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  • 1. Bechis, Seth K
    et al.
    Otsetov, Alexander G
    Ge, Rongbin
    Olumi, Aria F
    Personalized medicine for the management of benign prostatic hyperplasia.2014In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 192, no 1Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Benign prostatic hyperplasia affects more than 50% of men by age 60 years, and is the cause of millions of dollars in health care expenditure for the treatment of lower urinary tract symptoms and urinary obstruction. Despite the widespread use of medical therapy, there is no universal therapy that treats all men with symptomatic benign prostatic hyperplasia. At least 30% of patients do not respond to medical management and a subset require surgery. Significant advances have been made in understanding the natural history and development of the prostate, such as elucidating the role of the enzyme 5α-reductase type 2, and advances in genomics and biomarker discovery offer the potential for a more targeted approach to therapy. We review the current understanding of benign prostatic hyperplasia progression as well as the key genes and signaling pathways implicated in the process such as 5α-reductase. We also explore the potential of biomarker screening and gene specific therapies as tools to risk stratify patients with benign prostatic hyperplasia and identify those with symptomatic or medically resistant forms.

    MATERIALS AND METHODS: A PubMed® literature search of current and past peer reviewed literature on prostate development, lower urinary tract symptoms, benign prostatic hyperplasia pathogenesis, targeted therapy, biomarkers, epigenetics, 5α-reductase type 2 and personalized medicine was performed. An additional Google Scholar™ search was conducted to broaden the scope of the review. Relevant reviews and original research articles were examined, as were their cited references, and a synopsis of original data was generated with the goal of informing the practicing urologist of these advances and their implications.

    RESULTS: Benign prostatic hyperplasia is associated with a state of hyperplasia of the stromal and epithelial compartments, with 5α-reductase type 2 and androgen signaling having key roles in the development and maintenance of the prostate. Chronic inflammation, multiple growth factor and hormonal signaling pathways, and medical comorbidities have complex roles in prostate tissue homeostasis as well as its evolution into the clinical state of benign prostatic hyperplasia. Resistance to medical therapy with finasteride may occur through silencing of the 5α-reductase type 2 gene by DNA methylation, leading to a state in which 30% of adult prostates do not express 5α-reductase type 2. Novel biomarkers such as single nucleotide polymorphisms may be used to risk stratify patients with symptomatic benign prostatic hyperplasia and identify those at risk for progression or failure of medical therapy. Several inhibitors of the androgen receptor and other signaling pathways have recently been identified which appear to attenuate benign prostatic hyperplasia progression and may offer alternative targets for medical therapy.

    CONCLUSIONS: Progressive worsening of lower urinary tract symptoms and bladder outlet obstruction secondary to benign prostatic hyperplasia is the result of multiple pathways including androgen receptor signaling, proinflammatory cytokines and growth factor signals. New techniques in genomics, proteomics and epigenetics have led to the discovery of aberrant signaling pathways, novel biomarkers, DNA methylation signatures and potential gene specific targets. As personalized medicine continues to develop, the ability to risk stratify patients with symptomatic benign prostatic hyperplasia, identify those at higher risk for progression, and seek alternative therapies for those in whom conventional options are likely to fail will become the standard of targeted therapy.

  • 2. Bechis, Seth K
    et al.
    Otsetov, Alexander G
    Ge, Rongbin
    Wang, Zongwei
    Vangel, Mark G
    Wu, Chin-Lee
    Tabatabaei, Shahin
    Olumi, Aria F
    Age and Obesity Promote Methylation and Suppression of 5α-Reductase 2: Implications for Personalized Therapy of Benign Prostatic Hyperplasia.2015In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 194, no 4Article in journal (Refereed)
    Abstract [en]

    PURPOSE: In men with symptomatic benign prostatic hyperplasia 5α-reductase inhibitors are a main modality of treatment. More than 30% of men do not respond to the therapeutic effects of 5α-reductase inhibitors. We have found that a third of adult prostate samples do not express 5α-reductase type 2 secondary to epigenetic modifications. We evaluated whether 5α-reductase type 2 expression in benign prostatic hyperplasia specimens from symptomatic men was linked to methylation of the 5α-reductase type 2 gene promoter. We also identified associations with age, obesity, cardiac risk factors and prostate specific antigen.

    MATERIALS AND METHODS: Prostate samples from men undergoing transurethral prostate resection were used. We determined 5α-reductase type 2 protein expression and gene promoter methylation status by common assays. Clinical variables included age, body mass index, hypertension, hyperlipidemia, diabetes, prostate specific antigen and prostate volume. Univariate and multivariate statistical analyses were performed followed by stepwise logistic regression modeling.

