Pathological downstaging and survival after induction chemotherapy and radical cystectomy for clinically node-positive bladder cancer—Results of a nationwide population-based study

BackgroundInduction chemotherapy (IC) for clinically node-positive bladder cancer is applied without clinical evidence of improved outcome. Our objective was to compare complete pathological downstaging (pCD) and overall survival (OS) for IC versus upfront radical cystectomy (RC) in cT1-4aN1-3M0 urothelial carcinoma (UC).MethodsThis population-based study included 659 cN+ patients treated with RC between 1995 and 2013. IC was applied in 212 (32%) patients. We defined pCD as ≤(y)pT1N0 at RC. Multivariable analyses were preformed to identify independent predictors of pCD and OS.ResultsIn cN1 and cN2–3 patients, 31% and 19% of patients proved to be pN0 at upfront RC. In cN1, pCD was achieved in 39% following IC versus 5% for upfront RC (P < 0.001). In cN2–3 UC, rates were 27% versus 3% (P < 0.001). Three-year OS for pCD and ypCD were 81% and 84%, respectively. Three-year OS rates were 66% versus 37% (cN1) and 43% versus 22% (cN2-3), again in favour of IC (P < 0.001). In multivariable analyses, IC was associated with pCD (Odds ratio, 14; 95% confidence interval [CI], 7.4–25) and a 53% decreased risk of death (Hazard ratio [HR], 0.47; 95% CI, 0.36–0.61). Indication bias and unequal distributions of factors associated with OS (e.g. patients proceeding to RC) limit interpretation of our results.ConclusionsPatients with clinical nodal involvement should not be neglected. Up to 1/4 of patients with cN+ disease had pN0 at upfront RC. Moreover, IC followed by RC for clinically node-positive UC was associated with improved pathological downstaging compared with RC alone. A potential OS benefit for IC needs to be validated in a randomised trial.Take home messageIC followed by RC for clinically node-positive UC is associated with improved pathological downstaging compared with RC alone. A potential OS benefit for IC needs to be validated in a randomised trial.     

Perioperative treatment and radical cystectomy for bladder cancer – a population based trend analysis of 10,338 patients in the Netherlands

BackgroundIn Europe, population-based data concerning perioperative treatment (PT) and radical cystectomy (RC) are lacking. We assessed temporal trends in PT (neoadjuvant chemotherapy [NAC], neoadjuvant radiotherapy [NAR], adjuvant chemotherapy [AC], adjuvant radiotherapy [AR]) and RC in the Netherlands and identified patients' and hospital characteristics associated with PT.MethodsThis nationwide, retrospective, population-based study included cTa/is, T1-4, N0-3, M0-1 bladder cancer patients from the Netherlands Cancer Registry who underwent RC with curative intent between 1995 and 2013. PT-administration over time was compared with chi-square tests. Multivariable logistic regression analyses were performed to identify characteristics associated with PT usage. The sub-groups cT2-4N0M0 and cT2-4, N0 or NX, M0 or MX were separately analysed.ResultsIn total, 10,338 patients met inclusion criteria. Eighty-six percent did not receive PT, 7.0% received NAC (or induction chemotherapy [IC]), 3.2% NAR, 1.8% AC, and 2.1% AR. NAC usage increased from 0.6% in 1995 to 21% in 2013 (p < 0.001), application of NAR decreased from 15% to 0.4% (p < 0.001). Usage of AC and AR in 2013 was <1.5%. Comparable temporal trends were found in 6032 patients staged cT2-4N0M0. Multivariable logistic regression analysis revealed that younger age, ≥cT3, ≥cN1 and treatment in academic/teaching hospitals were associated with NAC or IC (all p < 0.05).ConclusionsThe increase in NAC administration in the Netherlands reflects a slow but steady adoption of evidence-based guidelines over the last two decades. Considerable variability in patients' and hospital characteristics in the likelihood of receiving NAC exists. Conversely, NAR, AR and AC are hardly administered anymore.     

