Prostatic Neoplasms: Aus G

Heidenreich A, Aus G, Bolla M, Joniau S, Matveev VB, Schmid HP, Zattoni F, Anonymous00089. · Servicio de Urología, Hospital Universitario de Colonia, Colonia, Alemania. · Actas Urol Esp. · Pubmed #19418833 links to  free full text

Abstract: OBJECTIVES: To present a summary of the 2007 version of the European Association of Urology (EAU) guidelines on prostate cancer (PCa). METHODS: A literature review of the new data emerging from 2004 to 2007 was performed by the working panel. The guidelines have been updated, and the level of evidence/grade of recommendation was added to the text based on a systematic review of the literature, which included a search of online databases and bibliographic reviews. RESULTS: A full version is available at the EAU Office or at www.uroweb.org. Systemic prostate biopsy under ultrasound guidance is the preferred diagnostic method. Active treatment is mostly recommended for patients with localized disease and a long life expectancy, with radical prostatectomy being shown to be superior to watchful waiting in a prospective randomized trial. Nerve-sparing radical prostatectomy represents the approach of choice in organ-confined disease; neoadjuvant androgen deprivation demonstrates no improvement of outcome variables. Radiation therapy should be performed with at least 72 and 78 Gy in low-risk and intermediate- to high-risk PCa, respectively. Monotherapeutic androgen deprivation is the standard of care in metastatic PCa; intermittent androgen deprivation might be an alternative treatment option for selected patients. Follow-up is largely based on prostate-specific antigen and a disease-specific history with imaging only indicated when symptoms occur. Cytotoxic therapy with docetaxel has emerged as the reference treatment for metastatic hormone-refractory PCa. CONCLUSIONS: The knowledge in the field of PCa is rapidly changing. These EAU guidelines on PCa summarize the most recent findings and put them into clinical practice.

Thompson I, Thrasher JB, Aus G, Burnett AL, Canby-Hagino ED, Cookson MS, D'Amico AV, Dmochowski RR, Eton DT, Forman JD, Goldenberg SL, Hernandez J, Higano CS, Kraus SR, Moul JW, Tangen CM, Anonymous00324. · American Urological Association Education and Research, Inc. · J Urol. · Pubmed #17509297 No free full text.

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Aus G, Abbou CC, Bolla M, Heidenreich A, Schmid HP, van Poppel H, Wolff J, Zattoni F, Anonymous00098. · No affiliation provided · Eur Urol. · Pubmed #16046052 No free full text.

Abstract: OBJECTIVES: The first summary of the European Association of Urology (EAU) guidelines on prostate cancer was published in 2001. These guidelines have been continuously updated since many important changes affecting the clinical management of patients with prostate cancer have occurred over the past years. The aim of this paper is to present a summary of the 2005 update of the EAU guidelines on prostate cancer. METHODS: A literature review of the new data has been performed by the working panel. The guidelines have been updated and level of evidence/grade of recommendation added to the text. This enables readers to better understand the quality of the data forming the basis of the recommendations. RESULTS: A full version is available at the EAU Office or at . Systemic prostate biopsies under ultrasound guidance is the preferred diagnostic method and the use of periprostatic injection of a local anaesthetic can significantly reduce pain/discomfort associated with the procedure. Active treatment (surgery or radiation) is mostly recommended for patients with localized disease and a long life expectancy with radical prostatectomy being the only treatment evaluated in a randomized controlled trial. Follow-up is at large based on prostate specific antigen (PSA) and a disease-specific history with imaging only indicated when symptoms occur. Cytotoxic therapy has become an option for selected patients with hormone refractory prostate cancer. CONCLUSION: The knowledge in the field of prostate cancer is rapidly changing. These EAU guidelines on prostate cancer summarize the most recent findings and put them into clinical practice.

Aus G, Abbou CC, Pacik D, Schmid HP, van Poppel H, Wolff JM, Zattoni F, Anonymous00242. · Department of Urology, Ryhov Hospital, Jönköping, Sweden. · Eur Urol. · Pubmed #11528184 No free full text.

Abstract: OBJECTIVES: To develop clinical guidelines for the management of patients with prostate cancer. METHODS: Guidelines were compiled by a working panel based on current literature following a literature review using MEDLINE. Already published structured analysis from national and international guidelines was used, and panel consensus was employed when literature evidence was absent or of poor quality. RESULTS: The full text of the guidelines is available through the EAU Central Office and the EAU website (www.uroweb.org). This article summarizes the main conclusions from the guidelines concerning the diagnosis and staging, treatment and follow-up of patients with prostate cancer. The diagnosis of prostate cancer should be based on histopathological or cytological examinations. N- and M-staging may be omitted in selected patients with a low serum prostate-specific antigen due to low risk of metastasis. Active treatment is warranted in most stages of prostate cancer but active monitoring is recommended for elderly patients with early stage tumours and is still optional in some other situations. Follow-up is based on a disease-specific history, serum-prostate-specific antigen supplemented by a digital rectal examination. Routine imaging is not necessary in asymptomatic patients. CONCLUSIONS: Prostate cancer is one of the most common malignancies in men. These guidelines have been drawn up to provide support in the management of this large group of patients.

