophageal cancer are squamous cell carcinoma, which comprises the majority of cases world-wide, and adenocarcinoma, which is diagnosed with increasing frequency and now accounts for more than 50% of cases in the western hemisphere. Smoking and alcohol consumption are strongly linked to squamous cell carcinoma, and the most important etiologic risk factor for adenocarcinoma is Barrett's esophagus, which occurs in 10 to 15% of patients with gastro-oesophageal reflux disease. Patients generally present with dysphagia and weight loss, and diagnosis is made via endoscopy and biopsy. The surgical treatment of esophageal cancer is dependent upon the location of the cancer, the depth of invasion, and the presence of lymph node metastasis. Smaller tumors that only involve the mucosal layer of the esophagus may be removed by endoscopic mucosal resection, but larger, more invasive tumors require esophageal resection. Esophagectomy can be approached via the trans-hiatal (Orringer), trans-thoracic (Ivor-Lewis), or three-field (McKeown) techniques, and anastomosis between the stomach and the shortened esophagus is achieved through either a gastric pull up or colonic/jejunal interposition. The addition of neoadjuvant chemotherapy for locally-advanced adenocarcinoma has been shown to increase survival compared with surgery alone, and is the standard treatment in these cases. Here, we present the case of a female patient with dysphagia who was found to have a locally-advanced distal esophageal adenocarcinoma. In this case, a minimally-invasive Ivor Lewis esophagectomy was performed with neoadjuvant chemotherapy.

Resection after neoadjuvant chemotherapy in advanced carcinoma of the gallbladder: a retrospective study.

Although rare over most of the world, Gallbladder cancer is very common in northern india. A delayed presentation, aggressive nature,lack of randomised trials and a poor prognosis have all contributed to the nihilistic halo encircling gallbladder cancer. None of the advances in oncology have been exploited enough to shatter the nihilistic halo. In this background we sought to analyze if the addition of neoadjuvant chemotherapy had any impact on the resectability, overall and disease free survival in patients with advanced carcinoma of the gallbladder. We reviewed the records of all patients who underwent surgery for carcinoma of the gall bladder from 2004 to 2010 at our institute retrospectively. Twenty-one patients received neoadjuvant chemotherapy and subsequently taken up for surgery. Outcome analysis of these 21 patients were done by Kaplan meier method and graphs plotted. Out of the 21 patients who were taken up for surgery after neoadjuvant chemotherapy, fourteen patients underwent R0 resection (Group 1). Seven patients had been rendered inoperable on exploration (Group 2). Thus about 66.67% of patients deemed resectable after neoadjuvant chemotherapy on imaging underwent R0 resection. The mean overall survival of the group 1 was 42.8months versus 6.6months of group 2(Hazard Ratio: 3.42). Neoadjuvant chemotherapy improves resectability in some patients with unresectable gall bladder cancer. Resection after neoadjuvant chemotherapy is feasible and may improve survival in a select group of patients. However randomized studies are required to establish its definitive role.

Efficacy of the Additional Neoadjuvant Chemotherapy to Concurrent Chemoradiotherapy for Patients with Locoregionally Advanced Nasopharyngeal Carcinoma: a Bayesian Network Meta-analysis of Randomized Controlled Trials.

Background: Due to the lack of studies, it remains unclear whether the additional neoadjuvant chemotherapy (NACT) to concurrent chemoradiotherapy (CCRT) is superior to CCRT alone for locoregionally advanced nasopharyngeal carcinoma (NPC). The main objective of this Bayesian network meta-analysis was to determine the efficacy of NACT+CCRT as compared with CCRT alone.Methods: We comprehensively searched databases and extracted data from randomized controlled trials involving NPC patients who received NACT+CCRT, CCRT, NACT+radiotherapy (RT), or RT. Overall survival (OS) with hazard ratio (HR), and locoregional recurrence rate (LRR) and distant metastasis rate (DMR) with relative risks (RRs), were concerned.Results: Nine trials involving 1988 patients were analyzed. In the network meta-analysis, there was significant benefit of NACT+CCRT over CCRT for DMR (RR=0.54, 95% credible interval [CrI]=0.27-0.94). However, NACT+CCRT had a tendency to worsen locoregional control significantly as compared with CCRT (RR =1.71, 95%CrI =0.94-2.84), and no significant improvement in OS was found (HR =0.73, 95%CrI=0.40-1.23).Conclusions: NACT+CCRT is associated with reduced distant failure as compared with CCRT alone, and whether the additional NACT can improve survival for locoregionally advanced NPC should be further explored. Optimizing regimens and identifying patients at high risk of metastasis may enhance the efficacy of NACT+CCRT.