The impact of postmastectomy and regional nodal radiation after neoadjuvant chemotherapy for clinically lymph node-positive breast cancer: a National Cancer Database (NCDB) analysis

BackgroundFollowing neoadjuvant chemotherapy (NAC), the optimal strategies for postmastectomy radiotherapy (PMRT) and regional nodal irradiation (RNI) after breast-conserving surgery (BCS) are controversial. In this analysis, we evaluate the impact of these radiotherapy (RT) approaches for women with clinically node-positive breast cancer treated with NAC in the National Cancer Database (NCDB).Patients and methodsWomen with cT1–3 cN1 M0 breast cancer treated with NAC were divided into four cohorts by surgery [Mastectomy (Mast) versus BCS] and post-chemotherapy pathologic nodal status (ypN0 versus ypN+). Overall survival (OS) was estimated using the Kaplan–Meier method and RT approaches were analyzed using the log-rank test, multivariate Cox models, and propensity score-matched analyses.ResultsFrom 2003 to 2011, 15 315 cases were identified including 3040 Mast-ypN0, 7243 Mast-ypN+, 2070 BCS-ypN0, and 2962 BCS-ypN+ patients. On univariate analysis, PMRT was associated with improved OS for both Mast-ypN0 (P = 0.019) and Mast-ypN+ (P < 0.001) patients. On multivariate analyses adjusted for factors including age, comorbidity score, cT stage, in-breast pathologic complete response, axillary surgery, ypN stage, estrogen receptor status and hormone therapy, PMRT remained independently associated with improved OS among Mast-ypN0 [hazard ratio (HR) = 0.729, 95% confidence interval (CI) 0.566–0.939, P = 0.015] and Mast-ypN+ patients (HR = 0.772, 95% CI 0.689–0.866, P < 0.001). No differences in OS were observed with the addition of RNI to breast RT for BCS-ypN0 or BCS-ypN+ patients. Propensity score-matched analyses demonstrated identical patterns of significance. On subset analysis, OS was improved with PMRT in each pathologic nodal subgroup (ypN0, ypN1, and ypN2-3) (all P < 0.05).ConclusionsIn the largest reported analysis of RT for cN1 patients treated with NAC, PMRT was associated with improved OS for all pathologic nodal subgroups. No OS differences were observed with the addition of RNI to breast RT.     

A comparison of the outcomes of neoadjuvant and adjuvant chemotherapy for clinical T2-T4aN0-N2M0 bladder cancer

BACKGROUND:

Despite evidence supporting perioperative chemotherapy, few randomized studies compare neoadjuvant and adjuvant chemotherapy for bladder cancer. Consequently, the standard of care regarding the timing of chemotherapy for locally advanced bladder cancer remains controversial. We compared patient outcomes following neoadjuvant or adjuvant systemic chemotherapy for cT2‐T4aN0‐N2M0 bladder cancer.

METHODS:

In a retrospective review of a single institutional database from 1988 through 2009, we identified patients receiving neoadjuvant or adjuvant multiagent platinum‐based systemic chemotherapy for locally advanced bladder cancer. Survival analysis was performed comparing disease‐specific survival (DSS) and overall survival (OS).

RESULTS:

A total of 146 patients received systemic perioperative chemotherapy (73 neoadjuvant, 73 adjuvant). Of these, 84% (122/146) received cisplatin‐based chemotherapy compared with carboplatin‐based chemotherapy (24/146, 16.4%). Most patients receiving cisplatin‐based chemotherapy were treated with methotrexate/vinblastine/adriamycin/cisplatin (79/122, 64.8%), whereas the remaining patients received gemcitabine/cisplatin (GC) (43/122, 35.2%). In multivariable analysis, there was no significant difference in DSS (P = .46) or OS (P = .76) between neoadjuvant or adjuvant chemotherapy groups. There was statistically significant improvement in DSS when patients received neoadjuvant GC rather than adjuvant GC (P = .049, hazard ratio, 10.6; 95% confidence interval, 1.01‐112.2).

CONCLUSION:

In this study, there was no statistically significant difference in OS and DSS between patients receiving neoadjuvant versus adjuvant systemic platinum‐based chemotherapy for locally advanced bladder cancer. In addition, there was no significant difference between neoadjuvant and adjuvant cisplatin‐ or carboplatin‐based chemotherapy. Chemotherapy sequence relative to surgery appeared less important than whether or not a patient actually received perioperative chemotherapy. Cancer 2011;. © 2011 American Cancer Society.     

Combined modality therapy of cT2N0M0 esophageal cancer: the University of Texas M. D. Anderson Cancer Center experience

BACKGROUND:

Treatment strategy for patients with adequately staged cT2N0M0 carcinoma of the thoracic esophagus is currently a subject of debate. This study analyzed the largest series of consecutive cT2N0M0 esophageal cancer patients treated with preoperative chemoradiotherapy.

METHODS:

Data from all patients with cT2N0M0 (assessment included endoscopic ultrasonography and computed tomography of the chest and abdomen) thoracic esophageal cancer who were treated with preoperative chemoradiation between 1997 and 2009 were analyzed. The Cox regression model and Kaplan‐Meier plots were used to analyze the data.

