Use Of Chemotherapy In Stage Research Articles

A comparison of chemotherapy use in stage IV pancreatic cancer.

257 Background: Palliative chemotherapy is the standard of care for stage IV pancreatic cancer patients (SFPC). Methods: This study compares the amount of chemotherapy given for SFPC across insurance types using the National Cancer Database (NCDB), which contains 70% of U.S. cancer cases. Results: The NCDB reported 115,512 patients diagnosed with SFPC from 2000 to 2009. Overall, 38.3% of SFPC patients received chemotherapy. The VAH (28.3%) and Medicare (29.7%) provided significantly less chemotherapy to SFPC patients as compared to Managed Care (48.2%), Private Insurance (46.7%), Tricare/Military (42.8%), Medicaid (37.8%), Medicare Plus Supplement (35.5%), and Uninsured (34.4%). From 2000 to 2009, the rate of chemotherapy for SFPC increased for both VAH (22.9% to 34.3%) and non-VAH (31.1% to 44.1%). At time of diagnosis, the percent of patients less than 60 at the VAH was 32%, non-VAH was 25.5% and Medicare was 7%. From age 20 to 59, the rate of chemo was stable at approximately 49%, but each successive decade demonstrated a marked reduction in use of chemotherapy (from 44% for 60 to 69 years of age to 21% for 80 to 89 and 5% for >90). The VAH PC population diagnosed with PC included 71.1% whites (W), 21.1% blacks (B), 4.8% Hispanics (H), 0.8% Asian-Pacific Islander (API), and 0.6% Native American (NA). Among all insurance types, only Medicaid (25%* B, 14%* H, 6%* API) and Uninsured (20% B, 15%* H, 4%* API) had a greater percentage of minorities. Compared to the average of all patients treated for SFPC (38.3%), blacks (34.7%*) and Hispanics (35.7%*) received less chemotherapy and whites received more (39.1%*). Conclusions: This is the largest study to analyze the use of chemotherapy in stage IV pancreatic cancer. Patients treated within the VAH were less likely to receive chemotherapy compared to all other patients except those with Medicare, who tend to be older at time of diagnosis. As age increases above 59, chemotherapy treatment for SFPC decreases. VAH patients receive less chemotherapy than Medicaid and Uninsured patients, though Medicaid and Uninsured have a greater percentage of minorities, who tend to get less chemotherapy for SFPC.

Time trends in chemotherapy (administration and costs) and relative survival in stage III colon cancer patients – a large population-based study from 1990 to 2008

Background. Use of adjuvant chemotherapy for stage III colon cancer has increased since several trials have shown the beneficial effect on survival. In this population-based study we show time trends in the administration and costs of chemotherapy and relative survival of patients with stage III colon cancer. Methods. All patients surgically treated for adenocarcinoma of the colon stage III between 1990 and 2008 in The Netherlands were included. Relative survival (using period analyses) and Relative Excess Risks of death (RER) were calculated. The costs of chemotherapy were estimated. Results. A total of 24 111 colon cancer patients with stage III were included in the cohort. The administration (from 9.5% in 1990 to 61.8% in 2008; p < 0.001) and costs of chemotherapy (from €38 467 in 1990 to €3 876 150 in 2008) increased during the study period. Multivariable relative survival improved for patients receiving adjuvant chemotherapy (RER 0.93; 95% CI 0.92–0.94; p < 0.001). In contrast, relative survival remained stable for patients, younger than 80 years, who did not receive chemotherapy (RER 1.00; 95% CI 1.00–1.01; p = 0.3). Patients aged 80 years and older without chemotherapy, relative survival increased during the study period (RER 0.98; 95% CI 0.97–0.99; p < 0.001). Conclusions. The administration, the costs of chemotherapy and the survival of patients with stage III colon cancer increased over time. Whereas the costs and administration of chemotherapy increased extensively, relative survival increased to a lesser extent. For patients treated with adjuvant chemotherapy relative survival increased equally in all age groups.

