Circulating tumour cells early predict progression-free and overall survival in advanced colorectal cancer patients treated with chemotherapy and targeted agents

Background: Early predictive markers for response are needed for advanced colorectal cancer (ACC) patients. We assessed the value of circulating tumour cells (CTC) in ACC patients treated with chemotherapy plus targeted agents (CAIRO2 phase III trial) and compared the results with computed tomography (CT) imaging.Materials and methods: CTC were determined at baseline and at different time points during treatment. Patients were stratified into low (less than three CTC per 7.5 ml of blood) or high CTC (three or more CTC per 7.5 ml of blood).Results: A total of 467 patients were assessable for CTC analysis. Among them, 129 patients (29%) with high baseline CTC had a significantly decreased progression-free survival [PFS; hazard ratio (HR) 1.5] and overall survival (OS; HR 2.2) compared with 322 patients with low baseline CTC. This difference remained statistically significant during treatment. The sensitivity and specificity of high CTC at baseline for the prediction of progressive disease on CT imaging were 16.7% and 70.1%, respectively, and of high CTC at 1–2 weeks after the start of treatment 20.0% and 95.1%, respectively. The combined analysis of CTC and CT imaging provided a more accurate outcome assessment than either modality alone.Conclusions: The CTC count before and during treatment independently predicts PFS and OS in ACC patients treated with chemotherapy plus targeted agents and provides additional information to CT imaging.     

Circulating endothelial cells in cancer patients do not express tissue factor

Numbers of circulating endothelial cells (CECs) are increased in cancer patients with progressive disease. Also, cancer patients have an increased risk for thrombotic events, being negatively associated with prognosis. Tissue factor (TF), the physiological initiator of coagulation, is present on the surface of many extravascular cells. In 34 samples from cancer patients and in seven from volunteers, CECs were quantified (with endothelium-specific anti-CD146 beads), and TF-activity assessed with a chromogenic assay. All samples displayed very limited TF-activity (patients: 1.6+/-3.1 microU; volunteers: 0.94+/-1.7 microU FXa/100 CECs, P = 0.30 by Mann-Whitney test). After in vitro TNFalpha-stimulation, CECs from both cancer patients and volunteers showed substantially increased TF-activity (endogenous activity: 17.3+/-6.4 microU; after TNFalpha-stimulation: 73.8+/-34.3 microU FXa; P = 0.028, Wilcoxon signed ranks test), reflecting the potential of CECs to generate biologically active TF. As the chromogenic assay determines a mean cellular TF-activity, we also analyzed immunohistochemical TF-antigen expression on CEC subsets. TF-antigen expression was undetectable. CECs isolated from cancer patients do not express TF. CECs can generate functional TF after stimulation and may therefore play a role in (intratumoral) coagulation induction and tumor angiogenesis.     

PTEN loss in circulating tumour cells correlates with PTEN loss in fresh tumour tissue from castration-resistant prostate cancer patients

Background:

PTEN gene loss occurs frequently in castration-resistant prostate cancer (CRPC) and may drive progression through activation of the PI3K/AKT pathway. Here, we developed a novel CTC-based assay to determine PTEN status and examined the correlation between PTEN status in CTCs and matched tumour tissue samples.

Methods:

PTEN gene status in CTCs was evaluated on an enrichment-free platform (Epic Sciences) by fluorescence in situ hybridisation (FISH). PTEN status in archival and fresh tumour tissue was evaluated by FISH and immunohistochemistry.

Results:

Peripheral blood was collected from 76 patients. Matched archival and fresh cancer tissue was available for 48 patients. PTEN gene status detected in CTCs was concordant with PTEN status in matched fresh tissues and archival tissue in 32 of 38 patients (84%) and 24 of 39 patients (62%), respectively. CTC counts were prognostic (continuous, P=0.001). PTEN loss in CTCs associated with worse survival in univariate analysis (HR 2.05; 95% CI 1.17–3.62; P=0.01) and with high lactate dehydrogenase (LDH) in metastatic CRPC patients.

Conclusions:

Our results illustrate the potential use of CTCs as a non-invasive, real-time liquid biopsy to determine PTEN gene status. The prognostic and predictive value of PTEN in CTCs warrants investigation in CRPC clinical trials of PI3K/AKT-targeted therapies.     

