De novo and recurrent metastatic breast cancer - A systematic review of population-level changes in survival since 1995.

BACKGROUND: Advances in breast cancer (BC) care have reduced mortality, but their impact on survival once diagnosed with metastasis is less well described. This systematic review aimed to describe population-level survival since 1995 for de novo metastatic BC (dnMBC) and recurrent MBC (rMBC). METHODS: We searched MEDLINE 01/01/1995-12/04/2021 to identify population-based cohort studies of MBC reporting overall (OS) or BC-specific survival (BCSS) over time. We appraised risk-of-bias and summarised survival descriptively for MBC diagnoses in 5-year periods from 1995 until 2014; and for age, hormone receptor and HER2 subgroups. FINDINGS: We identified 20 eligible studies (14 dnMBC, 1 rMBC, 5 combined). Potential sources of bias in these studies were confounding and shorter follow-up for the latest diagnosis period.For dnMBC, 13 of 14 studies reported improved OS or BCSS since 1995. In 2005-2009, the median OS was 26 months (range 24-30), a median gain of 6 months since 1995-1999 (range 0-9, 4 studies). Median 5-year OS was 23% in 2005-2009, a median gain of 7% since 1995-1999 (range -2 to 14%, 4 studies). For women ≥70 years, the median and 5-year OS was unchanged (1 study) with no to modest difference in relative survival (range: -1·9% (p = 0.71) to +2·1% (p = 0.045), 3 studies). For rMBC, one study reported no change in survival between 1998 and 2006 and 2007-2013 (median OS 23 months). For combined MBC, 76-89% had rMBC. Three of four studies observed no change in median OS after 2000. Of these, one study reported median OS improved for women ≤60 years (1995-1999 19·1; 2000-2004 22·3 months) but not >60 years (12·7, 11·6 months). INTERPRETATION: Population-level improvements in OS for dnMBC have not been consistently observed in rMBC cohorts nor older women. These findings have implications for counselling patients about prognosis, planning cancer services and trial stratification. FUNDING: SL was funded in part by a National Health and Medical Research Council (NHMRC) Project Grant ID: 1125433. NH was funded by the NBCF Chair in Breast Cancer Prevention grant (EC-21-001) and a NHMRC Investigator (Leader) grant (194410). BD and SAP were funded in part by the NHMRC Centre of Research Excellence in Medicines Intelligence (1196900).

Estimating survival in advanced cancer: a comparison of estimates made by oncologists and patients.

PURPOSE: To compare estimates of expected survival time (EST) made by patients with advanced cancer and their oncologists. METHODS: At enrolment patients recorded their "understanding of how long you may have to live" in best-case, most-likely, and worst-case scenarios. Oncologists estimated survival time for each of their patients as the "median survival of a group of identical patients". We hypothesized that oncologists' estimates of EST would be unbiased (~ 50% longer or shorter than the observed survival time [OST]), imprecise (< 33% within 0.67 to 1.33 times OST), associated with OST, and more accurate than patients' estimates of their own survival. RESULTS: Twenty-six oncologists estimated EST for 179 patients. The median estimate of EST was 6.0 months, and the median OST was 6.2 months. Oncologists' estimates were unbiased (56% longer than OST), imprecise (27% within 0.67 to 1.33 times OST), and significantly associated with OST (HR 0.88, 95% CI 0.82 to 0.93, p < 0.01). Only 41 patients (23%) provided a numerical estimate of their survival with 107 patients (60%) responding "I don't know". The median estimate by patients for their most-likely scenario was 12 months. Patient estimates of their most-likely scenario were less precise (17% within 0.67 to 1.33 times OST) and more likely to overestimate survival (85% longer than OST) than oncologist estimates. CONCLUSION: Oncologists' estimates were unbiased and significantly associated with survival. Most patients with advanced cancer did not know their EST or overestimated their survival time compared to their oncologist, highlighting the need for improved prognosis communication training. Trial registration ACTRN1261300128871.

The impact and indications for Oncotype DX on adjuvant treatment recommendations when third-party funding is unavailable.