RESULTS:

Data from 49 patients were analyzed. The median follow‐up was 28.46 months. Male sex and adenocarcinoma histology predominated. Pathologic complete response was observed 19 (39%) patients. The 10‐year actuarial overall survival (OS) for adenocarcinoma patients was >60%. In the univariate analysis for OS, squamous histology (P = .006), smoking (P = .015), and alcohol consumption (P = .032) were found to be associated with poor OS. In the univariate analysis for disease‐free survival (DFS), squamous histology (P = .009) and smoking (P = .014) were associated with poor DFS. In the multivariate analysis for OS, smoking was an independent prognosticator (P = .02). In the multivariate analysis for DFS, advanced pathologic stage (P = .05) and lymph node metastases (P = .006) were independent prognosticators. Patients with adenocarcinoma (P = .002) and those with pathologic N0 disease had better OS and DFS. Upward stage migration occurred in only 10% of patients.

CONCLUSIONS:

These data suggest that smoking and alcohol influence the long‐term outcome of patients with cT2N0M0 disease. Adenocarcinoma patients treated with trimodality therapy had an excellent actuarial 10‐year OS and a high rate of pathologic complete response. Trimodality therapy should be prospectively compared with primary surgery in these patients. Cancer 2011. © 2010 American Cancer Society.     

Indications for neoadjuvant treatment based on risk factors for poor prognosis before and after neoadjuvant chemotherapy alone in patients with locally advanced rectal cancer

IntroductionThe oncological benefit of neoadjuvant chemotherapy (NAC) alone for locally advanced rectal cancer (LARC) remains controversial. The aim of this study was to clarify the clinical risk factors for poor prognosis before and after NAC for decision making regarding additional treatment in patients with LARC.Materials and methodsWe examined a total of 96 patients with MRI-defined poor-risk locally advanced mid-low rectal cancer treated by NAC alone between 2006 and 2018. Survival outcomes and clinical risk factors for poor prognosis before and after NAC were analyzed.ResultsIn the median follow-up duration after surgery of 60 months (3–120), the rates of 5-year overall survival (OS), relapse-free survival (RFS), and local recurrence (LR) were 83.6%, 78.4%, and 8.2%, respectively. In the multivariate analyses, patients with cT4 disease had a significantly higher risk of poor OS (HR; 6.10, 95% CI; 1.32–28.15, P = 0.021) than those with cT3 disease. After NAC, ycN+ was significantly associated with a higher risk of poor OS (HR; 5.92, 95% CI; 1.27–27.62, P = 0.024) and RFS (HR; 2.55, 95% CI; 1.01–6.48, P = 0.048) than ycN-. In addition, patients with CEA after NAC (post-CEA) ≥ 5 ng/ml had a significantly higher risk LR (HR; 5.63, 95% CI; 1.06–29.93, P = 0.043).ConclusionNAC alone had an insufficient survival effect on patients with cT4 disease, ycN+, or an elevated post-CEA level. In contrast, NAC alone is a potential treatment for other patients with LARC.     

Neoadjuvant gemcitabine and cisplatin chemotherapy for locally advanced urothelial cancer of the bladder

BACKGROUND:

The purpose of this study was to investigate the effect of neoadjuvant chemotherapy with gemcitabine and cisplatin (GC) on pathologic down‐staging of patients with locally advanced urothelial cancer (UC) of the bladder.

METHODS:

This was a retrospective cohort study of patients treated with radical cystectomy (RC) for clinical stage cT2‐T4, N any, M0 bladder UC at Strong Memorial Hospital from 1999 to 2009. The primary exposure variable was use of neoadjuvant chemotherapy (GC vs none). The primary outcome was stage pT0 at RC. Secondary outcomes included other down‐staging end points in the bladder ( RESULTS: A total of 160 eligible patients were identified, of whom 25 were treated with neoadjuvant GC before RC (GC + RC) and 135 without neoadjuvant chemotherapy (RC only). Stage pT0 at cystectomy was found in 20% of patients in the GC + RC group and in 5% of patients in the RC group (adjusted risk difference [aRD] = 16%, P = .03). For other down‐staging end points, the estimated treatment effect was as follows (all point estimates favoring chemotherapy): P = .005); P = .004); P = .008); margins aRD = 8% (P = .41); nodes aRD = 4% (P = .74).

CONCLUSIONS:

Neoadjuvant GC was found to be capable of down‐staging UC in the bladder; however, no effect on disease in nodes was seen in this study. Cancer 2012;. © 2011 American Cancer Society.     