Quality indicators for colorectal cancer surgery and care according to patient-, tumor-, and hospital-related factors

BackgroundColorectal cancer (CRC) care has improved considerably, particularly since the implementation of a quality of care program centered on national evidence-based guidelines. Formal quality assessment is however still needed. The aim of this research was to identify factors associated with practice variation in CRC patient care.MethodsCRC patients identified from all cancer centers in South-West France were included. We investigated variations in practices (from diagnosis to surgery), and compliance with recommended guidelines for colon and rectal cancer. We identified factors associated with three colon cancer practice variations potentially linked to better survival: examination of ≥12 lymph nodes (LN), non-use and use of adjuvant chemotherapy for stage II and stage III patients, respectively.ResultsWe included 1,206 patients, 825 (68%) with colon and 381 (32%) with rectal cancer, from 53 hospitals. Compliance was high for resection, pathology report, LN examination, and chemotherapy use for stage III patients. In colon cancer, 26% of stage II patients received adjuvant chemotherapy and 71% of stage III patients. 84% of stage US T3T4 rectal cancer patients received pre-operative radiotherapy. In colon cancer, factors associated with examination of ≥12 LNs were: lower ECOG score, advanced stage and larger hospital volume; factors negatively associated were: left sided tumor location and one hospital district. Use of chemotherapy in stage II patients was associated with younger age, advanced stage, emergency setting and care structure (private and location); whereas under-use in stage III patients was associated with advanced age, presence of comorbidities and private hospitals.ConclusionsAlthough some changes in practices may have occurred since this observational study, these findings represent the most recent report on practices in CRC in this region, and offer a useful methodological approach for assessing quality of care. Guideline compliance was high, although some organizational factors such as hospital size or location influence practice variation. These factors should be the focus of any future guideline implementation.

Highlights in the adjuvant treatment of colon cancer from annual meetings 2011

The new biologic drugs that are active in the advanced setting of colon cancer have failed when used in the adjuvant setting. Both bevacizumab (NSABP C-08, AVANT-trial) and cetuximab (NO147 trial) added to oxaliplatin-based chemotherapy demonstrated no improvements in 3-year DFS compared with chemotherapy alone. However, subgroup analysis of the NO147 trial indicated that irinotecan and cetuximab might have a synergistic effect and the combination of FOLFIRI and cetuximab led to an improvement in 3-year DFS and 2-year OS compared with FOLFIRI alone. The encouraging results of this small patient cohort have to be confirmed by prospective trials. The use of adjuvant chemotherapy in stage II colon cancer remains controversial. Fluoropyrimidine-based chemotherapy should be discussed in high-risk stage II patients. The addition of oxaliplatin to fluoropyrimidine shows a trend toward improvement in DFS and OS at 5 years in patients with high-risk stage II colon cancer. In our opinion, this combination should be applied only in exceptional cases such as younger patients with accumulation of risk factors. Prognostic classifier like ColoPrint might identify high-risk patients who will benefit from chemotherapy on the basis of gene expression information in the primary tumor.

Effect of postoperative complications on adjuvant chemotherapy use in stage III colon cancer.