Aus G. · No affiliation provided · J Urol. · Pubmed #18801502 No free full text.

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Aus G. · No affiliation provided · Eur Urol. · Pubmed #17307285 No free full text.

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Damber JE, Aus G. · Department of Urology, Sahlgrenska University Hospital, Gothenburg, Sweden. · Lancet. · Pubmed #18486743 No free full text.

Abstract: In developed countries, prostate cancer is the second most frequently diagnosed cancer, and the third most common cause of death from cancer in men. Apart from age and ethnic origin, a positive family history is probably the strongest known risk factor. Clinically, prostate cancer is diagnosed as local or advanced, and treatments range from surveillance to radical local treatment or androgen-deprivation treatment. Androgen deprivation reduces symptoms in about 70-80% of patients with advanced prostate cancer, but most tumours relapse within 2 years to an incurable androgen-independent state. The recorded incidence of prostate cancer has substantially increased in the past two decades, probably because of the introduction of screening with prostate-specific antigen, the use of improved biopsy techniques for diagnosis, and increased public awareness. Trends in mortality from the disease are less clearcut. Mortality changes are not of the same magnitude as the changes in incidence, and in some countries mortality has been stable or even decreased. The disparity between reported incidence and mortality rates leads to the probable conclusion that only a small proportion of diagnosed low-risk prostate cancers will progress to life-threatening disease during the lifetime of the patient.

Heidenreich A, Aus G, Bolla M, Joniau S, Matveev VB, Schmid HP, Zattoni F, Anonymous00006. · Department of Urology, University Hospital Cologne, Cologne, Germany. · Eur Urol. · Pubmed #17920184 No free full text.

Abstract: OBJECTIVES: To present a summary of the 2007 version of the European Association of Urology (EAU) guidelines on prostate cancer (PCa). METHODS: A literature review of the new data emerging from 2004 to 2007 was performed by the working panel. The guidelines have been updated, and the level of evidence/grade of recommendation was added to the text based on a systematic review of the literature, which included a search of online databases and bibliographic reviews. RESULTS: A full version is available at the EAU Office or at www.uroweb.org. Systemic prostate biopsy under ultrasound guidance is the preferred diagnostic method. Active treatment is mostly recommended for patients with localized disease and a long life expectancy, with radical prostatectomy being shown to be superior to watchful waiting in a prospective randomized trial. Nerve-sparing radical prostatectomy represents the approach of choice in organ-confined disease; neoadjuvant androgen deprivation demonstrates no improvement of outcome variables. Radiation therapy should be performed with at least 72 and 78 Gy in low-risk and intermediate- to high-risk PCa, respectively. Monotherapeutic androgen deprivation is the standard of care in metastatic PCa; intermittent androgen deprivation might be an alternative treatment option for selected patients. Follow-up is largely based on prostate-specific antigen and a disease-specific history with imaging only indicated when symptoms occur. Cytotoxic therapy with docetaxel has emerged as the reference treatment for metastatic hormone-refractory PCa. CONCLUSIONS: The knowledge in the field of PCa is rapidly changing. These EAU guidelines on PCa summarize the most recent findings and put them into clinical practice.

Burnett AL, Aus G, Canby-Hagino ED, Cookson MS, D'Amico AV, Dmochowski RR, Eton DT, Forman JD, Goldenberg SL, Hernandez J, Higano CS, Kraus S, Liebert M, Moul JW, Tangen C, Thrasher JB, Thompson I, Anonymous00008. · The Johns Hopkins Hospital, 600 North Wolfe St., Marburg 407, Baltimore, Maryland 21287-2411, USA. · J Urol. · Pubmed #17570435 No free full text.

