The impact of age on first-line systemic therapy in patients with metachronous metastases from colorectal cancer.

OBJECTIVES: The paucity of evidence for the optimal use of systemic therapy in elderly patients with metastatic colorectal cancer (mCRC) poses significant challenges to cancer specialists. The present population-based study provides insight into the impact of age on palliative systemic therapy in patients with metachronous metastases from CRC, in order to optimize the decision-making process. METHODS: Data on the development and treatment of metachronous metastases were collected for patients with primary resected CRC diagnosed between 2003 and 2008 in the Eindhoven area of the Netherlands Cancer Registry. Patients undergoing surgery for metastases were excluded, resulting in a study population treated with palliative intent, with or without systemic therapy (n=746). RESULTS: 385 patients received palliative systemic therapy (52%). Patients aged ≥75years were less likely to receive systemic therapy (31% ≥75years vs 73% <60years) and more likely to receive single-agent chemotherapy than combination-chemotherapy. Elderly patients (≥75years) treated with capecitabine-oxaliplatin (CAPOX) received fewer cycles (51% ≤3 oxaliplatin cycles, 43% ≤3 capecitabine cycles) and lower cumulative dosages compared to patients aged <75years, although initial dosages were similar. If capecitabine monotherapy (CapMono) was administered, starting dosages were 2414mg/m2/d<75years and 1992mg/m2/d≥75years (p<0.05), but no differences in number of received cycles or cumulative dosages were observed. CONCLUSION: Age beginning at 75years significantly influenced palliative systemic therapy. Even in selected elderly patients, first-line treatment with CAPOX was associated with less cycles and lower cumulative dosages compared to younger patients. With single-agent fluoropyrimidine therapy, however, no such results were observed.

Age-related systemic treatment and survival of patients with metachronous metastases from colorectal cancer.

BACKGROUND: Although the spectrum of systemic treatment for metastatic colorectal cancer (mCRC) has widened, there is a paucity of evidence for the feasibility and optimal use of these systemic agents in elderly patients. The present study provides real world data on the age-related systemic treatment and survival of CRC patients with non-resectable metachronous metastases. METHODS: All consecutive patients with non-resectable metastases from primary resected CRC were extracted from the Eindhoven area of the Netherlands Cancer Registry (NCR). Patients receiving palliative systemic therapy were enrolled (n = 385). Systemic treatment and survival were analyzed according to age at diagnosis of metastases. RESULTS: Patients aged ≥75 years more often received first-line single-agent chemotherapy than their younger counterparts (63% vs. 32%, p < .0001). First-line single-agent chemotherapy was often prescribed without additional targeted therapy (78%). Advanced age (≥75 years) was associated with a lower probability of receiving all active cytotoxic agents compared to patients aged <60 years at time of diagnosis of metastases (odds ratio (OR) 0.2, 95% CI 0.10-0.77). In a multivariable Cox regression analysis with adjustment for age and other relevant prognostic factors, the total number of received systemic agents was the only predictor of death (hazard ratio (HR) 0.7, 95% CI 0.61-0.81). CONCLUSION: The beneficial effect of treatment with all active systemic agents on survival (simultaneously or sequentially prescribed) should be taken into account when considering systemic therapy in patients with mCRC. In light of our results, future studies are warranted to clarify the role of potential targeted therapy in elderly mCRC patients, who are often not candidates for combination chemotherapy and treatment with all active cytotoxic agents.

Challenging the dogma of colorectal peritoneal metastases as an untreatable condition: Results of a population-based study.

PURPOSE: To determine the impact of the implementation of novel systemic regimens and locoregional treatment modalities on survival at population level in colorectal cancer (CRC) patients presenting with peritoneal metastases (PMs). METHODS: All consecutive CRC patients with synchronous PM (<3 months) between 1995 and 2014 were extracted from the Eindhoven area of the Netherlands Cancer Registry. Trends in treatment and overall survival were assessed in four time periods. Multivariable regression analysis was used to analyse the impact of systemic and locoregional treatment modalities on survival. RESULTS: A total of 37,036 patients were diagnosed with primary CRC between 1995 and 2014. Synchronous PM was diagnosed in 1,661 patients, of whom 55% had also metastases at other sites (n = 917) and 77% received anticancer therapy (n = 1,273). Treatment with systemic therapy increased from 23% in 1995-1999 to 56% in 2010-2014 (p < 0.0001). Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) was applied since 2005 and increased from 10% in 2005-2009 to 23% in 2010-2014. Surgery for lymphatic or haematogenous metastases increased from 2% to 10% in these periods. Median overall survival of the complete cohort improved from 6.0 months in 1995-2000 to 12.5 months in 2010-2014 (p < 0.0001), with a doubling of survival for both PM alone and PM with other involved sites. The influence of year of diagnosis on survival (hazard ratio, 2010-2014 versus 1995-1999; 0.5, 95% confidence interval: 0.43-0.62; p < 0.0001) disappeared after including systemic therapy and locoregional treatment modalities in subsequent multivariable models. CONCLUSION: CRC patients presenting with PM are increasingly offered a multidisciplinary treatment approach, resulting in an increased overall survival for the entire cohort.