3608 Background: The National Quality Forum has endorsed the use of adjuvant chemotherapy in stage III colon cancer, yet a substantial treatment gap exists in the United States. Our objective was to evaluate the contribution of postoperative complications on the use of adjuvant therapy after colectomy for cancer. Methods: Patients from the National Surgical Quality Improvement Program and the National Cancer Data Base who underwent colon resection for cancer were linked (2006-2008). The association of complications on adjuvant chemotherapy use was assessed using multivariable regression models. Results: From 140 hospitals, 2368 patients underwent resection for stage III colon adenocarcinoma. Overall, 36.8% (871/2,368) patients were not treated with adjuvant therapy, of which 47.8% (416/871) had documented severe comorbidities or advanced age (≥80) as the reason for no adjuvant therapy receipt. Of the remaining 455 patients, 21.3% (97/455) had ≥1 serious complication that could account for adjuvant therapy omission. The remaining 41.1% (358/871) patients did not have a documented reason for not recieving adjuvant therapy. Complications associated with adjuvant therapy omission were abscess/anastomotic leak (OR 1.91, 95% CI 1.02-3.59), renal failure (OR 7.16, 95% CI 1.92-26.79), prolonged ventilation (OR 7.92, 95% CI 2.97-21.13), re-intubation (OR 5.69, 95% CI 2.13-15.18), and pneumonia (OR 4.05, 95% CI 2.07-7.90). Abscess/anastomotic leak was associated with a 28-day delay in time to adjuvant chemotherapy (73 vs. 45 days, p&lt;0.05). Superficial surgical site infection did not decrease adjuvant therapy receipt but delayed the time to its use (57 vs. 44 days, p&lt;0.05). The occurrence of postoperative sepsis was associated with a 15-day delay to adjuvant chemotherapy (60 vs. 45 days, p&lt;0.05). Conclusions: Serious postoperative complications explained nearly one quarter of the adjuvant chemotherapy treatment gap among stage III colon cancer patients. Postoperative complications affect treatment utilization and should be considered when calculating adherence with the Stage III adjuvant therapy for colon cancer measure. Judging provider performance using quality metrics is challenging without clinical data.

Effect of postoperative complications on adjuvant chemotherapy use in stage III colon cancer.

551 Background: The National Quality Forum has endorsed the use of adjuvant chemotherapy in stage III colon cancer yet a substantial treatment gap exists in the United States. Our objective was to evaluate the contribution of postoperative complications on the use of adjuvant therapy after colectomy for cancer. Methods: Patients from the ACS NSQIP and the NCDB who underwent colon resection for cancer were linked (2006-2008) to create a novel dataset containing robust information on comorbidities, complications, and oncologic variables. The association of complications on adjuvant chemotherapy use was assessed using multivariable regression models. Results: From 140 hospitals, 2414 patients underwent resection for stage III colon adenocarcinoma (open colectomy: 64%, laparoscopic colectomy: 36%). Overall, 896 (37.1%) patients were not treated with adjuvant therapy, of which 116 (12.9%) had documented severe comorbidities or advanced age as the reason for no adjuvant therapy receipt. Of the remaining 780 patients, 202 (25.9%) had a potential complication that could account for not receiving adjuvant therapy: 33 perioperative deaths and 169 patients with ≥1 serious complications including organ space infection (n=32), wound dehiscence (n=12), respiratory failure (n=48), pneumonia (n=45), renal failure (n=22) and septic shock (n=38). The remaining 611 patients did not have a documented reason for not receiving adjuvant chemotherapy. Complications independently associated with decreased adjuvant therapy use were renal failure (OR 0.17, 95% CI 0.0-0.59), respiratory failure (OR 0.23, 95% CI 0.11-0.51) and pneumonia (OR 0.36, 95% CI 0.18-0.75). Organ space infection was not associated with decreased use of adjuvant therapy, but significantly increased time to treatment (69 vs. 45 days, P&lt;0.05). Superficial SSI did not decrease adjuvant therapy use or delay treatment. Conclusions: Serious postoperative complications explained one quarter of the adjuvant chemotherapy treatment gap among stage III colon cancer patients and should be considered in quality assessment of colon cancer care. Judging provider performance on quality metrics is challenging without clinical data.

