Administration Of Perioperative Chemotherapy Research Articles

Hyperthermic Intraperitoneal Chemotherapy (HIPEC), Oncological Outcomes and Long-Term Survival among Patients with Gastric Cancer and Limited Peritoneal Disease Progression after Neoadjuvant Chemotherapy.

The role of surgery in stage IV gastric cancer with peritoneal metastasis (PM) remains unclear. The objective of the current single-center study was to define the impact of gastrectomy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on outcomes among Central European GC patients with limited peritoneal disease progression after neoadjuvant chemotherapy (NAC). Patients with histologically confirmed GC who underwent curative-intent multimodal treatment between 2013 and 2023 were included. Patients without adenocarcinoma, who did not undergo gastrectomy, had early (cT1) or metastatic GC at the time of initial diagnosis, who underwent multivisceral resection, incomplete cytoreduction or palliative care, died before planned curative-intent treatment, or had incomplete clinical or pathological missing information were excluded. A total of 74 patients who underwent curative-intent treatment for GC with PM were included in the final analytic cohort. Patients who underwent gastrectomy with CRS+HIPEC were less likely to achieve TOO (CRS+HIPEC: 28% vs. CRS: 57.1%, p = 0.033) compared with individuals after CRS alone. Specifically, patients who underwent gastrectomy with CRS+HIPEC had a higher likelihood of postoperative complications (CRS+HIPEC: 48% vs. CRS: 20.4%, p = 0.018) and longer hospital LOS (median, CRS+HIPEC: 12 vs. CRS: 10, p = 0.019). While administration of HIPEC did not impact long-term survival (median OS, CRS+HIPEC: 16 months vs. CRS: 12 months, p = 0.55), postoperative complications (median OS, CCI < 30:16 months vs. CCI > 30:5 months, p = 0.024) and ICU stay (median OS, no ICU stay: 16 months vs. ICU stay: 5 months, p = 0.008) were associated with worsened long-term survival among GC patients with PM. Data from the current study demonstrated a lack of survival benefit among advanced GC patients with PM undergoing gastrectomy with CRS+HIPEC when compared with individuals after gastrectomy with CRS alone. Administration of perioperative chemotherapy and achievement of TO failed to withstand the peritoneal disease progression during NAC.

Radical cystectomy plus chemotherapy in patients with pure squamous cell bladder carcinoma: a population-based study.

To test the effect of perioperative chemotherapy (CHT) on overall mortality (OM) and cancer-specific mortality (CSM) in patients with locally advanced or metastatic squamous cell carcinoma of the urinary bladder (SCC UB). Within the Surveillance, Epidemiology and End Results database (1988-2016), we identified 1,018 SCC UB patients (664 T3-4aN0M0, 197 TanyN1-3M0 and 156 T4bN0-3 or M1), who underwent radical cystectomy with or without perioperative chemotherapy administration. Inverse probability of treatment-weighting (IPTW), Kaplan-Meier plots and Cox-regression models (CRMs) were used. CHT was administrated in 116 (17.5%) T3-4aN0M0, 77 (39.1%) TanyN1-3M0 and 47 (30.1%) T4bN0-3 or M1 patients. IPTW-adjusted 2-year cancer-specific survival (CSS) was 66.5 vs. 71.5% (p = 0.19), 60.9 vs. 29.5% (p < 0.001) and IPTW-adjusted 1-year CSS was 46.2 vs. 31.1% (p = 0.03) for CHT vs. no CHT administration in T3-4aN0M0, TanyN1-3M0 and T4bN0-3 or M1, respectively. In multivariable IPTW-adjusted CRMs, chemotherapy was an independent predictor of lower CSM in TanyN1-3M0 (HR 0.44) and in T4bN0-3 or M1 (HR 0.60), but not in T3-4aN0M0 (p = 0.6) patients. Virtually the same results were obtained on OM, as well as without IPTW-adjustment and after stratification according to age and gender. The use of perioperative CHT in patients with SCC UB confers survival benefit in the presence of T4b disease, lymph node or distant metastases. Conversely, patients with locally advanced disease but negative lymph node invasion do not benefit from its use. Pending higher quality data from prospective trials, these data should encourage the use of perioperative CHT in those high-risk patient groups.