Abstract: PURPOSE: In conjunction with the assignment to update the Guidelines for Management of Clinically Localized Prostate Cancer, the American Urological Association Prostate Cancer Guideline Update Panel performed a side analysis of the reporting of erectile function outcomes in this clinical context as published in the medical literature. MATERIALS AND METHODS: Four National Library of Medicine PubMed(R) Services literature searches targeting articles published from 1991 through early 2004 were done to derive outcome reporting (efficacy or side effects) for the treatment of clinical stage T1 or T2 N0M0 prostate cancer. A database was constructed containing descriptions relating to erectile function as well as numerical frequency rates of complete erectile dysfunction, and partial and intact erectile function for various treatments. A literature review was also done, consisting of a PubMed Services search of current measures and protocols used for assessing erectile function outcomes and a survey of consensus opinion sources on the management of male sexual dysfunctions. RESULTS: Based on inclusion criteria 436 articles were selected. Of these articles database extraction from 100 pertaining to radical prostatectomy garnered various characterizations of erectile function, including qualitative descriptions, generic terminology and rating systems. Database extraction from 31 articles, in which results for at least 50 patients were reported, yielded ranges of rates for complete erectile dysfunction, partial erectile function and intact erectile function that were 26% to 100%, 16% to 48% and 9% to 86% for radical prostatectomy, 8% to 85%, 21% to 47% and 36% to 63% for external beam radiation, and 14% to 61%, 21% and 18% for interstitial radiation, respectively. The literature review showed an evolution in standards for studying and reporting erectile function outcomes. CONCLUSIONS: Clinical studies reporting erectile function outcomes after localized prostate cancer treatment often demonstrate poorly interpretable and inconsistent manners of assessment as well as widely disparate rates of erectile dysfunction and erectile function. Future studies must apply scientifically rigorous methodology and standard outcomes measures to advance this field of study.

Cookson MS, Aus G, Burnett AL, Canby-Hagino ED, D'Amico AV, Dmochowski RR, Eton DT, Forman JD, Goldenberg SL, Hernandez J, Higano CS, Kraus SR, Moul JW, Tangen C, Thrasher JB, Thompson I. · Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA. · J Urol. · Pubmed #17222629 No free full text.

Abstract: PURPOSE: The American Urological Association Prostate Guideline Update Panel was charged with updating the Guidelines for Clinically Localized Prostate Cancer. In assessing outcomes with treatment, it became apparent that a highly variable number of definitions exist with respect to biochemical recurrence. Herein, we review the variability in published definitions of biochemical recurrence and make recommendations directed toward improving this terminology by recommending a standard definition in patients treated with radical prostatectomy. MATERIALS AND METHODS: Four PubMed literature searches were performed between May 2001 and April, 2004 and covered articles published from 1991 through early 2004. The search terms included the MeSH major headings of prostate cancer and prostatic neoplasm. All potentially relevant articles were retrieved and a more detailed screen for relevance was performed. An article was considered relevant if it reported treatment outcomes of patients with clinical T1 or T2N0M0 prostate cancer. Data extractors recorded the definition of biochemical recurrence and definitions were then collapsed into categories representing the same criteria. The results of biochemical failure were subcategorized by initial treatment. RESULTS: Of 13,800 citations, a total of 436 articles were selected. Among these, a total of 145 articles contained 53 different definitions of biochemical recurrence for those treated with radical prostatectomy. Of these, the most common definition (35) was a prostate specific antigen of >0.2 ng/mL or a slight variation thereof. In addition, a total of 208 articles reported 99 different definitions of biochemical failure among those treated with radiation therapy. Of these, the American Society for Therapeutic Radiology and Oncology definition (70) and/or a variation thereof was the most commonly reported. In total, 166 different definitions of biochemical failure were identified. Following radical prostatectomy, the Panel recommends defining biochemical recurrence as an initial serum prostate specific antigen of > or =0.2 ng/mL, with a second confirmatory level of prostate specific antigen of >0.2 ng/mL. The Panel recommends the use of the American Society for Therapeutic Radiology and Oncology criteria for patients treated with radiation therapy and acknowledges that these criteria will soon be updated although not yet published. CONCLUSIONS: A high degree of variability in the definition of biochemical recurrence exists following treatment for localized prostate cancer. Strict definitions for biochemical recurrence are necessary to identify men at risk for disease progression and to allow meaningful comparisons among patients treated similarly. The Panel acknowledges the American Society for Therapeutic Radiology and Oncology criteria and future modifications thereof for those receiving radiation therapy and recommends the newly developed American Urological Association criteria for those treated with radical prostatectomy. The purpose for the establishment of this standard is for data reporting purposes and for comparison of similarly treated patients. It is not intended to represent a threshold value for which to initiate treatment. The Panel acknowledges that the clinical decision to initiate treatment will be dependent on multiple factors including patient and physician interaction rather than a specific prostate specific antigen threshold value.

Stenman UH, Abrahamsson PA, Aus G, Lilja H, Bangma C, Hamdy FC, Boccon-Gibod L, Ekman P. · Department of Clinical Chemistry, Helsinki University Central Hospital, Helsinki University, Helsinki, Finland. · Scand J Urol Nephrol Suppl. · Pubmed #16019759 No free full text.

