Carcinosarcomas of the Uterus: Prognostic Factors and Impact of Adjuvant Treatment.

BACKGROUND: Uncertainties remain about the most effective treatment for uterine carcinosarcoma (UCS), a rare but aggressive uterine cancer, due to the limited scope for randomized trials. This study investigates whether nodal excision or adjuvant therapies after hysterectomy offer a survival benefit, using multi-institutional clinical registry data from South Australia. METHODS: Data for all consecutive cases of UCS from 1980 to 2019 were extracted from the Clinical Cancer Registry. Clinical and treatment-related factors associated with disease-specific mortality (DSM) and all-cause mortality (ACM) were determined using multivariable Cox proportional hazards regression, with subgroup analyses by stage. RESULTS: Median follow-up for the 140 eligible cases was 21 months. 94% underwent hysterectomy, and 72% had an additional pelvic lymph node dissection (PLND). Furthermore, 16% received adjuvant chemotherapy; 11% adjuvant radiotherapy and 16% multimodal chemoradiotherapy, with an increase in the latter two modalities over time. DSM was reduced among those who underwent PLND (HR: 0.41; 95%CI: 0.23-0.74), adjuvant chemotherapy (HR: 0.39; 95%CI: 0.18-0.84) or multimodality treatment (HR: 0.11; 95%CI: 0.06-0.30) compared with hysterectomy alone for the whole cohort and for late stage disease (FIGO III/IV) but not for earlier stage disease, except for reduced DSM with multimodal therapy. Findings were similar for ACM. CONCLUSION: Our findings indicate better survival among those who received PLND, chemotherapy and multimodal adjuvant therapy, with the latter applying to early and late stage disease. However, cautious interpretation is warranted, due to potential "indication bias" and limited power. Further research into effective treatment modalities, ideally using prospective study designs, is needed.

Female breast cancer treatment and survival in South Australia: Results from linked health data.

OBJECTIVE: We investigated treatment and survival by clinical and sociodemographic characteristics for service evaluation using linked data. METHOD: Data on invasive female breast cancers (n = 13,494) from the South Australian Cancer Registry (2000-2014 diagnoses) were linked to hospital inpatient, radiotherapy and universal health insurance data. Treatments ≤12 months from diagnosis and survival were analysed, using adjusted odds ratios (aORs) from logistic regression, and adjusted sub-hazard ratios (aSHRs) from competing risk regression. RESULTS AND CONCLUSION: Five-year disease-specific survival increased to 91% for 2010-2014. Most women had breast surgery (90%), systemic therapy (72%) and radiotherapy (60%). Less treatment applied for ages 80+ vs <50 years (aOR 0.10, 95% CI 0.05-0.20) and TNM stage IV vs stage I (aOR 0.13, 95% CI 0.08-0.22). Surgical treatment increased during the study period and strongly predicted higher survival. Compared with no surgery, aSHRs were 0.31 (95% CI 0.26-0.36) for women having breast-conserving surgery, 0.49 (95% CI 0.41-0.57) for mastectomy and 0.42 (95% CI 0.33-0.52) when both surgery types were received. Patients aged 80+ years had lower survival and less treatment. More trial evidence is needed to optimise trade-offs between benefits and harms in these older women. Survival differences were not found by residential remoteness and were marginal by socioeconomic status.

Cancers of the corpus uteri treated in South Australian public hospitals: Trends in clinical management and survival across three decades.

OBJECTIVE: To investigate treatment and survival over three decades. METHODS: Clinical registry data from three major public hospitals analysed using Kaplan-Meier product-limit estimates and multivariate proportional hazard regression to determine disease-specific survival. RESULTS: Five-year survival increased from 75% to 84%. The adjusted hazard ratio (HR, 95% CI) was 0.56 (0.41, 0.77) for 2010-2016 compared with 1984-1989 and was higher for: ages 80+ years; more advanced stages; poorly differentiated tumours; and complex mixed epithelial and mesenchymal tumours and sarcomas. Treatment was by surgery (92%), radiotherapy (33%), chemotherapy (12%) and hormone therapy (10%). Adjusted analyses showed radiotherapy and hormone therapy were less common from 1990 and chemotherapy more common for 2010-2016. Treatment likelihood was lower for ages ≥80 years, mixed epithelial and mesenchymal tumours receiving surgery and chemotherapy, but higher for radiotherapy. Advanced cancers (FIGO stage IV) had less surgery but more non-surgical treatments. Marginal evidence presented of more hormone therapy for high socio-economic areas. CONCLUSIONS: Survival was equivalent to national figures for Australia and the United States, but potentially higher than for England and Wales. Cases aged 80+ years had less care and poorer survival. Findings illustrate the complementary roles of hospital and population-based registries in local service evaluation.

