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Prediction of survival in prostate cancer: aspects on localised, locally advanced and metastatic disease
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
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 [en]
Protstate cancer, oncology, PSA diagnosisk, TNM classification
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-14799ISBN: 9789173938297 (print)OAI: oai:DiVA.org:liu-14799DiVA: diva2:25290
Public defence
2008-10-24, Originalet, Qulturum, Hus B4, Länssjukhuset Ryhov, Jönköping, Jönköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2008-09-24 Created: 2008-09-24 Last updated: 2017-12-15Bibliographically approved
List of papers
1. Survival in prostate carcinoma - Outcomes from a prospective, population-based cohort of 8887 men with up to 15 years of follow-up: Results from three counties in the population-based National Prostate Cancer Registry of Sweden
Open this publication in new window or tab >>Survival in prostate carcinoma - Outcomes from a prospective, population-based cohort of 8887 men with up to 15 years of follow-up: Results from three counties in the population-based National Prostate Cancer Registry of Sweden
Show others...
2005 (English)In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 103, no 5, 943- 951 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND To decide on screening strategies and curative treatments for prostate carcinoma, it is necessary to determine the incidence and survival in a population that is not screened.

METHODS The 15-year projected survival data were analyzed from a prospective, complete, population-based registry of 8887 patients with newly diagnosed prostate carcinoma from 1987 to 1999.

RESULTS The median patient age at diagnosis was 75 years (range, 40-96 years), and 12% of patients were diagnosed before the age 65 years. The median follow-up was 80 months for patients who remained alive. In total, 5873 of 8887 patients (66.1%) had died, and 2595 of those patients (44.2%) died directly due to prostate carcinoma. The overall median age at death was 80 years (range, 41-100 years). The projected 15-year disease-specific survival rate was 44% for the whole population. In total, 18% of patients had metastases at diagnosis (M1), and their median survival was 2.5 years. Patients with nonmetastatic T1-T3 prostate carcinoma (age < 75 years at diagnosis; n = 2098 patients) had a 15-year projected disease-specific survival rate of 66%. Patients who underwent radical prostatectomy had a significantly lower risk of dying from prostate carcinoma (relative risk, 0.40) compared with patients who were treated with noncurative therapies or radiotherapy.

CONCLUSIONS The disease-specific mortality was comparatively high, but it took 15 years to reach a disease-specific mortality rate of 56%. These data form a truly population-based baseline on how prostate carcinoma will affect a population when screening is not applied and can be used for comparison with other health care strategies. Cancer 2005. © 2005 American Cancer Society.

Keyword
prostate carcinoma, registries, therapy, survival
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-14793 (URN)10.1002/cncr.20855 (DOI)
Available from: 2008-09-24 Created: 2008-09-24 Last updated: 2017-12-13
2. Long-term follow-up of conservatively managed incidental carcinoma of the prostate A multivariate analysis of prognostic factors
Open this publication in new window or tab >>Long-term follow-up of conservatively managed incidental carcinoma of the prostate A multivariate analysis of prognostic factors
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2007 (English)In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 41, no 2, 103-109 p.Article in journal (Refereed) Published
Abstract [en]

Objective: To evaluate the disease-specific mortality of conservatively managed incidental carcinoma of the prostate (T1a and T1b) in relation to prognostic factors.

Material and methods: Since 1987 all patients with prostate cancer have been recorded and followed in the population-based Prostate Cancer Register of the South-East Healthcare Region in Sweden, which is covered by four departments of pathology. At two of these departments, tissue was obtained from 197 consecutive, previously untreated patients (aged <80 years) with incidental carcinoma who underwent transurethral resection of the prostate between 1987 and 1991. The amount of tumour, Gleason score and levels of Ki-67, p53, chromogranin A and serotonin were determined. Univariate analysis and multiple Cox regression hazard analysis were used for analysis.

Results: During follow-up (mean 7.8 years; maximum 17.5 years), 158 patients (80%) had died, 33 of them of prostate cancer, corresponding to 17% of the entire cohort. Of 86 patients with Gleason score ≤5, three died of prostate cancer. Independent predictors of disease-specific mortality in multivariate analysis were category T1b prostate cancer, Gleason score >5 and high immunoreactivity of Ki-67.

Conclusions: Elderly men with category T1a and/or Gleason score 4-5 prostate cancer have a favourable prognosis with conservative management. Immunohistochemical staining with Ki-67 may be of help in situations where further prognostic information is required.

