The impact of total retrieved lymph nodes on staging and survival of patients with pT3 gastric cancer

BACKGROUND.

The incidence of lymph node metastasis is high in patients who have pT3 gastric cancer. However, the impact of total retrieved lymph nodes (tLNs) on staging and survival of these patients is not clear.

METHODS.

For this study, the authors examined 1895 patients with pT3 gastric cancer who underwent surgery at Yonsei University Medical College from January 1987 to June 2000.

RESULTS.

Four hundred sixty of 1895 patients (24.3%) were diagnosed with pT3N0 gastric cancer. Patients who had < 31 tLNs (25th percentile) had less advanced lymph node (N) stage than the other patients (P < .001). Lymph node metastasis had a positive association with the number of tLNs in a logistic regression analysis (P < .001; hazards ratio, 1.014; 95% confidence interval, 1.006–1.021). With a median follow‐up of 61.1 months, the overall 10‐year survival rate (10‐YSR) was 42.8%. Patients with pT3N0 disease who had < 31 tLNs had a 10‐YSR of only 55.4%. Although this 10‐YSR did not differ significantly from the rate for patients with N0 disease who had ≥31 tLNs (65.8%; P = .108), it approached the rate for the N1 group (53.3%; P = .207). In multivariable analyses, the number of tLNs emerged as an independent prognostic predictor in patients with pT3N2 and pT3N3 disease, but not in patients with pT3N0 or pT3N1 disease.

CONCLUSIONS.

Increasing numbers of tLNs may improve the accuracy of staging in patients who have pT3 gastric cancer. Because preoperative lymph node staging is difficult, a thorough lymph node dissection is mandatory in all serosa‐positive patients. Cancer 2007. © 2007 American Cancer Society.     

A phase 2 clinical trial of sequential neoadjuvant chemotherapy with ifosfamide,doxorubicin, and gemcitabine followed by cisplatin,gemcitabine, and ifosfamide in locally advanced urothelial cancer

BACKGROUND:

Neoadjuvant chemotherapy improves the survival of patients with high‐risk urothelial cancer. However, the lack of curative alternatives to cisplatin‐based chemotherapy is limiting for patients with neuropathy or hearing loss. Sequential chemotherapy also has not been well studied in the neoadjuvant setting. The authors explored sequential neoadjuvant ifosfamide‐based chemotherapy in a patient cohort at high risk of noncurative cystectomy.

METHODS:

Patients with muscle‐invasive cancer and lymphovascular invasion, hydronephrosis, clinical T3b and T4a (cT3b‐4a) disease (defined as a 3‐dimensional mass on examination under anesthetic or invasion into local organs), micropapillary tumors, or upper tract disease received 3 cycles of combined ifosfamide, doxorubicin, and gemcitabine followed by 4 cycles of combined cisplatin, gemcitabine, and ifosfamide. The primary endpoint was downstaging to pT1N0M0 disease or lower.

RESULTS:

At a median follow‐up of 85.3 months, the 5‐year overall survival (OS) and disease‐specific survival (DSS) rates for all 65 patients were 63% and 68%, respectively (95% confidence interval: 5‐year OS rate, 0.52%‐0.76%; 5‐year DSS rate, 0.58%‐0.81%). Pathologic downstaging to pT1N0 disease or lower occurred in 50% of patients who underwent cystectomy and in 60% of patients who underwent nephroureterectomy and was correlated with the 5‐year OS rate (pT1N0 disease or lower, 87%; pT2‐pT3aN0 disease, 67%; and pT3b disease or higher or lymph node‐negative disease, 27%; P ≤ .001 for pT1 or lower vs pT2 or higher). Variant histology was associated with an inferior 5‐year DSS rate (50% vs 83% in pure transitional cell carcinoma; P = .02). The most frequent grade 3 toxicities were infection (38%), febrile neutropenia (22%), and mucositis (18%). There were 3 grade 4 toxicities (myocardial infarction, thrombocytopenia, and vomiting) and 1 grade 5 toxicity in a patient who refused antibiotics for pneumonia.

CONCLUSIONS:

Sequential therapy was active and maintained the historic expectation of achieving a cure. The current results strongly reinforced previous experience suggesting that pathologic downstaging to pT1N0 disease or less is a useful surrogate for eventual cure in patients with urothelial cancer. Cancer 2013. © 2012 American Cancer Society.     

