Early participant-reported symptoms as predictors of adherence to anastrozole in the International Breast Cancer Intervention Studies II.

Background: Anastrozole reduces breast cancer risk in women at high risk, but implementing preventive therapy in clinical practice is difficult. Here, we evaluate adherence to anastrozole in the International Breast Cancer Intervention Study (IBIS)-II prevention and ductal carcinoma in situ (DCIS) trials, and its association with early symptoms. Patients and methods: In the prevention trial, 3864 postmenopausal women were randomized to placebo versus anastrozole. A total of 2980 postmenopausal women with DCIS were randomized to tamoxifen versus anastrozole. Adherence to trial medication was calculated using the Kaplan-Meier method and all P-values were two-sided. Results: In the prevention trial, adherence was 65.8% [anastrozole (65.7%) versus placebo (65.9%); HR = 0.97 (0.87-1.09), P = 0.6]. Adherence was lower for those reporting arthralgia in the placebo group (P = 0.02) or gynecological symptoms in the anastrozole group (P = 0.003), compared with those not reporting these symptoms at 6 months. In the DCIS study, adherence was 66.7% [anastrozole (67.5%) versus tamoxifen (65.8%); HR = 1.06 (0.94-1.20), P = 0.4]. Hot flashes were associated with greater adherence in the anastrozole arm (P = 0.02). In both studies, symptoms were mostly mild or moderately severe, and adherence decreased with increasing severity for most symptoms. Drop-outs were highest in the first 1.5 years of therapy in both trials. Conclusions: In the IBIS-II prevention and DCIS trials, over two-thirds of women were adherent to therapy, with no differences by treatment groups. Participants who reported specific symptoms in the IBIS-II prevention trial had a small but significant effect on adherence, which strengthened as severity increased. Strategies to promote adherence should target the first year of preventive therapy.

De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017.

The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were assessed in light of their intensity, duration and side-effects, seeking where appropriate to escalate or de-escalate therapies based on likely benefits as predicted by tumor stage and tumor biology. The Panel favored several interventions that may reduce surgical morbidity, including acceptance of 2 mm margins for DCIS, the resection of residual cancer (but not baseline extent of cancer) in women undergoing neoadjuvant therapy, acceptance of sentinel node biopsy following neoadjuvant treatment of many patients, and the preference for neoadjuvant therapy in HER2 positive and triple-negative, stage II and III breast cancer. The Panel favored escalating radiation therapy with regional nodal irradiation in high-risk patients, while encouraging omission of boost in low-risk patients. The Panel endorsed gene expression signatures that permit avoidance of chemotherapy in many patients with ER positive breast cancer. For women with higher risk tumors, the Panel escalated recommendations for adjuvant endocrine treatment to include ovarian suppression in premenopausal women, and extended therapy for postmenopausal women. However, low-risk patients can avoid these treatments. Finally, the Panel recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence. The Panel recognized that recommendations are not intended for all patients, but rather to address the clinical needs of the majority of common presentations. Individualization of adjuvant therapy means adjusting to the tumor characteristics, patient comorbidities and preferences, and managing constraints of treatment cost and access that may affect care in both the developed and developing world.

Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptor-positive breast cancer (ANZ0501 LATER): an open-label randomised, controlled trial.

BACKGROUND: Despite the effectiveness of adjuvant endocrine therapy in preventing breast cancer recurrence, breast cancer events continue at a high rate for at least 10 years after completion of therapy. PATIENTS AND METHODS: This randomised open label phase III trial recruited postmenopausal women from 29 Australian and New Zealand sites, with hormone receptor-positive early breast cancer, who had completed ≥4 years of endocrine therapy [aromatase inhibitor (AI), tamoxifen, ovarian suppression, or sequential combination] ≥1 year prior, to oral letrozole 2.5 mg daily for 5 years, or observation. Treatment allocation was by central computerised randomisation, stratified by institution, axillary node status and prior endocrine therapy. The primary outcome was invasive breast cancer events (new invasive primary, local, regional or distant recurrence, or contralateral breast cancer), analysed by intention to treat. The secondary outcomes were disease-free survival (DFS), overall survival, and safety. RESULTS: Between 16 May 2007 and 14 March 2012, 181 patients were randomised to letrozole and 179 to observation (median age 64.3 years). Endocrine therapy was completed at a median of 2.6 years before randomisation, and 47.5% had tumours of >2 cm and/or node positive. At 3.9 years median follow-up (interquartile range 3.1-4.8), 2 patients assigned letrozole (1.1%) and 17 patients assigned observation (9.5%) had experienced an invasive breast cancer event (difference 8.4%, 95% confidence interval 3.8% to 13.0%, log-rank test P = 0.0004). Twenty-four patients (13.4%) in the observation and 14 (7.7%) in the letrozole arm experienced a DFS event (log-rank P = 0.067). Adverse events linked to oestrogen depletion, but not serious adverse events, were more common with letrozole. CONCLUSION: These results should be considered exploratory, but lend weight to emerging data supporting longer duration endocrine therapy for hormone receptor-positive breast cancer, and offer insight into reintroduction of AI therapy. CLINICAL TRIALS NUMBER: Australian New Zealand Clinical Trials Registry (www.anzctr.org.au), ACTRN12607000137493.

