Early onset metastatic colorectal cancer in Australia.

BACKGROUND: Colorectal cancer (CRC) incidence and mortality rates have been increasing among young patients (YP), for uncertain reasons. It is unclear whether YP have a distinct tumor biology or merit a different treatment approach to older patients (OP). METHODS: We reviewed prospectively collected data from consecutive patients with metastatic CRC (MCRC) enrolled in the multi-site Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Australian registry. Clinicopathological features, treatment and survival outcomes were compared between YP (<50 years) and OP (≥50 years). RESULTS: Of 3692 patients diagnosed August 2009 - March 2023, 14 % (513) were YP. YP were more likely than OP to be female (52% vs. 40 %, P < 0.0001), have ECOG performance status 0-1 (94% vs. 81 %, P < 0.0001), to have a left-sided primary (72% vs. 63 %, P = 0.0008) and to have fewer comorbidities (90% vs. 60 % Charleston score 0, P < 0.0001). There were no differences in the available molecular status, which was more complete in YP. YP were more likely to have de novo metastatic disease (71% vs. 57 %, P < 0.0001). YP were more likely to undergo curative hepatic resection (27% vs. 17 %, P < 0.0001), to receive any chemotherapy (93% vs. 78 % (P < 0.0001), and to receive 3+ lines of chemotherapy (30% vs. 24 % (P < 0.0034)). Median first-line progression free survival (10.2 versus 10.6 months) was similar for YP vs OP, but overall survival (32.1 versus 25.4 months, HR = 0.745, P < 0.0001) was longer in YP. CONCLUSION: Known prognostic variables mostly favored YP versus OP with newly diagnosed mCRC, who were also more heavily treated. Consistent with this, overall survival outcomes were improved. This data does not support that CRC in YP represent a distinct subset of mCRC patients, or that a modified treatment approach is warranted.

Initial experience of TAS-102 chemotherapy in Australian patients with Chemo-refractory metastatic colorectal cancer.

For patients with refractory metastatic colorectal cancer (mCRC) treatment with Trifluridine/Tipiracil, also known as TAS-102, improves overall survival. This study aims to investigate the efficacy and safety of TAS-102 in a real-world population from Victoria, Australia. A retrospective analysis of prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry was undertaken. The characteristics and outcomes of patients receiving TAS-102 were assessed and compared to those enrolled in the registration study (RECOURSE). Across 13 sites, 107 patients were treated with TAS-102. The median age was 60 years (range: 31-83), compared to 63 for RECOURSE. Comparing registry TAS-102-treated and RECOURSE patients, 75% vs 100% were ECOG performance status 0-1, 74% vs 79% had initiated treatment more than 18 months from diagnosis of metastatic disease and 36% vs 49% were RAS wild-type. Median time on treatment was 10.4 weeks (range: 1.7-32). Median progression-free survival (PFS) was 3.3 months compared to 2 months in RECOURSE, while median overall survival was the same at 7.1 months. Two patients (2.3%) had febrile neutropenia and there were no treatment-related deaths, where TAS-102 dose at treatment initiation was at clinician discretion.TRACC registry patients treated with TAS-102 were younger than those from the RECOURSE trial, with similar overall survival observed. Less strict application of RECIST criteria and less frequent imaging may have contributed to an apparently longer PFS.

Survival impact of the Australian National Bowel Cancer Screening Programme.

BACKGROUND: The Australian National Bowel Cancer Screening Program (NBCSP) has been offering age-based faecal occult blood testing since 2006. With the rapid expansion of this programme, the NBCSP will ultimately offer biennial screening to all 50-74 years old by 2020. Participation rates remain low. Previous reports have described an increased proportion of earlier stage cancers in patients with NBCSP-detected tumours. METHODS: Data on consecutive patients enrolled into a prospective, comprehensive, multidisciplinary database at six Victorian hospitals were examined. Clinicopathologic and outcome data were compared for NBCSP and symptomatic presentation patients. RESULTS: We identified 3743 patients that presented with colorectal cancer (CRC) at participating hospitals since May 2006. Of 1930 patients aged between 50 and 70 years, 141 (7.3%) had a NBCSP detected cancer, 1441 (74.7%) presented with symptoms and 266 (13.8%) were diagnosed through screening outside of the NBCSP. Based on the American Society of Anaesthesiology score, the NBCSP patients were fitter. They had an earlier stage of diagnosis and were more likely to be female and less likely to have lymphovascular invasion or to present as an emergency. NBCSP detected patients had a lower rate of recurrence (HR 0.17, P = 0.0001) and fewer deaths (HR 0.19, P = 0.005). CONCLUSIONS: Patients with NBCSP-detected CRC have a markedly reduced risk of CRC recurrence and death compared with patients with a symptomatic presentation. The dominant driver of this appears to be earlier stage at diagnosis. Increased promotion of the impact of the NBCSP, including data related to the survival impact, should be undertaken to increase participation rates and achieve further survival gains.