The association between extent of lymphadenectomy and survival among patients with lymph node metastases undergoing radical cystectomy

BACKGROUND.

Long‐term survival in patients with lymph node‐positive bladder cancer who undergo cystectomy suggests a therapeutic role for lymphadenectomy. The objective of this study was to describe the association between extent of lymphadenectomy and survival in lymph node‐positive patients who underwent radical cystectomy.

METHODS.

The cohort consisted of patients from the Surveillance, Epidemiology, and End Results registry with transitional cell carcinoma who underwent cystectomy with lymphadenectomy and had at least 1 positive lymph node and no distant metastases. The Kaplan‐Meier method and multivariate Cox proportional‐hazards regression analyses were used to estimate differences in survival among different lymphadenectomy variables.

RESULTS.

In total, 1260 patients had at least 1 positive lymph node. A median of 9 lymph nodes were removed (range, 1–48 lymph nodes) with a median of 2 positive lymph nodes (range, 1–18 positive lymph nodes), and the median lymph node density was 22%. In multivariate analysis controlling for patient demographics, tumor classification, and year of diagnosis, the number of positive and total lymph nodes removed remained independent predictors of survival. There was an inverse association between the number of lymph nodes removed and the risk of death for all quartiles. Removal of > 10 lymph nodes was associated with increased overall survival (hazard ratio, 0.52; 95% confidence interval, 0.43–0.64). In addition, with a lymph node density from 0.1% to 12.5% as the referent group, each higher quartile experienced worse survival.

CONCLUSIONS.

An increased number of lymph nodes removed at the time of cystectomy was associated with improved survival in patients with lymph node‐positive bladder cancer. Improved survival was observed at a lower lymph node density threshold than previously reported. The current findings support performing a more extensive lymphadenectomy at the time of cystectomy. Cancer 2008. © 2008 American Cancer Society.     

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.     

Conditional survival in patients with pancreatic ductal adenocarcinoma resected with curative intent

BACKGROUND:

Prognosis after surgery for pancreatic ductal adenocarcinoma (PDAC) is typically reported from the date of surgery. Survival estimates, however, are dynamic and may change based on the time already survived. The authors sought to assess conditional survival among a large cohort of patients who underwent resection of PDAC.

METHODS:

Between 1970 and 2008, 1822 patients who underwent resection for PDAC with curative intent were identified. Kaplan‐Meier and Cox regression analyses were performed to validate established predictors of survival, and results were compared with 2‐year conditional survival.

RESULTS:

Actuarial survival was 18% at 5 years, with a median survival of 18 months. Multivariate analysis revealed that tumor size, lymph node ratio, and positive margins were associated with worse survival (all P < .001). Differences in actuarial versus conditional survival estimates were greater the more years already survived by the patient. The 2‐year conditional survival at 3 years—the probability of surviving to postoperative year 5 given that the patient had already survived 3 years—was 66% versus a 5‐year actuarial survival calculated from the time of surgery of 18%. Stratification of 2‐year conditional survival by lymph node ratio and margin status revealed that patients with high lymph node ratio or positive margins saw the greatest increase in 2‐year conditional survival as more time elapsed (both P ≤ .01).

CONCLUSIONS:

Differences in actuarial versus conditional survival estimates were more pronounced based on the additional years already survived by the patient. Conditional survival may be a helpful tool in counseling patients with PDAC, as it is a more accurate assessment of future survival for those patients who have already survived a certain amount of time. Cancer 2011. © 2011 American Cancer Society.     

Effect of a minimum lymph node policy in radical cystectomy and pelvic lymphadenectomy on lymph node yields,lymph node positivity rates,lymph node density,and survivorship in patients with bladder cancer

BACKGROUND:

Extended pelvic lymphadenectomy (PLND) during radical cystectomy (RC) reportedly improves bladder cancer‐specific survival. Lymph node counts are often a proxy for the extensiveness of a dissection. In the current study, the impact of an institutional policy requiring a minimum number of lymph nodes was assessed.

METHODS:

Patients undergoing RC and PLND for invasive bladder cancer between March 2000 and February 2008 were retrospectively reviewed at the study institution. Beginning March 1, 2004, a policy was established that at least 16 lymph nodes had to be examined. Specimens with <16 lymph nodes were resubmitted (including any fat) to detect additional lymph nodes. Lymph node yields, lymph node positivity, lymph node density (LND), and survivorship before and after policy implementation were compared.