OBJECTIVES: Industry-supported decision impact studies demonstrate that Oncotype Dx (ODX) changes treatment recommendations (TR) in 24-40% of hormone receptor+/HER2- patients. ODX is not reimbursed by third-party payers in Australia, potentially resulting in more selective use. We sought to evaluate the impact of self-funded ODX on TRs. METHODS: Data collected included demographics, tumor characteristics, indication for ODX and pre- and post-recurrence score (RS) TR. Primary endpoint was frequency of TR change and associations with TR change were sought. RESULTS: Eighteen physicians contributed 382 patients (median age 54). A total of 232 (61%) of tumors were T1 and were grade 1, 2 and 3 in 49 (13%), 252 (66%) and 79 (21%). A total of 257 (67%) were node negative. Assay indications were: confirm need for chemotherapy (CT) (36%), confirm omission of CT (40%) and genuine equipoise (24%). RS was low (≤17) in 55%, intermediate (18-31) in 36% and high (≥32) in 9%. Thirty-eight percent of patients had TR change post-ODX. Sixty-five percent of patients recommended CT pre-ODX changed to hormone therapy alone (HT)-more likely if lower grade and if ER and/or PR > 10%. Fourteen percent of patients with pre-ODX TR for HT added CT-more likely if ER and/or PR ≤10% and if Ki67 > 15% Overall, TR for CT decreased from 47% to 24%. CONCLUSION: Patient-funded ODX changed TRs in 38% of patients, de-escalating 65% from CT to HT and adding CT to 14% of those recommended HT. These changes were greater than an industry-funded study suggesting that physicians can identify situations where the assay may influence decisions.

How do oncologists make decisions about chemotherapy for their older patients with cancer? A survey of Australian oncologists.

PURPOSE: Oncologists are making treatment decisions on increasing numbers of older patients with cancer. Due to comorbidities and frailty that increase with age, such decisions are often complex. We determined factors influencing oncologists' decisions to prescribe chemotherapy for older adults. METHODS: Members of the Medical Oncology Group of Australia (MOGA) were invited to complete an online survey in February to April 2016. RESULTS: Ninety-three oncologists completed the survey of which 69 (74%) were consultants and 24 (26%) were trainees, with most (72, 77%) working predominantly in a public hospital-associated practice. The three highest ranked factors influencing decisions about (a) adjuvant chemotherapy were performance status, survival benefit of treatment, and life expectancy in the absence of cancer and about (b) palliative chemotherapy were performance status, patient preference, and quality of life. Most geriatric health domains are reportedly assessed routinely by the majority of respondents, though few routinely use geriatric screening tools (14%) or geriatric assessments (5%). In hypothetical patient scenarios, oncologists were less likely to prescribe palliative and adjuvant chemotherapy as age and rates of severe toxicity increased. CONCLUSION: Performance status was the most influential factor for oncologists when making a decision about chemotherapy for their older patients, and the importance of other factors differed according to treatment intent. Oncologists were less likely to recommend chemotherapy as patient age and treatment toxicity increased. The low uptake of geriatric assessments or screening tools provides scope for improved clinical assessment of older adults in treatment decision-making.

Improved quality of risk-reducing salpingo-oophorectomy in Australasian women at high risk of pelvic serous cancer.

OBJECTIVES: The quality of risk-reducing salpingo-oophorectomy (RRSO) performed in Australasian women was previously reported to be suboptimal. Here we describe the quality of RRSO performed since 2008 in women enrolled in the same cohort and determine whether it has improved. DESIGN: Prospective cohort study of women at high risk of pelvic serous cancer (PSC) in kConFab. Eligible women had RRSO between 2008 and 2014 and their RRSO surgical and pathology reports were reviewed. "Adequate" surgery and pathology were defined as complete removal and paraffin embedding of all ovarian and extra-uterine fallopian tube tissue, respectively. Associations between clinical factors and "adequate" pathology were assessed using logistic regression. Data were compared with published cohort data on RRSO performed prior to 2008 using Chi square test. RESULTS: Of 164 contemporary RRSOs performed in 78 centres, 158/159 (99%) had "adequate" surgery and 108/164 (66%) had "adequate" pathology. Surgery performed by a gynaecologic oncologist rather than a general gynaecologist [OR 8.2, 95%CI (3.6-20.4), p < 0.001], surgery without concurrent hysterectomy [OR 2.5, 95%CI (1.1-6.0), p = 0.03], more recent year of surgery [OR 1.4, 95%CI (1.1-1.8), p = 0.02], and clinical notation that indicated high risk [OR 19.4, 95%CI (3.1-385), p = 0.008] were independently associated with "adequate" pathology. Both surgery and pathology were significantly more likely to be "adequate" (p < 0.001) in this contemporary sample. CONCLUSION: The quality of RRSOs has significantly improved since our last report. Surgery by a gynaecologic oncologist who informs the pathologist that the woman is at high risk for PSC is associated with optimal RRSO pathology.

Use of palliative chemotherapy in patients aged 80 years and over with incurable cancer: experience at three Sydney cancer centres.