Circulating tumour cells in prostate cancer patients receiving salvage radiotherapy

Introduction

Within 10 years of radical prostatectomy (RP), up to 30% of prostate cancer (PCa) patients will have a rise in prostate-specific antigen (PSA), requiring radiation therapy (RT). However, with current technology, distinction between local and distant recurrent PCa is not possible. This lack of an accurate test constrains the decision whether to offer systemic or local treatment. We hypothesise tests for detecting circulating tumour cells (CTCs) within the blood may assist with clinical decision-making and in this pilot study we investigated whether CTCs could be detected in this patient population using the CellSearch® system.

Materials and methods

Blood samples were collected from PCa patients (n=26) prior to RT and 3 months following completion of RT. Samples were analysed for PSA level via immunoassay and CTC number using the CellSearch® system.

Results

CTCs could be detected in this patient population and following RT CTCs appeared to decrease. However, no association was observed between a higher PSA and an increased number of CTCs pre- or post-RT. Interestingly, patients who failed RT trended toward an increased/unchanged number of CTCs following RT vs. a decreased number in patients with RT response.

Conclusions

Our results demonstrate that CTCs can be detected in early-stage PCa and suggest the possibility that post-treatment reduction in CTC levels may be indicative of RT response. We are currently evaluating CTCs in a larger cohort of patients to validate our preliminary findings and further investigate the prognostic value of CTCs in this patient population.

     

A prognostic index model for predicting overall survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate after docetaxel

BackgroundFew prognostic models for overall survival (OS) are available for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with recently approved agents. We developed a prognostic index model using readily available clinical and laboratory factors from a phase III trial of abiraterone acetate (hereafter abiraterone) in combination with prednisone in post-docetaxel mCRPC.Patients and methodsBaseline data were available from 762 patients treated with abiraterone–prednisone. Factors were assessed for association with OS through a univariate Cox model and used in a multivariate Cox model with a stepwise procedure to identify those of significance. Data were validated using an independent, external, population-based cohort.ResultsSix risk factors individually associated with poor prognosis were included in the final model: lactate dehydrogenase > upper limit of normal (ULN) [hazard ratio (HR) = 2.31], Eastern Cooperative Oncology Group performance status of 2 (HR = 2.19), presence of liver metastases (HR = 2.00), albumin ≤4 g/dl (HR = 1.54), alkaline phosphatase > ULN (HR = 1.38) and time from start of initial androgen-deprivation therapy to start of treatment ≤36 months (HR = 1.30). Patients were categorized into good (n = 369, 46%), intermediate (n = 321, 40%) and poor (n = 107, 13%) prognosis groups based on the number of risk factors and relative HRs. The C-index was 0.70 ± 0.014. The model was validated by the external dataset (n = 286).ConclusionThis analysis identified six factors used to model survival in mCRPC and categorized patients into three distinct risk groups. Prognostic stratification with this model could assist clinical practice decisions for follow-up and monitoring, and may aid in clinical trial design.Trial registration numbersNCT00638690.     

Androgen receptor expression in circulating tumour cells from castration-resistant prostate cancer patients treated with novel endocrine agents

Background:

Abiraterone and enzalutamide are novel endocrine treatments that abrogate androgen receptor (AR) signalling in castration-resistant prostate cancer (CRPC). Here, we developed a circulating tumour cells (CTCs)-based assay to evaluate AR expression in real-time in CRPC and investigated nuclear AR expression in CTCs in patients treated with enzalutamide and abiraterone.

Methods:

CTCs were captured and characterised using the CellSearch system. An automated algorithm to identify CTCs and quantify AR expression was employed. The primary aim was to evaluate the association between CTC AR expression and prior treatment with abiraterone or enzalutamide.

Results:

AR expression in CTCs was evaluated in 94 samples from 48 metastatic CRPC patients. We observed large intra-patient heterogeneity of AR expression in CTCs. Prior exposure to abiraterone or enzalutamide was not associated with a change in CTCs AR expression (median intensity and distribution of AR-positive classes). In support of this, we also confirmed maintained nuclear AR expression in tissue samples collected after progression on abiraterone. AR staining also identified additional AR-positive CD45-negative circulating cells that were CK-negative/weak and therefore missed using standard protocols. The number of these events correlated with traditional CTCs and was associated with worse outcome on univariate analysis.

Conclusions:

We developed a non-invasive method to monitor AR nuclear expression in CTCs. Our studies confirm nuclear AR expression in CRPC patients progressing on novel endocrine treatments. Owing to the significant heterogeneity of AR expression in CTCs, studies in larger cohorts of patients are required to identify associations with outcome.     