RESULTS:

A total of 147 patients underwent surgery 4 years before policy implementation and 202 underwent surgery 4 years after. The median number of lymph nodes increased from 15 to 20. Percentage of cases with ≥16 lymph nodes increased from 42.9% to 69.3% (P <.01). The lymph node positivity rates did not change significantly, but the proportion of patients with LND <20% increased from 43.9% to 65.5% (P = .04). Overall survival increased from 41.5% to 72.3% (P <.01). Univariate and multivariate regression demonstrated that policy implementation, and subsequent increase in median lymph node yield, decreased mortality risk by 30% (hazards ratio [HR], 0.70; P = .04) and 48% (HR, 0.52; P = .01), respectively.

CONCLUSIONS:

Thorough evaluation of PLND specimens obtained at RC can be influenced by an institutional policy mandating a minimum number of lymph nodes. This could lead to greater confidence in pathologic staging and reliability of LND as a predictor of prognosis. Survival can improve due to increased awareness to perform a more thorough PLND. Cancer 2010. © 2010 American Cancer Society.     

Cost‐effectiveness analysis of immediate radical cystectomy versus intravesical Bacillus Calmette‐Guerin therapy for high‐risk,high‐grade (T1G3) bladder cancer

BACKGROUND:

Although both radical cystectomy and intravesical immunotherapy are initial treatment options for high‐risk, T1, grade 3 (T1G3) bladder cancer, controversy regarding the optimal strategy persists. Because bladder cancer is the most expensive malignancy to treat per patient, decisions regarding the optimal treatment strategy should consider costs.

METHODS:

A Markov Monte‐Carlo cost‐effectiveness model was created to simulate the outcomes of a cohort of patients with incident, high‐risk, T1G3 bladder cancer. Treatment options included immediate cystectomy and conservative therapy with intravesical Bacillus Calmette‐Guerin (BCG). The base case was a man aged 60 years. Parameter uncertainty was assessed with probabilistic sensitivity analyses. Scenario analyses were used to explore the 2 strategies among patients stratified by age and comorbidity.

RESULTS:

The quality‐adjusted survival with immediate cystectomy and BCG therapy was 9.46 quality‐adjusted life years (QALYs) and 9.39 QALYs, respectively. The corresponding mean per‐patient discounted lifetime costs (in 2005 Canadian dollars) were $37,600 and $42,400, respectively. At a willingness‐to‐pay threshold of $50,000 per QALY, the probability that immediate cystectomy was cost‐effective was 67%. Immediate cystectomy was the dominant (more effective and less expensive) therapy for patients aged <60 years, whereas BCG therapy was dominant for patients aged >75 years. With increasing comorbidity, BCG therapy was dominant at lower age thresholds.

CONCLUSIONS:

Compared with BCG therapy, immediate radical cystectomy for average patients with high‐risk, T1G3 bladder cancer yielded better health outcomes and lower costs. Tailoring therapy based on patient age and comorbidity may increase survival while yielding significant cost‐savings for the healthcare system. Cancer 2009. © 2009 American Cancer Society.     

Clinical benefits of a multivariate prediction model for bladder cancer

BACKGROUND:

It has been demonstrated that multivariate prediction models predict cancer outcomes more accurately than cancer stage; however, the effects of these models on clinical management are unclear. The objective of the current study was to determine whether a previously published multivariate prediction model for bladder cancer (“bladder nomogram”) improved medical decision making when referral for adjuvant chemotherapy was used as a model.

METHODS:

Data were analyzed from an international cohort study of 4462 patients who underwent cystectomy without chemotherapy from 1969 to 2004. The number of patients eligible for chemotherapy was determined using pathologic stage criteria (lymph node‐positive disease or pathologic T3 [pT3] or pT4 tumor classification) and for 3 cutoff levels on the bladder nomogram (10%, 25%, and 70% risk of recurrence with surgery alone). The number of recurrences was calculated by applying a relative risk reduction to the baseline risk among eligible patients. Clinical net benefit was then calculated by combining recurrences and treatments and weighting the latter by a factor related to drug tolerability.

RESULTS:

A nomogram cutoff outperformed pathologic stage for chemotherapy in every scenario of drug effectiveness and tolerability. For a drug with a relative risk of 0.80, with which clinicians would treat ≤20 patients to prevent 1 recurrence, use of the nomogram was equivalent to a strategy that resulted in 60 fewer chemotherapy treatments per 1000 patients without any increase in recurrence rates.