Monitoring TNM stage of female breast cancer and survival across the South Australian population, with national and international TNM benchmarking: A population-based cohort study.

OBJECTIVE: Using linked cancer registry and administrative data to monitor, tumour, node and metastases (TNM) stage and survival from female breast cancer in Australia. METHOD: Analysis of 2000-2014 diagnoses with linked population-based data to investigate: (1) sociodemographic predictors of advanced stage (stages III and IV), using unadjusted and adjusted logistic regression; and (2) sociodemographic factors and stage as predictors of breast cancer survival using competing risk regression. DESIGN: Population-based registry cohort. SETTING AND PARTICIPANTS: 14 759 South Australian women diagnosed in 2000-2014. PRIMARY AND SECONDARY OUTCOME MEASURES: Stage and survival. RESULTS: At diagnosis, 46% of women were classified as stage I, 39% as stage II, 12% as stage III and 4% as stage IV. After adjusting for sociodemographic factors, advanced stage was more common: (1) for ages <50 years; and although not statistically significant, for ages 80+ years; and (2) in women from socioeconomically disadvantaged areas. Compared with 2000-2004 diagnoses, stage and sociodemographic adjusted risks (sub-HRs (SHRs)) of breast cancer death were lower in 2005-2009 (SHR 0.75, 95% CI 0.67 to 0.83) and 2010-2015 (SHR 0.57, 95% CI 0.48 to 0.67). Compared with stage I, the SHR was 3.87 (95% CI 3.32 to 4.53) for stage II, 10.87 (95% CI 9.22 to 12.81) for stage III, and 41.97 (95% CI 34.78 to 50.65) for stage IV. Women aged 70+ years at diagnosis and those living in the most socioeconomically disadvantaged areas were at elevated risk of breast cancer death, independent of stage and sociodemographic factors. CONCLUSIONS: Stage varied by age, diagnostic period and socioeconomic status, and was a stronger predictor of survival than other statistically significant sociodemographic predictors. Achieving earlier diagnosis outside the original BreastScreen target of 50-69 years (as applying <2014) and in residents of socioeconomically disadvantaged areas likely would increase cancer survival at a population level.

Time from diagnosis to treatment of colorectal cancer in a South Australian clinical registry cohort: how it varies and relates to survival.

OBJECTIVES: Some early studies indicated lower survival with longer time from diagnosis to cancer treatment, but others showed the reverse. We investigated time to treatment of colorectal cancer and associations with survival. SETTING AND PARTICIPANTS: Clinical registry data for colorectal cancer cases diagnosed in 2000-2010 at four major public hospitals in South Australia and treated by surgery (n=1675), radiotherapy (n=616) and/or systemic therapy (n=1556). DESIGN: A historic cohort design, with rank-order tests for ordinal clinical and sociodemographic predictors and multiple logistic regression for comparing time from diagnosis to treatment. Unadjusted Kaplan-Meier estimates and adjusted Cox proportional hazards regression were used to investigate disease-specific survival by time to treatment. OUTCOME MEASURES: Time to treatment and survival from diagnosis to death from colorectal cancer. RESULTS: Treatment (any type) commenced for 87% of surgical cases <60 days of diagnosis, with 80% having surgery within this period. Of those receiving radiotherapy, 59% began this treatment <60 days, and of those receiving systemic therapy, the corresponding proportion was 56%. Adjusted analyses showed treatment delay >60 days was more likely for rectal cancers, 2006-2010 diagnoses, residents of northern than other metropolitan regions and for surgery, younger ages <50 years and unexpectedly, those residing closer to metropolitan services. Adjusting for clinical and sociodemographic factors, and diagnostic year, better survival occurred in <2 years from diagnosis for time to treatment >30 days. Survival in the 3-10 years postdiagnosis generally did not differ by time to treatment, except for lower survival for any treatment >90 days for surgical cases. CONCLUSIONS: The lower survival <2 years from diagnosis for treatment <30 days of diagnosis is consistent with other studies attributed to preferencing more complicated cases for earlier care. Lower 3-10 years survival for surgical cases first treated >90 days from diagnosis is consistent with previously reported U-shaped relationships.

Pre-diagnostic colonoscopies reduce cancer mortality - results from linked population-based data in South Australia.