Abstract: The incidence of prostate cancer has increased dramatically during the last 10-15 years and it is now the commonest cancer in males in developed countries. The increase is mainly caused by the increasing use of opportunistic screening or case-finding based on the use of prostate-specific antigen (PSA) testing in serum. With this approach, prostate cancer is detected 5-10 years before giving rise to symptoms and on average 17 years before causing the death of the patient. While this has led to detection of prostate cancer at a potentially curable stage, it has also led to substantial overdiagnosis, i.e. detection of cancers that would not surface clinically in the absence of screening. A major challenge is thus to identify the cases that need to be treated while avoiding diagnosing patients who will not benefit from being diagnosed and who will only suffer from the stigma of being a cancer patient. It would be useful to have prognostic markers that could predict which patients need to be diagnosed and which do not. Ideally, it should be possible to measure these markers using non-invasive techniques, i.e. by means of serum or urine tests. As it is very useful for both early diagnosis and monitoring of prostate cancer, PSA is considered the most valuable marker available for any tumor. Although the prognostic value of PSA is limited, measurement of the proportion of free PSA has improved the identification of patients with aggressive disease. Furthermore, the rate of increase in serum PSA reflects tumor growth rate and prognosis but, due to substantial physiological variation in serum PSA, reliable estimation of the rate of PSA increase requires follow-up for at least 2 years. Algorithms based on the combined use of free and total PSA and prostate volume in logistic regression and neural networks can improve the diagnostic accuracy for prostate cancer, and assays for minor subfractions of PSA and other new markers may provide additional prognostic information. Markers of neuroendocrine differentiation are useful for the monitoring of androgen-independent disease and various bone markers are useful in patients with metastatic disease.

Aus G, Adolfsson J, Selli C, Widmark A. · Department of Urology, Ryhov Hospital, Jönköping, Sweden. · Scand J Urol Nephrol. · Pubmed #12002354 No free full text.

Abstract: OBJECTIVE: To describe and evaluate treatment alternatives for patients with clinical T3 prostate cancer. MATERIAL AND METHODS: Literature review with main focus on recent studies in order to include the impact of prostate specific antigen (PSA). The possibility of using neoadjuvant/adjuvant hormonal therapy in combination with surgery or radiation was assessed. Results were related to life expectancy, tumour grade and serum PSA. RESULTS: M and N-staging is mandatory before treatment with curative intent. Watchful waiting is an option for selected patients but early hormonal therapy seems to offer some survival advantages. Standard 65-70Gy external beam radiation is not sufficient for these patients with extracapsular disease but better results are obtained with dose-escalation (beyond 70Gy) and/or adjuvant hormonal therapy. Radical prostatectomy may be an option for patients with long life expectancy and "early" tumours, neoadjuvant hormonal withdrawal is of no proven value. CONCLUSIONS: Patients with a long life expectancy should not be denied treatment with curative intent solely based on the finding of extracapsular disease.

Schmid HP, Adolfsson J, Aus G. · Department of Urology, Westfälische Wilhelms University, Münster, Germany. · Eur Urol. · Pubmed #11752854 No free full text.

Abstract: OBJECTIVES: To evaluate the concept of active monitoring only in the management of patients with prostate cancer. METHODS: Literature review. RESULTS: Active monitoring may be recommended in patients with stage T1a, well- and moderately-differentiated disease. Patients with a life expectancy exceeding 10 years are recommended re-evaluation with PSA, TRUS and biopsies of the residual prostate. This treatment is also indicated in patients with stage T1b-T2b, well- and moderately-differentiated tumours and a life expectancy of less than 10 years. Active monitoring is optional in patients with stage T1b-T2b, Gleason 2-4 prostate cancer and a life expectancy of 10-15 years. It is also optional in asymptomatic patients with locally advanced disease, stage T3-T4 which are well- and moderately-differentiated and have a short life expectancy. A very rare asymptomatic patient with M1 disease and the possibility of close follow-up may be offered active monitoring. CONCLUSIONS: Active monitoring is still a viable option for selected patients diagnosed with prostate cancer.

Aus G, Gunnarsson G, Nodbrant P. · Dept of Urology, Länssjukhuset Ryhov, Jönköping, Sweden. · Lakartidningen. · Pubmed #11037589 No free full text.

Abstract: The incidence of prostate cancer is increasing and, due to the use of PSA, more and more patients are diagnosed with localized disease. These patients may be offered treatment with the intent to cure. Traditionally, this has been either by radical prostatectomy or some form of radiation therapy. This article describes the minimally invasive method with permanent seed implantation. The procedure, indications, contraindications, side effects and results from the literature 28 patients have been treated so far with acceptable proximate side effects and reductions in serum-PSA as expected.