CONCLUSIONS:

The authors concluded that referring patients who undergo cystectomy to adjuvant chemotherapy on the basis of a multivariate model is likely to lead to better patient outcomes than the use of pathologic stage. Further research is warranted to evaluate the clinical effects of multivariate prediction models. Cancer 2009. © 2009 American Cancer Society.     

Nomograms provide improved accuracy for predicting survival after radical cystectomy.

AIMS: To develop multivariate nomograms that determine the probabilities of all-cause and bladder cancer-specific survival after radical cystectomy and to compare their predictive accuracy to that of American Joint Committee on Cancer (AJCC) staging. METHODS: We used Cox proportional hazards regression analyses to model variables of 731 consecutive patients treated with radical cystectomy and bilateral pelvic lymphadenectomy for bladder transitional cell carcinoma. Variables included age of patient, gender, pathologic stage (pT), pathologic grade, carcinoma in situ, lymphovascular invasion (LVI), lymph node status (pN), neoadjuvant chemotherapy (NACH), adjuvant chemotherapy (ACH), and adjuvant external beam radiotherapy (AXRT). Two hundred bootstrap resamples were used to reduce overfit bias and for internal validation. RESULTS: During a mean follow-up of 36.4 months, 290 of 731 (39.7%) patients died; 196 of 290 patients (67.6%) died of bladder cancer. Actuarial all-cause survival estimates were 56.3% [95% confidence interval (95% CI), 51.8-60.6%] and 42.9% (95% CI, 37.3-48.4%) at 5 and 8 years after cystectomy, respectively. Actuarial cancer-specific survival estimates were 67.3% (62.9-71.3%) and 58.7% (52.7-64.2%) at 5 and 8 years, respectively. The accuracy of a nomogram for prediction of all-cause survival (0.732) that included patient age, pT, pN, LVI, NACH, ACH, and AXRT was significantly superior (P=0.001) to that of AJCC staging-based risk grouping (0.615). Similarly, the accuracy of a nomogram for prediction of cancer-specific survival that included pT, pN, LVI, NACH, and AXRT (0.791) was significantly superior (P=0.001) to that of AJCC staging-based risk grouping (0.663). CONCLUSIONS: Multivariate nomograms provide a more accurate and relevant individualized prediction of survival after cystectomy compared with conventional prediction models, thereby allowing for improved patient counseling and treatment selection.     

Age-adjusted Charlson comorbidity score is associated with treatment decisions and clinical outcomes for patients undergoing radical cystectomy for bladder cancer

BACKGROUND.

By using the age‐adjusted Charlson comorbidity index (ACCI), the authors characterized the impact of age and comorbidity on disease progression and overall survival after radical cystectomy (RC) for transitional cell carcinoma of the bladder. Also evaluated was whether ACCI was associated with clinicopathologic and treatment characteristics.

METHODS.

The authors evaluated 1121 patients treated by RC for transitional cell carcinoma of the bladder at a single institution (1990–2004). Logistic regression was used to determine the relation between ACCI and clinical features. They evaluated the association between ACCI and overall and progression‐free survival by using multivariate survival‐time models with pathologic stage and nodal status as covariates.

RESULTS.

ACCI scores increased during the study period (P = .009). Extravesical disease was present in 43% of patients with ACCI ≤2, 49% with ACCI 3–5, and 56% with ACCI >5 (P = .051). Despite their higher prevalence of extravesical disease, patients with higher ACCI were less likely to have lymph‐node dissection (odds ratio, 0.55 and 0.35, respectively, for ACCI 3–5 and >5 vs ≤2; P = .005), and when it was performed, fewer lymph nodes were evaluated (P < .0005). Patients with higher ACCI were also less likely to have postoperative chemotherapy (odds ratio, 0.70 and 0.66, respectively, for ACCI 3–5 and >5 vs ≤2; P = .04). Higher ACCI was significantly associated with lower overall (P < .005) but not recurrence‐free (P = .17) survival after RC.

CONCLUSIONS.

Age and comorbidity among patients who underwent RC at a cancer referral hospital increased with time. Both age and comorbidity were associated with treatment selection and survival and should, therefore, be considered when comparing outcomes after RC. Cancer 2008. © 2008 American Cancer Society.     