Randomised phase III study of neoadjuvant chemotherapy with methotrexate,doxorubicin, vinblastine and cisplatin followed by radical cystectomy compared with radical cystectomy alone for muscle-invasive bladder cancer: Japan Clinical Oncology Group Study JCOG0209

BackgroundThis study aimed to determine the clinical benefit of neoadjuvant methotrexate, doxorubicin, vinblastine, and cisplatin (MVAC) in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy.Patients and methodsPatients with MIBC (T2-4aN0M0) were randomised to receive two cycles of neoadjuvant MVAC followed by radical cystectomy (NAC arm) or radical cystectomy alone (RC arm). The primary end point was overall survival (OS). Secondary end points were progression-free survival, surgery-related complications, adverse events during chemotherapy, proportion with no residual tumour in the cystectomy specimens, and quality of life. To detect an improvement in 5-year OS from 45% in the RC arm to 57% in the NAC arm with 80% power, 176 events were required per arm.ResultsPatients (N = 130) were randomly assigned to the RC arm (N = 66) and the NAC arm (N = 64). The patient registration was terminated before reaching the initially planned number of patients because of slow accrual. At the second interim analysis just after the early stoppage of patient accrual, the Data and Safety Monitoring Committee recommended early publication of the results because the trial did not have enough power to draw a confirmatory conclusion. OS of the NAC arm was better than that of the RC arm, although the difference was not statistically significant [hazard ratio 0.65, multiplicity adjusted 99.99% confidence interval 0.19–2.18, one-sided P = 0.07]. In the NAC arm and the RC arm, 34% and 9% of the patients had pT0, respectively (P < 0.01). In subgroup analyses, OS in almost all subgroups was in favour of NAC.ConclusionsThis trial showed a significantly increased pT0 proportion and favourable OS of patients who received neoadjuvant MVAC. NAC with MVAC can still be considered promising as a standard treatment.UMIN Clinical Trials Registry IdentifierC000000093.     

Impact of perioperative chemotherapy on survival in patients with advanced primary urethral cancer: results of the international collaboration on primary urethral carcinoma

BackgroundTo investigate the impact of perioperative chemo(radio)therapy in advanced primary urethral carcinoma (PUC).Patients and methodsA series of 124 patients (86 men, 38 women) were diagnosed with and underwent surgery for PUC in 10 referral centers between 1993 and 2012. Kaplan–Meier analysis with log-rank testing was used to investigate the impact of perioperative chemo(radio)therapy on overall survival (OS). The median follow-up was 21 months (mean: 32 months; interquartile range: 5–48).ResultsNeoadjuvant chemotherapy (NAC), neoadjuvant chemoradiotherapy (N-CRT) plus adjuvant chemotherapy (ACH), and ACH was delivered in 12 (31%), 6 (15%) and 21 (54%) of these patients, respectively. Receipt of NAC/N-CRT was associated with clinically node-positive disease (cN+; P = 0.033) and lower utilization of cystectomy at surgery (P = 0.015). The objective response rate to NAC and N-CRT was 25% and 33%, respectively. The 3-year OS for patients with objective response to neoadjuvant treatment (complete/partial response) was 100% and 58.3% for those with stable or progressive disease (P = 0.30). Of the 26 patients staged ≥cT3 and/or cN+ disease, 16 (62%) received perioperative chemo(radio)therapy and 10 upfront surgery without perioperative chemotherapy (38%). The 3-year OS for this locally advanced subset of patients (≥cT3 and/or cN+) who received NAC (N = 5), N-CRT (N = 3), surgery-only (N = 10) and surgery plus ACH (N = 8) was 100%, 100%, 50% and 20%, respectively (P = 0.016). Among these 26 patients, receipt of neoadjuvant treatment was significantly associated with improved 3-year relapse-free survival (RFS) (P = 0.022) and OS (P = 0.022). Proximal tumor location correlated with inferior 3-year RFS and OS (P = 0.056/0.005).ConclusionIn this series, patients who received NAC/N-CRT for cT3 and/or cN+ PUC appeared to demonstrate improved survival compared with those who underwent upfront surgery with or without ACH.     

Quality of pathologic response and surgery correlate with survival for patients with completely resected bladder cancer after neoadjuvant chemotherapy

BACKGROUND:

In a retrospective study of Southwestern Oncology Group (SWOG)‐S8710/INT‐0080 (radical cystectomy [RC] alone vs 3 cycles of neoadjuvant chemotherapy [NC] with methotrexate, vinblastine, doxorubicin, and cisplatin before RC for bladder cancer), factors found to be associated with improved overall survival (OS) included pathologic complete response, defined as P0; treatment with NC; completion of RC with negative surgical margins; and ≥10 pelvic lymph nodes (LNs) removed.