SPARC, FOXP3, CD8 and CD45 Correlation with Disease Recurrence and Long-Term Disease-Free Survival in Colorectal Cancer

BackgroundSPARC is a matricellular protein involved in tissue remodelling, cell migration and angiogenesis, while forkhead box P3 (FOXP3) protein functions as a transcription factor involved in immune cell regulation. Both SPARC and FOXP3 can play an anti-tumorigenic role in cancer progression. The aim was to determine if SPARC, FOXP3, CD8 and CD45RO expression levels are associated with colorectal cancer (CRC) stage, disease outcome and long-term cancer-specific survival (CSS) in stage II and III CRC.Methods and FindingsSPARC expression was initially assessed in 120 paired normal and stage I-IV CRCs. Subsequently, approximately 1000 paired patient samples of stage II or III CRCs in tissue microarrays were stained for SPARC, FOXP3, CD8 or CD45RO. Proportional hazards modelling assessed correlations between these markers and clinicopathological data, including disease outcome and cancer specific survival (CSS). Both SPARC and FOXP3 expression were significantly greater in CRC than normal colon (p<0.0001). High SPARC expression correlated with good disease outcome (≥60 mths without disease recurrence, p = 0.0039) and better long-term CSS in stage II CRC (<0.0001). In stage III CRC, high SPARC expression correlated with better long-term CSS (p<0.0001) and less adjuvant chemotherapy use (p = 0.01). High FOXP3 correlated with a good disease outcome, better long-term CSS and less adjuvant chemotherapy use in stage II (p<0.0037, <0.0001 and p = 0.04 respectively), but not in stage III CRC. High CD8 and CD45RO expression correlated with better disease outcome in stage II CRC, and better CSS, but the differences were not as marked as for SPARC and FOXP3.ConclusionsThese data suggest that high SPARC and FOXP3 are associated with better disease outcome in stage II CRC and may be prognostic indicators of CSS. Further assessment of whether these markers predict patients at high risk of recurrence with stage II CRC and functional studies of these effects are underway

Optimal use of adjuvant chemotherapy in stage II colorectal cancer

The prognosis of stage II colorectal cancer varies. Whether or not to perform adjuvant chemotherapy on patients with stage II colorectal cancer is a controversial issue. The aims of this study were to identify relevant risk factors for the prognosis of stage II colorectal cancer and to evaluate the need for adjuvant chemotherapy. Between January 2000 and January 2005, 443 patients with stage II colorectal cancer who had received radical surgery at the Sun Yat-sen University Cancer Center were retrospectively analyzed. The overall survival rates and survival curves were analyzed using the Kaplan-Meier method and log-rank test. Univariate and multivariate prognostic analyses were performed using the Cox regression model. Patients with certain important risk factors were analyzed according to whether they received adjuvant chemotherapy, and four chemotherapeutic regimens were classified into sub-groups and analyzed. Univariate analyses showed that intestinal obstruction or perforation, type 2 diabetes mellitus, an inadequate surgical margin, and sampling of less than 12 lymph nodes were risk factors that correlated with poor prognosis. Patients with an intestinal obstruction or perforation and insufficient lymph node samples achieved higher 5-year survival rates with adjuvant chemotherapy than with surgery alone. Intestinal obstruction or perforation, sampling of less than 12 lymph nodes, and inadequate surgical margins were identified as risk factors for poor survival, and patients with either of the first two factors benefited from adjuvant chemotherapy. Moreover, the use of capecitabine alone may be insufficient for patients with an intestinal obstruction or perforation.

Stage I breast cancer in a regional oncology practice in Israel 2002–2006: Clinicopathologic features, risk estimation and planned therapy of 328 consecutive patients

We present the clinicopathologic features and treatment plans of 328 consecutive stage I (T1N0M0) breast cancer patients seen at a regional medical center in Israel. Predicted 10-year mortality risk was calculated using the Adjuvant! Online website. The 21-gene recurrence score (RS) (OncotypeDx™) was obtained on a minority of patients. Eighty-nine per cent of patients had estrogen receptor (ER) and/or progesterone receptor (PgR) positive tumors. In 43.3% of patients history of an invasive malignancy was reported in a first degree relative and in 15.5% specifically breast and/or ovarian cancer was reported. Chemotherapy was added to endocrine therapy in 59 ER/PgR positive patients, decreasing predicted 10-year mortality risk by a median of 1.8%. Individualized risk estimation by genetic analysis may further decrease the use of chemotherapy in stage I patients. Breast cancer screening may provide an opportunity to identify cancer prone families.