Relationship among circulating tumor cells,CEA and overall survival in patients with metastatic colorectal cancer

BackgroundWe previously reported results of a prospective trial evaluating the significance of circulating tumor cells (CTCs) in patients with metastatic colorectal cancer (mCRC). This secondary analysis assessed the relationship of the CTC number with carcinoembryonic antigen (CEA) and overall survival.Patients and methodsPatients with mCRC had CTCs measured at baseline and specific time points after the initiation of new therapy. Patients with a baseline CEA value ≥10 ng/ml and CEA measurements within ±30 days of the CTC collection were included.ResultsWe included 217 patients with mCRC who had a CEA value of ≥10 ng/ml. Increased baseline CEA was associated with shorter survival (15.8 versus 20.7 months, P = 0.012). Among all patients with a baseline CEA value of ≥25 ng/ml, patients with low baseline CTCs (<3, n = 99) had longer survival than those with high CTCs (≥3, n = 58; 20.8 versus 11.7 months, P = 0.001). CTCs added prognostic information at the 3–5- and 6–12-week time points regardless of CEA. In a multivariate analysis, CTCs at baseline but not CEA independently predicted survival and both CTCs and CEA independently predicted survival at 6–12 weeks.ConclusionsThis study demonstrates that both CEA and CTCs contribute prognostic information for patients with mCRC.     

Analysis of overall survival in patients with nonmetastatic castration-resistant prostate cancer treated with vaccine, nilutamide, and combination therapy

PURPOSE: We reported previously the first randomized study of any kind in patients with nonmetastatic, castrate-resistant prostate cancer. The study employed vaccine, the hormone nilutamide, and the combined therapy (crossover for each arm) with an endpoint of time to progression. We now report survival analyses at 6.5 years from the initiation of therapy with a median potential follow-up of 4.4 years. EXPERIMENTAL DESIGN: Forty-two patients were randomized to receive either a poxvirus-based prostate-specific antigen (PSA) vaccine or nilutamide. Patients in either arm who developed increasing PSA without radiographic evidence of metastasis could cross over to receive the combined therapies. RESULTS: Median survival among all patients was 4.4 years from date of enrollment. Median survival exhibited a trend toward improvement for patients initially randomized to the vaccine arm (median, 5.1 versus 3.4 years; P = 0.13). Starting from the on-study date, the retrospectively determined subset of 12 patients who initially received vaccine and then later received nilutamide suggested improved survival compared with the 8 patients who began with nilutamide and subsequently were treated with vaccine (median, 6.2 versus 3.7 years; P = 0.045). A subgroup analysis of patients randomized to the vaccine arm versus the nilutamide arm showed substantial improvements in survival if at baseline patients had a Gleason score <7 (P = 0.033) and PSA <20 ng/dL (P = 0.013) or who had prior radiation therapy (P = 0.018). CONCLUSIONS: These data indicate that patients with nonmetastatic castration-resistant prostate cancer (D0.5) who receive vaccine before second-line hormone therapy may potentially result in improved survival compared with patients who received hormone therapy and then vaccine. These data also suggest that patients with more indolent disease may derive greater clinical benefit from vaccine alone or vaccine before second-line hormone therapy compared with hormone therapy alone or hormone therapy followed by vaccine. These findings have potential implications for both the design and endpoint analysis of larger vaccine combination therapy trials.     

Reduced-dose docetaxel for castration-resistant prostate cancer has no inferior impact on overall survival in Japanese patients

Background

In clinical practice, an adapted regimen with dose reduction is applied to castration-resistant prostate cancer (CRPC) treated with docetaxel because of its toxicity. However, there are few reports on the impact of dose reduction on survival.

Methods

Fifty-seven patients with CRPC treated with first-line docetaxel in a single institution from 2005 to 2008 were evaluated retrospectively.

Results

The median follow-up period was 20.5 months. Twenty-eight patients (49 %) received a standard 60 mg/m² regimen (SR), and 29 patients (51 %) received an adapted regimen (AR) with dose reduction. There was no difference in their baseline characteristics. The prostate-specific antigen response rates were not significantly different between the SR and AR groups (50 vs. 62 %, p = 0.36). Progression-free survival (PFS) and overall survival (OS) were also not significantly different between the groups (PFS 5.3 vs. 7.3 months, p = 0.39; OS 26.4 vs. 27.1 months, p = 0.53, respectively). No significant difference in the incidence of grade 3 or 4 adverse events was noted between the groups (89 vs. 83 %, p = 0.70). In multivariate analysis, hemoglobin and alkaline phosphatase were significant predictive factors for OS (hazard ratios 2.81 and 2.39, p = 0.012 and 0.024, respectively).