METHODS:

The authors used stratified Cox regression to retrospectively study the association of quality of pathologic response after RC with OS in the subset of S8710 patients who received NC and RC with negative surgical margins.

RESULTS:

Of 154 patients who received NC, 68 (44.2%) were <P2 (P0, Pa, P1, or carcinoma in situ [CIS]) at RC, 46 (29.9%) were P0, and the remainder had P2+ disease or did not undergo RC. In 115 patients who had RC with negative surgical margins, compared with P0 patients, those with residual Pa, P1, or CIS appeared to have worse OS (P = .054); OS was significantly worse for patients with residual P2+ disease (P = .0006). LN–positive (LN+) disease was found to be associated with worse OS than LN–negative (LN?) disease (P = .0005). Patients with LN? disease (ie, those with <10 LNs removed) appeared to have inferior OS compared with those with 10+ LNs removed (P = .079). The combination of pre‐NC clinical stage and post‐RC pathologic stage was found to be predictive of OS (P < .0001).

CONCLUSIONS:

NC and RC with negative surgical margins for bladder cancer followed by pathologic P0 and LN? disease were found to correlate with improved OS. A combination of baseline clinical stage and post‐RC pathologic stage may better predict OS. Cancer 2009. © 2009 American Cancer Society.     

背阔肌肌皮瓣在新辅助化疗后cT4局部晚期乳腺癌创面修复中的应用

目的:探讨背阔肌肌皮瓣（LDMF）在新辅助化疗（NAC）后cT4局部晚期乳腺癌（cT4-LABC）创面修复中的应用效果。方法:回顾性分析2017年12月至2020年08月间我科收治14例cT4-LABC患者，在经过抗感染和NAC达到临床获益（PR+SD）后，局部行乳腺癌根治性切除术，并即刻应用LDMF修复胸壁缺损。结果:14例患者中13例（13/14，92.9%）完成既定周期的NAC，1例仅完成2周期NAC（剔除研究）。在纳入研究的13例患者中，无CR和PD病例，PR 12例（12/13，92.31%），SD 1例（1/13，7.69%），NAC临床获益率100%（13/13）。13例患者均成功完成手术，手术时间4～6小时，术中出血200～300 mL，术后2例皮肤缺血坏死（2/13，15.38%），通过换药自行愈合，拔管后8例供区出现少量血清肿（8/13，61.54%），通过抽液、加压包扎处理后消失。随访1～36个月，中位随访22个月，1例局部复发（1/13，7.69%）、3例远处转移（3/13，23.08%）、2例死亡（2/13，15.38%），所有患者背阔肌功能良好，上肢活动基本正常。结论:cT4-LABC在保证全身治疗有效后，局部手术时应用LDMF即刻修复胸壁缺损切实可行，效果确切，值得推广。     

Oncologic feasibility of D1+ gastrectomy for patients with cT1N1, cT2N0-1, or cT3N0 gastric cancer

IntroductionD2 gastrectomy has shown a survival benefit in patients with highly advanced gastric cancer; however, it remains unclear whether D2 gastrectomy is required for patients with early-stage advanced gastric cancer or early gastric cancer with limited lymph node metastasis. This analysis aimed to clarify the oncologic feasibility of D1+ gastrectomy in patients with cT1N1, cT2N0-1, or cT3N0 gastric cancer.MethodsThis retrospective cohort analysis included 466 patients with cT1N1, cT2N0-1, or cT3N0 gastric cancer who received curative gastrectomy with either D2 or D1+ dissection. Surgical outcomes were compared between the D2 group (n = 406) and the D1+ group (n = 60).ResultsThe number of patients with higher age and higher comorbidity index was greater in the D1+ group than in the D2 group. Postoperative complications were significantly lower in the D1+ group than in the D2 group (10.0% vs. 26.8%, p = 0.004). No statistically significant difference in 5-year overall survival (p = 0.146) and disease-specific survival (p = 0.807) between the groups was noted. The incidence of local recurrences (p = 0.500) and that of lymph node recurrences (p = 1.000) were also similar between the groups. Multivariable analysis for overall survival identified age, clinical node-positive status, high Charlson score (≥3), advanced pathological stage (≥III), and postoperative complication (grade ≥ II) as independent prognostic factors. The propensity score-matched analysis showed very similar survival outcomes between the groups.ConclusionD1+ gastrectomy may be oncologically feasible for patients with cT1N1, cT2N0-1, or cT3N0 stage gastric cancer.     