Increasing Rates of Perioperative Chemotherapy are Associated With Improved Survival in Men With Urothelial Bladder Cancer With Prostatic Stromal Invasion

Our objective was to test whether the rates of perioperative chemotherapy (CHT) administration in patients with urothelial bladder cancer (UCUB) with prostatic stromal invasion (pT4a) changed over time. Moreover, we tested the effect of CHT on overall mortality (OM), as well as on cancer-specific mortality (CSM) in this patient population. Within the Surveillance, Epidemiology, and End Results database (2004-2016), we identified 1513 men with non-metastatic UCUB with prostatic stromal invasion who underwent radical cystectomy with lymph node dissection, with or without CHT administration. Estimated annual percentage change analyses, inverse probability of treatment-weighting (IPTW), Kaplan-Meier plots, Cox regression models, and landmark analyses were performed. Overall, 732 (48.4%) patients with pT4a UCUB disease underwent radical cystectomy with perioperative CHT administration between 2004 and 2016. The CHT administration rate increased from 29.0% in 2004 to 64.8% in 2016 (P< .001). In IPTW-adjusted analyses, the 5-year overall survival was 47.7% versus 39.8%, and cancer-specific survival was 53.6 versus 50.1%, for with versus without CHT administration, respectively. After multivariable and IPTW-adjusted Cox regression models, administration of CHT independently predicted lower OM (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.52-0.73), as well as lower CSM (HR, 0.66; 95% CI, 0.55-0.80). even after 3-month landmark analyses (OM HR, 0.64; 95% CI 0.54-0.76; CSM HR, 0.70; 95% CI, 0.58-0.85). The use of CHT in patients with pT4a UCUB increased from low to moderate in the most contemporary era. However, based on its impressive reduction in OM, as well as in CSM, further increases in CHT administration rates should be highly encouraged in this patient population.

Preoperative therapy and long-term survival in gastric cancer: One size does not fit all

BackgroundThe administration of perioperative chemotherapy represents the Western standard of care for patients with locally advanced gastric cancer. The aim of this study is to determine if the administration of the preoperative component of the perioperative regimen is beneficial in the entire population of patients with locally advanced gastric cancer. MethodsSeventy patients undergoing preoperative therapy were compared with 347 patients undergoing upfront gastrectomy. Survival analyses were conducted with Kaplan-Meier curves and Cox regression. Patients undergoing preoperative therapy or undergoing upfront gastrectomy were matched 1:1 using the propensity score matching (PSM) method, and a survival analysis was conducted on matched patients. A subgroup analysis was conducted by tumor location and Lauren histotype. ResultsIn patients undergoing preoperative therapy, factors significantly associated with survival were T and N downstaging, type of gastrectomy, resection status and Lauren histotype. Preoperative therapy was not significantly associated with survival (p = 0,761 before PSM and p = 0,519 after PSM). After PSM, the independent variables significantly associated with survival were type of gastrectomy, type of lymphadenectomy, R status and postoperative therapy. In the subgroup analysis, preoperative therapy demonstrated a selective association with the location of the tumor (p = 0,055) and with Lauren intestinal histotype (p = 0,002). ConclusionsPreoperative therapy had a non-significant impact on survival in the entire population of gastric cancer patients. The advantage of preoperative therapy seems to be limited to patients with proximal tumors and an intestinal histology. Future studies should better evaluate the diverse response of the different phenotypes of gastric cancer to preoperative therapy.

Nomogram-based risk prediction of local and distant relapse after radical cystectomy, and role of perioperative chemotherapy, in patients with muscle-invasive bladder cancer (MIBC): A multicenter study.