Keyword
Prostate cancer, prognostic factors, incidental carcinoma, survival, p53, Ki-67, chromogranin A
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-14794 (URN)10.1080/00365590600991268 (DOI)
Available from: 2008-09-24 Created: 2008-09-24 Last updated: 2017-12-13
3. Prognostic Factors and Survival in Node-Positive (N1) Prostate Cancer: A Prospective Study Based on Data from a Swedish Population-Based Cohort
Open this publication in new window or tab >>Prognostic Factors and Survival in Node-Positive (N1) Prostate Cancer: A Prospective Study Based on Data from a Swedish Population-Based Cohort
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2003 (English)In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 43, no 6, 627-631 p.Article in journal (Refereed) Published
Abstract [en]

Objective: At presentation of prostate cancer, patients with proven lymph node metastasis (N1) are comparatively rare. It is difficult to give prognostic information based on the present literature. The aim of this study was to evaluate the impact of known risk factors in patients with pelvic node involvement and without distant metastasis.

Methods: From the population-based, prospective prostate cancer tumour registry of the South–East Region in Sweden, we collected data on all 181 patients with N1, M0 prostate cancer diagnosed from January 1987 to October 2000 with a follow-up to December 2001. Mean follow-up was 62 months. Pre-operative risk factors as age, T-category, serum PSA, tumour grade and also primary treatment given was correlated to the outcome.

Results: Median age at diagnosis was 65 years. Cancer-specific survival was highly variable with 5-year survival of 72%, a median of 8 years and the projected 13-year figure was 31%. T-category, age, PSA or treatment did not affect the outcome while poorly differentiated tumours had a tendency towards lower cancer-specific survival (p=0.0523) when compared to well and moderately differentiated tumours.

Conclusions: This population-based cohort of prostate cancer patients with pelvic node involvement treated principally with non-curative intent had a median cancer-specific survival of 8 years. Preoperatively known risk factors seem to have but a modest impact on the prognosis for patients in this stage of the disease.

Keyword
Prostate cancer; Lymph node metastasis; N-category; Prognosis; Risk factors; Treatment
National Category
Cancer and Oncology Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-14795 (URN)10.1016/S0302-2838(03)00156-8 (DOI)
Available from: 2008-09-24 Created: 2008-09-24 Last updated: 2017-12-13
4. Prediction of Survival of Metastatic Prostate Cancer Based on Early Serial Measurements of Prostate Specific Antigen and Alkaline Phosphatase
Open this publication in new window or tab >>Prediction of Survival of Metastatic Prostate Cancer Based on Early Serial Measurements of Prostate Specific Antigen and Alkaline Phosphatase
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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.

Keyword
Prostatic neoplasms, prostate-specific antigen, alkaline phosphatase, survival
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-14796 (URN)10.1016/j.juro.2007.08.132 (DOI)
Available from: 2008-09-24 Created: 2008-09-24 Last updated: 2017-12-13
5. PSA Kinetics Provide Improved Prediction of Survival in Metastatic Hormone-Refractory Prostate Cancer
Open this publication in new window or tab >>PSA Kinetics Provide Improved Prediction of Survival in Metastatic Hormone-Refractory Prostate Cancer
Show others...
2008 (English)In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 72, no 4, 903-907 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: To assess the value of prostate-specific antigen (PSA) kinetics in predicting survival and relate this to the baseline variables in men with metastatic hormone-refractory prostate cancer (HRPC).

Methods: The data from 417 men with HRPC were included in a logistic regression model that included hemoglobin, PSA, alkaline phosphatase, Soloway score, and performance status pain analgesic score at baseline. The posttreatment variables included the PSA level halving time after the start of treatment, PSA level at nadir, interval to nadir, PSA velocity (PSAV), PSA doubling time after reaching a nadir, patient age, and treatment. These variables were added to the baseline model, forming new logistic regression models that were tested for net reclassification improvement.

Results: The area under the receiver operating characteristics curve for the baseline model was 0.67. Of all variables related to PSA kinetics, the PSAV was the best predictor. The addition of PSAV to the baseline model increased the area under the receiver operating characteristics curve to 0.81. Only a moderate increase in the area under the receiver operating characteristics curve (0.83) was achieved by combining the baseline model in a multivariate model with PSAV, PSA doubling time, interval to nadir, and patient age at diagnosis of HRPC.

Conclusions: The PSAV alone gave a better prediction of survival value than all other PSA kinetics variables. By combining PSAV with the variables available at baseline, a better ground for treatment decision-making in men with HRPC can be achieved.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-14797 (URN)10.1016/j.urology.2008.05.026 (DOI)
Available from: 2008-09-24 Created: 2008-09-24 Last updated: 2017-12-13

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