Trends in neoadjuvant chemotherapy versus surgery-first in stage I HER2-positive breast cancer patients in the National Cancer DataBase (NCDB)

Background

Neoadjuvant chemotherapy (NAC) is the standard of care for locally advanced HER2?+?breast cancer (BC). Optimal sequencing of treatment (NAC vs. surgery first) is less clear cut in stage I (T1N0) HER2?+?BC, where information from surgical pathology could impact adjuvant treatment decisions. Utilizing the NCDB, we evaluated the trend of NAC use compared to upfront surgery in patients with small HER2?+?BC.

Methods

We identified NCDB female patients diagnosed with T1 N0 HER2?+?BC from 2010 through 2015. Prevalence ratios (PR) using multivariable robust Poisson regression models were calculated to measure the association between baseline characteristics and the receipt of NAC. Analysis of trends over time was denoted by annual percent change (APC) of NAC versus surgery upfront.

Results

Of the 14,949 that received chemotherapy and anti-HER2 therapy during the study period, overall 1281 (8.6%) received NAC and 13,668 (91.4%) received adjuvant treatment. Patients receiving NAC increased annually from 4.2% in 2010 to 17.3% in 2015, with the most rapid increase occurring between years 2013 (8.5%) and 2014 (14.2%). The greatest increase was seen in patients with cT1c tumors with an APC of 37.8% over the study period (95% CI 29.0, 47.3%, p?<?0.01), although a significant trend was likewise seen in patients with cT1a (APC?=?26.1%,95% CI 1.59, 56.6%), and cT1b (APC?=?27.4%, 95% CI 18.0, 37.7%) tumors. Predictors of neoadjuvant therapy receipt were age younger than 50 (PR?=?1.69, 95% CI 1.52, 1.89), Mountain/Pacific area (PR?=?1.24, 95% CI 1.05, 1.46), and estrogen receptor negativity (ER??PR?+?: PR?=?2.01, 95% CI 1.51, 2.68; ER??PR??: PR?=?1.49, 95% CI 1.32, 1.69).

Conclusions

Neoadjuvant therapy for T1 N0 HER2?+?BC increased over the study period and was mostly due increased use in clinical T1c tumors. This may be consistent with secular change in Pertuzumab treatment following FDA approval in 2013.

     

Micropapillary bladder cancer: a clinico-pathological characterization and treatment analysis

Purpose

Micropapillary bladder cancer (MPBC) is a very rare and aggressive variant of urothelial carcinoma (UC). The aim of this study was to investigate the clinico-pathological characteristics, treatment, and prognosis of MPBC to improve the understanding of this invasive disease.

Methods

We reviewed the records of 6 patients with MPBC who were evaluated and treated at our hospital between 2009 and 2015, and additionally reviewed 38 cases reported in the literature.

Results

In 44 cases, 36 cases (81.8%) were male and 8 cases (18.2%) were female, with a male:female ratio of 4.5:1; the median age of the patients was 68 years (range 45–91 years). A majority (81.8%) of patients with cT1 above or with lymph node and distant metastasis (cT2N0 in 18.2%, cT3-4N0 in 13.6%, cTanyN+ in 43.2%, and cTanyM+ in 6.8%). There was a high grade in 70.5% of patients. Lymphovascular invasion (LVI) was present in 61.4% of patients, and LVI in cT2 was more common than in cT1 (71.4 vs 22.2%). 52.3% of patients were treated with radical cystectomy (RC). After a mean follow-up of 16.2 months, 77.3% of patients developed distant metastases, and 47.7% of patients died of the disease. The mean overall survival (OS) was 28.9 months and the median OS was 20 months, and the amount of micropapillary (MPP) is correlated inversely with prognosis.

Conclusions

Micropapillary bladder cancer is a rare variant of UC associated with a poor prognosis, which often presents at an advanced stage with LVI and distant metastases. The optimal treatment strategy is early RC combined with chemotherapy.

     

Optimization of Patient Selection for Neoadjuvant Chemotherapy in Muscle-invasive Urothelial Carcinoma of the Bladder

Background

Radical cystectomy (RC) is delayed in a subset of patients who respond poorly to neoadjuvant chemotherapy (NAC). The present study investigated the clinicopathologic characteristics predicting extravesical disease at RC and the factors associated with NAC tolerability to improve patient selection and the sequence of definitive therapy.