448 Background: Neoadjuvant and adjuvant chemotherapy improve relapse-free survival (RFS) and overall survival of patients (pts) with MIBC. Limited information is available regarding risk prediction of local (RL) vs. distant relapse (RD), including role of perioperative chemotherapy (POC), added to radical cystectomy (Cy). Methods: Data from 1,559 pts, treated at 29 centers from the U.S., Europe, Israel, and Canada, were collected. Pts received Cy for MIBC from 02/90 to 12/13. Of these pts, 782 (50.2%) received POC and Cy, 777 (49.8%) Cy alone. RL and RD were defined as follows: pelvic lymph-nodes/soft tissue only and any extra-pelvic recurrences, respectively. Cumulative incidence methods were used to estimate time-to-(TT) RL/RD, which accounts for the competing risk of other types of relapse. Univariable and multivariable (MVA) Cox regression analyses were performed from the complete-case dataset (n = 1,082). Risk groups were defined according to the number of adverse factors, with corresponding nomogram-based RL and RD risk estimation. All tests were two-sided and statistical significance was defined as a p-value of 0.05 or less. Results: A total of 830 pts (55%) developed a relapse, 447 in the Cy group and 383 in the Cy+POC group. On MVA, POC administration was associated with longer TTRL (p &lt; 0.001) and TTRD (p &lt; 0.001). Other factors associated with RL: histology (non-UC, odds ratio [OR] = 1.47, 95%CI: 1.07-2.01, p = 0.022), pT-stage (p &lt; 0.001), pN-stage (p = 0.038), surgical margins (p &lt; 0.001). For RD: Charlson score (p = 0.006), pT-stage (p &lt; 0.001), pN-stage (p &lt; 0.001). The c-index of the model for RL was 0.685 (95% bootstrapped CI: 0.664-0.718), and for RD was 0.684 (0.655-0.721). Three risk group categories were obtained for both endpoints (0, 1-2, and &gt; 2 risk factors). Results were confirmed after applying 90-day or 180-day landmark analyses, pending external validation. Conclusions: In the largest study that separately analyzed RL and RD risk, we were able to provide risk tools that may be used to optimize locoregional treatments and compare POC benchmark with new drugs in the perioperative setting.

Clinical Outcomes of Perioperative Chemotherapy in Patients With Locally Advanced Penile Squamous-Cell Carcinoma: Results of a Multicenter Analysis

The prognosis of patients with locally advanced penile squamous-cell carcinoma is primarily related to the extent of lymph node metastases. Surgery alone yields suboptimal results, and there is a paucity of data on these patients' outcomes. This retrospective study evaluated patients who received neoadjuvant or adjuvant chemotherapy from 1990 onward at 12 centers. Cox models were used to investigate prognostic factors for relapse-free survival and overall survival (OS). Among the 201 included patients, 39 (19.4%) had disease of T3-4 and N0 clinical stage; the remaining patients had clinical lymph node involvement (cN+). Ninety-four patients received neoadjuvant chemotherapy (group 1), 78 received adjuvant chemotherapy (group 2), and 21 received both (group 3). Eight patients for whom the timing of perioperative chemotherapy administration was unavailable were included in the Cox analyses. Forty-three patients (21.4%) received chemoradiation. Multivariate analysis for OS (n=172) revealed bilateral disease (P= .035) as a negative prognostic factor, while pelvic cN+ tended to be nonsignificantly associated with decreased OS (P= .076). One-year relapse-free survival was 35.6%, 60.6%, and 45.1% in the 3 groups, respectively. One-year OS was 61.3%, 82.2%, and 75%, respectively. No significant differences were seen on univariable analyses for OS between the groups (P= .45). Platinum type of chemotherapy and chemoradiation were not significantly associated with any outcome analyzed. Benchmark survival estimates for patients receiving perioperative chemotherapy for locally advanced penile squamous-cell carcinoma have been provided, with no substantial differences observed between neoadjuvant and adjuvant administration. This analysis may result in improved patient information, although prospective studies are warranted.

Preoperative determinant of early postoperative renal function following radical cystectomy and intestinal urinary diversion.

To identify preoperative factors correlated with postoperative early renal function in patients who had undergone radical cystectomy (RC) and intestinal urinary diversion. We retrospectively identified 201 consecutive bladder cancer patients without distant metastasis who had undergone RC at our institution between 2003 and 2012. The estimated glomerular filtration rate (eGFR) was calculated using the modified Chronic Kidney Disease Epidemiology equation before RC and 3months following RC. Univariate and stepwise multiple linear regression analyses were applied to estimate postoperative renal function and to identify significant preoperative predictors of postoperative renal function. Patients who had undergone intestinal urinary diversion and were available for the collection of follow-up data (n=164) were eligible for the present study. Median preoperative and postoperative eGFRs were 69.7 (interquartile range [IQR] 56.3-78.0) and 70.7 (IQR 57.3-78.1), respectively. In univariate analyses, age, preoperative proteinuria, thickness of abdominal subcutaneous fat tissue (TSF), preoperative serum creatinine level, preoperative eGFR, and urinary diversion type were significantly associated with postoperative eGFR. In a stepwise multiple linear regression analysis, preoperative eGFR, age, and TSF were significant factors for predicting postoperative eGFR (p<0.001, p=0.02, and p=0.046, respectively). The estimated postoperative eGFRs correlated well with the actual postoperative eGFRs (r=0.65, p<0.001). Preoperative eGFR, age, and TSF were independent preoperative factors for determining postoperative renal function in patients who had undergone RC and intestinal urinary diversion. These results may be used for patient counseling before surgery, including the planning of perioperative chemotherapy administration.

