| 1. |
- Adam, Meike, et al.
(författare)
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Functional Outcomes and Quality of Life After Radical Prostatectomy Only Versus a Combination of Prostatectomy with Radiation and Hormonal Therapy
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 71:3, s. 330-336
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Tidskriftsartikel (refereegranskat)abstract
- Background: While the optimal use and timing of secondary therapy after radical prostatectomy (RP) remain controversial, there are limited data on patient-reported outcomes following multimodal therapy.Objective: To assess the impact of additional radiation therapy (RT) and/or androgen deprivation therapy (ADT) on urinary continence, potency, and quality of life (QoL) after RP.Design, setting, and participants: Among 13 150 men who underwent RP from 1992 to 2013, 905 received RP + RT, 407 RP + ADT and 688 RP + RT + ADT.Outcome measurements and statistical analyses: Urinary function, sexual function, and overall QoL were evaluated annually using self-administered validated questionnaires. Propensity score-matched and bootstrap analyses were performed, and the distributions for all functional outcomes were analyzed as a function of time after RP.Results and limitations: Patients who received RP + RT had a 4% higher overall incontinence rate 3 yr after surgery, and 1% higher rate for severe incontinence (> 3 pads/24 h) compared to matched RP-only patients. ADT further increased the overall and severe incontinence rates by 4% and 3%, respectively, compared to matched RP + RT patients. RP + RT was associated with an 18% lower rate of potency compared to RP alone, while RP + RT + ADT was associated with a further 17% reduction compared to RP + RT. Additional RT reduced QoL by 10% and additional ADT by a further 12% compared to RP only and RP + RT, respectively. The timing of RT after RP had no influence on continence, but adjuvant compared to salvage RT was associated with significantly lower potency (37% vs 45%), but higher QoL (60% vs 56%). Limitations of our study include the observational study design and potential for selection bias in the treatments received.Conclusions: Secondary RT and ADT after RP have an additive negative influence on urinary function, potency, and QoL. Patients with high-risk disease should be counseled before RP on the potential net impairment of functional outcomes due to multimodal treatment.Patient summary: Men with high-risk disease choosing surgery upfront should be counseled on the potential need for additional radiation and or androgen deprivation, and the potential net impairment of functional outcomes arising from multimodal treatment.
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| 2. |
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| 3. |
- Haese, Alexander, et al.
(författare)
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Human glandular kallikrein 2 levels in serum for discrimination of pathologically organ-confined from locally-advanced prostate cancer in total PSA-levels below 10 ng/ml
- 2001
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 49:2, s. 101-109
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We measured serum levels of human glandular kallikrein 2 (hK2) in patients treated with radical retropubic prostatectomy (rrP) for clinically localized prostate cancer (PCa) with a total PSA (tPSA)-level below 10 ng/ml to investigate whether hK2 can be applied to preoperatively distinguish organ-confined (pT2a/b) from nonorgan-confined (> or = pT3a)-PCa more accurately than total PSA. Further, we evaluated hK2, free- and tPSA-concentrations in all pathologic stages of PCa. METHODS: 161 serum samples from men scheduled for rrP were collected 1 day before surgery prior to any prostatic manipulation. Pathologic work-up revealed > or = pT3a-PCa in 48 and pT2a/b-PCa in 113 patients. HK2-levels in serum were measured using an immunofluorometric assay with an analytical sensitivity of 0.5 pg/ml, a functional sensitivity of 5 pg/ml and insignificant cross-reactivity with PSA (< 0.005%). Total (tPSA) and free PSA (fPSA) levels were measured using a commercially available assay from which we calculated %fPSA and an algorithm that combined