Schmid HP, Semjonow A, Aus G, Hertle L. · Department of Urology, Westfälische Wilhelms-University, Münster, Germany. · Urol Int. · Pubmed #11025425 No free full text.

Abstract: Neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy or radiation therapy for clinically localized prostate cancer has regained interest in recent years but proof of its clinical benefit with respect to patient survival is still pending. We reviewed the literature regarding NHT in prostate cancer; only studies with a high evidence level were included for analysis. Five prospective randomized trials of NHT in radical prostatectomy-treated patients could be identified. Despite significantly lower numbers of positive surgical margins in the NHT group, prostate specific antigen failure rates were similar in the NHT group and the surgery only group. Data on disease-free and overall survival are not yet available. The two prospective randomized studies of NHT in radiation-treated patients could demonstrate better local control of the tumor in the NHT group. However, there was no difference in overall survival between the NHT arm and the radiation only arm. Future clinical research should consider type and duration of hormonal treatment and evaluate potential surrogate end points. To date, there is no hard evidence in favor of NHT prior to radical prostatectomy or external beam irradiation. NHT in prostate cancer should only be applied within controlled trials.

Beerlage HP, Thüroff S, Madersbacher S, Zlotta AR, Aus G, de Reijke TM, de la Rosette JJ. · University Hospital Nijmegen, The Netherlands. · Eur Urol. · Pubmed #10671777 No free full text.

Abstract: INTRODUCTION: Prostate cancer is the leading malignancy in men today and an increase in detected localized prostate cancers is expected in the years to come. Even though radical prostatectomy is an effective treatment, it is associated with a considerable morbidity in some cases and efforts are made to provide minimally invasive alternative treatment options with equal efficacy but fewer side effects. METHODS: Cryosurgical ablation of the prostate (CSAP), brachytherapy, high-intensity focused ultrasound (HIFU) and radiofrequency interstitial tumor ablation (RITA) were evaluated after a literature review from a Medline Search (1966-1998). Furthermore, personal experience and latest data from the authors were taken into account. RESULTS: All alternative treatments nowadays make use of sophisticated technology, including the latest ultrasound devices for exact planning and monitoring of treatment, leading to increased safety compared to treatments in the 1960s and 1970s. Five-year results of CSAP show a PSA <1 ng/ml in 60% of cases whereas brachytherapy is able to achieve PSA <1 ng/ml in 80% of cases in a selected group. Recent outcome data come close to results of radical prostatectomy series. HIFU and RITA are promising new technologies that proved to be able to induce extensive necrosis, but the follow-up is too short to determine their definite places in the treatment of prostate cancer. CONCLUSION: Two alternative treatment options for localized prostate carcinoma, CSAP and brachytherapy, have been studied with a sufficient number of patients and an adequate follow-up. The overall results of brachytherapy are favorable when compared to CSAP and are in the same range as the outcome after radical prostatectomy. HIFU and RITA are relatively new techniques based on sophisticated technology that are very promising at present, but a longer follow-up is mandatory.

Aus G, Damber JE, Khatami A, Lilja H, Stranne J, Hugosson J. · Department of Urology, Sahlgrens University Hospital, Göteborg, Sweden. · Arch Intern Med. · Pubmed #16157829 links to  free full text

Abstract: BACKGROUND: The aim of the present study was to evaluate the future cumulative risk of prostate cancer in relation to levels of prostate-specific antigen (PSA) in blood and to determine whether this information could be used to individualize the PSA testing interval. METHODS: The study included 5855 of 9972 men (aged 50-66 years) who accepted an invitation to participate in a prospective, randomized study of early detection for prostate cancer. We used a protocol based on biennial PSA measurements starting from 1995 and 1996. Men with serum PSA levels of 3.0 ng/mL or more were offered prostate biopsies. RESULTS: Among the 5855 men, 539 cases of prostate cancer (9.2%) were detected after a median follow-up of 7.6 years (up to July 1, 2003). Cancer detection rates during the follow-up period in relation to PSA levels were as follows: 0 to 0.49 ng/mL, 0% (0/958); 0.50 to 0.99 ng/mL, 0.9% (17/1992); 1.00 to 1.49 ng/mL, 4.7% (54/1138); 1.50 to 1.99 ng/mL, 12.3% (70/571); 2.00 to 2.49 ng/mL, 21.4% (67/313); 2.50 to 2.99 ng/mL, 25.2% (56/222); 3.00 to 3.99 ng/mL, 33.3% (89/267); 4.00 to 6.99 ng/mL, 38.9% (103/265); 7.00 to 9.99 ng/mL, 50.0% (30/60); and for men with an initial PSA of 10.00 ng/mL or higher, 76.8% (53/69). Not a single case of prostate cancer was detected within 3 years in 2950 men (50.4% of the screened population) with an initial PSA level less than 1 ng/mL. CONCLUSIONS: Retesting intervals should be individualized on the basis of the PSA level, and the large group of men with PSA levels of less than 1 ng/mL can safely be scheduled for a 3-year testing interval.