    RESULTS: Body mass index and age significantly correlated with methylation of the 5α-reductase type 2 gene promoter (p <0.05) whereas prostate volume, prostate specific antigen or benign prostatic hyperplasia medication did not correlate. Methylation highly correlated with 5α-reductase protein expression (p <0.0001). In a predictive model increasing age and body mass index significantly predicted methylation status and protein expression (p <0.01).

    CONCLUSIONS: Increasing age and body mass index correlate with increased 5α-reductase type 2 gene promoter methylation and decreased protein expression in men with symptomatic benign prostatic hyperplasia. These results highlight the interplay among age, obesity and gene regulation. Our findings suggest an individualized epigenetic signature for symptomatic benign prostatic hyperplasia, which may be important to choose appropriate personalized treatment options.

  • 3. Berglund, Anders
    et al.
    Garmo, Hans
    Tishelman, Carol
    Holmberg, Lars
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Lambe, Mats
    Comorbidity, treatment and mortality: a population based cohort study of prostate cancer in PCBaSe Sweden2011In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 185, no 3, p. 833-840Article in journal (Refereed)
    Abstract [en]

    Purpose

    We examined associations among comorbidity, treatment decisions and mortality in patients with prostate cancer.

    Materials and Methods

    A total of 77,536 men diagnosed with prostate cancer between 1997 and 2006 were identified in PCBaSe Sweden from the National Prostate Cancer Register of Sweden. Logistic, Cox and competing risk regression were used to assess associations among Charlson comorbidity index, treatment and mortality. The Charlson comorbidity index was categorized into no (0), mild (1) and severe comorbidity (2+).

    Results

    In men with low risk prostate cancer 5,975 of the 13,245 (45.1%) patients without comorbidity underwent radical prostatectomy compared to 256 of the 1,399 (18.9%) men with severe comorbidity. Following adjustment for age and period of diagnosis, radical prostatectomy was less likely to be offered to men with severe comorbidity (OR 0.48, 95% CI 0.41–0.55). In men with high risk prostate cancer, radiotherapy was more common (range 7.7% to 21.3%) than radical prostatectomy (range 3.0% to 11.2%) regardless of comorbidity burden. All cause and competing cause but not prostate cancer specific mortality were increased in men with severe comorbidity (all cause HR 1.99, 95% CI 1.93–2.05; competing cause sHR 2.66, 95% CI 2.56–2.78; prostate cancer specific sHR 0.98, 95% CI 0.93–1.03). The cumulative probability of prostate cancer death given no death from competing causes was significantly higher in men with severe comorbidity in all risk groups (p <0.01).

    Conclusions

    Comorbidity affects treatment choices, and is associated with all cause, competing cause and conditional prostate cancer specific mortality. An increased conditional prostate cancer specific mortality in men with severe comorbidity may reflect less aggressive treatment, impaired tumor defense, lifestyle factors and poor general health behavior.

  • 4.
    Friðriksson, Jón Örn
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Holmberg, Erik
    Adolfsson, Jan
    Lambe, Mats
    Bill-Axelson, Anna
    Carlsson, Stefan
    Hugosson, Jonas
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Rehospitalization after radical prostatectomy in a nationwide, population-based study2014In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 192, no 1, p. 112-119Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate readmission frequencies during the 90 days following radical prostatectomy and to assess readmission risk associated with potentially related variables.

    MATERIALS AND METHODS: Using the population-based, nationwide database Prostate Cancer data Base Sweden (PCBaSe), we identified men diagnosed with incident prostate cancer between 2000 and 2011 who underwent radical prostatectomy (RP) as their primary treatment, and we used logistic regression analysis to examine the association of the risk of 90-day postoperative readmission with surgical method, calendar period, tumor risk category, hospital case load, and patient characteristics.

    RESULTS: During the 90 postoperative days, 2,317 (10%) of the 24,122 men identified were non-electively readmitted, specifically 10% after retropubic radical prostatectomy (RRP), 9% after robot-assisted RP (RALP) and 11% after laparoscopic RP (LRP). The range in the readmission frequency between hospitals was 0-35%. A higher risk of readmission was associated with early calendar period (2009-2011 vs. 2000-2002: odds ratio (OR), 0.71; 95% confidence interval (CI), 0.61-0.83), greater age (≥70 years vs. <60 years: OR, 1.17; 95% CI, 1.00-1.36), higher risk category (high vs. low-risk category: OR, 1.78; 95% CI, 1.57-2.03), high comorbidity (Charlson comorbidity index ≥3 vs. 0: OR, 1.77; 95% CI, 1.29-2.44), and low hospital surgical volume (≥150 vs. <30 RPs per year: OR, 0.70; 95% CI, 0.60-0.81).