Factors affecting uptake and adherence to breast cancer chemoprevention: a systematic review and meta-analysis.

BACKGROUND: Preventive therapy is a risk reduction option for women who have an increased risk of breast cancer. The effectiveness of preventive therapy to reduce breast cancer incidence depends on adequate levels of uptake and adherence to therapy. We aimed to systematically review articles reporting uptake and adherence to therapeutic agents to prevent breast cancer among women at increased risk, and identify the psychological, clinical and demographic factors affecting these outcomes. DESIGN: Searches were carried out in PubMed, CINAHL, EMBASE and PsychInfo, yielding 3851 unique articles. Title, abstract and full text screening left 53 articles, and a further 4 studies were identified from reference lists, giving a total of 57. This review was prospectively registered with PROSPERO (CRD42014014957). RESULTS: Twenty-four articles reporting 26 studies of uptake in 21 423 women were included in a meta-analysis. The pooled uptake estimate was 16.3% [95% confidence interval (CI) 13.6-19.0], with high heterogeneity (I(2) = 98.9%, P < 0.001). Uptake was unaffected by study location or agent, but was significantly higher in trials [25.2% (95% CI 18.3-32.2)] than in non-trial settings [8.7% (95% CI 6.8-10.9)] (P < 0.001). Factors associated with higher uptake included having an abnormal biopsy, a physician recommendation, higher objective risk, fewer side-effect or trial concerns, and older age. Adherence (day-to-day use or persistence) over the first year was adequate. However, only one study reported a persistence of ≥ 80% by 5 years. Factors associated with lower adherence included allocation to tamoxifen (versus placebo or raloxifene), depression, smoking and older age. Risk of breast cancer was discussed in all qualitative studies. CONCLUSION: Uptake of therapeutic agents for the prevention of breast cancer is low, and long-term persistence is often insufficient for women to experience the full preventive effect. Uptake is higher in trials, suggesting further work should focus on implementing preventive therapy within routine care.

PIK3CA Mutation, Aspirin Use after Diagnosis and Survival of Colorectal Cancer. A Systematic Review and Meta-analysis of Epidemiological Studies.

AIMS: Regular aspirin use has been associated with inhibition of the whole spectrum of colorectal carcinogenesis, including prevention of metastases and reduced total mortality in colorectal cancer. Preclinical data show that aspirin down-regulates PI3 kinase (PI3K) signalling activity through cyclo-oxygenase-2 (COX-2) inhibition, leading to the hypothesis that the effect of aspirin might be different according to PIK3CA mutational status, but epidemiological studies have led to conflicting results. The aim of this study was to assess the relationship between PIK3CA status and the efficacy of regular use of aspirin after diagnosis on overall survival in colorectal cancer patients. MATERIALS AND METHODS: We identified studies that compared post-diagnosis aspirin efficacy in colorectal cancer patients identified by PIK3CA status. Hazard ratios for overall survival were meta-analysed according to PIK3CA status by inverse variance weighting. A pooled test for treatment by PIK3CA status interaction was carried out by weighted linear meta-regression. All statistical tests were two-sided. RESULTS: The overall effect of aspirin was not significant (summary risk estimate = 0.82; 95% confidence interval 0.63-1.08, P = 0.16; I(2) = 57%). In PIK3CA mutant disease (n = 588), aspirin use reduced total mortality by 29% (summary risk estimate = 0.71; 95% confidence interval 0.51-0.99, P = 0.04; I(2) = 0%), whereas in PIK3CA wild-type disease (n = 4001), aspirin use did not reduce overall mortality (summary risk estimate = 0.93; 95% confidence interval 0.61-1.40; P = 0.7; I(2) = 80%) (P interaction = 0.39). There was a beneficial trend for aspirin on cancer-specific survival in PI3KCA mutated subjects (summary risk estimate = 0.37, 95% confidence interval 0.11-1.32, P = 0.1), albeit with high heterogeneity (Q chi-squared = 3.41, P = 0.07, I(2) = 70.7%). CONCLUSION: These findings suggest that the benefit of post-diagnosis aspirin treatment on overall mortality in colorectal cancer may be more marked in PIK3CA mutated tumours, although the low number of studies prevents definitive conclusions. Trials addressing this issue are warranted to assess the efficacy of aspirin in the adjuvant setting.

