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Prediction of Survival of Metastatic Prostate Cancer Based on Early Serial Measurements of Prostate Specific Antigen and Alkaline Phosphatase
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Department of Surgery, University Hospital of Lund, Lund, Sweden.
Oncological Center, Umeå University Hospital, Umeå, Sweden .
eRegional Oncological Center and Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
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2008 (English)In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 179, no 1, 117-123 p.Article in journal (Refereed) Published
Abstract [en]

Purpose: We determined how serial measurements of prostate specific antigen and alkaline phosphatase can be used to predict survival early in the course of hormone treated metastatic prostate cancer.

Materials and Methods: The study was based on a prospective randomized trial of 915 patients with metastatic prostate carcinoma designed to compare parenteral estrogen (polyestradiol phosphate) vs total androgen blockade. We included 697 men who survived at least 6 months and had complete serial measurements of prostate specific antigen and alkaline phosphatase. Six models were constructed based on prostate specific antigen and alkaline phosphatase at start, and after 6 months of treatment, alkaline phosphatase flare and relative prostate specific antigen velocity. We constructed time dependent receiver operating characteristic curves with corresponding area under the curve to predict death from prostate cancer within 3 years.

Results: The best variables to predict outcome were alkaline phosphatase at 6 months (AUC 0.79 for polyestradiol phosphate and 0.72 for total androgen blockade), alkaline phosphatase at baseline (AUC 0.70 for polyestradiol phosphate and total androgen blockade) and prostate specific antigen at 6 months (AUC 0.70 for polyestradiol phosphate and total androgen blockade). Prostate specific antigen and alkaline phosphatase levels 6 months after start of treatment give better prediction of survival than baseline levels.

Conclusions: Alkaline phosphatase at start of treatment and alkaline phosphatase and prostate specific antigen after 6 months can be used to predict survival of hormone treated metastatic prostate cancer.

Place, publisher, year, edition, pages
2008. Vol. 179, no 1, 117-123 p.
Keyword [en]
Prostatic neoplasms, prostate-specific antigen, alkaline phosphatase, survival
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-14796DOI: 10.1016/j.juro.2007.08.132OAI: oai:DiVA.org:liu-14796DiVA: diva2:25285
Available from: 2008-09-24 Created: 2008-09-24 Last updated: 2017-12-13
In thesis
1. Prediction of survival in prostate cancer: aspects on localised, locally advanced and metastatic disease
Open this publication in new window or tab >>Prediction of survival in prostate cancer: aspects on localised, locally advanced and metastatic disease
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background and aims: The clinical course of prostate cancer is highly variable and difficult to predict.Stage at presentation, grade and PSA at diagnosis are traditionally used to predict outcome. The aimof this thesis was to identify strategies for improved survival prediction in men with prostate cancer.The way in which prostate cancer affects a population based‐cohort and how routinely measuredvariables can be used to predict survival in an intermediate to long follow‐up period were explored.From this large cohort we separately evaluated how survival can be predicted in men with incidentalcarcinoma (T1a and b) and locally advanced disease (lymph node‐ positive). Immunohistochemistrywas added to routinely measured variables in the subgroup of men with incidental carcinoma.Furthermore, we assessed how the outcome of metastatic disease may be predicted from informationavailable at diagnosis, and during the first six months after treatment. Finally we predicted survivalfor men with metastatic hormone‐refractory prostate cancer (HRPC).

Material and methods: From the Swedish South‐East Region Prostate Cancer Register data on 8887men were studied and the impact of tumour grade, serum PSA concentration, TNM classification andtreatment was studied in relation to survival.Furthermore, an evaluation of the disease‐specific mortality of conservatively managed incidentalcarcinoma in relation to T‐category, Gleason score, p53, Ki‐67, Chromogranin A and serotonin wasmade. From the same register we studied whether common predictive factors such as serum‐PSA, Tcategoryand biopsy tumour grade could be used to better assess the prognosis of men with nodepositiveprostate cancer. Using data from the clinical trial SPCG‐5 we studied the possibility of serialmeasurements of PSA and ALP being to predict survival early in the course of hormone‐treatedmetastatic prostate cancer. From the same trial, we also assessed the value of PSA kinetics inpredicting survival and related this to baseline variables in men with metastatic HRPC.

Results: In the South–East Region, where screening was seldom done the median age at diagnosisand death was 75 and 80 years respectively, and 12% were diagnosed before the age of 65 years. Hightumour grade, high serum PSA and high T category were associated with poor outcome. The projected 15‐year disease‐specific survival rate was 44% for the whole population. In total, 18% ofpatients had metastases at diagnosis and their median survival was 2.5 years.

In the cohort of men with incidental carcinoma, 17% died of prostate cancer. Of 86 patients withGleason score ≤5, three died of prostate cancer. Independent predictors of disease‐specific mortality inmultivariate analysis were category T1b prostate cancer, Gleason score >5 and high immunoreactivityof Ki‐67. Men with lymph‐node positive disease have a median cancer‐specific survival of 8 years.Preoperatively known factors such as PSA, T‐category, age, mode of treatment, failed to predictoutcome, but there was a weak, not statistically significant difference in cancer‐specific survival inrelation to tumour grade.

Initial ALP, and ALP and PSA after 6 months of treatment were the serum markers that provided thebest prognostic information about the long‐term outcome of metastatic prostate cancer. In men withHRPC, PSA velocity alone gave a better prediction of survival than all other PSA kinetic variables.

Conclusion: In an almost unscreened population, prostate cancer is the elderly mans disease but themortality is high. Ki‐67 may be of value in addition to stage and Gleason score for predicting theprognosis in men with incidental carcinoma.The impact of lymph node metastases on survival overrides all other commonly used prognosticfactors.

By following ALP and PSA for 6 months it is possible to predict outcome in metastatic prostate cancer.This gives a much better prediction than baseline PSA and helps to select men with a poor prognosis.By combining PSAV with the variables available at baseline, a better ground for treatment decisionmakingin men with HRPC is achieved.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2008. 68 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1073
Keyword
Protstate cancer, oncology, PSA diagnosisk, TNM classification
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-14799 (URN)9789173938297 (ISBN)
Public defence
2008-10-24, Originalet, Qulturum, Hus B4, Länssjukhuset Ryhov, Jönköping, Jönköping, 13:00 (Swedish)
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Available from: 2008-09-24 Created: 2008-09-24 Last updated: 2017-12-15Bibliographically approved

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Varenhors, Eberhard

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Department of Clinical and Experimental MedicineFaculty of Health SciencesUrology Department of Urology in Östergötland
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