A closer look at the number of lymph nodes examined in colorectal cancer: A VAMC experience

e15117 Background: Retrieval of 12 lymph nodes (LN) is a current benchmark in colorectal cancer (CRC) resections according to the National Quality Forum (NQF). Series of multiple institutions contain variability in surgical and pathologic techniques for lymph node retrieval. To ensure consistency in retrieving lymph nodes for satisfactory staging, we present a 12 year experience by a single surgeon and single pathology lab at one VAMC on 157 patients (mean age 67) undergoing CRC resection. Furthermore, the use of chemotherapy for Stage II patients &lt;12 LN retrieved is controversial and yields only a small survival benefit. Methods: The records of 157 patients from one surgeon's case log from 1994–2007 were reviewed. Strict guidelines were applied to remove the same distribution of pericolonic fat. The lab followed a two step approach to LN dissection: Step 1 search for grossly identifiable LN; Step 2 overnight Carnoy's immersion to find smaller LN. Statview and SAS software analyzed 1)Overall survival (OS) and association with finding &gt;12LN; 2)Number of LN identified and impact on AJCC tumor stage (TS) and overall survival; 3)Number of LN and WHO tumor grade (TG) with OS; 4)The impact of number of positive LN on OS. Results: Our mean LN found (14.75) is higher than the 12 recommended by the NQF and is not significantly associated with OS regardless of AJCC TS(p=0.06). The mean LN per TS was I=13.4(N=41)/II=16.3(N=56)/ III=14.3(N=38)/IV 14.2(N=22). Number of LN identified was not statistically significant in predicting TS(p=0.42) or OS(p=0.24). WHO TG is significantly associated to decreased OS, but only in AJCC TS II/III/IV and not stage I (Ip&gt;0.05/IIp=0.008/ IIIp=0.01/IVp=0.025). Higher number of positive LN was associated with lower OS (per each +LN, survival decreases by 0.15 months p=0.001) Conclusions: Contrary to multicenter studies, total number of LN identified does not impact AJCC TS or OS. Higher WHO TG and higher number of positive LN is associated with worse OS. This suggests that the tumor biology is more indicative of OS rather than host response (reactive lymphoid tissue) to the tumor. Stage II patients &lt;12 LN may not be ‘high risk’ and adjuvant chemotherapy based on this factor alone should be reconsidered. Further studies would be warranted. No significant financial relationships to disclose.

Adjuvant Treatment of Resected Lung Cancer

Lung cancer is the leading cause of cancer mortality worldwide, and efforts to improve outcomes of patients with this disease require a multidisciplinary approach. While surgical resection is the optimal treatment for early stage lung cancer, the high rates of recurrence after resection pose a distinct challenge. In recent years, substantial evidence has accumulated to support adjuvant chemotherapy in Stage II and III non-small cell lung cancer (NSCLC). A recent meta-analysis of large clinical trials of cisplatin-based adjuvant chemotherapy for resected NSCLC showed that the 5-year survival benefit in favor of chemotherapy was 5.3% (hazard ratio for death, 0.89; 95% confidence interval, 0.82-0.96; P = 0.005). The use of adjuvant chemotherapy in Stage I NSCLC remains controversial. Current and future efforts are being directed toward identification of prognostic and predictive markers to select patients at highest risk for recurrence, and of chemotherapeutic agents to which their tumors are most likely to respond. The role of targeted therapies, including those directed at the epidermal growth factor receptor and vascular endothelial growth factor in adjuvant treatment, is currently under investigation. At this time, there are no data to support the routine use of adjuvant radiation treatment, except in cases in which surgical margins are positive.