BACKGROUND: Octogenarians represent a growing population reviewed in medical oncology clinics, yet there is a paucity of data on how chemotherapy is tolerated in this age group. AIM: To describe the use of palliative first-line chemotherapy in patients 80 years and over and factors associated with its use. METHODS: We identified all new patients aged 80 years or older diagnosed with incurable advanced solid organ cancer and seen in one of three Sydney medical oncology outpatient clinics between January 2009 and December 2013. Patient, disease and treatment details were summarised and factors associated with chemotherapy use explored. RESULTS: Of 420 eligible patients, 100 (24%) started first-line chemotherapy. Younger age at diagnosis was the only factor associated with receiving chemotherapy (median 82.9 vs 84.1 years, P = 0.002). A total of 78% of patients had single-agent chemotherapy, and 41% received a full dose for the first cycle. During treatment, 54% experienced toxicity, necessitating dose reduction, delay or omission, and 32% were hospitalised. These events were associated with receipt of combination chemotherapy (OR 5.1; P = 0.04) and full-dose chemotherapy for cycle 1 (OR 3.5; P = 0.02). Radiological disease control was achieved in 60%. Chemotherapy was stopped because of progressive disease (48%), toxicity (37%) or completion of planned course (17%). CONCLUSION: A quarter of patients 80 years and older received first-line palliative chemotherapy. Despite most receiving a modified dose, one third were hospitalised during treatment. These findings highlight the need for careful clinical assessment and selection of older cancer patients for chemotherapy.

More than just the median: Calculating survival times for patients with HER2 positive, metastatic breast cancer using data from recent randomised trials.

OBJECTIVES: To estimate worst-case, typical and best-case scenarios for survival as a communication aid for managing patients with HER2-positive metastatic breast cancer (MBC) starting HER2-targeted therapies. METHODS: We sought randomised trials of HER2-targeted therapies and recorded the following percentiles (representative scenarios) from each OS curve: 90th (worst-case), 75th (lower-typical), 50th (median), 25th (upper-typical) and 10th (best-case). We then tested whether we could estimate these percentiles for each OS curve by multiplying its median by four simple multiples: 0.25 (to derive the 90th percentile), 0.5 (75th), 2 (25th) and 3 (10th). Estimates were deemed accurate if within 0.75-1.33 times the actual value. RESULTS: We identified 15 trials with 4798 patients. For first-line, single-agent HER2-targeted therapy (15 treatment groups), the median (interquartile range [IQR]) for median OS was 33.3 months (29.1-38.4), and for each percentile was: 90th 9.5 months (7.7-11.0); 75th 19.2 months (16.4-20.8); and 25th 50.6 months (47.1-63.3). The 10th percentile was unavailable for all treatment groups. For first-line dual HER2-targeted therapy (1 treatment group), the median OS was 56.5 months. Simple multiples of the median OS accurately estimated the: 90th percentile in 79%; 75th percentile in 100%; and 25th percentile in 89% of OS curves. CONCLUSIONS: Surprisingly little is known of survival beyond the median for HER2-positive MBC. Longer trial follow-up is required to help clinicians estimate and explain the best-case scenario. Simple multiples of the median OS provide a reasonable framework for estimating then explaining survival times to patients.

Doctor-to-doctor communication of prognosis in metastatic cancer: a review of letters from medical oncologists to referring doctors.

BACKGROUND: Shared understanding of prognosis is vital for optimal, multidisciplinary, clinical decision making. AIMS: This study aims to determine the frequency and nature of prognostic information in medical oncologists' letters to referring doctors for patients with metastatic cancer. METHODS: We reviewed all consultation letters (to June 2014) for new patients with metastatic cancer presenting to medical oncologists at Concord and Macarthur Cancer Centres between June 2012 and June 2013. We recorded the presence and nature of prognostic information in the letters, patients' characteristics and survival. Characteristics associated with inclusion of prognostic information were explored. RESULTS: We analysed 1344 letters pertaining to 272 patients with a median survival of 13 months. The median number of letters per patient was 4 (interquartile range 1-7), with 50% written by trainees. The terms 'metastatic' or 'stage IV cancer' were included in letters for 253 patients (93%), treatment was described as 'palliative' for 174 patients (64%) and the word 'incurable' was included for 93 (34%). Only 31 patients (11%) had a quantitative estimate of prognosis in any correspondence: median or average survival in 14, general time frame in 12 and, best case, typical and worst case scenarios in 5. Inclusion of quantitative prognostic information was not associated with patient age, cancer type, treatment plan, trainee authoring letter or shorter survival. CONCLUSION: Inclusion of quantitative prognostic information in written correspondence from medical oncologists regarding patients with metastatic cancer was infrequent. Encouraging oncologists to include quantitative prognostic information in their letters could improve communication between oncologists, referring doctors and patients.