Developing a national database for metastatic colorectal cancer management: perspectives and challenges.

BACKGROUND: The changing treatment landscape for metastatic colorectal cancer creates multiple potential treatment strategies. An Australian-centric database capturing comprehensive information across a range of treatment locations would create a valuable resource enabling multiple important research questions to be addressed. AIMS: To establish a collection of a consensus dataset capturing treatment and outcomes at multiple public and private hospitals across Australia. METHODS: An electronic database was developed by a panel of clinicians, to capture an agreed dataset for patients with newly diagnosed metastatic colorectal cancer. Of particular interest were clinician decision-making, the impact of comorbidities and the frequency of major adverse events. RESULTS: Since July 2009, data collection has been established at six public and eight private hospitals across three Australian states and territories. Successful linkage and analysis, with support from BioGrid Australia, of selected data on the initial 864 patients demonstrates that data can be captured from diverse sites, including public and private practice, that multiple factors impact on treatment delivered and outcomes achieved and that comprehensive data on rare but important adverse events can be captured. As a clinical research tool, the project has been highly successful, generating multiple presentations at national and international conferences related to a diverse range of research questions. CONCLUSIONS: Multistate, project-specific data collection involving large numbers of patients is achievable. Providing invaluable insight into the routine clinical management of metastatic colorectal cancer in the era of targeted therapies, this also creates a significant resource for research, including many questions not being addressed by clinical trials.

An initial watch and wait approach is a valid strategy for selected patients with newly diagnosed metastatic colorectal cancer.

BACKGROUND: A range of treatments are available for patients with metastatic colorectal cancer (mCRC). An initial period without active treatment, a 'watch and wait approach', is variably employed in routine practice; however, there is no data to support this approach. PATIENTS AND METHODS: We prospectively collected data regarding clinician treatment recommendations for patients with newly diagnosed mCRC in addition to subsequent treatment and outcomes. Follow-up and management was according to standard protocols. RESULTS: Seven hundred and thirty-six patients (59.1% male, 40.9% female) with mCRC (January 2003-December 2010) were analysed; the median age was 67.9 years (range 26.2-95.5). Three hundred and seventy-seven patients (51.2%) received immediate chemotherapy. For 133 (18.1%), treatment was considered inappropriate. 34 patients (4.6%) declined therapy. For 192 (26.1%), a watch and wait policy was adopted and 168 (87.5%) of these received treatment, at a median of 3.7 months (range 2-35 months) from diagnosis. Compared with patients immediately treated, the number receiving all active chemotherapy agents (30.4 versus 39.3%) was similar and median survival (27 versus 17 months, P = 0.0008) was superior. CONCLUSIONS: Our study demonstrates that a substantial minority of patients underwent an initial watch and wait approach. Ultimately, they received a similar treatment exposure to patients treated immediately and the survival outcomes were not compromised.

Preliminary analysis of the cost-effectiveness of the National Bowel Cancer Screening Program: demonstrating the potential value of comprehensive real world data.