hK2 and PSA-levels [hK2] x [tPSA/fPSA]. Means, medians, and ranges were calculated for pT2a/b vs. >/= pT3a-PCa and for all pathologic stages. Statistical significance of differences was calculated using Mann-Whitney-U and Kruskal-Wallis tests. Calculation of receiver-operator-characteristic (ROC) curves were performed for hK2, [hK2] x [tPSA/fPSA] and tPSA to compare diagnostic performance. RESULTS: A mean tPSA level in serum of 6.12 ng/ml in > or = pT3a-PCa was not significantly different (P = 0.366) from 5.78 ng/ml in pT2a/b-PCa. Also, there were no statistically significantly different levels of fPSA (P = 0.947) or %fPSA (0.292) for these two groups. By contrast, mean hK2-level in pT2a/b-PCa of 80 pg/ml was significantly different (P = 0.004) from a mean hK2 level of 120 pg/ml in > or = pT3a-PCa as shown by Mann-Whitney-analysis Moreover, the algorithm of [hK2] x [tPSA/fPSA] was significantly lower (P = 0.0004) in pT2a/b-PCa vs. > or = pT3a-PCa. Calculation of areas under curve (AUC) by receiver-operator-characteristics (ROC) demonstrated that the AUC for hK2 (0.64) was larger and the AUC for [hK2] x [tPSA/fPSA] (=0.68) significantly larger (P = 0.007) compared to the AUC of tPSA (0.55). Furthermore, Kruskal-Wallis Test revealed a highly significant correlation to pathologic stage using hK2 (P = 0.008) and [hK2] x [tPSA/fPSA] (P = 0.0015) compared to no significant differences in serum concentration of tPSA (P = 0.296). Also at tPSA-levels from 10-20 ng/ml, the hK2-levels in pT2a/b-PCa were close to significantly different (P = 0.051) from those in men with >/= pT3a-PCa, while the algorithm of [hK2] x [tPSA/fPSA] in that tPSA-range was significantly lower (P = 0.002) in pT2a/b-PCa compared to > or = pT3a0-PCa. CONCLUSIONS: Highly significant differences in serum concentration enable hK2 to be a powerful predictor of organ-confined disease and pathologic stage of clinically localized prostate cancer, especially in the PSA-range below 10 ng/ml. As such, there are important clinical consequences for the application of hK2 for the adequate treatment of prostate cancer patients, i.e., the option of nerve-sparing surgery.
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| 4. |
- Lonergan, Peter E., et al.
(författare)
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Prospective validation of microseminoprotein-β added to the 4Kscore in predicting high-grade prostate cancer in an international multicentre cohort
- 2021
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Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 128:2, s. 218-224
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To prospectively evaluate the performance of a pre-specified statistical model based on four kallikrein markers in blood (total prostate-specific antigen [PSA], free PSA, intact PSA, and human kallikrein-related peptidase 2), commercially available as the 4Kscore, in predicting Gleason Grade Group (GG) ≥2 prostate cancer at biopsy in an international multicentre study at three academic medical centres, and whether microseminoprotein-β (MSP) adds predictive value. Patients and Methods: A total of 984 men were prospectively enrolled at three academic centres. The primary outcome was GG ≥2 on prostate biopsy. Three pre-specified statistical models were used: a base model including PSA, age, digital rectal examination and prior negative biopsy; a model that added free PSA to the base model; and the 4Kscore. Results: A total of 947 men were included in the final analysis and 273 (29%) had GG ≥2 on prostate biopsy. The base model area under the receiver operating characteristic curve of 0.775 increased to 0.802 with the addition of free PSA, and to 0.824 for the 4Kscore. Adding MSP to the 4Kscore model yielded an increase (0.014–0.019) in discrimination. In decision-curve analysis of clinical utility, the 4Kscore showed a benefit starting at a 7.5% threshold. Conclusion: A prospective multicentre evaluation of a pre-specified model based on four kallikrein markers (4Kscore) with the addition of MSP improves the predictive discrimination for GG ≥2 prostate cancer on biopsy and could be used to inform biopsy decision-making.
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| 5. |
- Martin, Neil E, et al.