Treatment of Metastatic Urothelial Carcinoma After Previous Cisplatin-based Chemotherapy for Localized Disease: A Retrospective Comparison of Different Chemotherapy Regimens

BackgroundOptimal chemotherapy for patients who received cisplatin for localized urothelial carcinoma (UC) and develop metastatic disease is unclear. We compared the efficacy of platinum-based (PBC) versus non–platinum-based (NPBC) first-line chemotherapy for metastasis.Patients and MethodsData were collected from the Retrospective International Study of Cancers of the Urothelial Tract (RISC), a database of 3024 patients from 28 international academic centers from 2005 to 2012. Patient inclusion criteria included: (1) predominant UC; (2) any primary tumor site; (3) cT2-4, cN0-N2, cM0; (4) prior receipt of perioperative/radiation cisplatin-containing chemotherapy; and (5) receipt of cytotoxic chemotherapy in the first-line metastatic setting. Multivariate Cox proportional hazards models were used to show progression-free survival (PFS) and overall survival (OS) from the first day of chemotherapy for metastatic disease to date of censor.ResultsEligibility criteria was met by 132 patients (n = 74 PBC; n = 58 NPBC). The median OS was 8.13 months (interquartile range, 4.87-16.64 months) and 8.77 months (interquartile range, 4.01-13.49 months) for PBC and NPBC, respectively. Neither OS (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.64-1.69; P = .87) nor PFS (HR, 0.86; 95% CI, 0.56-1.31; P = .48) differed for PBC versus NPBC. However, for patients who received chemotherapy more than a year after perioperative/radiation chemotherapy, OS was superior for PBC over NPBC (HR, 0.31; 95% CI, 0.10-0.92; P = .03).ConclusionsThere is no significant outcome difference between PBC and NPBC in patients with metastatic UC who previously received cisplatin-based chemotherapy for localized disease. However, if over a year has elapsed, return to PBC is associated with superior OS.     

Are We Overtreating Patients With T1a HER2+ Breast Cancer? An Analysis of the National Cancer Database

IntroductionThe potential benefit of systemic therapy in patients with T1a HER2+ cancers is not well understood, and no consensus guidelines exist. We sought to investigate practice patterns of chemotherapy use in this population.MethodsFrom the National Cancer Database (2013-2018), we identified female patients with HER2+ cancers staged as cT1aN0 or pT1aN0 and stratified by receipt of chemotherapy. Using univariate and multivariable analyses we assessed the clinicopathologic features associated with the receipt of chemotherapy. We also compared rates of overall survival (OS).ResultsOf 5176 women with cT1aN0 HER2+ cancers, 88 (2%) received neoadjuvant chemotherapy. Younger age and hormone-receptor (HR) negative tumors were factors independently associated with receipt of neoadjuvant chemotherapy (all P < .001). Of 11,688 women with pT1aN0 HER2+ cancers, 5,588 (48%) received adjuvant chemotherapy. Rates of use increased over the analysis period from 39% in 2013 to 53% in 2018 (P < .001). Factors independently associated with receipt of adjuvant chemotherapy included younger age, having a poorly differentiated tumor, exhibiting lymphovascular invasion, undergoing adjuvant radiation (all P < .001). There were no differences in OS when comparing those who did and did not receive chemotherapy in either group.ConclusionsThe use of chemotherapy in patients with HER2+ T1a cancers is increasing over time and is, as expected, more common among patients with unfavorable clinicopathologic features. Since no prognostic algorithm currently exists, more prospective data is needed to understand which of these patients may derive benefit from systemic therapy and which may safely avoid the morbidity of chemotherapy.     

Impact of Variant Histology on Occult Nodal Metastasis after Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: A Review of the National Cancer Database

Up to 14% of bladder urothelial carcinoma has variant histology (VH), which is associated with a higher incidence of occult regional lymph node metastasis. Neoadjuvant chemotherapy (NAC) is the gold-standard for resectable cT2-4 disease as it achieves pathologic complete response (pCR) in select patients at the time of radical cystectomy (RC). A landmark trial demonstrated chemosensitivity and pT0 status in the setting of VH. pT0N+ pathology in patients undergoing subsequent RC has prompted concerns about post-chemotherapy bladder preservation. We investigate how VH impacts pathologic primary site and nodal downstaging post-NAC. We queried the National Cancer Database for cT2-4N0M0 patients who underwent NAC and RC between 2004 and 2016. These patients were stratified into pure urothelial cell carcinoma (UCC) and VH. The rate of downstaging to ≤pT1 was analyzed, along with pN+ status. Overall survival was analyzed using the Kaplan-Meier method and multivariable Cox proportional hazards regression model. Multivariable models were adjusted for demographic and clinicopathologic variables. Of 5,335 patients, 92.1% were UCC and 7.9% VH. UCC was associated with better unadjusted survival and lower adjusted odds of being pN+ (aOR = 0.60, P < .001). Squamous cell, glandular, and sarcomatoid histologies were significantly associated with decreased adjusted odds of any pT downstage. Neuroendocrine histology (NE) trended towards increased adjusted odds of downstage to pT0N0. Patients with VH were more likely to harbor occult regional lymph node metastasis in the setting of intravesical pCR. NE had the highest pT0N0 rate, with potential implications on post-NAC bladder preservation. These findings reinforce the role of RC after NAC especially for VH.     