Statistical controversies in clinical research: long-term follow-up of clinical trials in cancer.

Long-term follow-up is an important unmet need for the full analysis of new treatments for cancer. Earlier detection of cancer and more effective treatment have led to many more patients surviving for more than 5 and even 10 years, so that evaluating late recurrences and side-effects is an increasingly important issue. This is particularly relevant for oestrogen receptor-positive breast cancer, where the existence of late recurrences is well documented. However, survival for other cancers, notably prostate, colorectal and cervix cancer, has dramatically increased in recent years due to screening and better treatment of early lesions. Trials of preventive therapies have an even greater need for long follow-up. Here, we review these issues and suggest ways in which provision for long-term follow-up can be improved.

Validation of an RNA cell cycle progression score for predicting death from prostate cancer in a conservatively managed needle biopsy cohort.

BACKGROUND: The natural history of prostate cancer is highly variable and difficult to predict accurately. Better markers are needed to guide management and avoid unnecessary treatment. In this study, we validate the prognostic value of a cell cycle progression score (CCP score) independently and in a prespecified linear combination with standard clinical variables, that is, a clinical-cell-cycle-risk (CCR) score. METHODS: Paraffin sections from 761 men with clinically localized prostate cancer diagnosed by needle biopsy and managed conservatively in the United Kingdom, mostly between 2000 and 2003. The primary end point was prostate cancer death. Clinical variables consisted of centrally reviewed Gleason score, baseline PSA level, age, clinical stage, and extent of disease; these were combined into a single predefined risk assessment (CAPRA) score. Full data were available for 585 men who formed a fully independent validation cohort. RESULTS: In univariate analysis, the CCP score hazard ratio was 2.08 (95% CI (1.76, 2.46), P<10(-13)) for one unit change of the score. In multivariate analysis including CAPRA, the CCP score hazard ratio was 1.76 (95% CI (1.44, 2.14), P<10(-6)). The predefined CCR score was highly predictive, hazard ratio 2.17 (95% CI (1.83, 2.57), χ(2)=89.0, P<10(-20)) and captured virtually all available prognostic information. CONCLUSIONS: The CCP score provides significant pretreatment prognostic information that cannot be provided by clinical variables and is useful for determining which patients can be safely managed conservatively, avoiding radical treatment.

Background risk of breast cancer influences the association between alcohol consumption and mammographic density.

BACKGROUND: Alcohol consumption has been suggested to increase risk of breast cancer through a mechanism that also increases mammographic density. Whether the association between alcohol consumption and mammographic density is modified by background breast cancer risk has, however, not been studied. METHODS: We conducted a population-based cross-sectional study of 53 060 Swedish women aged 40-74 years. Alcohol consumption was assessed using a web-based self-administered questionnaire. Mammographic density was measured using the fully-automated volumetric Volpara method. The Tyrer-Cuzick prediction model was used to estimate risk of developing breast cancer in the next 10 years. Linear regression models were used to evaluate the association between alcohol consumption and volumetric mammographic density and the potential influence of Tyrer-Cuzick breast cancer risk. RESULTS: Overall, increasing alcohol consumption was associated with higher absolute dense volume (cm(3)) and per cent dense volume (%). The association between alcohol consumption and absolute dense volume was most pronounced among women with the highest (⩾5%) Tyrer-Cuzick 10-year risk. Among high-risk women, women consuming 5.0-9.9, 10.0-19.9, 20.0-29.9, and 30.0-40.0 g of alcohol per day had 2.6 cm(3) (95% confidence interval (CI), 0.2-4.9), 2.9 cm(3) (95% CI, -0.6 to 6.3), 4.6 cm(3) (95% CI, 1.5-7.7), and 10.8 cm(3) (95% CI, 4.8-17.0) higher absolute dense volume, respectively, as compared with women abstaining from alcohol. A trend of increasing alcohol consumption and higher absolute dense volume was seen in women at low (⩽3%) risk, but not in women at moderate (3.0-4.9%) risk. CONCLUSION: Alcohol consumption may increase breast cancer risk through increasing mammographic density, particularly in women at high background risk of breast cancer.