Bevacizumab in Addition to Palliative Chemotherapy for Patients With Peritoneal Carcinomatosis of Colorectal Origin: A Nationwide Population-Based Study.

BACKGROUND: Most patients with colorectal cancer (CRC) presenting with peritoneal carcinomatosis (PC) rely on palliative systemic treatment options. However, data on the use and effect of systemic treatment strategies, including targeted agents for the palliative treatment of colorectal PC, are lacking. We conducted a nationwide population-based study with data from the period in which the targeted agent bevacizumab was introduced in the Netherlands. PATIENTS AND METHODS: The present study included all patients diagnosed from 2007 to 2014 with synchronous PC from CRC treated with only palliative systemic therapy. We assessed the use of bevacizumab, the standard choice of targeted treatment, in addition to first-line chemotherapy. Multivariable logistic regression analyses were performed to calculate the predictors for the additional prescription of bevacizumab. Survival estimates were calculated, and multivariable Cox analyses were performed to estimate the hazard ratios (HRs) of death stratified by the treatment received. RESULTS: A total of 1235 patients received palliative chemotherapy, of whom 436 also received bevacizumab (35%). Patients aged ≥ 75 years and patients with PC from colonic tumors were less likely to receive chemotherapy plus bevacizumab. The addition of bevacizumab to palliative chemotherapy was associated with an improved overall median survival of 7.5 versus 11 months in both patients with isolated PC and those with concomitant extraperitoneal metastases. The improvement remained after adjustment for patient and tumor characteristics (HR, 0.7; 95% confidence interval, 0.64-0.83). CONCLUSION: The results of the present nationwide population-based study support the rationale for bevacizumab in addition to palliative chemotherapy for patients with PC of CRC and underline the need for ongoing efforts to precisely determine the role of targeted therapy in the treatment of PC.

The Prognostic Relevance of Histological Subtype in Patients With Peritoneal Metastases From Colorectal Cancer: A Nationwide Population-Based Study.

BACKGROUND: With evolving treatment possibilities for peritoneal metastases (PM) from colorectal cancer (CRC), adequate prognostication and patient selection for treatment becomes increasingly important. We investigated the prognostic relevance of commonly identified histological subtypes in PM of CRC (adenocarcinoma [AC], mucinous AC [MC], and signet-ring cell carcinoma [SC]), which is currently unclear. PATIENTS AND METHODS: This study involved 4277 patients diagnosed with synchronous PM from CRC between 2005 and 2012 in The Netherlands. Kaplan-Meier analysis and log-rank testing were performed to estimate survival. Subsequently a Cox proportional hazard model was used to calculate hazard ratios for the risk of death. RESULTS: Most of the CRC patients were diagnosed with AC (n = 3008; 70%), whereas MC and SC were found in 958 (22%) and 311 (7%) patients, respectively. SC was associated with the highest risk of death in colon and rectal cancer, with median survival rates of respectively, 6.6 and 6.9 months. For MC, median survival varied from 10.9 months in colon and 9.8 months in rectal cancer (P > .05). In colon cancer, MC was associated with a significantly lower risk of death compared with AC (hazard ratio, 0.9; 95% confidence interval, 0.79-0.95). In rectal cancer, no such effect was observed. AC was associated with a significantly poorer survival rate in the case of primary colonic tumor localization (7.4 months in colon vs. 10.9 months in rectal cancer). CONCLUSION: Histological subtype is an important prognostic factor in patients with synchronous PM of colorectal origin. This knowledge will aid clinicians in counseling of patients and clinical decision-making regarding possible treatment options.