Hugosson J, Aus G, Lilja H, Lodding P, Pihl CG. · Department of Urology, Sahlrenska University Hospital, Gothenburg, Sweden. · Cancer. · Pubmed #15042673 links to  free full text

Abstract: BACKGROUND: The purpose of the current study was to evaluate the effectiveness of a prostate carcinoma screening program in which serum prostate-specific antigen (PSA) levels were measured. METHODS: From a group of 20,000 men born between January 1, 1930, and December 31, 1944, 10,000 men were randomized into a screening group and 10,000 were randomized into a control group. Patients in the screening group were invited to undergo initial PSA testing between 1995 and 1996 and then were invited to receive testing every second year thereafter for 8 years (for a total of 4 PSA tests). Men with PSA levels > or =3 ng/mL (or > or =2.54 ng/mL, in the third and fourth screening rounds) were invited to undergo clinical investigation, which included sextant biopsy of the prostate. By linking to the regional cancer registry, the authors were able to obtain the true and expected incidence rates for the screening and control groups. RESULTS: The screening participation rate was high (73%). A total of 884 malignancies have been detected to date, with 640 having been detected in the screening group. There was an early and marked shift toward more favorable disease stage and grade for malignancies detected on repeat screening. In the fourth screening round, only 2 of 82 detected malignancies were classified as advanced disease. Of the 227 screen-detected tumors on which surgery was performed, only 20 (8.8%) had small volume (<0.2 cm3). Forty-three interval malignancies were detected, but only five were accompanied by symptoms. At 8 years, the cumulative disease incidence rate among screening participants was 7.3%, compared with 2.4% in the control arm. The incidence rate observed in the screening population corresponds to the cumulative incidence rate observed in the Swedish male population at age 72 years. CONCLUSIONS: Biennial PSA screening was very successful in diagnosing prostate carcinoma at an early stage, when curative treatment typically is effective. In addition, the results regarding interval malignancies were favorable. Thus, decreased mortality should be observed on long-term follow-up. The lead time associated with screening appears to fall within the range described in earlier studies involving frozen sera (i.e., 5-9 years).

Zackrisson B, Aus G, Bergdahl S, Lilja H, Lodding P, Pihl CG, Hugosson J. · Departments of Urology and Pathology, Sahlgrenska University Hospital, Göteborg, Sweden. · J Urol. · Pubmed #15017207 No free full text.

Abstract: PURPOSE: We evaluated the significance of focal prostate cancer found in sextant biopsies in men participating in a biennial prostate specific antigen (PSA) based screening program. MATERIALS AND METHODS: In 1995, 10000 men 50 to 65 years old were randomized to biennial screening with PSA testing. Sextant biopsies were recommended when total PSA was 3 ng/ml or greater at screening rounds 1 and 2, and 2.54 ng/ml or greater at subsequent screening rounds. Focal cancer was defined as total a core cancer length of less than 3 mm in the biopsy specimen. Low volume cancer was defined as a total tumor volume of less than 0.5 cm in the radical retropubic prostatectomy specimen. RESULTS: The number of men who underwent biopsy and the number of cancers detected in the 5 possible sets of biopsies were 1725 and 402, 706 and 124, 307 and 36, 103 and 9, and 13 and 0, respectively. The risk of detecting focal cancer was 7.9%, 10.2%, 7.5%, 5.8% and 0%, respectively, but the relative ratio (focal-to-all cancers) increased 34%, 58%, 64%, 67% and, not applicable, respectively. In men with a total core cancer length of less than 10 mm there was no correlation between core cancer length and total tumor volume, as measured in the prostatectomy specimen. Two-thirds of men with a total core cancer length of less than 3 mm had a tumor volume of greater than 0.5 cm, while the risk of low volume cancer was less than 5% only in men with a total core cancer length of greater than 10 mm. CONCLUSIONS: In a repeat PSA based screening program sextant biopsies are of little or no value for predicting tumor volume.

