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Imaging and Treatment Outcome of Potentially Curable Prostate Cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The over-all aim of the present study was to compare the results of treatment with curative intent, with conservative treatment in men with prostate cancer (PCa) without distant metastases.

In a population-based cohort in Sweden, the predictive value of prostate-specific antigen (PSA) was evaluated and the relative survival of men considered plausible candidates for treatment with curative intent was investigated.

We also evaluated the association between curative treatment and cause-specific mortality, and over-all as well as relative survival in men diagnosed with PCa with a serum PSA level between 20 and 100 ng/ml.

Due to the uncertainly of transrectal ultrasound-guided biopsy in the diagnosis of PCa, we created a model for prostate imaging  to increase the safety of guided Core Needle Biopsy (CNB) in men with suspect PCa, thereby improving staging. 

Material and methods. The cohorts in the first three studies were prospectively included in a population-based register (the National Prostate Cancer Register). Study IV was a clinical study on patients included between 2010 and 2011.

Results. Regardless of Gleason Score, a positive relationship between survival and serum PSA level categories in patients with a PSA level> 4 ng/ml was found, but a paradoxical inverse relationship was observed in men with a PSA level < 4 ng/ml. Men with a well-differentiated tumour had a 5-year relative survival exceeding 100% regardless of treatment. The survival rate for moderately and poorly differentiated tumours was poor for men managed conservatively. The 10-year cause-specific mortality for patients with PSA 20-50 ng/ml was 36% for patients treated without and 13% for patients treated with curative intent. For patients with a PSA 50-100 ng/ml the 10-year cause-specific mortality was 55% for conservative and 20% for patients treated with curative intent.

PCa detection by CNB, magnetic resonance imaging (MR) with ADC (Apparent diffusion coefficient), magnetic resonance spectroscopic imaging (MRSI) and Positron Emission Tomography (PET/CT) ¹¹C Acetate imaging applied to 10 sections of the prostate demonstrated clear conformity between MRI ADC mapping and postoperative findings, showing high specificity (87%) and sensitivity (95%).

Conclusion. The inverse relationship between relative survival and PSA at levels below 4 ng/ml should be considered when choosing a PSA cut-off level. Outcome differs little between conservative management and treatment with curative intent in men with localised well- to moderately differentiated tumours over a 10-yr period. For men with poorly differentiated tumours, on the other hand, choice of treatment is crucial for outcome. Treatment with curative intent is beneficial in the group of men with prostate cancer and PSA levels between 20 and 100 ng/ml without distant metastases. A combination of MRI , diffusion ADC and MRSI may provide an improved model for imaging of the prostate for targeted biopsy.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. , 81 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 759
National Category
Urology and Nephrology Cancer and Oncology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:uu:diva-171754ISBN: 978-91-554-8326-5 (print)OAI: oai:DiVA.org:uu-171754DiVA: diva2:512288
Public defence
2012-05-18, Auditorium Minus, Gustavianum, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2012-04-27 Created: 2012-03-27 Last updated: 2013-07-10Bibliographically approved
List of papers
1. The impact of prostate-specific antigen level at diagnosis on the relative survival of 28,531 men with localized carcinoma of the prostate
Open this publication in new window or tab >>The impact of prostate-specific antigen level at diagnosis on the relative survival of 28,531 men with localized carcinoma of the prostate
2008 (English)In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 112, no 4, 813-9 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: To evaluate the predictive value of prostate-specific antigen (PSA) in a population-based cohort, the authors analyzed relative survival in all men with localized prostate cancer who were registered in the Swedish National Prostate Cancer Register (NPCR) from 1996 to 2005. METHODS: All men aged <75 years with localized tumors were identified in the NPCR. A Poisson regression analysis was performed using observed death as response and the expected death rate as offset. The expected and observed numbers of survivors were calculated with stratification for PSA level and 3 categories of tumor differentiation (Gleason score 2-6, 7, and 8-10). The regression model included PSA as linear splines with a breakpoint at a PSA level of 4 ng/mL and with tumor differentiation as a categoric variable. RESULTS: The Poisson regression analysis indicated a U-shaped curve for all 3 groups, with a negative correlation between PSA and relative survival in men with PSA levels <4 ng/mL and a positive correlation for men with PSA levels >4 ng/mL. The correlation was significant for all 3 groups, but the negative correlation between PSA and relative survival was significantly more pronounced in the group with Gleason scores from 8 to 10 than in the other 2 Gleason score groups. CONCLUSIONS: The demonstration of an inverse correlation between PSA level and relative survival in the group of men with PSA levels <4 ng/mL indicated the presence of a small but clinically important subgroup with undifferentiated tumors who have cells that have lost the ability to secrete PSA. This group should be taken into consideration when deciding on treatment and when choosing a cutoff level in PSA screening programs.