Response to Neoadjuvant Chemotherapy and Survival in Micropapillary Urothelial Carcinoma: Data From a Tertiary Referral Center and the Surveillance,Epidemiology, and End Results (SEER) Program

BackgroundMicropapillary urothelial carcinoma (MPC) is a rare urothelial carcinoma variant with conflicting data guiding clinical practice. In this study, we explored oncologic outcomes in relation to neoadjuvant chemotherapy (NAC) in a retrospective cohort of patients with MPC, alongside data from Surveillance, Epidemiology, and End Results (SEER)-Medicare.Patients and MethodsWe retrospectively identified patients with MPC or conventional urothelial carcinoma (CUC) without any variant histology undergoing radical cystectomy (RC) in our institution (2003-2018). SEER-Medicare was also queried to identify patients diagnosed with MPC (2004-2015). Clinicopathologic data and treatment modalities were extracted. Overall survival (OS) was estimated with the Kaplan-Meier method. Mann-Whitney-Wilcoxon and chi-square tests were used for comparative analysis and Cox regression for identifying clinical covariates associated with OS.ResultsOur institutional database yielded 46 patients with MPC and 457 with CUC. In SEER-Medicare, 183 patients with MPC were identified, and 63 (34%) underwent RC. In the institutional cohort, patients with MPC had significantly higher incidence of cN+ (17% vs. 8%), pN+ stage (30% vs. 17%), carcinoma-in-situ (43% vs. 25%), and lymphovascular invasion (30% vs. 16%) at RC versus those with CUC (all P < .05). Pathologic complete response (ypT0N0) to NAC was 33% for MPC and 35% for CUC (P = .899). Median OS was lower for institutional MPC versus CUC in univariate analysis (43.6 vs. 105.3 months, P = .006); however, MPC was not independently associated with OS in the multivariate model. Median OS was 25 months in the SEER MPC cohort for patients undergoing RC, while NAC was not associated with improved OS in that group.ConclusionPathologic response to NAC was not significantly different between MPC and CUC, while MPC histology was not an independent predictor of OS. Further studies are needed to better understand biological mechanisms behind its aggressive features as well as the role of NAC in this histology variant.     

The Impact of Postoperative Conformal Radiotherapy after Radical Surgery on Survival and Recurrence in Pathologic T3N0M0 Esophageal Carcinoma: A Propensity Score-Matched Analysis

IntroductionThe role of conformal radiotherapy (cRT) in thoracic esophageal squamous cell carcinoma (TESCC) has not been addressed in adjuvant settings. The aim of this study was to investigate whether postoperative radiotherapy using cRT after an R0 resection improves outcomes in pT3N0M0 TESCC compared with resection alone.MethodsThis study included 678 patients with pT3N0M0 TESCC who were treated at the Cancer Hospital, Chinese Academy of Medical Sciences, from January 2004 to December 2011. The patients were divided into two groups: a surgery plus cRT group (S+cRT group) comprising patients who underwent cRT after an R0 resection and a surgery group (S group), comprising a control group of patients who underwent an R0 resection alone. Propensity score matching was used to create patient groups that were balanced across several covariates (n = 83 in each group). Outcome measures included overall survival (OS), disease-free survival (DFS), and recurrence.ResultsIn the overall study cohort, 5-year OS (75.2% versus 58.5%, p = 0.004) and DFS (71.8% versus 49.2%, p = 0.001) rates were significantly higher in the S+cRT group than in the S group. These data were confirmed in the matched samples (5-year OS, 75.7% versus 58.8% [p = 0.017]; DFS, 71.7% versus 50.3% [p = 0.009]). The overall (p = 0.001) and locoregional (p = 0.004) recurrence rates in the S+cRT group were significantly lower than in the S group. Multivariate Cox analyses in the matched samples revealed that surgery and postoperative cRT were independently associated with longer OS (hazard ratio = 0.505, 95% confidence interval: 0.291–0.876, p = 0.015) and longer DFS (hazard ratio = 0.513, 95% confidence interval: 0.309–0.854, p = 0.010) than resection alone.ConclusionsPostoperative radiotherapy using cRT is strongly associated with improved OS and DFS in patients with pT3N0M0 TESCC. A multicenter, randomized phase III clinical trial is warranted to confirm these findings.