Identifying clinically relevant prognostic subgroups of postmenopausal women with node-positive hormone receptor-positive early-stage breast cancer treated with endocrine therapy: a combined analysis of ABCSG-8 and ATAC using the PAM50 risk of recurrence score and intrinsic subtype.

BACKGROUND: In the adjuvant treatment of hormone receptor-positive (HR+) breast cancer, variables like tumour size, grade and nodal status have great impact on therapy decisions. As most node-positive patients with HR+ breast cancer currently receive adjuvant chemotherapy improved methods for characterization of individuals' metastasis risk are needed to reduce overtreatment. PATIENTS AND METHODS: Tissue specimens from node-positive patients of the ABCSG-8 and ATAC trials who received adjuvant tamoxifen and/or anastrozole were included in this study. Analysing RNA from paraffin blocks using the PAM50 test, the primary objective was to evaluate the prognostic information of the risk of recurrence (ROR) score added to combined clinical standard variables in patients with one positive node (1N+) and in patients with two or three positive nodes (2-3N+), using log-likelihood ratio tests. RESULTS: At a median follow-up of 9.6 years, distant metastases occurred in 97 (18%) of 543 node-positive patients. In a multivariate analysis, the PAM50-derived ROR score provided reliable prognostic information in addition to and beyond established clinical factors for 1N+ (P < 0.0001) and 2-3N+ patients (P = 0.0002). Ten-year distant recurrence risk was significantly increased in the high-risk compared with the low-risk group derived from ROR score for 1N+ [25.5%, 95% confidence interval (CI) 17.5% to 36.1%versus 6.6%, 95% CI 3.3% to 12.8%] and compared with the combined low/intermediate risk group for 2-3N+ patients (33.7%, 95% CI 25.5% to 43.8% versus 12.5%, 95% CI 6.6% to 22.8%). Additionally, the luminal A intrinsic subtype (IS) exhibited significantly lower risk of distant recurrence compared with the luminal B subtype in 1N+ and 2-3N+ patients. CONCLUSION: PAM50 ROR score and IS can identify node-positive patient subgroups with limited risk of metastasis after endocrine therapy, for whom adjuvant chemotherapy can be spared. The PAM50 test is a valuable tool in determining treatment of node-positive early-stage breast cancer patients.

Estimates of benefits and harms of prophylactic use of aspirin in the general population.

BACKGROUND: Accumulating evidence supports an effect of aspirin in reducing overall cancer incidence and mortality in the general population. We reviewed current data and assessed the benefits and harms of prophylactic use of aspirin in the general population. METHODS: The effect of aspirin for site-specific cancer incidence and mortality, cardiovascular events was collated from the most recent systematic reviews. Studies identified through systematic Medline search provided data regarding harmful effects of aspirin and baseline rates of harms like gastrointestinal bleeding and peptic ulcer. RESULTS: The effects of aspirin on cancer are not apparent until at least 3 years after the start of use, and some benefits are sustained for several years after cessation in long-term users. No differences between low and standard doses of aspirin are observed, but there were no direct comparisons. Higher doses do not appear to confer additional benefit but increase toxicities. Excess bleeding is the most important harm associated with aspirin use, and its risk and fatality rate increases with age. For average-risk individuals aged 50-65 years taking aspirin for 10 years, there would be a relative reduction of between 7% (women) and 9% (men) in the number of cancer, myocardial infarction or stroke events over a 15-year period and an overall 4% relative reduction in all deaths over a 20-year period. CONCLUSIONS: Prophylactic aspirin use for a minimum of 5 years at doses between 75 and 325 mg/day appears to have favourable benefit-harm profile; longer use is likely to have greater benefits. Further research is needed to determine the optimum dose and duration of use, to identify individuals at increased risk of bleeding, and to test effectiveness of Helicobacter pylori screening-eradication before starting aspirin prophylaxis.