BACKGROUND/AIM: The complexity and cost of treating cancer patients is escalating rapidly and increasingly difficult decisions are being made regarding which interventions provide value for money. BioGrid Australia supports collection and analysis of comprehensive treatment and outcome data across multiple sites. Here, we use preliminary data regarding the National Bowel Cancer Screening Program (NBCSP) and stage-specific treatment costs for colorectal cancer (CRC) to demonstrate the potential value of real world data for cost-effectiveness analyses (CEA). METHODS: Data regarding the impact of NBCSP on stage at diagnosis were combined with stage-specific CRC treatment costs and existing literature. An incremental CEA was undertaken from a government healthcare perspective, comparing NBCSP with no screening. The 2008 invited population (n= 681,915) was modelled in both scenarios. Effectiveness was expressed as CRC-related life years saved (LYS). Costs and benefits were discounted at 3% per annum. RESULTS: Over the lifetime and relative to no screening, NBCSP was predicted to save 1265 life years, prevent 225 CRC cases and cost an additional $48.3 million, equivalent to a cost-effectiveness ratio of $38,217 per LYS. A scenario analysis assuming full participation improved this to $23,395. CONCLUSIONS: This preliminary CEA based largely on contemporary real world data suggests population-based faecal occult blood test screening for CRC is attractive. Planned ongoing data collection will enable repeated analyses over time, using the same methodology in the same patient populations, permitting an accurate analysis of the impact of new therapies and changing practice. Similar CEA using real world data related to other disease types and interventions appears desirable.

Predictors of clinic non-attendance: opportunities to improve patient outcomes in colorectal cancer.

AIM: Colorectal cancer is one of the few tumour types, where routine patient follow up has been demonstrated to impact significantly on survival. Patients who fail to attend regular clinic reviews may compromise their outcome, but the frequency at which this occurs is unknown. Identifying the extent of this problem, and the factors that predict non-attendance, may provide opportunities to improve patient outcomes. METHODS: Utilizing the Australian Comprehensive Cancer Outcomes and Research Database (ACCORD) colorectal database at Royal Melbourne and Western Hospitals and the Hospital Patient Management System (HOMER) we collected attendance data for colorectal surgical and oncology outpatient clinic appointments. RESULTS: A total of 619 patients (368 men and 251 women) with curatively treated Australian ClinicoPathological Staging System (ACPS) Stage A, B and C colorectal cancer was identified from the two sites over 1988-2008. Twenty-one per cent (n= 130) of patients failed to attend one or more appointments. Patients who failed to attend were more likely to require the services of an interpreter (25% vs 18%; P= 0.007), to have a smoking history and to have not received adjuvant therapy. Tumour site, patient age, sex and comorbidities were not associated with non-attendance. CONCLUSION: A significant percentage of patients fail to attend routine clinic visits to colorectal speciality clinics. Patients at risk of non-attendance can be identified. More research is needed to identify barriers as to why patients do not attend appointments and to develop measures that may improve patient attendance.

Phase II study of paclitaxel and vinorelbine (Pacl-Vin) in hormone-refractory metastatic prostate cancer: double tubulin targeting.

BACKGROUND: Androgen ablation is the standard treatment for advanced prostate cancer. However, most patients will eventually develop progressive hormone-refractory prostate cancer (HRPC). The aim of the Pacl-Vin study was to determine the efficacy and safety of paclitaxel in combination with vinorelbine in patients with HRPC, following from a phase I trial. METHODS: Thirty castrate patients with progressive, metastatic prostate cancer were enrolled. Patients were treated with paclitaxel 40 mg/m2, vinorelbine 20 mg/m2 intravenously on day 1 and day 8 of a 21-day cycle. RESULTS: Two patients demonstrated a partial response and seven patients had stable disease from a cohort of 10 patients with measurable disease. Of 30 patients assessable for prostate-specific antigen (PSA) response, 19 showed stable disease, which was maintained for at least 4 weeks, while six (20%) experienced>or=50% decline in PSA levels. Median overall survival was 7.3 months (interquartile range (IQR): 4.7-9.9 months). Median progression-free survival was 3.3 months (IQR: 2.5-7.0 months). Improvement in quality of life measures was noted after three cycles of therapy. Grade 3 and 4 toxicities were: neutropenia 8%, febrile neutropenia 4%, infection 2%, anaemia 3%, lethargy 1% and somnolescence 1%. One patient died as a result of neutropenic sepsis. CONCLUSION: In a poor prognostic cohort of patients paclitaxel and vinorelbine is a tolerable regimen, with a 20% PSA and objective response rate. The majority of patients achieved PSA stability. Furthermore, quality of life parameters, such as pain, were improved. However, the low level of activity of this regimen precludes its further testing.

Linking data from hospital and cancer registry databases: should this be standard practice?