Hugosson J, Aus G, Bergdahl S, Fernlund P, Frösing R, Lodding P, Pihl CG, Lilja H. · Department of Urology, Sahlgrenska University Hospital, Göteborg, Sweden. · BJU Int. · Pubmed #14983953 No free full text.

Abstract: OBJECTIVE: To report the initial results from Sweden of a large population-based randomized study of screening using prostate-specific antigen (PSA) to detect prostate cancer, as the efficacy of such screening to decrease prostate cancer mortality has not yet been proven. METHODS: From the population registry men aged 50-66 years were randomized to screening (9973) and to future controls (9973). Men randomized to screening were invited to have their serum measured for free PSA (fPSA) and total PSA (tPSA) in serum using the Prostatus f/tPSA assay (Perkin-Elmer, Turku, Finland). Men with a tPSA of < 3.0 ng/mL were not further investigated, while those with a tPSA of > or = 3.0 ng/mL were investigated with a digital rectal examination (DRE), transrectal ultrasonography (TRUS) and sextant biopsies. RESULTS: Of those invited, 60% accepted PSA testing and 11.3% had a tPSA of > or = 3.0 ng/mL. Altogether 145 cancers were detected (positive predictive value, PPV, 24%); none were stage M1, two were stage N+ and 10 stage T3-4. Most (59%) cancers were impalpable and 39% were both impalpable and invisible on TRUS. At biopsy, 7% were Gleason score 2-4, 71% 5-6, 19% 7 and 2% Gleason score 8-10. A threshold tPSA of > or = 4.0 ng/mL would have detected 109 cancers in 366 biopsied men (PPV 30%) while cancer detection would have been 14% higher with a PPV of 36% using a threshold tPSA of > or = 3.0 ng/mL combined with a f/tPSA threshold of < or = 18%. CONCLUSIONS: PSA screening detects early-stage low-grade prostate cancer. Both the sensitivity and specificity can be increased by incorporating f/tPSA with a tPSA threshold of < 4 ng/mL.

Aus G, Becker C, Franzén S, Lilja H, Lodding P, Hugosson J. · Department of Urology, Sahlgrens University Hospital, S41345 Göteborg, Sweden. · Eur Urol. · Pubmed #14734000 No free full text.

Abstract: OBJECTIVE: To evaluate the cumulative risk of having a prostate cancer diagnosis in a repeated screening situation in relation to the free-to-total prostate specific antigen ratio (F/T-PSA). PATIENTS AND METHODS: The present study includes 1385 men (aged 50-70 years) who underwent prostate biopsy for the first time in the screening program that started in 1995. In case of a benign finding, the men have been followed biennially and new biopsies performed in case of persistently elevated PSA. The cumulative risk to be diagnosed with prostate cancer until July 1, 2002 was calculated by the Kaplan-Meier method and comparison was made between different levels of T-PSA and F/T-PSA ratios. RESULTS: Of 2129 biopsies 469 showed cancer. The cumulative 5-year risk to be diagnosed with prostate cancer was significantly dependent of the F/T-ratio. The risk for men with a T-PSA of 3-5.99 g/ml was 16% [6-25%] for those who had a ratio of >30% and 44% [34-60%] for those with a ratio of <10%. The corresponding difference for patients with a T-PSA of 6-9.99 g/ml was even more pronounced: 21% [0-42%] vs. 80% [64-96%]. CONCLUSION: By completing the T-PSA measurement with the F/T-PSA ratio it is possible to significantly better assess the cumulative prostate cancer risk within the next five years (without the aid of further urological work-up).

Aus G, Abrahamsson PA, Ahlgren G, Hugosson J, Lundberg S, Schain M, Schelin S, Pedersen K. · Department of Urology, Ryhov Hospital, Jönköping, Sweden. · BJU Int. · Pubmed #12230618 No free full text.

Abstract: OBJECTIVE: To describe the outcome, assessed as the level of prostate specific antigen (PSA), of a mature (more than half the events recorded) prospective randomized study with a median follow-up of 82 months of neoadjuvant hormonal therapy before radical prostatectomy, as this has been suggested to decrease the rate of positive surgical margins (i.e. provide greater potential to completely excise the tumour). PATIENTS AND METHODS: From December 1991 to March 1994, 126 patients with clinically localized prostate cancer were randomized between direct radical prostatectomy or a 3-month course of a gonadotrophin-releasing hormone analogue before surgery. The patients were followed by PSA determinations and a value of > 0.5 ng/mL used to define progression. RESULTS: The incidence of positive surgical margins decreased from 45.5% to 23.6% (P = 0.016) with hormone treatment. Despite this there was no difference in PSA progression-free survival at the last follow-up; it was 51.5% for those undergoing radical prostatectomy only and 49.8% for those who received hormonal pretreatment (P = 0.588). CONCLUSIONS: Three months of neoadjuvant hormonal therapy before radical prostatectomy offers no benefit to the patient and cannot be recommended for routine clinical use.