Neoadjuvant Chemoradiation in Patient with Localy Advanced Rectal Cancer

Abstract Introduction. Neoadjuvant (preoperative) concomitant chemoradiotherapy (CRT) has become a standard treatment of locally advanced rectal adenocarcinoma. Aim of the study is to analyze efficacy of neoadjuvant CRT and survival rates in patients with locally advanced rectal cancer. Materials and methods. Retrospective study of 60 locally advanced rectal cancer patients who underwent neoadjuvant radiotherapy with or without addition of neoadjuvant chemotherapy in Clinic of Oncology of Pauls Stradiņš Clinical University Hospital from 2007 to 2012 was done. Results. Long-course radiotherapy (45-50.4 Gy) received 52 patients. Median time from diagnosis to radiotherapy was 35.8 days. Median time to surgery was 47.7 days. Pathological complete remission (pCR) of the primary rectal cancer was not observed. Distribution by pathologic staging was as follows: 28.8% Stage I (7.7% T1N0M0), 32.7% Stage II and 38.5% Stage III. Downstaging occurred in 93.7% in concomitant chemoradiation with Ftorafur, 61.9% in combination with 5FU/LV, and 53.3% in radiation without chemotherapy. Median PFS and OS were not met. In median follow up of 22.6 month overall survival was 90.3%, and PFS - 88%. Conclusions. Addition of chemotherapy to neoadjuvant radiotherapy is increasing tumor downstaging rate. Ftorafur in concomitant neoadjuvant chemoradiation showed increased downstaging compared to standard 5FU therapy. Response to preoperative therapy improves survival in patient with locally advanced rectal cancer.

Outcomes and predictive factors for salvage therapy after local--regional recurrence following neoadjuvant chemotherapy and breast conserving therapy.

There are few data addressing local-regional recurrence (LRR) and salvage therapies in patients treated with neoadjuvant chemotherapy (NCT) compared to those treated with surgery first. We characterize the clinical course and predictive features of salvage treatment for LRR after breast conserving therapy (BCT) analyzed by initial treatment. We identified 1,589 patients who underwent BCT; 1,141 (72%) patients underwent initial surgery, and 448 (28%) received NCT. Kaplan-Meier and Cox regression analyses were performed to analyze factors associated with overall survival (OS), local control (LC) of recurrence, and distant metastasis-free survival (DMFS) following LRR. 56 patients had a LRR, for a crude recurrence rate of 3%. For patients with potentially curable recurrence (excluding distant metastases within 3months of LRR), the 5-year OS, LC, and DMFS rates were 52, 77, and 69%. On multivariate analysis, initial pathologically negative node status and use of surgery for salvage were significant factors associated with higher OS. Additionally, older age was associated with higher LC rates after salvage. Estrogen receptor-positive disease and surgery for LRR were associated with reduced risk of distant metastases; regional recurrence and use of initial adjuvant chemotherapy were associated with increased risk of distant metastases. For each of these endpoints, the addition of NCT to the multivariate model did not approach significance. LRR is an uncommon event after BCT and many patients with LRR remain curable (5-year OS >50%). Our data indicate that NCT does not compromise salvage after LRR, providing further assurance that this strategy is safe for appropriately selected breast cancer patients.