BACKGROUND: Varying amounts of data related to cancer diagnosis, treatment and/or outcome are routinely collected by many disparate groups. Routinely combining data from these sources could improve data quality and utility for audit and research purposes. The aim of this study is to demonstrate the benefits of linkage between oncology databases. METHODS: We examined colorectal cancer (CRC) data recorded by the Victorian Cancer Registry and two hospital clinical databases between January 2000 and December 2005. Where data were in common, the completeness and accuracy of each dataset were examined. Where content differed, the potential value of making this additional data available to the other database was examined. RESULTS: Of the 831 cases recorded at the hospitals, 822 (98.9%) were also recorded on the cancer registry. Eight of the 913 cases (0.87%) recorded as having CRC by the registry did not have CRC. Errors in recording of tumour site and tumour or nodal stage were frequent in both databases. Metastasis stage was recorded in only 29 of 822 (3.5%) registry cases examined. Discordance for diagnosis date and death date was also frequent, although the difference was typically minor. Adding additional death data from the registry to the clinical database significantly altered stage-specific and overall survival figures. CONCLUSION: A multidirectional flow of data between hospital and registry databases provides multiple opportunities to improve data quality and utility. While issues around data ownership and usage need to be considered, the advantages of routine data linkage are readily apparent.

Preoperative investigations for metastatic staging of colon and rectal cancer across multiple centres--what is current practice?

OBJECTIVE: The optimal strategy for elective distant staging of colorectal carcinoma (CRC) has yet to be defined, with current guidelines based on small and limited series. One specific issue requiring review is the value of routine computerized tomographic (CT) chest examination. Also lacking is data on current routine clinical practice. METHOD: A retrospective chart review of consecutive cases of elective surgery for CRC from five hospitals. RESULTS: Two hundred and fifty-seven cases were reviewed, 128 colon and 129 rectal primaries. 164 (64%) of patients overall, ranging from 45% to 88% across the individual centres, had a preoperative serum CEA level performed. CT abdomen/pelvis was performed in 222 (86%) of cases, ranging from 69% to 98% per centre. CT chest was performed in 95 (37%) of cases, 47% of rectal vs 29% of colon cancers (P = 0.004). In 17 cases (18%) CT chest examinations revealed abnormalities suspicious for metastatic disease, leading to a change in management in six (35%) of these cases. Of the 17 cases with an abnormal CT chest, in only 5 of the 14 (36%) where carcinoembryonic antigen (CEA) levels were also recorded was this increased, and in only three (21%) was this markedly (> 10 microg/l) elevated. CONCLUSIONS: Substantial variability exists in the preoperative evaluation of patients with CRC. Many patients do not have a CEA and/or abdominal imaging performed. Where performed, CT chest revealed suspicious findings in a significant number of patients, the vast majority of whom had a normal or near normal CEA. Future studies are required to define optimal preoperative staging.

Surveillance following treatment for colorectal cancer in Australia. Has best practice been adopted by medical oncologists?

BACKGROUND: Intensive follow up after surgery for colorectal cancer is associated with a significant survival advantage and is endorsed by expert panels, but are physicians convinced of the benefit? METHODS: A questionnaire was mailed to all members of the Medical Oncology Group of Australia, assessing surveillance practices after completion of adjuvant treatments. RESULTS: Responses were obtained from 141 (55%) medical oncologists of which 121 were considered evaluable. Thirteen per cent (n = 16) routinely did not carry out follow-up investigations. Of those carrying out surveillance, 47% (n = 51) nominated identifying potentially resectable metastatic disease as prime consideration. Many (44%) were motivated by patient reassurance and expectation. Carcinoembryonic antigen levels were commonly monitored 3 monthly in years 1 (77%, n = 85) and 2 (57%, n = 63) and 6 monthly thereafter (67%, n = 74). Eighty per cent (n = 88) carried out computed tomography (CT) surveillance 1 year after surgery, 69% (n = 76) at year 2 and 55% (n = 60) at year 3. Twenty-six per cent (n = 29) continued scanning annually up to 5 years. Inclusion of CT chest was routine for 33% (n = 36) and never carried out by 11% (n = 12). CONCLUSION: A significant minority (13%) of oncologists carry out no follow-up investigations, despite level I evidence of a survival advantage similar to standard adjuvant therapies. Further education and study of physician attitudes and reservations to routine surveillance are required.