Escalation and Intensification of Radiotherapy for Stage III Non-small Cell Lung Cancer: Opportunities for Treatment Improvement

In this overview we review and model how radiotherapy tumour control and complication rates vary with dose, fractionation, schedule duration, irradiated volume and use of chemotherapy for stage III non-small cell lung cancer (NSCLC), and use the modelling to study the effectiveness of different NSCLC dose-escalation approaches being developed in the UK. Data have been collated for pneumonitis, lung fibrosis, early and late oesophagitis, cord and cardiac complications, and local progression-free survival at 30 months. Dependences of the various end points on treatment-related factors are catalogued and analysed using the linear-quadratic incomplete repair model to account for dose and fractionation effects, making linear corrections for differences in schedule duration, and loosely characterising volume effects using parallel- and series-type concepts. Tolerance limits are calculated for the different end points and distilled into ranges of prescribed dose likely to be tolerable when delivered in 2.5 and 4 week radiation and 6 week chemoirradiation schedules using conformal techniques. Worthwhile (∼20%) gains in 30 month local progression-free survival should be achievable at safely deliverable levels of dose escalation. The analysis suggests that longer schedules may be more beneficial than shorter ones, but this finding is governed by the relative rates of tumour and oesophageal accelerated proliferation, which are quite imprecisely known. Consequently escalated 2.5, 4 and 6 week schedules are being developed; each should lead to useful improvements in local control but it is not yet known which schedule will be most effective.

Management of early and advanced colorectal cancer: Therapeutic issues

The staging of colorectal cancer, therapeutic decision making in the management of early and advanced colorectal cancer, and dilemmas posed by drug-related toxicity are discussed. Staging of colorectal cancer occurs after surgery and is based on the extent of disease invasiveness and dissemination. Surgery is the primary treatment for stage I disease. Adjuvant chemotherapy is recommended after resection in selected high-risk patients with stage II disease and in all patients with stage III disease. Convenience of administration, tolerability, and patient factors not necessarily age may be considerations in decisions about adjuvant therapy after resection. Treatment of stage IV colorectal cancer is based on the type of prior therapy and patient-specific factors. Recently, significant improvements in survival have been achieved through the use of combination chemotherapy and monoclonal antibody regimens. Bevacizumab in combination with chemotherapy is first-line therapy for stage IV disease. Age alone should not preclude the use of chemotherapy in stage IV colorectal cancer, although the ability to tolerate drug-related toxicity may be a consideration. The optimal duration of chemotherapy in patients with early and metastatic colorectal cancer is unclear. The optimal approach to the treatment of colorectal cancer depends on several considerations, including patient-specific factors.

Trends in chemotherapy (CT) utilization for colorectal cancer: A provincial population-based analysis

17014 Background: Significant advances have been made in the treatment of colorectal cancer in both the adjuvant and metastatic setting. The purpose of this study is to examine CT prescribing patterns for adjuvant therapy of colon cancer and metastatic colorectal cancer over the last 15 years in British Columbia, Canada. Methods: All patients (pts) with stage 2 or 3 colon cancer, or stage 4 colorectal cancer at presentation referred to the BC Cancer Agency during a one year period for three time cohorts: 1990, 2000 and 2004, were reviewed. A pt was considered to be treated with CT if they received a cycle of CT within 6 months of referral. Results: A total of 1421 pts were included: stage 2/3 n=915, stage 4 n=506. Chemotherapy utilization increased significantly from 1990 to 2004 for adjuvant CT (1990: 49 (29%), 2000: 129 (45%), 2004: 235 (52%), p&lt;0.001) and for palliative CT (1990: 41(35%), 2000: 100 (51%), 2004 120 (63%), p&lt;0.001). The proportion of pts with stage 2 disease treated with adjuvant CT dramatically increased (1990: 3(4%), 2000: 38 (26%), 2004: 50 (30%), p&lt;0.001). CT utilization was associated with a later time cohort and younger age of presentation ( Table 1 ). The use of palliative CT was significantly associated with male gender (p=0.025). This gender bias was not observed in the adjuvant setting. Among pts &gt;70y, only 25% (99/394) received adjuvant CT [1990: 5(8%), 2000:38 (28%), 2004: 57 (28%] and 31% (50/162) received palliative CT [1990:4 (15%), 2000:17 (24%), 2004:30 (45%)]. Conclusions: In this population-based cohort, adjuvant and palliative CT utilization has increased since 1990 however there is room for improvement. Despite the lack of conclusive evidence, the use of adjuvant CT for stage II disease has increased significantly. Female pts appear less likely to receive palliative CT. Despite evidence that the elderly can accrue similar proportional benefits, the majority of referred pts &gt;70y did not receive adjuvant or palliative CT. Such discrepancies in CT utilization require further investigation. [Table: see text] No significant financial relationships to disclose.