Changes in oncological outcomes after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma treated in the last two decades: a retrospective analysis based on a multicenter collaborative study.

We investigated chronological changes in the outcomes of patients with upper urinary tract urothelial carcinomatreated in the past two decades, during which there was an important change in treatment paradigm. A retrospective review was conducted of 1180 urinary tract urothelial carcinoma patients who underwent radical nephroureterectomy in multicenter collaborative institutions between 1996 and 2015. The patients were divided into four groups according to the year when radical nephroureterectomy was performed, as follows: 1996-2000 (period 1; P1), 2001-05 (P2), 2006-10 (P3) and 2011-15 (P4). Variables including tumor grade, T and N categories, administration of perioperative chemotherapy and treatment outcomes were compared among the four groups. There were 146 (12%), 312 (27%), 459 (39%) and 263 (22%) patients in the P1, P2, P3 and P4 groups, respectively. The proportion of patients harboring pT2/3 and Grade 3 tumors increased gradually from 42% (P1) to 58% (P4) and from 49% (P1) to 65% (P4), respectively. The 5-year disease-free survival rates were 74%, 74%, 73% and 75%, and the 5-year overall survival rates were 74%, 65%, 67% and 72% for the P1, P2, P3, and P4 groups, respectively. Multivariate analysis with adjustment for possible confounding factors revealed no significant differences in disease-specific survival, overall survival or intravesical recurrence-free survival among the four groups. Despite advances in diagnostic instruments, surgery and systemic chemotherapy, the clinical outcome of urinary tract urothelial carcinoma after radical surgery has not significantly improved over the last two decades, and further research is therefore required.

Patterns and Predictors of Chemotherapy Use for Resected Non-Small Cell Lung Cancer

Chemotherapy combined with surgical resection improves survival in patients with stage II to IIIA non-small cell lung cancer (NSCLC) and may benefit selected patients with stage IB disease. We sought to evaluate chemotherapy use in resected stage IB to IIIA NSCLC over time and to identify predictors of perioperative chemotherapy administration. Patients with resected stage IB to IIIA NSCLC were identified from the National Cancer Data Base (2002 to 2011). Administration of chemotherapy was assessed over time. Hierarchical regression models were developed to assess patient, hospital, and tumor-level characteristics predicting perioperative chemotherapy administration. In 55,016 stage IB patients, chemotherapy use significantly increased between 2002 and 2011 from 5.3% to 15.1% (p < 0.001). In 57,033 patients with stage II to IIIA disease, perioperative chemotherapy administration also significantly increased from 29.3% to 58.4% (p < 0.001). Multivariable analyses demonstrated stage IB and II to IIIA patients were less likely to receive chemotherapy if they were older, treated at an academic center (vs community), had more comorbidities, or had lower-grade tumors (all p < 0.05). Stage IB patients with tumors sized 4 cm or larger were more likely to receive chemotherapy (odds ratio, 3.16; 95% confidence interval, 2.73 to 3.65) than those with tumors smaller than 4 cm. Compared with stage IIA patients, stage IIB patients were no more likely to receive perioperative chemotherapy (odds ratio, 1.06; 95% confidence interval, 0.96 to 1.17), whereas stage IIIA patients received chemotherapy significantly more often (odds ratio, 2.82; 95% confidence interval, 2.55 to 3.11). The use of chemotherapy has significantly increased in patients with resected stage IB to IIIA NSCLC. Although clinicians have increasingly adopted evidence-based recommendations, significant treatment gaps persist and represent areas for quality improvement.

Toxicity and survival outcomes of adjuvant chemoradiation for gastric and gastroesophageal junction cancer patients treated in period 2006-2009: an institutional experience.