Expression of the calpain system is associated with poor clinical outcome in gastro-oesophageal adenocarcinomas

Surgery is critical in the management of gastro-oesophageal cancer, and the addition of neo-adjuvant chemotherapy has proved to be of benefit. The calpain system has been implicated in tumour progression and response to various anti-cancer therapies, and therefore expression of the system was determined in this tumour type. Two cohorts of gastro-oesophageal adenocarcinomas were investigated for calpain-1, calpain-2, calpain-9 and calpastatin expression using conventional immunohistochemistry. 88 patients who received neo-adjuvant chemotherapy and 140 patients who received surgery alone were investigated using a tissue microarray approach. Calpain-1, calpain-2 and calpastatin expression was associated with adverse cancer-specific survival in the neo-adjuvant cohort (P = 0.004, P = 0.001 and P = 0.012 respectively); which remained significant in multivariate analysis (Hazard ratio (HR) = 0.337; 95% confidence interval (CI) = 0.140-0.81; P = 0.015, HR = 0.375; 95% CI = 0.165-0.858; P = 0.020 and HR = 0.481; 95% CI = 0.257-0.900; P = 0.022 respectively). Calpain-1 and calpastatin expression was also associated with adverse cancer specific survival in the primary surgery cohort (P = 0.001 and P = 0.013 respectively); which remained significant in multivariate analysis (HR = 0.309; 95% CI = 0.159-0.601; P = 0.001 and HR = 0.418; 95% CI = 0.205-0.850; P = 0.016 respectively). Calpain-9 expression was not associated with cancer-specific survival in the neo-adjuvant and primary surgery cohorts. Determining the expression levels of calpain-1, calpain-2 and calpastatin may provide clinically relevant prognostic information for gastro-oesophageal adenocarcinomas; these findings warrant further studies in larger cohorts of patients.

Treatment of muscle-invasive and metastatic bladder cancer: Update of the EAU guidelines

ContextNew data regarding treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. ObjectiveTo review the new EAU guidelines for MiM-BC with a specific focus on treatment. Evidence acquisitionNew literature published since the last update of the EAU guidelines in 2008 was obtained from Medline, the Cochrane Database of Systematic Reviews, and reference lists in publications and review articles and comprehensively screened by a group of urologists, oncologists, and a radiologist appointed by the EAU Guidelines Office. Previous recommendations based on the older literature on this subject were also taken into account. Levels of evidence (LEs) and grades of recommendations (GRs) were added based on a system modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence. Evidence synthesisCurrent data demonstrate that neoadjuvant chemotherapy in conjunction with radical cystectomy (RC) is recommended in certain constellations of MiM-BC. RC remains the basic treatment of choice in localised invasive disease for both sexes. An attempt has been made to define the extent of surgery under standard conditions in both sexes. An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. In contrast to neoadjuvant chemotherapy, current advice recommends the use of adjuvant chemotherapy only within clinical trials. Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for medical or personal reasons. In metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin remains cisplatin-containing combination chemotherapy. With the advent of vinflunine, second-line chemotherapy has become available. ConclusionsIn the treatment of localised invasive bladder cancer (BCa), the standard treatment remains radical surgical removal of the bladder within standard limits, including as-yet-unspecified regional lymph nodes. However, the addition of neoadjuvant chemotherapy must be considered for certain specific patient groups. A new drug for second-line chemotherapy (vinflunine) in metastatic disease has been approved and is recommended.

Tratamiento del cáncer de vejiga con invasión muscular y metastásico: actualización de la Guía Clínica de la EAU

ContextNew data regarding treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. ObjectiveTo review the new EAU guidelines for MiM-BC with a specific focus on treatment. Evidence acquisitionNew literature published since the last update of the EAU guidelines in 2008 was obtained from Medline, the Cochrane Database of Systematic Reviews, and reference lists in publications and review articles and comprehensively screened by a group of urologists, oncologists, and a radiologist appointed by the EAU Guidelines Office. Previous recommendations based on the older literature on this subject were also taken into account. Levels of evidence (LEs) and grades of recommendations (GRs) were added based on a system modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence. Evidence synthesisCurrent data demonstrate that neoadjuvant chemotherapy in conjunction with radical cystectomy (RC) is recommended in certain constellations of MiM-BC. RC remains the basic treatment of choice in localised invasive disease for both sexes. An attempt has been made to define the extent of surgery under standard conditions in both sexes. An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. In contrast to neoadjuvant chemotherapy, current advice recommends the use of adjuvant chemotherapy only within clinical trials. Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for medical or personal reasons. In metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin remains cisplatin-containing combination chemotherapy. With the advent of vinflunine, second-line chemotherapy has become available. ConclusionsIn the treatment of localised invasive bladder cancer (BCa), the standard treatment remains radical surgical removal of the bladder within standard limits, including as-yet-unspecified regional lymph nodes. However, the addition of neoadjuvant chemotherapy must be considered for certain specific patient groups. A new drug for second-line chemotherapy (vinflunine) in metastatic disease has been approved and is recommended.