Conclusions

A reduced-dose regimen of docetaxel has no inferior impact on OS. Further studies on the optimal dose of docetaxel for Japanese patients are required.     

Marker genes for circulating tumour cells predict survival in metastasized breast cancer patients

We investigated the prognostic significance of circulating breast cancer cells in peripheral blood detected by quantitative RT-PCR of marker genes in patients with advanced breast cancer. Blood samples from 94 breast cancer patients with metastatic disease (M1) were examined for circulating tumour cells by studying the mRNA expression of CK19, p1B, PS2 and EGP2 by real-time PCR. Using a score function, developed for predicting circulating tumour cells by quadratic discriminant analysis (QDA), the four expression levels were combined into a single discriminant value. Tumour cells were present in 24 out of 94 (31%) of the patients. In 77% (72 out of 94) of the patients distant metastatic disease was localised in the bone. In 36% (26 out of 72) of the patients with bone metastases at the time of blood sampling, a positive QDA for the four genes was found, in contrast to only 14% (three out of 22) without bone involvement. Overall survival rates by Kaplan-Meier revealed no prognostic effect for the presence of bone metastases (P=0.93). However, patients with a positive QDA value did have a progression-free survival at 1 year of 3% and overall survival at 2 years of 17%, against 22 and 36% for patients with a negative QDA value (P=0.015 and 0.0053, respectively). Breast cancer patients with metastatic disease have a significantly worse progression-free and overall survival when circulating tumour cells can be detected in their peripheral blood.     

PIAS1 is a crucial factor for prostate cancer cell survival and a valid target in docetaxel resistant cells

Occurrence of an inherent or acquired resistance to the chemotherapeutic drug docetaxel is a major burden for patients suffering from different kinds of malignancies, including castration resistant prostate cancer (PCa). In the present study we address the question whether PIAS1 targeting can be used to establish a basis for improved PCa treatment. The expression status and functional relevance of PIAS1 was evaluated in primary tumors, in metastatic lesions, in tissue of patients after docetaxel chemotherapy, and in docetaxel resistant cells. Patient data were complemented by functional studies on PIAS1 knockdown in vitro as well as in chicken chorioallantoic membrane and mouse xenograft in vivo models. PIAS1 was found to be overexpressed in local and metastatic PCa and its expression was further elevated in tumors after docetaxel treatment as well as in docetaxel resistant cells. Furthermore, PIAS1 knockdown experiments revealed an increased expression of tumor suppressor p21 and declined expression of anti-apoptotic protein Mcl1, which caused diminished cell proliferation and tumor growth in vitro and in vivo. In summary, the presented data indicate that PIAS1 is crucial for parental and docetaxel resistant PCa cell survival and is therefore a promising new target for treatment of primary, metastatic, and chemotherapy resistant PCa.     

The quest for the 'bony Grail' of detecting circulating tumour cells in patients with prostate cancer

Prostate cancer is the most common cancer and the second leadingcause of death from cancer in males in most Western countries.Most prostate cancer deaths are caused by haematogenous metastaticspread and subsequent tumour cell growth in distant organs,especially the bones [1]. Currently, treatment of patients withdisseminated prostate cancer is based on direct cytotoxicityagainst tumour cells, via androgen deprivation therapy or docetaxel-basedchemotherapy [2]. Cells shed by carcinoma circulate in the blood of patients withsolid tumours and circulating tumour cells (CTCs) are presentin patients with various carcinomas with a wide range of incidencesand frequencies [3]. The detection of CTCs in cancer patientsyields prognostic information and might help tailor systemictherapies to the individual needs of cancer patients [4]. A major problem in the evaluation of the treatment of advancedprostate     

Prognostic significance of circulating tumor cells in advanced non-small cell lung cancer patients treated with docetaxel and gemcitabine

Purpose

To evaluate the association in the change of circulating tumor cell (CTC) levels and clinical outcomes (PFS and OS) in patients with advanced non-small cell lung cancer (NSCLC) treated homogenously with docetaxel and gemcitabine administered every 2 weeks.

Methods

We prospectively evaluated 37 patients for CTC levels at baseline and after 2 months of chemotherapy (before third cycle). Detection was carried out with the CellSearch system.