    CONCLUSIONS: Readmission rates after different RP methods were similar, ranging from 9% to 11%, with a wide variation between hospitals. Readmission rates can be used as an indicator of perioperative care quality, but potential confounders need to be adjusted to avoid bias.

  • 5.
    Holmström, Benny
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Holmberg, Erik
    Egevad, Lars
    Adolfsson, Jan
    Johansson, Jan-Erik
    Hugosson, Jonas
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Outcome of primary versus deferred radical prostatectomy in the National Prostate Cancer Register of Sweden follow-up study2010In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 184, no 4, p. 1322-1327Article in journal (Refereed)
    Abstract [en]

    Purpose We assessed outcomes in terms of adverse pathology and prostate cancer specific mortality in men who underwent primary or deferred radical prostatectomy.

    Materials and Methods In the National Prostate Cancer Register of Sweden Follow-Up Study men 70 years old or younger at diagnosis with localized low to intermediate risk prostate cancer diagnosed from 1997 to 2002 were identified. Outcome in terms of adverse pathology, namely upgrading of Gleason score, positive surgical margins and extraprostatic extension, as well as prostate cancer specific mortality, was assessed in 2,344 men who underwent primary radical prostatectomy and 222 who underwent deferred radical prostatectomy after an initial period of surveillance.

    Results Upgrading of Gleason score in surgical specimens vs core biopsies was less frequent after primary (25%) vs deferred radical prostatectomy (38%), p <0.001. There was no significant difference in the percentage of men who underwent primary vs deferred radical prostatectomy for positive surgical margins (33% vs 24%) or extraprostatic extension (27% vs 25%), and there was no difference in any 1 or more of the 3 adverse pathology features (55% vs 56%). After a median followup of 8 years 0.7% of men in the primary radical prostatectomy group and 0.9% in the deferred radical prostatectomy group had died of prostate cancer.

    Conclusions There was no significant difference in the presence of any 1 or more adverse pathology features or in prostate cancer specific mortality after primary compared to deferred radical prostatectomy. However, longer followup is needed to conclusively evaluate the role of deferred radical prostatectomy.

  • 6.
    Häggström, S
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Lissbrant, I F
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, A
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Damber, J E
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Testosterone induces vascular endothelial growth factor synthesis in the ventral prostate in castrated rats.1999In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 161, no 5, p. 1620-5Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Recent studies suggest that the vasculature is important for the control of prostate growth. Castration induces an involution of the prostate gland and its vasculature. Replacement of testosterone stimulates endothelial cell proliferation and normalizes vascular volumes and blood flow several days before organ regrowth. Antiangiogenesis treatment inhibits the growth of prostate tumors. Understanding the regulation of the prostate vasculature may therefore provide important knowledge of the mechanisms responsible for the growth of non-malignant and malignant prostate tissue. Castration induced regression and testosterone stimulated regrowth of the prostatic vasculature have here been used to study the involvement of the angiogenic factor vascular endothelial growth factor (VEGF) and its receptors flt-1 and flk-1/KDR in the regulation of the prostatic vasculature.

    MATERIALS AND METHODS: VEGF, flt-1, and flk-1/KDR levels were quantified in the rat ventral prostate following castration and testosterone replacement. Methods used were competitive RT-PCR, Western blot and immunohistochemistry.

    RESULTS: VEGF mRNA and protein levels were significantly decreased by castration and testosterone treatment induced VEGF synthesis in the rat ventral prostate epithelium. Flt-1 and flk-1/KDR receptor levels were unaffected by castration and testosterone treatment.

    CONCLUSIONS: Castration down regulates VEGF and testosterone induces VEGF synthesis in epithelial cells in the rat ventral prostate.

  • 7.
    Jacobsen, Jan
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences.
    Rasmuson, Torgny
    Grankvist, Kjell
    Ljungberg, Börje
    Vascular endothelial growth factor as prognostic factor in renal cell carcinoma2000In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Journal of Urology, Vol. 163, no 1, p. 343-347Article in journal (Refereed)
  • 8. Loeb, Stacy
    et al.
    Berglund, Anders
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Population Based Study of Use and Determinants of Active Surveillance and Watchful Waiting for Low and Intermediate Risk Prostate Cancer2013In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 190, no 5, p. 1742-1749Article in journal (Refereed)
    Abstract [en]

    Purpose: Prior studies have reported the underuse of deferred treatment (ie active surveillance or watchful waiting) for low risk prostate cancer in the United States. We examined contemporary trends in active surveillance and watchful waiting in the nationwide Swedish prostate cancer registry. We also examined factors associated with selection of deferred management, which might provide insight into the rational diffusion of this important management strategy.