Improving decision making about clinical trial participation - a randomised controlled trial of a decision aid for women considering participation in the IBIS-II breast cancer prevention trial.

BACKGROUND: Decision aids may improve informed consent in clinical trial recruitment, but have not been evaluated in this context. This study investigated whether decision aids (DAs) can reduce decisional difficulties among women considering participation in the International Breast Cancer Intervention Study-II (IBIS-II) trial. METHODS: The IBIS-II trial investigated breast cancer prevention with anastrazole in two cohorts: women with increased risk (Prevention), and women treated for ductal carcinoma in situ (DCIS). Australia, New Zealand and United Kingdom participants were randomised to receive a DA (DA group) or standard trial consent materials (control group). Questionnaires were completed after deciding about participation in IBIS-II (post decision) and 3 months later (follow-up). RESULTS: Data from 112 Prevention and 34 DCIS participants were analysed post decision (73 DA; 73 control); 95 Prevention and 24 DCIS participants were analysed at follow-up (58 DA; 61 control). There was no effect on the primary outcome of decisional conflict. The DCIS-DA group had higher knowledge post decision, and the Prevention-DA group had lower decisional regret at follow-up. CONCLUSIONS: This was the first study to evaluate a DA in the clinical trial setting. The results suggest DAs can potentially increase knowledge and reduce decisional regret about clinical trial participation.

Uptake of tamoxifen in consecutive premenopausal women under surveillance in a high-risk breast cancer clinic.

BACKGROUND: Randomised trials of tamoxifen versus placebo indicate that tamoxifen reduces breast cancer risk by approximately 33%, yet uptake is low. Approximately 10% of women in our clinic entered the IBIS-I prevention trial. We assess the uptake of tamoxifen in a consecutive series of premenopausal women not in a trial and explore the reasons for uptake through interviews. METHODS: All eligible women between 33 and 46 years at ≥17% lifetime risk of breast cancer and undergoing annual mammography in our service were invited to take a 5-year course of tamoxifen. Reasons for accepting (n=15) or declining (n=15) were explored using semi-structured interviews. RESULTS: Of 1279 eligible women, 136 (10.6%) decided to take tamoxifen. Women >40 years (74 out of 553 (13.4%)) and those at higher non-BRCA-associated risk were more likely to accept tamoxifen (129 out of 1109 (11.6%)). Interviews highlighted four themes surrounding decision making: perceived impact of side effects, the impact of others' experience on beliefs about tamoxifen, tamoxifen as a 'cancer drug', and daily reminder of cancer risk. CONCLUSIONS: Tamoxifen uptake was similar to previously ascertained uptake in a randomised controlled trial (IBIS-I). Concerns were similar in women who did or did not accept tamoxifen. Decision making appeared to be embedded in the experience of significant others.

Focal amplification of the androgen receptor gene in hormone-naive human prostate cancer.

BACKGROUND: Androgen receptor (AR)-gene amplification, found in 20-30% of castration-resistant prostate cancer (CRPCa) is proposed to develop as a consequence of hormone-deprivation therapy and be a prime cause of treatment failure. Here we investigate AR-gene amplification in cancers before hormone deprivation therapy. METHODS: A tissue microarray (TMA) series of 596 hormone-naive prostate cancers (HNPCas) was screened for chromosome X and AR-gene locus-specific copy number alterations using four-colour fluorescence in situ hybridisation. RESULTS: Both high level gain in chromosome X (≥4 fold; n=4, 0.7%) and locus-specific amplification of the AR-gene (n=6, 1%) were detected at low frequencies in HNPCa TMAs. Fluorescence in situ hybridisation mapping whole sections taken from the original HNPCa specimen blocks demonstrated that AR-gene amplifications exist in small foci of cells (≤ 600 nm, ≤1% of tumour volume). Patients with AR gene-locus-specific copy number gains had poorer prostate cancer-specific survival. CONCLUSION: Small clonal foci of cancer containing high level gain of the androgen receptor (AR)-gene develop before hormone deprivation therapy. Their small size makes detection by TMA inefficient and suggests a higher prevalence than that reported herein. It is hypothesised that a large proportion of AR-amplified CRPCa could pre-date hormone deprivation therapy and that these patients would potentially benefit from early total androgen ablation.