Referral to Medical Oncology: A Crucial Step in the Treatment of Older Patients with Stage III Colon Cancer

Adjuvant chemotherapy for stage III colon cancer produces a substantial survival benefit, but many older patients do not receive chemotherapy. This study examines factors associated with medical oncology consultation and evaluates the impact of such consultation on chemotherapy use. We used the Surveillance Epidemiology and End Results-Medicare linked database and identified 7,569 patients, aged 66-99, with stage III colon cancer diagnosed from 1992-1999. Modified Poisson regression was used to assess the relative risk for seeing a medical oncologist and for receiving chemotherapy as a function of individual characteristics. 78.08% of patients saw a medical oncologist within 6 months of diagnosis. Patients who were female, white, married, had low comorbidity scores, were diagnosed in more recent years, or had four or more positive lymph nodes were more likely to see a medical oncologist. Patients seeing a medical oncologist were 10 times more likely to receive chemotherapy (odds ratio, 9.98; 95% confidence interval, 8.21-12.14), after controlling for demographic and tumor characteristics. Chemotherapy use increased over time, but was substantially lower among older, black, and unmarried patients. Referral to medical oncology is one of the most important factors associated with receipt of chemotherapy among older patients with stage III colon cancer. Comorbidity decreases the likelihood of receiving chemotherapy, but its effect is the same for those who see a medical oncologist and all patients combined. Ensuring that high-risk patients are referred to medical oncology is a crucial step in quality care for patients with colon cancer.

Population based study of prognostic factors in stage II colon cancer

3619 Background: Guidelines for the use of adjuvant chemotherapy in stage II colorectal cancer state this treatment may be considered to patients whose tumours show features of poor prognosis. The aim of the current study was to evaluate the prognostic significance of commonly reported clinical and pathological features of this disease. Methods: A population-based observational study encompassing all stage II colon cancer patients diagnosed in the state of Western Australia from 1993–2003 inclusive. A total of 1306 cases treated by surgery alone were identified and had a median follow-up of 59 months (range 0–145). Results: Multivariate analysis revealed the only independent prognostic factors for disease-specific survival were T4 stage (HR=1.75, 95%CI [1.32–2.32], P&lt;0.0001) and vascular invasion (HR=1.63, 95%CI [1.15–2.30], P&lt;0.0001). In the younger patient group (≤75 yrs) who are more likely to be considered for chemotherapy, the same two features showed independent prognostic significance but with higher HR values (1.96 and 2.73 respectively). T4 and/or the presence of vascular invasion identified a “poor” prognosis group comprising 26% of younger cases and having a 5-year survival rate of 71%. The remaining “good” prognosis group showed 84% survival at 5 years follow-up. Conclusion: This study highlights the importance of accurate pathological assessment of T stage and vascular invasion for the prognostic stratification of stage II colon cancer and their subsequent consideration for adjuvant chemotherapy. No significant financial relationships to disclose.

Should adjuvant chemotherapy become standard treatment for patients with stage II colon cancer?