Surgical resection is the mainstay of gastric or gastroesophageal junction cancer treatment and has curative potential for patients with early-stage disease. In order to improve the poor survival rates, there are two complementary treatment strategies used at most - perioperative chemotherapy based on UK Magic trial or adjuvant chemoradiation based on INT-0116 trial. Daily treatment decision making should be led also by institutional experiences with toxicity evaluation. We evaluated survival and toxicity outcomes of 47 consecutive patients who underwent adjuvant chemoradiation in our institution in the years 2006-2009. 45Gy in 5 weeks with concurrent two cycles of FUFA Mayo regimen chemotherapy were administrated as part of combined treatment. The acute toxicity was relatively mild (CTCAE scale): grade 2 nausea in 26%, vomiting in 13%, and diarrhoea grade 1 in 15% and general abdominal discomfort in 57% of patients. Grade 3 haematological and infectious complications in 6% and 2% respectively. Late adverse events were as follows: grade 1 esophageal toxicity in 17%, signs of mild chronic esophageal ulceration and esophageal stenosis in 9% of patients (50% of them had tracheoesophageal fistula). The Kaplan- Meier estimate of the median overall survival was 30.5 months with median 25.7 months disease free survival. The overall survival was statistically significantly affected by the amount of removed positive lymph nodes. For the proper evaluation of radiotherapy role in multimodal treatment approach, results of other clinical trials investigating role of concurrent radiotherapy in administration of perioperative chemotherapy will be necessary. Meanwhile, two equally approaches are possible, all having their pros and cons. Institutional toxicity evaluation is recommended in order to provide the best care possible. Keywords: adjuvant chemoradiation, gastric cancer, early toxicity, late toxicity, survival outcomes.

Radical nephroureterectomy for pathologic T4 upper tract urothelial cancer: can oncologic outcomes be improved with multimodality therapy?

To report the outcomes of patients with pathologic T4 UTUC and investigate the potential impact of peri-operative chemotherapy combined with radical nephroureterectomy (RNU) and regional lymph node dissection (LND) on oncologic outcomes. Patients with pathologic T4 UTUC were identified from the cohort of 1464 patients treated with RNU at 13 academic centers between 1987 and 2007. Oncologic outcomes were stratified according to utilization of perioperative systemic chemotherapy and regional LND as an adjunct to RNU. The study included 69 patients, 42 males (61%) with median age 73 (range 43-98). Median follow-up was 17 months (range: 6-88). Lymphovascular invasion was found in 47 (68%) and regional lymph node metastases were found in 31 (45%). Peri-operative chemotherapy was utilized in 29 (42%) patients. Patients treated with peri-operative chemotherapy and RNU with LND demonstrated superior oncologic outcomes compared to those not treated by chemotherapy and/or LND during RNU (3Y-DFS: 35% vs. 10%; P = 0.02 and 3Y-CSS: 28% vs. 14%; P = 0.08). In multivariate Cox regression analysis, administration of peri-operative chemotherapy and utilization of LND during RNU was associated with lower probability of recurrence (HR: 0.4, P = 0.01), and cancer specific mortality (HR: 0.5, P = 0.06). Pathological T4 UTUC is associated with poor prognosis. Peri-operative chemotherapy combined with aggressive surgery, including lymph node dissection, may improve oncological outcomes. Our findings support the use of aggressive multimodal treatment in patients with advanced UTUC.

Changes in treatment patterns and their influence on long-term survival in patients with stages I-III gastric cancer in The Netherlands

Studies investigating perioperative chemotherapy and/or radiotherapy changed the treatment of curable gastric cancer in The Netherlands. These changes were evaluated including their influence on survival. Data on patients diagnosed with gastric cancer from 1989 to 2009 were obtained from The Netherlands Cancer Registry. Changes over time in surgery and administration of perioperative chemotherapy, 30-day mortality, 5-year survival and adjusted relative excess risk (RER) of dying were analyzed with multivariable regression for cardia and noncardia cancer. In stages I and II disease, most patients underwent surgery. Since 2005, more patients are treated with (neo)adjuvant chemotherapy. Postoperative mortality ranged from 1% to 7% and 0.4% to 12.2% in cardia and noncardia cancer (<55 to 75+ years). Five-year survival for cardia cancer and noncardia cancer stages I-III and X (unknown stage) was 33% and 50% (2005-2008). The RER of dying was associated with period of diagnosis, age, gender, region, stage, (neo)adjuvant chemotherapy in case of cardia cancer and type of gastric resection in case of noncardia cancer. Administration of (neo)adjuvant chemotherapy has increased. No improvement in long-term survival could yet be seen, though it is still too early to expect an improvement in survival as a result of the use of chemotherapy.