Effectiveness and cost-effectiveness of peri-operative versus post-operative chemotherapy for resectable colorectal liver metastases

BackgroundThe role of neo-adjuvant chemotherapy prior to hepatectomy in patients with resectable colorectal liver metastases is currently a matter of debate. The aim of the present study was to analyse life-expectancy, quality adjusted life-expectancy and cost-effectiveness of the two chemotherapeutic strategies. MethodsA Markov decision model was developed, on the basis of parameters derived from an extensive literature search of the last ten years, to compare outcomes of peri-operative versus post-operative chemotherapy. ResultsLife-expectancy observed for peri-operative chemotherapy was 54.56months and 52.62months with post-operative chemotherapy only; the quality-adjusted life-expectancy with peri-operative chemotherapy was 39.33 quality-adjusted life-months (QALMs) and 37.84 QALMs with post-operative chemotherapy. Peri-operative chemotherapy results in an increase in total costs of 1180€ over ten years and in an incremental cost-effectiveness ratio (ICER) of 791.9€/QALM. The model was more sensitive to the expected 3-year recurrence-free survival (RFS) and cost of hepatic resection: with respect to an expected 3-year RFS⩽25% the peri-operative approach was more cost-effective than post-operative strategy but differences in average cost-effectiveness were small. The relationship between ICER and cost of hepatic resection was inverse because the higher the cost of hepatic resection, the higher the cost saving due to patients becoming unresectable during neo-adjuvant therapy. ConclusionsIn the treatment of resectable colorectal liver metastases, the addition of neo-adjuvant chemotherapy could be cost-effective because it makes it possible to avoid hepatic resection in patients who do not respond to the neo-adjuvant approach; however, the life-expectancy of the two strategies is very similar.

Nasopharyngeal carcinoma

With the improvement in local control achieved by more precise imaging and radiotherapy, the predominant mode of failure for nasopharyngeal carcinoma is distant metastases. Concurrent cisplatin-radiotherapy with or without adjuvant chemotherapy is the standard treatment approach for stages IIB and above disease. The addition of neoadjuvant chemotherapy has been most promising, and phase III trial results are awaited. Quantitative Epstein-Barr virus (EBV) DNA can be applied clinically for disease monitoring and follow-up, and may in future be used for risk stratification strategies. Targeted therapies against epidermal growth factor receptor and angiogenesis have demonstrated activity, and immunotherapeutic approaches are being investigated.

Multimodality therapy in penile cancer: when and which treatments?

Metastatic penile cancer typically comes to attention while the clinical extent of disease is limited to the inguinal or pelvic lymph nodes. Primary surgical management of lymph node metastases achieves tumor control and long-term survival for only a small percentage of these patients. To determine the optimal use of multimodality treatment in locally advanced penile cancer, we conducted a literature review. Relevant English-language literature was identified with the use of Medline; additional cited works not detected on the initial search were also reviewed. There is an emerging strategy of preoperative (neoadjuvant) combination chemotherapy to improve the progression-free survival of penile cancer patients with bulky regional lymph node metastases. Radiotherapy for inguinal metastases and postoperative (adjuvant) radiation for selected patients has also been effective in this setting. In patients with lymph node metastases, the benefit of ilioinguinal lymphadenectomy may be extended by the addition of neoadjuvant chemotherapy. Postoperative radiotherapy can be offered depending on the amount of residual disease after chemotherapy. Chemo-radiotherapy has been successful in squamous cell cancers from other sites (vulva and anal canal) and may be considered for unresectable penile cancer.