BACKGROUND: To investigate the association between pre-diagnostic colonoscopy and colorectal cancer mortality in South Australia. METHODS: Colonoscopy histories were obtained for colorectal cancer patients diagnosed in 2003-2013 using linked Medical Benefits Schedule (MBS) claims, hospital-inpatient and cancer-registry data. Colonoscopy histories included the year of colonoscopy, numbers of examinations, and the time from first colonoscopy to diagnosis. Histories of multiple exposures to colonoscopies, and exposures of greater than a year from initial colonoscopy to diagnosis, were regarded as indicators of screening or surveillance activity. Colonoscopies occurring within one year of diagnosis were regarded as more likely to be a response to cancer symptoms than those occurring > 1 year before diagnosis. Associations between colonoscopy history and post-diagnostic survival were analysed using sub-hazard ratios (SHRs) from competing risk regression adjusted for socio-demographic and cancer characteristics. RESULTS: Having pre-diagnostic colonoscopy was associated with an unadjusted reduction in risk of colorectal cancer death of 17% (SHR: 0.83, 95% CI 0.78-0.89). After adjusting for time period and sociodemographic characteristics, the risk of colorectal cancer death reduced by 17% for one pre-diagnostic colonoscopy examination; 27% for two pre-diagnostic colonoscopy examinations; and 45% for three or more pre-diagnostic colonoscopy examinations. Those with a time of over one year from first colonoscopy in the study window to diagnosis, when compared with less than one year, had a 17% lower risk of colorectal cancer death in this adjusted analysis. These reductions were substantially reduced or eliminated when also adjusting for less advanced stage. CONCLUSIONS: Pre-diagnostic colonoscopy, and more so, multiple colonoscopies and first colonoscopy occurring over one year from initial colonoscopy to diagnosis, were associated with longer survival post diagnosis. This was largely explained by less advanced cancer stage at the time of diagnosis.

Exploring the added value of hospital-registry data for showing local service outcomes: cancers of the ovary, fallopian tube and peritoneum.

OBJECTIVES: To explore the added value of hospital-registry data on invasive epithelial ovarian, tubal and peritoneal cancers. DESIGN: Historic cohort analyses. METHODS: Unadjusted and adjusted regression. SETTING: Major South Australian hospitals. PARTICIPANTS: 1596 women (1984-2015 diagnoses). RESULTS: 5-Year and 10-year survival was 48% and 41%, respectively, equivalent to relative survival for Australia and the USA. After adjusting for age, clinical and geographic factors, risk of ovarian cancer death was 25% lower in 2010-2015 than 1984-1989. Women generally had surgical treatment (87%) in their first round of care. This was more common for younger patients (adjusted OR (95% CIs) 0.17 (0.04 to 0.65) for 80+ vs <40 years) and earlier International Federation of Gynecology and Obstetrics stages (adjusted OR 0.48 (0.13 to 1.78) for stage IIIB/C and 0.13 (0.04 to 0.45) for stage IV vs stage IA). Most (74%) had systemic therapy, which was more common for advanced stages (adjusted ORs >15.0 for stages III and IV vs stage IA). Few (9%) had radiotherapy. Women generally had systemic therapy (74%), without difference by service accessibility and socioeconomic disadvantage, suggesting equity. However, surgery was less common for residents of the most compared with least remote areas (adjusted OR 0.49 (0.24 to 0.99)); and more common prior to adjustment in the highest versus lowest socioeconomic category (unadjusted OR 1.55 (1.01 to 2.39)), but this elevation did not apply after adjustment (adjusted OR 0.19 (0.63 to 2.25)), with the difference largely explained by stage. CONCLUSIONS: Hospital-registry data add value for assessing local service delivery. Equivalent survival to Australia-wide and USA survival, and temporal gains after adjusting for stage and other patient characteristics are reassuring. Survival gains may reflect therapeutic benefits of more extensive surgery and improved chemotherapy regimens.

Using hospital registries in Australia to extend data availability on vulval cancer treatment and survival.