Cytologically proven axillary lymph node metastases are eradicated in patients receiving preoperative chemotherapy with concurrent trastuzumab for HER2‐positive breast cancer

BACKGROUND:

The axillary pathologic complete response rate (pCR) and the effect of axillary pCR on disease‐free survival (DFS) was determined in patients with HER2‐positive breast cancer and biopsy‐proven axillary lymph node metastases who were receiving concurrent trastuzumab and neoadjuvant chemotherapy. The use of neoadjuvant chemotherapy is reported to result in pCR in the breast and axilla in up to 25% of patients. Patients achieving a pCR have improved DFS and overall survival. To the authors' knowledge, the rate of eradication of biopsy‐proven axillary lymph node metastases with trastuzumab‐containing neoadjuvant chemotherapy regimens has not been previously reported.

METHODS:

Records were reviewed of 109 consecutive patients with HER2‐positive breast cancer and axillary metastases confirmed by ultrasound‐guided fine‐needle aspiration biopsy who received trastuzumab‐containing neoadjuvant chemotherapy followed by breast surgery with complete axillary lymph node dissection. Survival was evaluated by the Kaplan‐Meier method. Clinicopathologic factors and DFS were compared between patients with and without axillary pCR.

RESULTS:

Eighty‐one patients (74%) achieved a pCR in the axilla. Axillary pCR was not associated with age, estrogen receptor status, grade, tumor size, initial N classification, or median number of lymph nodes removed. More patients with an axillary pCR also achieved a pCR in the breast (78% vs 25%; P < .001). At a median follow‐up of 29.1 months, DFS was significantly greater in the axillary pCR group (P = .02).

CONCLUSIONS:

Trastuzumab‐containing neoadjuvant chemotherapy appears to be effective in eradicating axillary lymph node metastases in the majority of patients treated. Patients who achieve an axillary pCR are reported to have improved DFS. The success of pCR with concurrent trastuzumab and chemotherapy in eradicating lymph node metastases has implications for surgical management of the axilla in these patients. Cancer 2010. © 2010 American Cancer Society.     

Natural history of surgically treated bladder carcinoma with extravesical tumor extension

BACKGROUND: The current TNM classification for bladder carcinoma stratifies extravesical extension into microscopic (pT3a) and macroscopic (pT3b) tumor involvement. The authors evaluated the outcomes of patients with pT3a and pT3b disease after radical cystectomy. METHODS: Patients (n = 129) with transitional cell carcinoma of the bladder treated with radical cystectomy alone demonstrated pathologic extravesical tumor extension: 37 (29%) had pT3a disease and 92 (71%) had pT3b disease. No patient received any adjuvant therapy. With a median follow-up of 13.6 years, the presence of lymph node involvement, margin positivity, local (pelvic) and distant disease recurrence, and clinical outcomes were determined. RESULTS: Of the 129 patients, 43 (33%) had lymph node tumor involvement: 13 of 37 patients with pT3a disease (35%) and 30 of 92 patients with pT3b disease (33%). The 10-year recurrence-free and overall survival for the entire group was 54% and 20%, respectively. No statistical difference between pT3a and pT3b disease was observed with regard to recurrence-free (P = 0.54) and overall (P = 0.66) survival. Lymph node involvement was predictive of a significantly worse 10-year recurrence-free survival (32%) compared with lymph node-negative disease (60%; P = 0.003). Local disease recurrence was reported to occur in 12 patients (9%), whereas 37 patients (29%) were reported to develop distant metastases. Among those who had disease recurrence, the type of disease recurrence (local or distant) was not found to be associated with tumor stage (pT3a vs, pT3b, P = 0.47). CONCLUSIONS: This cohort of surgically managed patients provided insight into the long-term natural history of pathologically confirmed extravesical bladder carcinoma after radical cystectomy. There was no important difference in the incidence of lymph node involvement, survival rates, and disease recurrence rates between patients with microscopic and macroscopic extravesical extension. Adjuvant protocols should be undertaken for these high-risk patients to further improve on these clinical outcomes.     

Depth of invasion determines the postresectional prognosis for patients with T1 extrahepatic cholangiocarcinoma

BACKGROUND:

We tested the hypothesis that in patients with T1 extrahepatic cholangiocarcinoma (EHC), prognosis postresection is significantly different for those with tumors that are limited to the mucosa than for those with tumors that have invaded (but not penetrated) the fibromuscular layer.