Estimating scenarios for survival time in men starting systemic therapies for castration-resistant prostate cancer: a systematic review of randomised trials.

BACKGROUND: We sought to estimate worst-case, typical and best-case scenarios for survival in men starting systemic therapies for castration resistant prostate cancer (CRPC). METHODS: We sought randomised phase 3 trials of systemic therapies for CRPC and recorded the following percentiles (represented scenario) from Kaplan-Meier overall survival (OS) curves: 90th (worst-case), 75th (lower-typical), 50th (median), 25th (upper-typical) and 10th (best-case). We determined the accuracy of using simple multiples of the median OS to estimate the other selected percentiles from each curve: 0.25 for 90th, 0.5 for 75th, 2 for 25th and 3 for 10th. Estimates were deemed accurate if within 0.75-1.33 times the actual value. FINDINGS: We reviewed 23 trials (13,909 men) with 48 treatment groups including 28 of chemotherapy, and three of novel hormonal agents. In trials of first-line docetaxel, the mean (interquartile range) for median OS was 19 months (17-20), and for each scenario was: worst-case 7 months (6-8); lower-typical 12 months (11-13); upper-typical 29 months (27-31); and best-case 40 months (34-44). For trials of novel hormonal agents after chemotherapy the mean values were: median OS 17 months, worst-case 5 months, lower-typical 9 months, upper-typical 24 months and best-case not reported. Simple multiples of the median gave accurate estimates of the worst-case scenario in 72% of OS curves, lower-typical in 89%, upper-typical in 84% and best-case in 84%. INTERPRETATION: Simple multiples of the median OS from randomised trials provided accurate estimates of worst-case, typical and best-case scenarios for survival time in men starting systemic therapies for CRPC.

Survival times of women with metastatic breast cancer starting first-line chemotherapy in routine clinical practice versus contemporary randomised trials.

BACKGROUND: Survival times of women starting first-line chemotherapy for metastatic breast cancer (MBC) in routine clinical practice were determined and compared with those from a systematic review of randomised clinical trials. METHODS: We identified women with MBC starting first-line chemotherapy from June 2003 to February 2011 and recorded their demographics, tumour and treatment characteristics, and survival times from the start of chemotherapy. Their survival distribution was summarised by the following percentiles (represented scenarios for survival): 90th (worst-case), 75th (lower-typical), 25th (upper-typical) and 10th (best-case), which were compared with the same percentiles from our systematic review of first-line chemotherapy trials. RESULTS: The 273 women had a median age of 56 years, and a median time from diagnosis of MBC of 3 months. Eastern Cooperative Oncology Group performance status was 0-1 in 80%. Tumours were hormone receptor positive in 69%, human epidermal growth factor receptor 2 (HER2)-positive in 27% and triple negative in 13%. Survival times in months in routine clinical practice (vs the systematic review) were: 90th percentile 4 (6); 75th percentile 9 (12); median 20 (22); 25th percentile 36 (36) and 10th percentile 61 (56). Independent predictors of overall survival included HER2-positive disease (hazard ratio (HR) 0.49, P = 0.0002), hormone receptor positive disease (HR 0.51, P = 0.0004), Eastern Cooperative Oncology Group performance status 0-1 (HR 0.36, P < 0.0001) and adjuvant chemotherapy (HR 1.86, P = 0.0002). CONCLUSION: Median and better survival times in routine practice were similar to those from randomised clinical trials; however, survival times worse than the median were shorter, likely reflecting patient selection in trials. Oncologists should adjust trial-based survival estimates for patients not meeting typical trial eligibility criteria.

Using scenarios to explain life expectancy in advanced cancer: attitudes of people with a cancer experience.