Results

Nine of the 37 patients (24 %) had ≥2 CTCs at the baseline determination. Median progression-free survival (PFS) was 4.3 months (95 % CI 2.5–8.3) for patients with CTC 0–1 as compared to 9.4 months (95 % CI 1.2–12.2) for those with CTC ≥2 (p = 0.3506). Median overall survival (OS) was 8.1 (95 % CI 2.8–16.3) and 12.2 (95 % CI 1.4–12.2) months for patients with 0–1 CTCs and ≥2 CTCs, respectively (p = 0.7639). Patients with a second CTC quantification were classified as: group 1, CTC = 0–1 at baseline and CTC = 0–1 after second chemotherapy cycle (18 patients); group 2, CTC ≥2 at baseline and CTC = 0–1 after second determination (5 patients). Median PFS was 7.7 and 9.9 months for group 1 and group 2, respectively (p = 0.4467).

Conclusions

CTCs ≥2 at baseline were detected only in 24 % of this group of patients with advanced NSCLC and poor performance status. No significant differences in PFS and OS between patients with or without CTCs at baseline were observed.     

Circulating tumor cells versus imaging--predicting overall survival in metastatic breast cancer.

PURPOSE: The presence of >or=5 circulating tumor cells (CTC) in 7.5 mL blood from patients with measurable metastatic breast cancer before and/or after initiation of therapy is associated with shorter progression-free and overall survival. In this report, we compared the use of CTCs to radiology for prediction of overall survival. EXPERIMENTAL DESIGN: One hundred thirty-eight metastatic breast cancer patients had imaging studies done before and a median of 10 weeks after the initiation of therapy. All scans were centrally reviewed by two independent radiologists using WHO criteria to determine radiologic response. CTC counts were determined approximately 4 weeks after initiation of therapy. Specimens were analyzed at one of seven laboratories and reviewed by a central laboratory. RESULTS: Interreader variability for radiologic responses and CTC counts were 15.2% and 0.7%, respectively. The median overall survival of 13 (9%) patients with radiologic nonprogression and >or=5 CTCs was significantly shorter than that of the 83 (60%) patients with radiologic nonprogression and <5 CTCs (15.3 versus 26.9 months; P=0.0389). The median overall survival of the 20 (14%) patients with radiologic progression and <5 CTCs was significantly longer than the 22 (16%) patients with >or=5 CTCs that showed progression by radiology (19.9 versus 6.4 months; P=0.0039). CONCLUSIONS: Assessment of CTCs is an earlier, more reproducible indication of disease status than current imaging methods. CTCs may be a superior surrogate end point, as they are highly reproducible and correlate better with overall survival than do changes determined by traditional radiology.     

Clinical value of circulating endothelial cells and circulating tumor cells in metastatic breast cancer patients treated first line with bevacizumab and chemotherapy

BackgroundWe investigated whether circulating tumor cells (CTCs) and circulating endothelial cells (CECs) predict clinical outcome of first-line chemotherapy combined with bevacizumab in metastatic breast cancer patients.Patients and methodsIn a French substudy of the MO19391 trial, CTC and CEC counts (CellSearch system) at baseline and changes after two cycles of treatment were correlated with time to progression (TtP).ResultsCTC and CEC levels were not correlated in the 67 patients included. At baseline, CTC positivity was a significant prognostic marker for TtP at a threshold of 3 CTC/7.5 ml (P < 0.05) but not at 5 CTC/7.5 ml (P = 0.09). Baseline CEC levels (median 17 CEC/4 ml, range 1–769) were associated with age ≥45 years (P = 0.01), elevated lactate dehydrogenase (P < 0.01) and not with TtP at any threshold. Changes of CTC count during treatment were not a surrogate of TtP, with any of the model tested (threshold based or relative decrease in percent). However, increase in CEC count was associated with improved TtP, at the threshold of 20 CEC/4 ml (P < 0.01).ConclusionBevacizumab combined with first-line chemotherapy may modify the predictive value of CTC during treatment possibly due to impaired tumor cells intravasation through vessels endothelium. Variations in CEC levels appear to be a promising early surrogate marker of TtP under antiangiogenic treatment.     

Hypertension and overall survival in metastatic colorectal cancer patients treated with bevacizumab-containing chemotherapy

Background:

Hypertension (HTN) is a common toxicity of anti-VEGF (vascular endothelial growth factor) antibody treatment. It may be a marker of VEGF signalling pathway inhibition and therefore represent a cancer biomarker in metastatic colorectal cancer (mCRC) patients treated with chemotherapy and bevacizumab.