METHODS:

A retrospective analysis was conducted of 33 consecutive patients with pathologic T1 (pT1) EHC tumors. According to the depth of invasion, the pT1 tumors were divided into 2 groups: Group 1, tumors that were limited to the mucosa (mucosal tumors); and Group 2, tumors that had invaded (but not penetrated) the fibromuscular layer (fibromuscular layer‐invasive tumors). Long‐term outcomes after resection were compared between the 2 groups for a median follow‐up time of 175 months.

RESULTS:

Eighteen patients had mucosal tumors and 15 patients had tumors that had invaded the fibromuscular layer. None of the patients with mucosal tumors had lymphovascular invasion, whereas 3 of the patients with fibromuscular layer‐invasive tumors had lymphovascular invasion (P = .083). Overall survival after resection was better in Group 1 than in Group 2 (cumulative 10‐year survival rate, 100% vs 52%; P = .024). The rate of disease‐free survival after resection was higher in Group 1 than in Group 2 (cumulative disease‐free 10‐year survival rate, 100% vs 56%; P = .022).

CONCLUSIONS:

The long‐term outcome after resection for EHC is significantly better for patients with mucosal tumors than for patients with fibromuscular layer‐invasive tumors. This suggests that the depth of tumor invasion affects the postresection prognosis for patients with pT1 EHC. Cancer 2010. © 2010 American Cancer Society.     

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.     

A population‐based competing‐risks analysis of the survival of patients treated with radical cystectomy for bladder cancer

BACKGROUND.

Patients treated with radical cystectomy represent a very heterogeneous group with respect to cancer‐specific and other‐cause mortality. Comorbidities and comorbidity‐associated events represent very important causes of mortality in those individuals. The authors examined the rates of cancer‐specific and other‐cause mortality in a population‐based radical cystectomy cohort.

METHODS.

The authors identified 11,260 patients treated with radical cystectomy for urothelial carcinoma of the urinary bladder between 1988 and 2006 within 17 Surveillance, Epidemiology, and End Results registries. Patients were stratified into 20 strata according to patient age and tumor stage at radical cystectomy. Smoothed Poisson regression models were fitted to obtain estimates of cancer‐specific and other‐cause mortality rates at specific time points after radical cystectomy.

RESULTS.

After stratification according to disease stage and patient age, cancer‐specific mortality emerged as the main cause of mortality in all patient strata. Nonetheless, at 5 years after radical cystectomy, between 8.5% and 27.1% of deaths were attributable to other‐cause mortality. The 3 most common causes of other‐cause mortality were other malignancies, heart disease, and chronic obstructive pulmonary disease. The most prominent effect on cancer‐specific mortality was exerted by locally advanced bladder cancer stages. Conversely, age was the main determinant of other‐cause mortality. Interestingly, even after adjusting for bladder cancer pathologic stage, cancer‐specific mortality was higher in older individuals than their younger counterparts.

CONCLUSIONS.

The current study provides a valuable graphical aid for prediction of cancer‐specific and other‐cause mortality according to disease stage and patient age. It can help clinicians to better stratify the risk‐benefit ratio of radical cystectomy. Hopefully, these findings will be considered in treatment decision making and during informed consent before radical cystectomy. Cancer 2011. © 2010 American Cancer Society.     

Evaluation of the use of prophylactic cranial irradiation in small cell lung cancer

BACKGROUND:

Prophylactic cranial irradiation has been used in patients with small cell lung cancer to reduce the incidence of brain metastasis after primary therapy. The purpose of this study was to evaluate the effects of prophylactic cranial irradiation (PCI) on overall survival and cause‐specific survival.

METHODS:

A total of 7995 patients with limited stage small cell lung cancer diagnosed between 1988 and 1997 were retrospectively identified from centers participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. Of them, 670 were identified as having received PCI as a component of their first course of therapy. Overall survival and cause‐specific survival were estimated by the Kaplan‐Meier method, comparing patients treated with or without prophylactic whole‐brain radiotherapy. The Cox proportional hazards model was used in the multivariate analysis to evaluate potential prognostic factors.

RESULTS:

The median follow‐up time was 13 months (range, 1 month to 180 months). Overall survival at 2 years, 5 years, and 10 years was 23%, 11%, and 6%, respectively, in patients who did not receive PCI. In patients who received PCI, the 2‐year, 5‐year, and 10‐year overall survival rates were 42%, 19%, and 9%, respectively (P = <.001). The cause‐specific survival rate at 2 years, 5 years, and 10 years was 28%, 15%, 11%, respectively, in patients who did not receive PCI and 45%, 24%, 17%, respectively, in patients who did receive PCI (P = <.001). On multivariate analysis of cause‐specific and overall survival, age at diagnosis, sex, grade, extent of primary disease, size of disease, extent of lymph node involvement, and PCI were found to be significant (P = <.001). The hazards ratios for disease‐specific and all cause mortality were 1.13 and 1.11, respectively, for those not receiving PCI.