1437 UNDERSTANDING AVOIDANCE, REFUSAL AND ABANDONMENT OF CHEMOTHERAPY BEFORE AND AFTER RADICAL CYSTECTOMY FOR BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Invasive (I)1 Apr 20131437 UNDERSTANDING AVOIDANCE, REFUSAL AND ABANDONMENT OF CHEMOTHERAPY BEFORE AND AFTER RADICAL CYSTECTOMY FOR BLADDER CANCER Ahmed Aboumohamed, Shabnam Rehman, Alice Crane, Andrew Stegemann, Rakeeba Din, Yi Shi, Gregory Wilding, Ellis Levine, Saby George, Donald Trump, and Khurshid Guru Ahmed AboumohamedAhmed Aboumohamed Buffalo, NY More articles by this author , Shabnam RehmanShabnam Rehman Buffalo, NY More articles by this author , Alice CraneAlice Crane Buffalo, NY More articles by this author , Andrew StegemannAndrew Stegemann Buffalo, NY More articles by this author , Rakeeba DinRakeeba Din Buffalo, NY More articles by this author , Yi ShiYi Shi Buffalo, NY More articles by this author , Gregory WildingGregory Wilding Buffalo, NY More articles by this author , Ellis LevineEllis Levine Buffalo, NY More articles by this author , Saby GeorgeSaby George Buffalo, NY More articles by this author , Donald TrumpDonald Trump Buffalo, NY More articles by this author , and Khurshid GuruKhurshid Guru Buffalo, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2791AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES National Comprehensive Cancer Network (NCCN) guidelines recommend consideration of neoadjuvant chemotherapy for T2 and T3 disease with no nodal involvement. Adjuvant chemotherapy is recommended for patients with a disease stage higher than pT2 and/or nodal involvement and lymphovascular invasion. Yet, perioperative chemotherapy is used relatively infrequently as a standard of care. We sought to analyze the trends in administration of perioperative chemotherapy at our institution as well as changes implemented to improve the utilization of neoadjuvant chemotherapy. METHODS The cystectomy database was queried to identify patients with disease ≥cT2 and >pT2 with or without nodal involvement and/or positive surgical margins that were eligible for perioperative chemotherapy. RESULTS Out of 242 patients, 148 (61%) were eligible for neoadjuvant chemotherapy (NAC). Consultation for NAC was sought for 44 (29%) patients while 104 (71%) did not receive consultation. Out of 44 patients, 36% received NAC, 7% refused, 32% were recommended immediate cystectomy and remaining 25% did not receive NAC for co-morbidities, advanced age and/or non-urothelial histology. Of the remainder 104 patients, 6% refused consultation and 58% were not referred for unknown reasons. For remaining 36% patients, reasons for not receiving a consultation remained uncertain, but appeared to be medical co-morbidities and/or obstructive tumor causing nephropathy (Figure). On final pathology, 136 (56%) patients were eligible for adjuvant chemotherapy (AC). AC consultation was sought for 107 (79%) patients. Of these, 35% received AC, 22% refused, and in 5% it was aborted due to adverse effects. 30% patients were not recommended AC due to comorbidities, non-urothelial histology and protracted recovery. 8%received salvage chemotherapy for metastatic disease. For remaining 29 (21%) patients, 11 were lost for follow-up, 10 expired and 8 were not consulted for unclear reasons. CONCLUSIONS Multi-disciplinary approach is needed to optimize utilization of perioperative chemotherapy in bladder cancer. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e589 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ahmed Aboumohamed Buffalo, NY More articles by this author Shabnam Rehman Buffalo, NY More articles by this author Alice Crane Buffalo, NY More articles by this author Andrew Stegemann Buffalo, NY More articles by this author Rakeeba Din Buffalo, NY More articles by this author Yi Shi Buffalo, NY More articles by this author Gregory Wilding Buffalo, NY More articles by this author Ellis Levine Buffalo, NY More articles by this author Saby George Buffalo, NY More articles by this author Donald Trump Buffalo, NY More articles by this author Khurshid Guru Buffalo, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Up-front Hepatic Resection for Metastatic Colorectal Cancer Results in Favorable Long-term Survival