Methods:

A total of 101 consecutive patients with mCRC were treated with standard chemotherapy combined with bevacizumab at dose of 2.5 mg kg⁻¹ per week in a single centre. The median follow-up time of the patients alive was 64 months. Blood pressure was measured before each bevacizumab infusion, and HTN was graded according to common toxicity criteria for adverse events version 3.0.

Results:

Overall, 57 patients (56%) developed ⩾grade 1 HTN (median blood pressure 168/97 mm Hg), whereas 44 (44%) remained normotensive when treated with bevacizumab-containing chemotherapy regimen. Overall response rate was higher among patients with HTN (30 vs 20% P=0.025). Hypertension was associated with improved progression-free survival (10.5 vs 5.3 months; P=0.008) and overall survival (25.8 vs 11.7 months; P<0.001), and development of HTN within 3 months had an independent, prognostic influence in a multivariate landmark survival analysis together with other known mCRC prognostic factors (P=0.007). There was no association between HTN and development of thromboembolic complications.

Conclusion:

Hypertension may predict outcome of bevacizumab-containing chemotherapy in mCRC. These data require confirmation in prospective studies including pharmacodynamic and pharmacokinetic analyses.     

Metastasis-free survival is associated with overall survival in men with PSA-recurrent prostate cancer treated with deferred androgen deprivation therapy

BackgroundClinical trials in men with biochemically recurrent prostate cancer (BRPC) have been hampered by long survival times, making overall survival (OS) a difficult end point to reach. Intermediate end points are needed in order to conduct such trials within a more feasible time frame.Patients and methodsThis is a retrospective analysis of 450 men with BRPC following prostatectomy treated at a single institution between 1981 and 2010, of which 140 developed subsequent metastases. Androgen deprivation therapy (ADT) was deferred until after the development of metastases. Cox regression models were developed to investigate factors influencing OS.ResultsMedian metastasis-free survival (MFS) was 10.2 years [95% confidence interval (CI) 7.6–14.0 years]; median OS after metastasis was 6.6 years (95%CI 5.8–8.4 years). Multivariable Cox regressions identified four independently prognostic variables for OS: MFS (HR 0.77; 95% CI 0.63–0.94), number of metastases (≤3 versus ≥4; HR 0.50; 95% CI 0.29–0.85), pain (absent versus present; HR 0.43; 95% CI 0.25–0.72), and bisphosphonate use (yes versus no; HR 0.60; 95% CI 0.37–0.98).ConclusionsMFS emerged as an independent predictor of OS in men with BRPC treated with deferred ADT after the development of metastases. MFS may be a reasonable intermediate end point in future clinical trials. This observation requires prospective validation.     

Docetaxel dose-intensity effect on overall survival in patients with metastatic castrate-sensitive prostate cancer

Several studies assessed the association of docetaxel dose intensity (DI) and efficacy in metastatic castrate-resistant prostate cancer (mCRPC) patients with contradicting conclusions. In this retrospective analysis, we will assess whether the docetaxel DI used in patients with metastatic castrate-sensitive prostate cancer (mCSPC) is associated with overall survival (OS). All patients with mCSPC treated at The Ottawa Hospital Cancer Centre that received docetaxel chemotherapy between June 2014 and September 2017 were identified. The association between relative dose intensity (RDI) and OS was assessed using univariate and multivariable Cox model adjusting for age, Gleason score, burden of disease, visceral involvement, de novo metastases and baseline prostate-specific antigen (PSA). Eighty-one patients were included in the analysis. Only 35 patients (43%) were able to complete the planned treatment with a RDI of at least 90%. On a univariate analysis, higher RDI and number of cycles of docetaxel received were associated with longer OS. For every 10% decrease in RDI, the risk of death increased by 23% (HR 1.23, 95% CI 1.09–1.4, P = 0.001). For every increment of one cycle (and up to six), the risk of death decreased by 27% (HR 0.73, 95% CI 0.61–0.88, P = 0.001). On multivariate analysis, reduced RDI was the only predictor significantly associated with OS (HR 1.18, 95% CI 1.02–1.36, P = 0.026). Our study suggests that in mCSPC, reduced docetaxel RDI is associated with shorter survival. Unnecessary dose reductions, treatment delays and early discontinuation should be avoided. Granulocyte colony-stimulating factor may be considered to maintain standard DI.