BACKGROUND: The value of hospital registries for describing treatment and survival outcomes for vulval cancer was investigated. Hospital registry data from four major public hospitals in 1984-2016 were used because population-based data lacked required treatment and outcomes data. Unlike population registries, the hospital registries had recorded FIGO stage, grade and treatment. METHODS: Unadjusted and adjusted disease-specific survival and multiple logistic regression were used. Disease-specific survivals were explored using Kaplan-Meier product-limit estimates. Hazards ratios (HRs) were obtained from proportional hazards regression for 1984-1999 and 2000-2016. Repeat analyses were undertaken using competing risk regression. RESULTS: Five-year disease-specific survival was 70%, broadly equivalent to the five-year relative survivals reported for Australia overall (70%), the United Kingdom (70%), USA (72%), Holland (70%), and Germany (Munich) (68%). Unadjusted five-year survival tended to be lower for cancers diagnosed in 2000-2016 than 1984-1999, consistent with survival trends reported for the USA and Canada, but higher for 2000-2016 than 1984-1999 after adjusting for stage and other covariates, although differences were small and did not approach statistical significance (p ≥ 0.40). Surgery was provided as part of the primary course of treatment for 94% of patients and radiotherapy for 26%, whereas chemotherapy was provided for only 6%. Less extensive surgical procedures applied in 2000-2016 than 1984-1999 and the use of chemotherapy increased over these periods. Surgery was more common for early FIGO stages, and radiotherapy for later stages with a peak for stage III. Differences in treatment by surgery and radiotherapy were not found by geographic measures of remoteness and socioeconomic status in adjusted analyses, suggesting equity in service delivery. CONCLUSIONS: The data illustrate the complementary value of hospital-registry data to population-registry data for informing local providers and health administrations of trends in management and outcomes, in this instance for a comparatively rare cancer that is under-represented in trials and under-reported in national statistics. Hospital registries can fill an evidence gap when clinical data are lacking in population-based registries.

Metastatic Colorectal Cancer Treatment and Survival: the Experience of Major Public Hospitals in South Australia Over Three Decades.

BACKGROUND: Registry data from four major public hospitals indicate trends over three decades from 1980 to 2010 in treatment and survival from colorectal cancer with distant metastases at diagnosis (TNM stage IV). MATERIALS AND METHODS: Kaplan-Meier product-limit estimates and Cox proportional hazards models for investigating disease-specific survival and multiple logistic regression analyses for indicating first-round treatment trends. RESULTS: Two-year survivals increased from 10% for 1980-84 to 35% for 2005-10 diagnoses. Corresponding increases in five-year survivals were from 3% to 16%. Time-to-event risk of colorectal cancer death approximately halved (hazards ratio: 0.48 (0.40, 0.59) after adjusting for demographic factors, tumour differentiation, and primary sub-site. Survivals were not found to differ by place of residence, suggesting reasonable equity in service provision. About 74% of cases were treated surgically and this proportion increased over time. Proportions having systemic therapy and/or radiotherapy increased from 12% in 1980-84 to 61% for 2005-10. Radiotherapy was more common for rectal than colonic cases (39% vs 7% in 2005-10). Of the cases diagnosed in 2005-10 when less than 70 years of age, the percentage having radiotherapy and/or systemic therapy was 79% for colorectal, 74% for colon and 86% for rectum (and RS)) cancers. Corresponding proportions having: systemic therapies were 75%, 71% and 81% respectively; radiotherapy were 24%, 10% and 46% respectively; and surgery were 75%, 78% and 71% respectively. Based on survey data on uptake of offered therapies, it is likely that of these younger cases, 85% would have been offered systemic treatment and among rectum (and RS) cases, about 63% would have been offered radiotherapy. CONCLUSIONS: Pronounced increases in survivals from metastatic colorectal cancer have occurred, in keeping with improved systemic therapies and surgical interventions. Use of radiotherapy and/or systemic therapy has increased markedly and patterns of change accord with clinical guideline recommendations.

Myeloid leukaemia treatment and survival--the South Australian experience, 1977 to 2002.

OBJECTIVE: To evaluate trends in survival and treatment for myeloid leukaemia in South Australia during 1977-2002, using population-based survival data plus data on survival and treatment of patients at three teaching hospitals. METHODS: Population data were analysed using relative survival methods and hospital registry data using disease-specific survival. Univariate and multivariable analyses were undertaken. Multiple logistic regression analysis was used to investigate factors associated with first-line chemotherapy. RESULTS: South Australia recorded 1,572 new cases of acute myeloid leukaemia (AML) in 1977-2002, together with 536 cases of chronic myeloid leukaemia (CML). Of these cases, 42.6% were recorded in teaching hospital registries. The five-year survival for AML at the teaching hospitals of 14.5% was similar to the corresponding 12.0% for South Australia as a whole. The five-year survival for CML at these hospitals was higher, however, at 48.1% compared with 37.5% for all South Australian cases. Younger patients had higher survivals, both for AML and CML. An increase in survival was evident for more recently diagnosed cases for both leukaemia types, after adjusting for age. This increase in survival was accompanied by an increase over time in the proportion of patients at teaching hospitals having a primary course of chemotherapy. Cytarabine in combination with other agents was the most common induction therapy for AML. While hydroxyurea was the most common first-line treatment of CML, there were changes in clinical policies towards higher-dose treatments, plus trials of new agents and combination therapies. CONCLUSIONS: Secular gains in survival have occurred from AML and CML in association with an increased use of chemotherapy.