CONCLUSIONS:

Significantly improved overall and cause‐specific survival was observed in patients treated with prophylactic cranial irradiation on unadjusted and adjusted analyses. This study concurs with the previously published European experience. Prophylactic cranial irradiation should be considered for patients with limited stage small cell lung cancer. Cancer 2009. © 2008 American Cancer Society.     

Favorable prognosis in patients with T1a/T1bN0 triple-negative breast cancers treated with multimodality therapy

BACKGROUND:

The authors evaluated the clinical characteristics, natural history, and outcomes of patients who had ≤1 cm, lymph node‐negative, triple‐negative breast cancer (TNBC).

METHODS:

After excluding patients who had received neoadjuvant therapy, 1022 patients with TNBC who underwent definitive breast surgery during 1999 to 2006 were identified from an institutional database. In total, 194 who had lymph node‐negative tumors that measured ≤1 cm comprised the study population. Clinical data were abstracted, and survival outcomes were analyzed.

RESULTS:

The median follow‐up was 73 months (range, 5‐143 months). The median age at diagnosis was 55.5 years (range, 27‐84 years). Tumor (T) classification was microscopic (T1mic) in 16 patients (8.2%), T1a in 49 patients (25.3%), and T1b in 129 patients (66.5%). Most tumors were poorly differentiated (n = 142; 73%), lacked lymphovascular invasion (n = 170; 87.6%), and were detected by screening (n = 134; 69%). In total, 129 patients (66.5%) underwent breast‐conserving surgery, and 65 patients (33.5%) underwent mastectomy. One hundred thirteen patients (58%) received adjuvant chemotherapy, and 123 patients (63%) received whole‐breast radiation. The patients who received chemotherapy had more adverse clinical and disease features (younger age, T1b tumor, poor tumor grade; all P < .05). Results from testing for the breast cancer (BRCA) susceptibility gene were available for 49 women: 19 women had BRCA1 mutations, 7 women had BRCA2 mutations, and 23 women had no mutations. For the entire group, the 5‐year local recurrence‐free survival rate was 95%, and the 5‐year distant metastasis‐free survival rate was 95%. There was no difference between patients with T1mic/T1a tumors and patients with T1b tumors in the distant recurrence rate (94.5% vs 95.5%, respectively; P = .81) or in the receipt of chemotherapy (95.9% vs 94.5%, respectively; P = .63).

CONCLUSIONS:

Excellent 5‐year locoregional and distant control rates were achievable in patients with TNBC who had tumors ≤1.0 cm, 58% of whom received chemotherapy. These results identified a group of patients with TNBC who had favorable outcomes after early detection and multimodality treatment. Cancer 2012. © 2012 American Cancer Society.     

Predicting the survival of bladder carcinoma patients treated with radical cystectomy

BACKGROUND: Clinical outcomes vary for patients treated with radical cystectomy. The authors sought to identify factors associated with the survival of patients treated with radical cystectomy for urothelial carcinoma of the urinary bladder. METHODS: The authors studied 218 patients treated with radical cystectomy for urothelial carcinoma between 1980 to 1984. Patient ages ranged from 41 to 78 years (mean, 64 years). Using the 1997 TNM system, T classifications were Ta (17 patients), T1 (44), T2 (71), T3a (42), T3b (14), T4a (28), and T4b (2). Thirty-two patients had lymph node metastasis at the time of surgery. Histologic grade was determined according to the newly proposed World Health Organization and International Society of Urological Pathology grading system; tumor was low grade in 43 patients and high grade in 175. The male-to-female ratio was 4.9 to 1. The mean follow-up of patients still alive was 13.1 years (median, 13.8 years; range, 30 days to 18 years). Cox proportional hazards models were used to determine the impact of numerous clinical and pathologic findings on survival. RESULTS: Ten-year local recurrence free, distant metastasis free, cancer specific, and all-cause survival were 71%, 73%, 67%, and 41%, respectively. In univariate analysis, cancer size, T classification, and lymph node status were associated with distant metastasis free, cancer specific, and all-cause survival. Histologic grade and surgical margin status were significantly associated with worse cancer specific and all-cause survival, but not with distant metastasis free survival. In multivariate analysis, cancer size, margin status, T classification, and lymph node status were identified as significantly associated with cancer specific survival after adjustment for age and gender. CONCLUSIONS: Long term survival is achieved in a significant number of patients treated with radical cystectomy. In this study, patients with organ-confined (< or = pT2) and small size (< or = 3 cm) cancer had favorable 10-year distant metastasis free (93%) and cancer specific survival (88%) after cystectomy. Tumor size, margin status, extravesical involvement, and lymph node metastasis are important pathologic factors and should be considered as stratification variables in identifying patients for whom adjuvant chemotherapy should be evaluated in clinical trials.     