Hepatic metastasis from colorectal cancer (CRC) is best managed with a multimodal approach; however, the optimal timing of liver resection in relation to administration of perioperative chemotherapy remains unclear. Our strategy has been to offer up-front liver resection for patients with resectable hepatic metastases, followed by post-liver resection chemotherapy. We report the outcomes of patients based on this surgical approach. A retrospective review of all patients undergoing liver resection for CRC metastases over a 5-year period (2002-2007) was performed. Associations between clinicopathologic factors and survival were evaluated by the Cox proportional hazard method. A total of 320 patients underwent 336 liver resections. Median follow-up was 40 (range 8-80) months. The majority (n=195, 60.9%) had metachronous disease, and most patients (n=286, 85%) had a major hepatectomy (>3 segments). Thirty-six patients (11%) received preoperative chemotherapy, predominantly for downstaging unresectable disease. Ninety-day mortality was 2.1%, and perioperative morbidity occurred in 68 patients (20.2%). Actual disease-free survival at 3 and 5 years was 46.2% and 42%, respectively. Actual overall survival (OS) at 3 and 5 years was 63.7% and 55%, respectively. Multivariate analysis identified four factors that were independently associated with differences in OS (hazard ratio; 95% confidence interval): size of metastasis>6 cm (2.2; 1.3-3.5), positive lymph node status of the primary CRC (N1 (2.0; 1.0-3.8), N2 (2.4; 1.2-4.9)), synchronous disease (2.1; 1.3-3.5), and treatment with chemotherapy after liver resection (0.42; 0.23-0.75). Up-front surgery for patients with resectable CRC liver metastases, followed by chemotherapy, can lead to favorable OS.

Molecular signatures that predict nodal metastasis in bladder cancer: does the primary tumor tell tales?

Evaluation of: Smith SC, Baras AS, Dancik G et al. A 20-gene model for molecular nodal staging of bladder cancer: development and prospective assessment. Lancet Oncol. 12, 137–143 (2011).Accurate identification of nodal status in patients with bladder cancer is important in determining their prognosis and administration of perioperative chemotherapy. In this article, we review the study by Smith and colleagues, documenting the identification of a 20-gene model that can predict nodal stage in patients with bladder cancer based on the profiles of their primary tumors. The gene-expression model generated in this study was able to identify node-positive disease based on tumor tissues obtained from patients in a Phase III bladder cancer trial cohort. The model was able to predict nodal status independent of standard clinicopathologic prognostic criteria. This study adds the agnostic profiling dimension to prior investigations that have attempted to define molecular signatures that predict nodal metastasis in bladder cancer patients based on the primary tumors’ gene-expression profiles.

Klotho predicts good clinical outcome in patients with limited-disease small cell lung cancer who received surgery

Background The important role of surgery in early-stage small cell lung cancer (SCLC) has been recognized, and curative surgical resection is recommended. However, the role of adjuvant chemotherapy for stage I SCLC has not yet been evaluated, and novel approaches focusing on the specific genomic characteristics of SCLC may be invaluable for customized therapy. In this study, we focused on the Klotho gene, which is an anti-aging gene known to be a potential tumor suppressor. We investigated whether the expression of Klotho, assessed by immunohistochemistry, can predict survival in patients with resected SCLC. Methods The medical records of patients diagnosed as having limited-disease (LD) SCLC and treated by surgical resection ( n = 30) at Tokyo Medical University Hospital were retrospectively reviewed. The expression status of Klotho, and of the ATP-binding cassette (ABC) transporters MRP1, MDR and breast cancer resistant protein (BCRP), which can cause resistance to anticancer drugs, including irinotecan, was assessed by immunohistochemical analysis in resected surgical specimens of patients with early-stage SCLC. Results Of the 30 patients, Klotho expression was seen in the specimens from 18 patients (60.0%), but not in those of the remaining 12 patients (40.0%). The immunostaining for Klotho was mostly localized in the cytoplasm. The expression of Klotho was significantly associated with the overall survival (OS) (ratio 0.088; 95% confidence interval 0.019–0.409; P = 0.002). The administration of perioperative chemotherapy had no significant effect in improving the survival, as assessed by the Kaplan–Meier method. However, the patients showing Klotho expression in the resected specimens in p-stage I and II, may have benefited from perioperative chemotherapy. A multivariate analysis revealed no significant association between the expression status of MRP1, MDR or BCRP and the OS. Conclusion Expression of Klotho was predictive of a favorable outcome following resection in limited-disease SCLC patients, and the Klotho expression status may serve as a new biomarker for the need of additional therapies to be developed in the future.