    Materials and Methods: We identified 57,713 men with very low risk (T1c, Gleason 6 or less, prostate specific antigen less than 10 ng/ml, prostate specific antigen density less than 0.20 ng/ml/cc, 2 or fewer positive biopsy cores or less than 25% of cores positive), low risk (T1-T2, Gleason 6 or less, and prostate specific antigen less than 10 ng/ml) and intermediate risk prostate cancer (T1-T2, Gleason 7 and/or prostate specific antigen 10 to 20 ng/ml) in the PCBaSe (Prostate Cancer database Sweden) from 1998 to 2011. Subclassification of very low risk disease, and active surveillance vs watchful waiting was possible beginning in 2007. We examined primary treatment selection by risk group and used logistic regression to evaluate factors associated with deferred treatment.

    Results: Overall 13,272 (46%) men with low risk and 8,695 (30%) with intermediate risk prostate cancer chose deferred treatment. Since 2007, 59%, 41% and 16% of very low, low and intermediate risk prostate cancer, respectively, chose active surveillance. Age was by far the strongest determinant of deferred treatment. Education, marital status and comorbidity were significantly but weakly associated with deferring treatment.

    Conclusions: Deferred treatment for low and intermediate risk prostate cancer was frequently used in Sweden. Dissociating diagnosis from treatment in men with a low risk of progression can decrease the rate of overtreatment.

  • 9. Loeb, Stacy
    et al.
    Lambe, Mats
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Urology, Uppsala University Hospital, Uppsala, Sweden.
    Re: Editorial Comment on Use of Phosphodiesterase Type 5 Inhibitors for Erectile Dysfunction and Risk of Malignant Melanoma2016In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 195, no 4, p. 1172-1173Article in journal (Refereed)
  • 10. Lose, G
    et al.
    Mattiasson, A
    Walter, S
    Lalos, O
    Umeå University, Faculty of Medicine, Clinical Sciences, Obstetrics and Gynaecology.
    van Kerrebroeck, P
    Abrams, P
    Freeman, R
    Clinical experiences with desmopressin for long-term treatment of nocturia.2004In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 172, no 3, p. 1021-1025Article in journal (Refereed)
  • 11.
    Lundström, Karl-Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Drevin, Linda
    Carlsson, Stefan
    Garmo, Hans
    Loeb, Stacy
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Bill-Axelson, Anna
    Nationwide Population Based Study of Infections after Transrectal Ultrasound Guided Prostate Biopsy2014In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 192, no 4, p. 1116-1122Article in journal (Refereed)
    Abstract [en]

    Purpose: Transrectal ultrasound guided biopsy is the gold standard for detecting prostate cancer but international reports suggest that increasing risks are associated with the procedure. We estimated incidence and risk factors for infection after prostate biopsy as well as 90-day mortality using a nationwide Swedish sample. Material and Methods: We performed a population based study of 51,321 men from PCBaSe between 2006 and 2011. Primary outcome measures were dispensed prescriptions of antibiotics for urinary tract infection and hospitalization with a discharge diagnosis of urinary tract infection. Multivariable logistic regression was used to examine risk factors for infection in men who underwent prostate biopsy. Results: During the 6 months before biopsy the background incidence of urinary tract infection was approximately 2%. Within 30 days after biopsy 6% of the men had a dispensed prescription for urinary tract antibiotics and 1% were hospitalized with infection. The strongest risk factors for an antibiotic prescription were prior infection (OR 1.59, 95% CI 1.45-1.73), high Charlson comorbidity index (OR 1.25, 95% CI 1.11-1.41) and diabetes (OR 1.32, 95% CI 1.17-1.49). Risk of an antibiotic prescription after biopsy decreased from 2006 to 2011 (OR 0.79, 95% CI 0.70-0.90) but the risk of hospital admission increased (OR 2.14, 95% CI 1.58-2.94). No significant increase was observed in 90-day mortality. Conclusions: Severe infections with hospitalization after prostate biopsy are increasing in Sweden. The risk of post-biopsy infection is highest in men with a history of urinary tract infection and those with significant comorbidities.