Cancer of the esophagus and esophagogastric junction

BACKGROUND:

Previous American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) stage groupings for esophageal cancer have not been data driven or harmonized with stomach cancer. At the request of the AJCC, worldwide data from 3 continents were assembled to develop data‐driven, harmonized esophageal staging for the seventh edition of the AJCC/UICC cancer staging manuals.

METHODS:

All‐cause mortality among 4627 patients with esophageal and esophagogastric junction cancer who underwent surgery alone (no preoperative or postoperative adjuvant therapy) was analyzed by using novel random forest methodology to produce stage groups for which survival was monotonically decreasing, distinctive, and homogeneous.

RESULTS:

For lymph node‐negative pN0M0 cancers, risk‐adjusted 5‐year survival was dominated by pathologic tumor classification (pT) but was modulated by histopathologic cell type, histologic grade, and location. For lymph node‐positive, pN+M0 cancers, the number of cancer‐positive lymph nodes (a new pN classification) dominated survival. Resulting stage groupings departed from a simple, logical arrangement of TNM. Stage groupings for stage I and II adenocarcinoma were based on pT, pN, and histologic grade; and groupings for squamous cell carcinoma were based on pT, pN, histologic grade, and location. Stage III was similar for histopathologic cell types and was based only on pT and pN. Stage 0 and stage IV, by definition, were categorized as tumor in situ (Tis) (high‐grade dysplasia) and pM1, respectively.

CONCLUSIONS:

The prognosis for patients with esophageal and esophagogastric junction cancer depends on the complex interplay of TNM classifications as well as nonanatomic factors, including histopathologic cell type, histologic grade, and cancer location. These features were incorporated into a data‐driven staging of these cancers for the seventh edition of the AJCC/UICC cancer staging manuals. Cancer 2010. © 2010 American Cancer Society.     

Post-therapy pathologic stage and survival in patients with pancreatic ductal adenocarcinoma treated with neoadjuvant chemoradiation

BACKGROUND:

Neoadjuvant chemoradiation before surgery is an emerging treatment modality for pancreatic ductal adenocarcinoma (PDAC). However, analysis of prognostic factors is limited for patients with PDAC treated with neoadjuvant chemoradiation and pancreaticoduodenectomy (PD).

METHODS:

The study population was comprised of 240 consecutive patients with PDAC who received neoadjuvant chemoradiation and PD and was compared with 60 patients who had no neoadjuvant therapy between 1999 and 2007. Clinicopathologic features were correlated with disease‐free survival (DFS) and overall survival (OS).

RESULTS:

Among the 240 treated patients, the 1‐year and 3‐year DFS rates were 52% and 32%, with a median DFS of 15.1 months. The 1‐year and 3‐year OS rates were 95% and 47%, with a median OS of 33.5 months. By univariate analysis, DFS was associated with age, post‐therapy tumor stage (ypT), lymph node status (ypN), number of positive lymph nodes, and American Joint Committee on Cancer (AJCC) stage, whereas OS was associated with intraoperative blood loss, margin status, ypT, ypN, number of positive lymph nodes, and AJCC stage. By multivariate analysis, DFS was independently associated with age, number of positive lymph nodes, and AJCC stage, and OS was independently associated with differentiation, margin status, number of positive lymph nodes, and AJCC stage. In addition, the treated patients had better OS and lower frequency of lymph node metastasis than those who had no neoadjuvant therapy.

CONCLUSIONS:

In patients with PDAC who received neoadjuvant chemoradiation and subsequent PD, post‐therapy pathologic AJCC stage and number of positive lymph nodes are independent prognostic factors. Cancer 2012. © 2011 American Cancer Society.