Prognostic value of PTEN loss in men with conservatively managed localised prostate cancer.

BACKGROUND: The natural history of prostate cancer is highly variable and difficult to predict. We report on the prognostic value of phosphatase and tensin homologue (PTEN) loss in a cohort of 675 men with conservatively managed prostate cancer diagnosed by transurethral resection of the prostate. METHODS: The PTEN status was assayed by immunohistochemistry (PTEN IHC) and fluorescent in situ hybridisation (PTEN FISH). The primary end point was death from prostate cancer. RESULTS: The PTEN IHC loss was observed in 18% cases. This was significantly associated with prostate cancer death in univariate analysis (hazard ratio (HR)=3.51; 95% CI 2.60-4.73; P=3.1 × 10(-14)). It was highly predictive of prostate cancer death in the 50% of patients with a low risk score based on Gleason score, PSA, Ki-67 and extent of disease (HR=7.4; 95% CI 2.2-24.6; P=0.012) ), but had no prognostic value in the higher risk patients. The PTEN FISH loss was only weakly associated with PTEN IHC loss (κ=0.5). Both PTEN FISH loss and amplification were univariately predictive of death from prostate cancer, but this was not maintained in the multivariate analyses. CONCLUSION: In low-risk patients, PTEN IHC loss adds prognostic value to Gleason score, PSA, Ki-67 and extent of disease.

Comparing the performance of six human papillomavirus tests in a screening population.

BACKGROUND: Several new assays have been developed for high-risk HPV testing of cervical samples; we compare six HPV tests in a screening population. METHODS: Residual material from liquid-based PreservCyt samples was assayed. Four tests (Hybrid Capture 2, Cobas, Abbott and Becton-Dickinson (BD)) measured HPV DNA while two used RNA (APTIMA and NorChip). RESULTS: Positivity rates ranged from 13.4 to 16.3% for the DNA-based tests with a significantly lower positivity rate for the Abbott assay. The Gen-Probe APTIMA assay was positive in 10.3% of women, which was significantly lower than all the DNA tests; the NorChip PreTect HPV-Proofer test was much lower at 5.2%. 40 CIN2+ cases were identified, of which 19 were CIN3+. All CIN3+ cases were HPV positive by all tests except for one, which was negative by the Abbott assay and five which were negative by the NorChip test. CONCLUSION: All HPV tests except NorChip showed high sensitivity for high-grade lesions positive by cytology, suggesting co-testing is unnecessary when using HPV tests. Positivity rates in cytology-negative specimens were similar for the DNA-based tests, but lower for the APTIMA test suggesting this maintains the high sensitivity of DNA tests, but with better specificity.

Prognostic value of Ki-67 for prostate cancer death in a conservatively managed cohort.

BACKGROUND: Standard clinical parameters cannot accurately differentiate indolent from aggressive prostate cancer. Our previous work showed that immunohistochemical (IHC) Ki-67 improved prediction of prostate cancer death in a cohort of conservatively treated clinically localised prostate cancers diagnosed by transurethral resection of the prostate (TURP). Here, we present results in a more clinically relevant needle biopsy cohort. METHODS: Biopsy specimens were microarrayed. The percentage of Ki-67 positively stained malignant cells per core was measured and the maximum score per individual used in analysis of time to death from prostate cancer using a Cox proportional hazards model. RESULTS: In univariate analysis (n=293), the hazard ratio (HR) (95% confidence intervals) for dichotomous Ki-67 (≤ 10%, >10%) was 3.42 (1.76, 6.62) χ(2) (1 df)=9.8, P=0.002. In multivariate analysis, Ki-67 added significant predictive information to that provided by Gleason score and prostate-specific antigen (HR=2.78 (1.42, 5.46), χ(2) (1 df)=7.0, P=0.008). CONCLUSION: The IHC Ki-67 scoring on prostate needle biopsies is practicable and yielded significant prognostic information. It was less informative than in the previous TURP cohort where tumour samples were larger and more comprehensive, but in more contemporary cohorts with larger numbers of biopsies per patient, Ki-67 may prove a more powerful biomarker.