Pre-operative chemotherapy in patients with resectable non-small cell lung cancer (NSCLC): First results of the MRC LU22/NVALT/EORTC 08012 multi-centre randomised trial

7518 Aims: Although surgery offers the best chance of cure for patients with NSCLC, the overall 5-year survival rate is modest, and improvements are urgently required. This intergroup trial was designed to investigate whether, in patients with operable NSCLC of any stage, neo-adjuvant platinum-based chemotherapy prior to surgery would improve outcomes. Methods: Patients were randomised to receive either surgery alone (S), or 3 cycles of platinum-based chemotherapy prior to surgery (CT-S). Results: 519 patients were randomised (261 S, 258 CT-S) from 70 centres in the UK, the Netherlands, Germany and Belgium. The median age of the patients was 63 years, 72% were male, 59% were PS 0, and 50% had squamous cell histology. The majority were clinical stage I (17% Ia, 45% Ib, 3% IIa, 29% IIb, 7% IIIa), and 12% received mitomycin/vinblastine/cisplatin (MVP), 7% mitomycin/ifosfamide/cisplatin (MIC), 45% vinorelbine/cisplatin, 12% carboplatin/docetaxel, and 25% cisplatin/gemcitabine. The trial showed that neo-adjuvant chemotherapy was feasible (76% of patients received all 3 cycles of chemotherapy), resulted in a good response rate (4% CR, 45% PR, and only 2% PD), appeared to cause down-staging in about 20% of patients, and did not affect the type of surgery performed, the post-operative complication rate, or quality of life. However, there was no evidence of a benefit in terms of progression-free survival (282 events, HR 0.98, 95% CI 0.77,1.23) or overall survival (232 deaths, HR 1.04, 95% CI 0.81, 1.35), and more patients were reported as having brain metastases in the CT-S group (30 CT-S vs 11 S patients). Exploratory analyses showed no evidence that any subgroup of patients benefited from the addition of neo-adjuvant chemotherapy. Conclusions: This intergroup trial, which is the largest trial of neo-adjuvant chemotherapy in patients with resectable NSCLC, indicated that the addition of neo-adjuvant platinum-based chemotherapy did not lead to a benefit in overall survival. However, a 19% survival benefit or a 35% detriment cannot be excluded and this result needs to be considered in the context of all other relevant randomised trials of neo-adjuvant chemotherapy for NSCLC. [Table: see text]

Preoperative chemotherapy in patients with resectable non-small cell lung cancer: results of the MRC LU22/NVALT 2/EORTC 08012 multicentre randomised trial and update of systematic review

Although surgery offers the best chance of cure for patients with non-small cell lung cancer (NSCLC), the overall 5-year survival rate is modest, and improvements are urgently needed. In the 1990s, much interest was generated from two small trials that reported striking results with neo-adjuvant chemotherapy, and therefore our intergroup randomised trial was designed to investigate whether, in patients with operable non-small cell lung cancer of any stage, outcomes could be improved by giving platinum-based chemotherapy before surgery. Patients were randomised to receive either surgery alone (S), or three cycles of platinum-based chemotherapy followed by surgery (CT-S). Before randomisation, clinicians chose the chemotherapy that would be given from a list of six standard regimens. The primary outcome measure was overall survival, which was analysed on an intention-to-treat basis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN25582437. 519 patients were randomised (S: 261, CT-S: 258) from 70 centres in the UK, Netherlands, Germany, and Belgium. Most (61%) were clinical stage I, with 31% stage II, and 7% stage III. Neo-adjuvant chemotherapy was feasible (75% of patients received all three cycles of chemotherapy), resulted in a good response rate (49% [95% CI 43%-55%]) and down-staging in 31% (25%-37%) of patients, and did not alter the type or completeness of the surgery (lobectomy: S: 56%, CT-S: 60%, complete resection: S: 80%, CT-S: 82%). Post-operative complications were not increased in the CT-S group, and no impairment of quality of life was observed. However, there was no evidence of a benefit in terms of overall survival (hazard ratio [HR] 1.02, 95% CI 0.80-1.31, p=0.86). Updating the systematic review by addition of the present result suggests a 12% relative survival benefit with the addition of neoadjuvant chemotherapy (1507 patients, HR 0.88, 95% CI 0.76-1.01, p=0.07), equivalent to an absolute improvement in survival of 5% at 5 years Although there was no evidence of a difference in overall survival with neo-adjuvant chemotherapy, the result is statistically consistent with previous trials, and therefore adds considerable weight to the current evidence.