PURPOSE: We sought the attitudes of people with a cancer experience to using best case, worst case, and typical scenarios for survival to explain life expectancy. METHODS: Oncology clinic attendees and Breast Cancer Network Australia (BCNA) members completed a survey describing two formats for explaining life expectancy to a hypothetical patient with advanced cancer-providing either three scenarios for survival or just the median survival time. RESULTS: Characteristics of the 505 respondents from outpatient clinics (n = 251) and BCNA (n = 254) were median age of 58 years, female 74 %, and breast primary 64 %. More respondents agreed that explaining three scenarios (vs. median survival) would make sense (93 vs. 75 %), be helpful (93 vs. 69 %), convey hope (68 vs. 44 %), and reassure (60 vs. 40 %), while fewer respondents agreed that explaining three scenarios (vs. median survival) would upset people (24 vs. 36 %); all p values < 0.001. Most respondents agreed that each scenario should be presented: best case 89 %, worst case 82 %, and typical 92 %. For information about their own prognosis, 88 % preferred all three scenarios and 5 % a single estimate of the median. Respondents with higher education were more likely to agree that presenting three scenarios would be helpful (95 vs. 90 %, p = 0.05). Respondents with breast cancer were more likely to agree that explaining three scenarios would upset people (31 vs. 13 %, p < 0.001). CONCLUSIONS: Most respondents judged presentation of best case, worst case, and typical scenarios preferable and more helpful and reassuring than presentation of just the median survival time when explaining life expectancy to patients with advanced cancer.

Estimating typical, best-case and worst-case life expectancy scenarios for patients starting chemotherapy for advanced non-small-cell lung cancer: a systematic review of contemporary randomized trials.

INTRODUCTION: We sought to estimate life expectancy scenarios for patients starting chemotherapy for advanced non-small-cell lung cancer (NSCLC). METHODS: We searched for randomized first-line chemotherapy trials published from January 2000 to April 2008. We recorded median time to progression (TTP) and median overall survival (OS) and extracted the following percentiles (represented scenario) from each OS curve: 90th (worst-case), 75th (lower-typical), 25th (upper-typical) and 10th (best-case). For each OS curve we divided these percentiles (scenarios) in turn by the median to determine if a simple relationship existed between each scenario and the median. RESULTS: From 60 trials (29,657 patients), the mean for median TTP was 4.8 months (interquartile range [IQR] 4.0-5.3), the mean for median OS was 9.2 months (IQR 8.1-10.1) and the mean ratio for median OS to median TTP was 2.0 (IQR 1.7-2.2). The mean (IQR) in months for each OS scenario was: worst-case, 2.4 (1.9-2.7); lower-typical, 4.8 (4.2-5.4); upper-typical, 16.3 (14.4-18.1); and best-case, 25 (21.0-28.0). The mean values (IQR) for each scenario divided by the median were: worst-case/median 0.26 (0.21-0.29); lower-typical/median 0.53 (0.5-0.57); upper-typical/median 1.81 (1.69-1.93) and best-case/median 2.84 (2.57-3.19). These values can be approximated by the simple multiples: 0.25, 0.5, 2 and 3. Independent predictors of longer OS were ECOG PS<2, adenocarcinoma, and longer TTP; all p-values<0.001. CONCLUSION: Simple multiples of an OS curve's median provided accurate estimates of typical (half to double the median), best-case (triple the median), and worst-case (one quarter of the median) life expectancy scenarios for patients starting chemotherapy for advanced NSCLC.

Adequacy of risk-reducing gynaecologic surgery in BRCA1 or BRCA2 mutation carriers and other women at high risk of pelvic serous cancer.

The aim of this study was to describe the type of risk-reducing gynaecologic surgery (RRGS) and the extent of pathological evaluation being undertaken for Australasian women at high familial risk of pelvic serous cancer. Surgical and pathology reports were reviewed for women with BRCA1/BRCA2 mutations, or a family history of breast and ovarian cancer, who underwent RRGS between 1998 and 2008. "Adequate" surgery was defined as complete removal of all ovarian and extra-uterine fallopian tube tissue. "Adequate" pathology was defined as paraffin embedding of all removed ovarian and tubal tissue. Predictors of adequacy were assessed using logistic regression. There were 201 women, including 173 mutation carriers, who underwent RRGS. Of these, 91% had adequate surgery and 23% had adequate pathology. Independent predictors of adequate surgery were surgeon type (OR = 20; 95% CI 2-167; P = 0.005 for gynaecologic oncologists versus general gynaecologists), more recent surgery (OR = 1.33/year; 95% CI 1.07-1.67; P = 0.012) and younger patient age (OR = 0.93/year of age; 95% CI 0.87-0.99; P = 0.028). Independent predictors of adequate pathology were more recent surgery (OR = 1.26/year; 95% CI 1.06-1.49; P = 0.008) and surgeon type (OR = 3.1; 95% CI 1.4-6.7; P = 0.004 for gynaecologic oncologists versus general gynaecologists). Four serous ovarian cancers and one endometrioid endometrial cancer were detected during surgery or pathological examination. In conclusion Australasian women attending a specialist gynaecologic oncologist for RRGS are most likely to have adequate surgery and pathological examination. Additional education of clinicians and consumers is needed to ensure optimal surgery and pathology in these women.