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The impact of time to metastasis on overall survival in patients with prostate cancer

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Abstract

Purpose

Time to metastasis is often used as a surrogate parameter of treatment success in clinical trials for prostate cancer. However, it has not been shown that there is a clear correlation between time to metastasis and overall survival. Our objective was to evaluate the impact of time to metastasis on OS in patients with prostate cancer.

Methods

Between 2008 and 2015, 269 patients with mPCa were included in this retrospective study with a median follow-up of 7.1 years. Patients were divided into three groups: (1) Presentation with metastasis within three months of initial diagnosis (de-novo-M); (2) patients free of metastasis initially but developed metastasis more than 6 months prior to castration resistance (CSPC-M); (3) patients who developed metastasis within 6 months of becoming castration resistant or after (CRPC-M).

Results

There was a significant decrease in OS when metastases were present at diagnosis (median 6.39 years) compared to CRPC-M (19.07) and CSPC-M (18.19 years). De-novo-M and CSPC-M showed a longer OS from occurrence of metastasis to death when compared to CRPC-M, although reaching CRPC earlier. There was no difference in OS between the groups once castration resistance was reached. Time from initial diagnosis to metastasis and to CRPC was correlated with OS and remained important prognosticators in multivariate Cox-regression (p < 0.01 for both).

Conclusions

Time from diagnosis to CRPC (all patients) and time to metastasis (for CRPC-M and CSPC-M patients) are significant prognosticators of overall survival and are therefore valid surrogates in a study setting. Therefore, time to CRPC should be prolonged as long as possible.

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Acknowledgements

Dr. Frees held a scholarship from the “Deutsche Forschungsgemeinschaft” (DFG).

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Authors and Affiliations

  1. Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada

    Sebastian Frees, Shusuke Akamatsu, Samir Bidnur, Claudia Chavez-Munoz, Werner Struss, Martin Gleave, Kim N. Chi & Alan So

  2. Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada

    Daniel Khalaf, Bernhard J. Eigl & Kim N. Chi

  3. Department of Urology, University Medical Center, University of Mainz, Mainz, Germany

    Sebastian Frees

  4. Dept. of Urologic Sciences, University of British Columbia, Gordon and Leslie Diamond Health Care Centre, 2775 Laurel St. 6th Floor, Vancouver, BC, V5Z1M9, Canada

    Alan So

Authors
  1. Sebastian Frees
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  2. Shusuke Akamatsu
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  3. Samir Bidnur
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  4. Daniel Khalaf
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  5. Claudia Chavez-Munoz
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  8. Martin Gleave
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Contributions

S. Frees Protocol/project development, Data collection or management, Data analysis, Manuscript writing/editing. S. Akamatsu Protocol/project development, Data collection or management, Manuscript writing/editing. S. Bidnur Manuscript writing/editing. D. Khalaf Data collection or management. C. Chavez-Munoz Data analysis, Manuscript writing/editing. W.Struss Data collection or management, Manuscript writing/editing. B. J Eigl Protocol/project development, Manuscript writing/editing. M. Gleave Protocol/project development, Manuscript writing/editing. K. N. Chi Protocol/project development, Manuscript writing/editing. A. I. So Protocol/project development, Data analysis, Manuscript writing/editing.

Corresponding author

Correspondence to Alan So.

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Conflict of interest

The authors declare that they have no conflict of interest.

Statement of human rights

For this type of study formal consent is not required.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Electronic supplementary material

Below is the link to the electronic supplementary material.

345_2018_2236_MOESM1_ESM.pdf

Supplementary material 1 (PDF 465 kb). Supplementary Fig. 2: Survival from time of metastasis. Kaplan–Meier analysis of the overall survival of patients from time of metastasis. Supplementary Fig. 3: Time from diagnosis to metastasis (CRPC-M vs CSPC-M). Kaplan–Meier analysis of the time from diagnosis to metastasis. Supplementary Fig. 4: a Pearson correlation of time from diagnosis to metastasis and time from diagnosis to death. b Pearson Correlation of time from diagnosis to CRPC and time from diagnosis to death

345_2018_2236_MOESM2_ESM.pdf

Supplementary material 2 (PDF 448 kb). Supplementary Fig. 5: Time from CRPC to death. Kaplan–Meier analysis of the overall survival of patients from time of becoming castration resistant. Supplementary Fig. 6:De- novo-M compared to all other patients divided into groups according to time to metastasis. Kaplan–Meier analysis of the overall survival of patients comparing de-novo-metastasis and groups of different time intervals of metastasis

345_2018_2236_MOESM3_ESM.pdf

Supplementary material 3 (PDF 331 kb). Supplementary Fig. 1: Schematic timeline of a typical course of patients with prostate cancer and the division used in this paper according to the time point of metastasis. Above: Initial non-metastatic prostate cancer, that is treated with an initial therapy, mostly in a curative intent, then biochemical failure which is typically treated with Androgen deprivation therapy (ADT). Patients become castration resistant followed by a secondary ADT or chemotherapy and finally ending in the death of the patient. Below: Patients with initially metastatic prostate cancer receive ADT and once becoming castration resistant chemotherapy or secondary ADT. De novo-M: Patients that presented with clinical evidence of metastasis within 3 months of initial diagnosis; CSPC-M (castration sensitive prostate cancer with metastasis): Patients who were free of metastasis initially but developed metastasis more than 6 months prior to castration resistance; CRPC-M (castration resistant prostate cancer with metastasis) patients who developed metastasis within 6 months of becoming castration resistant or after. Abbreviations: CRPC: castration resistant prostate cancer

345_2018_2236_MOESM4_ESM.docx

Supplementary material 4 (DOCX 142 kb). Supplementary Table 1: Multivariate Cox- regression: A: Prognosticators influencing OS for patients with CRPC-M and CSPC-M; B: Prognosticators influencing OS for all patients

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Frees, S., Akamatsu, S., Bidnur, S. et al. The impact of time to metastasis on overall survival in patients with prostate cancer. World J Urol 36, 1039–1046 (2018). https://doi.org/10.1007/s00345-018-2236-4

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  • DOI: https://doi.org/10.1007/s00345-018-2236-4

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