Adjuvant chemotherapy is regarded as standard treatment for patients with stage III colon cancer; however, use of chemotherapy after surgery in patients with stage II disease remains controversial because of a lack of level I evidence. In 2005, the Minimum Clinical Recommendations, issued by the European Society for Medical Oncology (ESMO), did not advocate use of chemotherapy in stage II disease, but did state that chemotherapy "may be considered in selected node-negative patients". Similarly, in 2004, treatment recommendations from the American Society of Clinical Oncology (ASCO) for stage II colon cancer proposed that there might be some "patients with stage II disease that could be considered for adjuvant therapy, including patients with inadequately sampled nodes, T4 lesions, perforation, or poorly differentiated histology". Consequently, use of adjuvant chemotherapy in patients with stage II colon cancer is not universal. In this Debate, Alberto Sobrero from Genoa, Italy, and Claus-Henning Köhne from Oldenburg, Germany, present the arguments for and against the use of this type of treatment.

Adjuvant Treatment of Stage II Colon Cancer: Is There a True No-Chemotherapy Group?

In this issue of Annals of Surgical Oncology, Andre et al. present an exhaustive review of the controversial management in the use of adjuvant chemotherapy for stage II colon cancers. The authors review the results of the most recent clinical trials and metaanalyses investigating the value of adjuvant chemotherapy for stage II patients. They emphasize that this is a heterogenous patient population that includes patients with T2, T3, and T4 lesions, tumor perforation, and tumor differentiation, all of whom are believed to be N0. This heterogeneous population is the reason that 5-year survival rates for stage II colon cancer range from a high of 70% to a low of 30%. It is because of this same heterogeneity and the relatively rare event of stage II colon carcinoma that trials attempting to evaluate the treatment efficacy of adjuvant chemotherapy have had insufficient power. Even larger trials that have included both stage II and stage III colon carcinomas have been insufficient to demonstrate a durable benefit in this rare group. It has been estimated, as the authors have pointed out, that to detect a 4% survival benefit at 5 years in stage II colon cancer by using a median of 75% 5-year survival as a baseline would require 4700 patients. The rapid expansion in chemotherapeutic options has made the care of colon cancer patients more complex and optimistic. In the past, when only 5-fluorouracil chemotherapy was an option, there was little enthusiasm for giving chemotherapy in a subset of patients with a 5-year survival rate of 75%. However, now, with a myriad of options, there is considerable enthusiasm for identifying all stages and/or subsets of patients who may receive any form of benefit from additional chemotherapy. To most, this represents an advance in treatment, as has been seen in breast and prostate therapy. The core question remains as to what is a clinically relevant benefit from additional chemotherapy? Is a 5-year increase of 4.3% for stage II colon cancers clinically relevant? If this translates into an improvement of 3 months in overall survival, which is half the duration of the treatment itself (6 months of adjuvant therapy), is it worthwhile in all stage II patients? One of the key areas in which surgery has been lacking has been established surgical criteria for colon resections in cancer. Only until recently has there been a recommendation for at least 12 lymph nodes to be evaluated in all surgically treated colon cancers. This minimum number of lymph nodes retrieved has been demonstrated to improve 5-year survival, through a stage migration effect, and to be highly predictive of survival in both lymph node–negative and lymph node–positive patients. Adequate lymph node identification has been difficult to standardize because of the variability of both surgical technique and pathologic lymph harvest. One technique that may demonstrate the ability to increase lymph node retrieval and possibly improve lymph node stage sensitivity and specificity is sentinel lymph node biopsy. The successful conclusion of this multi-institutional trial of this technique demonstrated the feasibility and possible benefit (Bilchik et al., unpublished data). Received November 29, 2005; accepted December 6, 2005; published online April 13, 2006. Address correspondence and reprint requests to: Robert C. G. Martin, MD; E-mail: robert.martin@louisville.edu.