  • 12. MacLennan, Steven
    et al.
    Lam, Thomas
    Imamura, Mari
    Dahm, Philipp
    Canfield, Steven
    Ljungberg, Börje
    Urology Unit, University of Aberdeen, Aberdeen, United Kingdom.
    N'Dow, James
    Re: comparative effectiveness for survival and renal function of partial and radical nephrectomy for localized renal tumors: a systematic review and meta-analysis2013In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 189, no 3, p. 1166-1167Article in journal (Other academic)
  • 13. Steinsvik, E Andreas Svaboe
    et al.
    Fosså, Sophie D
    Axcrona, Karol
    Fransson, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Dahl, Alv A
    Do perceptions of adverse events differ between patients and physicians? Findings from a randomized, controlled trial of radical treatment for prostate cancer2010In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 184, no 2, p. 525-531Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Previous cross-sectional studies show considerable discrepancies between patient and physician ratings of adverse events after prostate cancer treatment. We used data from a randomized, controlled trial to examine such discrepancies.

    MATERIAL AND METHODS: The Scandinavian Prostate Cancer Groups Study 7 randomized men with locally advanced prostate cancer to antiandrogen monotherapy or to the same hormone treatment combined with external beam radiotherapy after 3 months of total androgen blockade. We selected a subsample of 333 men with valid ratings at baseline, and at 12 and 24-month followup for this prospective substudy. We also examined a cross-sectional sample of 305 men at the end of radiotherapy. We compared patient and physician ratings of frequency of daytime and nighttime urination, urinary incontinence, erectile dysfunction, bowel problems, nausea/vomiting, breast tenderness and gynecomastia.

    RESULTS: Perfect agreement between patient and physician ratings was observed in 70% to 100% of cases at baseline, in 73% to 98% at 12 months and in 65% to 97% at 24 months. There were 1% to 20% changes in perfect agreement with time. With patient ratings as the gold standard physicians more often underrated than overrated adverse events, except bowel problems, which were overrated at all posttreatment points.

    CONCLUSIONS: In a randomized, controlled trial of external beam radiotherapy and hormone manipulation physicians recorded pelvis related adverse events in acceptable accordance with their patients with prostate cancer. The oncologist tendency to overestimate bowel problems after radiotherapy needs further investigation. Our positive findings from a formal trial should not be transferred to daily clinical practice without further studies of discrepancies in routine clinical practice.

  • 14.
    Thellenberg, Camilla
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences.
    Malmer, Beatrice
    Tavelin, Björn
    Grönberg, Henrik
    Second primary cancers in men with prostate cancer: an increased risk of male breast cancer2003In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 169, no 4, p. 1345-1348Article in journal (Refereed)
  • 15.
    Thellenberg Karlsson, Camilla
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology. Onkologi.
    Malmer, Beatrice
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology. Onkologi.
    Wiklund, Fredrik
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology. Onkologi.
    Grönberg, Henrik
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology. Onkologi.
    Breast cancer as a second primary in patients with prostate cancer: estrogen treatment or association with family history of cancer?2006In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 176, no 2, p. 538-543Article in journal (Refereed)
  • 16. Vellekoop, Annelies
    et al.
    Loeb, Stacy
    Folkvaljon, Yasin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Regional Cancer Centre, Uppsala University Hospital, Uppsala.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York.
    Population Based Study of Predictors of Adverse Pathology among Candidates for Active Surveillance with Gleason 6 Prostate Cancer2014In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 191, no 2, p. 350-357Article in journal (Refereed)
    Abstract [en]

    Purpose: Approximately a third of prostate cancer cases with a Gleason score of 6 are upgraded at radical prostatectomy. We studied trends and predictors of upgrading and up staging among men with Gleason 6 prostate cancer who were potential candidates for active surveillance in a population based cohort.

    Materials and Methods: From 2007 to 2011, 13,159 men were diagnosed with Gleason 6, clinical stage T1c/T2 prostate cancer in the NPCR (National Prostate Cancer Register of Sweden). Of these men 4,500 underwent radical prostatectomy, including 2,205 with data on the extent of prostate cancer in the biopsy cores. Logistic regression was used to examine variables associated with adverse pathology (defined as upgrading to Gleason 7 or greater, or up staging to pT3 or greater) in the full group and in potential candidates for active surveillance using 6 current published protocols.

    Results: Among Swedish men with clinically localized Gleason 6 prostate cancer approximately 50% had adverse pathology at radical prostatectomy. Of the men who met the study inclusion criteria of 6 different active surveillance protocols, adverse pathology was present in 33% to 45%. Predictors of adverse pathology were older age, higher prostate specific antigen, prostate specific antigen density greater than 0.15 ng/ml/cm(3), palpable disease and extent of cancer greater than 4 mm on biopsy. Larger prostate volume had an inverse relationship with adverse pathology.

    Conclusions: More than a third of men meeting the most stringent active surveillance criteria had adverse pathology at radical prostatectomy in this population based cohort. Active surveillance programs should consider prostate specific antigen density and extent of cancer on biopsy for patient selection.

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