Aus G, Pileblad E, Hugosson J. · Department of Urology, Sahlgrenska University Hospital, S-41345, Göteborg, Sweden. · Eur Urol. · Pubmed #12160583 No free full text.

Abstract: OBJECTIVE: To study the complications and oncological outcome after cryosurgical ablation of the prostate (CSAP). METHODS: Fifty-four patients with prostate cancer were entered into this prospective phase II trial of CSAP. Patients were followed with serum PSA determinations, follow-up biopsies at 3-6 months postoperatively and a questionnaire to assess complications. A PSA of >1 ng/ml or a positive biopsy was interpreted as progression. RESULTS: Mean follow-up was 58.5 months. Patients needed a suprapubic catheter postoperatively for in mean 18 days. Transient penile numbness occurred in 15%. Bothersome sloughing of dead tissue was noticed by 15% of patients and 15% needed a transurethral resection. Nine patients (17%) developed strictures and five patients stone formation in the prostatic urethra. One patient developed a perennial fistula. Thirty-nine out of 43 patients reporting on potency become impotent, nine patients developed a slight stress incontinence and one severe incontinence.At median follow-up, the actuarial progression-free survival was 38.9%. Fourteen out of 50 patients biopsied (28%) had remaining cancer in their prostates. CONCLUSION: High complication rates in combination with poor oncological outcome has made us stop using this treatment modality.

Ahlegren G, Pedersen K, Lundberg S, Aus G, Hugosson J, Abrahamsson P. · Department of Urology, University Hospital, Malmö, Malmö, Sweden. · Urology. · Pubmed #11113749 No free full text.

Abstract: OBJECTIVES: To study neuroendocrine (NE) tumor cell differentiation in prostate cancer in relation to failure after radical prostatectomy. METHODS: Radical prostatectomy specimens from 103 of 111 patients randomized to 3-month neoadjuvant luteinizing hormone-releasing hormone-analogue treatment (neoadjuvant group) or to surgery alone (control group) were available for analysis. Immunohistochemistry using antibodies to chromogranin A (CGA) enabled detection of tumor cells with NE differentiation. NE differentiation was scored as NE-negative (0 to 1+) or NE-positive (2 to 3+). The number of CGA-positive cells/cm(2) tumor area on the slides was assessed in a separate analysis. The patients were followed up for 39 months after surgery, and a prostate-specific antigen value of 0.5 ng/mL or greater in two consecutive blood samples was considered biochemical failure. RESULTS: Kaplan-Meier analysis stratified for neoadjuvant hormonal treatment showed the failure rate to be significantly greater among those with NE-positive tumors than among those with NE-negative tumors. However, the number of CGA-positive cells/cm(2) was not a variable of prognostic significance. Instead, both NE differentiation and the CGA-positive cell count correlated with the tumor area on the slides (P = 0.0001). Multivariate analysis revealed the tumor area on the slide (P <0.0001) and positive surgical margins (P = 0.03) to be the only significant predictors of biochemical failure. CONCLUSIONS: The extension of NE differentiation in prostate cancer correlates with tumor volume and is not an independent prognostic factor of failure after radical prostatectomy.

Ahlgren G, Pedersen K, Lundberg S, Aus G, Hugosson J, Abrahamsson PA. · Department of Urology, Lund University, University Hospital, Malmö, Sweden. · Prostate. · Pubmed #10679756 No free full text.

Abstract: BACKGROUND: We studied the extent of neuroendocrine (NE) tumor cell differentiation and its relation to regressive changes in prostate cancer after 3-month hormonal treatment. METHODS: Radical prostatectomy specimens from 103 patients, randomized to 3-month neoadjuvant LH-RH-analogue treatment (neoadjuvant group) or to surgery alone (control group), were available for analysis. The effects of hormonal treatment in terms of positive surgical margins, the degree of histopathological changes, and tumor cell proliferation were evaluated in relation to NE-differentiation assessed with antibodies against chromogranin A (CGA). RESULTS: Both the number of CGA-positive cells/cm(2) (P < 0.003) and the proportion of NE-positive tumors (P = 0.07) were greater in the neoadjuvant group than in the control group. No correlation existed between NE-differentiation and the effects of the neoadjuvant hormonal treatment; nor did NE-differentiation correlate to the decrease in serum PSA. CONCLUSIONS: Neuroendocrine differentiation in prostate cancer increases after 3 months of neoadjuvant hormonal treatment but does not correlate to the effects of hormonal treatment.