Chronic kidney disease after nephroureterectomy for upper tract urothelial carcinoma and implications for the administration of perioperative chemotherapy

The prevalence of chronic kidney disease (CKD) in patients with upper tract urothelial carcinoma (UTUC) is poorly defined, both before and after nephrouretectomy. Although multimodal treatment paradigms for UTUC are under-developed, this has important implications on patients' ability to receive cisplatin-based combination chemotherapy (CBCC). Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease formula in 336 patients with UTUC, who were treated at the Cleveland Clinic by nephroureterectomy since 1992. An eGFR cutoff of 60 mL/min/1.73 m(2) was used to determine the presence of CKD and eligibility for CBCC. Median age was 72 years and median preoperative eGFR was 59 mL/min/1.73m(2). Before nephroureterectomy, only 48% of patients were eligible to receive CBCC and this decreased to 22% postoperatively (P < .001). In the 144 patients with pT2-pT4 and/or pN1-pN3 disease who are suitable to receive CBCC, these proportions were 40% and 24%, respectively (P = .009). Although 50 patients overall received some form of perioperative chemotherapy, only 3 and 11 patients received neoadjuvant and adjuvant CBCC, respectively. CKD is prevalent in the UTUC population and a minority of patients has an optimal eGFR to receive neoadjuvant CBCC. Nephrouretectomy may eliminate CBCC as a therapeutic option in 49% of high-risk patients if it is deferred to the adjuvant setting. Multimodal treatment strategies for UTUC should focus on neoadjuvant chemotherapy, as few patients are eligible for adjuvant CBCC because of the substantial decline in eGFR caused by nephroureterectomy.

Factors associated with perioperative systemic chemotherapy for bladder cancer: A population based study

4701 Background: There has recently been increased attention in the use of perioperative chemotherapy for bladder cancer. The patterns of treatment with perioperative chemotherapy for this disease outside the setting of clinical trials have not, to our knowledge, been well-examined. We used the SEER-Medicare database to evaluate the frequency of administration of perioperative chemotherapy for patients undergoing radical cystectomy. We further analyzed the demographic, cancer-specific, and diagnostic information available in the SEER and Medicare claims databases for factors that may be associated with chemotherapy administration. Methods: Using the SEER-Medicare database, we identified eligible patients 65 years of age or older who underwent radical cystectomy for bladder cancer between 1992 and 1999. We used logistic regression analysis to examine the associations between perioperative chemotherapy administration and several demographic and tumor-specific variables. These variables included: age at cystectomy; sex; marital status; ethnicity; SEER registry site; year of cystectomy; tumor histology; grade; stage at diagnosis; nodal status; and presence of synchronous upper urinary tract cancer. Results: A total of 1,353 patients were identified who met the criteria for inclusion in our analysis, of which 247 (18.3%) received perioperative chemotherapy. There were no correlations between the odds of receiving perioperative chemotherapy and most demographic variables, including age at the time of cystectomy, sex, race, socioeconomic and educational background. Stage IV and node-positive disease were associated with a significant increase in the odds of receiving perioperative chemotherapy. No differences in chemotherapy administration were found based on ratio of positive nodes, cancer histology, cancer grade, or synchronous upper urinary tract disease. Conclusion: Odds of receiving perioperative chemotherapy for bladder cancer are not associated with most demographic factors. However, tumor-specific factors, namely node positivity and stage IV tumors, are associated with odds of receiving such therapy. No significant financial relationships to disclose.

Trends in long-term survival following liver resection for hepatic colorectal metastases.

To examine trends in outcomes of patients undergoing resection at a single tertiary care referral center over a 16-year period. Hepatic resection is considered the treatment of choice in selected patients with colorectal metastasis confined to the liver. Although a variety of retrospective studies have demonstrated improvements in short-term outcomes in recent years, changes in long-term survival over time are less well-established. Data from 226 consecutive patients undergoing potentially curative liver resection for colorectal metastases between 1984 and 1999 were analyzed. Actuarial survival rates related to prognostic determinants were analyzed using the log-rank test. The median survival for the entire cohort was 46 months, with 5- and 10-year survival rates of 40% and 26% respectively. Ninety-three patients operated on between 1984 and 1992 were found to have an overall survival of 31% at 5 years, compared to 58% for the 133 patients operated on during the more recent period (1993-1999). Both overall and disease-free survival were significantly better in the recent time period compared with the earlier period on both univariate and multivariate analyses. Other independent factors associated with improved survival included number of metastatic tumors < or = 3, negative resection margin, and CEA < 100. Comparisons were made between time periods for a variety of patient, tumor and treatment-related factors. Among all parameters studied, only resection type (anatomical versus nonanatomical), use of intraoperative ultrasonography, and perioperative chemotherapy administration differed between the early and recent time periods. Long-term survival following liver resection for colorectal metastases has improved significantly in recent years at our institution. Although the reasons for this survival trend are not clear, contributing factors may include the use of newer preoperative and intraoperative imaging, increased use of chemotherapy, and salvage surgical therapy.