Keyword
prostate cancer, prostate-specific antigen, relative survival, prognosis, Gleason score, population-based
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-88072 (URN)10.1002/cncr.23235 (DOI)000253023700010 ()18098207 (PubMedID)
Available from: 2009-01-20 Created: 2009-01-20 Last updated: 2015-06-24Bibliographically approved
2. Tumour Grade, Treatment, and Relative Survival in a Population-based Cohort of Men with Potentially Curable Prostate Cancer
Open this publication in new window or tab >>Tumour Grade, Treatment, and Relative Survival in a Population-based Cohort of Men with Potentially Curable Prostate Cancer
2010 (English)In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 57, no 4, 631-638 p.Article in journal (Refereed) Published
Abstract [en]

Background: There is insufficient information regarding the benefit of treatment with curative intent for men with localised poorly differentiated prostate cancer (PCa). Objective: To evaluate relative survival in men with potentially curable PCa in relation to Gleason score (GS) and treatment as practiced in the community at large. Design, setting, and participants: A population-based study including all men with localised PCa registered in Sweden's National Prostate Cancer Register. Interventions: Hormonal therapy, watchful waiting, and treatment with curative intent. Measurements: The ratio of observed deaths to expected deaths, determined from survival in the general male population of the same age, was assessed using Poisson regression analysis, with GS and treatment as covariates. Interaction between GS and treatment was tested in a multivariate Cox proportional hazard analysis. Results and limitations: A total of 31 903 men with potentially curable tumour (T1-T3, N0/NX, M0/MX, age < 75 yr, and prostate-specific antigen [PSA] < 20 ng/ml) were identified. GS was recorded for 28 454 of these men. Some 19 606 men (60.8%) were treated with curative intent, and 12 645 men (39.2%) were given either hormonal treatment or expectant management. The ratios between observed and expected survival gradually increased for men with GS 10, with GS to 3.3 for men treated conservatively and to 1.4 for men treated with curative intent. There was a significant interaction between GS and treatment, with a relatively greater benefit from treatment with curative intent for men with high-grade tumours. The results have to be interpreted with some caution, as there was no randomisation between the treatment groups. Conclusions: Survival for men with well-differentiated tumours is close to that of the general population, regardless of treatment, but the outcome is dismal for men with poorly differentiated tumours, whichever treatment is applied. Nevertheless, men with poorly differentiated tumours benefit more from curative treatment than do men with well-differentiated tumours.

Keyword
Epidemiology, Conservative management, Curative management, Prostate cancer, Radical prostatectomy, Radiotherapy
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-136812 (URN)10.1016/j.eururo.2009.03.007 (DOI)000275739300020 ()
Available from: 2010-12-14 Created: 2010-12-14 Last updated: 2017-12-11Bibliographically approved
3. Treatment with curative intent and survival in men with high-risk prostate cancer: A population-based study of 11 380 men with serum PSA level 20–100 ng/mL
Open this publication in new window or tab >>Treatment with curative intent and survival in men with high-risk prostate cancer: A population-based study of 11 380 men with serum PSA level 20–100 ng/mL
Show others...
2013 (English)In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 111, no 3, 381-388 p.Article in journal (Refereed) Published
Abstract [en]

Study Type - Prognosis inception (cohort)

Level of Evidence 2

What's known on the subject? and What does the study add?

There are two randomized controlled trials showing that radiotherapy can be beneficial for men with locally advanced prostate cancer. The present study confirms the importance of curative treatment for men with high-risk prostate cancer.

OBJECTIVE:

•  To investigate the influence of curative treatment on cause-specific mortality in men diagnosed with prostate cancer (PCa) with serum prostate-specific antigen (PSA) levels between 20 and 100 ng/mL.

MATERIALS AND METHODS:

•  Patients with PCa (T1-4, N0/N1/NX, M0/MX), PSA 20-100 ng/mL and age ≤75 years were identified in the National Prostate Cancer Register of Sweden.

•  Data on co-morbidity diagnoses were obtained from the National Patient Register and cause of death from the Cause of Death Register.

•  Following adjustment for age at diagnosis, co-morbidity burden, Gleason score, T-category, PSA level and cause-specific mortality in relation to treatment were estimated using Cox regression analysis.

RESULT:

•  A total of 11 380 men were diagnosed with PCa between 1996 and 2008 and fulfilled the inclusion criteria.

•  The cumulative 10-year PCa-specific mortality was 36% for patients receiving only palliative treatment and 13% for those treated with curative intent.

•  For the 8462 (74%) patients with PSA levels from 20 to 50 ng/mL at diagnosis, the hazard ratio for death from PCa was 0.23 (95% confidence interval 0.19-0.27) for those treated with curative intent compared with those given palliative treatment after adjusting for age, co-morbidity, T category, PSA level and Gleason score. The corresponding hazard ratio was 0.22 (95% confidence interval 0.17-0.30) for patients with PSA levels from 51 to 100 ng/mL.

CONCLUSION:

•  Treatment with curative intent for men with high-risk PCa was associated with reduced cause-specific mortality and should be considered even when serum PSA exceeds 20 ng/mL.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-190088 (URN)10.1111/j.1464-410X.2012.11320.x (DOI)000315395200022 ()22758210 (PubMedID)
Available from: 2013-01-07 Created: 2013-01-07 Last updated: 2017-12-06Bibliographically approved
4. Imaging of the prostate indicating area for targeted biopsy
Open this publication in new window or tab >>Imaging of the prostate indicating area for targeted biopsy
(English)Manuscript (preprint) (Other academic)
National Category
Urology and Nephrology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-171753 (URN)
Available from: 2012-03-27 Created: 2012-03-27 Last updated: 2012-05-21

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