(författare)
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Defining a Standard Set of Patient-centered Outcomes for Men with Localized Prostate Cancer
- 2015
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 67:3, s. 460-467
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Value-based health care has been proposed as a unifying force to drive improved outcomes and cost containment.OBJECTIVE: To develop a standard set of multidimensional patient-centered health outcomes for tracking, comparing, and improving localized prostate cancer (PCa) treatment value.DESIGN, SETTING, AND PARTICIPANTS: We convened an international working group of patients, registry experts, urologists, and radiation oncologists to review existing data and practices.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The group defined a recommended standard set representing who should be tracked, what should be measured and at what time points, and what data are necessary to make meaningful comparisons. Using a modified Delphi method over a series of teleconferences, the group reached consensus for the Standard Set.RESULTS AND LIMITATIONS: We recommend that the Standard Set apply to men with newly diagnosed localized PCa treated with active surveillance, surgery, radiation, or other methods. The Standard Set includes acute toxicities occurring within 6 mo of treatment as well as patient-reported outcomes tracked regularly out to 10 yr. Patient-reported domains of urinary incontinence and irritation, bowel symptoms, sexual symptoms, and hormonal symptoms are included, and the recommended measurement tool is the Expanded Prostate Cancer Index Composite Short Form. Disease control outcomes include overall, cause-specific, metastasis-free, and biochemical relapse-free survival. Baseline clinical, pathologic, and comorbidity information is included to improve the interpretability of comparisons.CONCLUSIONS: We have defined a simple, easily implemented set of outcomes that we believe should be measured in all men with localized PCa as a crucial first step in improving the value of care.PATIENT SUMMARY: Measuring, reporting, and comparing identical outcomes across treatments and treatment centers will provide patients and providers with information to make informed treatment decisions. We defined a set of outcomes that we recommend being tracked for every man being treated for localized prostate cancer.
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| 6. |
- Murphy, Declan G., et al.
(författare)
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Downsides of Robot-assisted Laparoscopic Radical Prostatectomy: Limitations and Complications
- 2010
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 57:5, s. 735-746
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Tidskriftsartikel (refereegranskat)abstract
- Context: Robot-assisted laparoscopic radical prostatectomy (RALP) using the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) is now in widespread use for the management of localised prostate cancer (PCa). Many reports of the safety and efficacy of this procedure have been published. However, there are few specific reports of the limitations and complications of RALP. Objective: The primary purpose of this review is to ascertain the downsides of RALP by focusing on complications and limitations of this approach. Evidence acquisition: A Medline search of the English-language literature was performed to identify all papers published since 2001 relating to RALP. Papers providing data on technical failures, complications, learning curve, or other downsides of RALP were considered. Of 412 papers identified, 68 were selected for review based on their relevance to the objective of this paper. Evidence synthesis: RALP has the following principal downsides: (1) device failure occurs in 0.2-0.4% of cases; (2) assessment of functional outcome is unsatisfactory because of nonstandardised assessment techniques; (3) overall complication rates of RALP are low, although higher rates are noted when complications are reported using a standardised system; (4) long-term oncologic data and data on high-risk PCa are limited; (5) a steep learning curve exists, and although acceptable operative times can be achieved in <20 cases, positive surgical margin (PSM) rates may require experience with >80 cases before a plateau is achieved; (6) robotic assistance does not reduce the difficulty associated with obese patients and those with large prostates, middle lobes, or previous surgery, in whom outcomes are less satisfactory than in patients without such factors; (7) economic barriers prevent uniform dissemination of robotic technology. Conclusions: Many of the downsides of RALP identified in this paper can be addressed with longer-term data and more widespread adoption of standardised reporting measures. The significant learning curve should not be understated, and the expense of this technology continues to restrict access for many patients. (C) 2009 European Association of Urology. Published by Elsevier B. V. All rights reserved.
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| 7. |
- Nickel, Katrin F., et al.
(författare)
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The polyphosphate-factor XII pathway drives coagulation in prostate cancer-associated thrombosis
- 2015
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 126:11, s. 1379-1389
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is a leading cause of thrombosis. We identify a new procoagulant mechanism that contributes to thromboembolism in prostate cancer and allows for safe anticoagulation therapy development. Prostate cancer-mediated procoagulant activity was reduced in plasma in the absence of factor XII or its substrate of the intrinsic coagulation pathway factor XI. Prostate cancer cells and secreted prostasomes expose long chain polyphosphate on their surface that colocalized with active factor XII and initiated coagulation in a factor XII-dependent manner. Polyphosphate content correlated with the procoagulant activity of prostasomes. Inherited deficiency in factor XI or XII or high-molecular-weight kininogen, but not plasma kallikrein, protected mice from prostasome-induced lethal pulmonary embolism. Targeting polyphosphate or factor XII conferred resistance to prostate cancer-driven thrombosis in mice, without increasing bleeding. Inhibition of factor XII with recombinant 3F7 antibody reduced the increased prostasome-mediated procoagulant activity in patient plasma. The data illustrate a critical role for polyphosphate/factor XII-triggered coagulation in prostate cancer-associated thrombosis with implications for anticoagulation without therapy-associated bleeding in malignancies.
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| 8. |
- van der Poel, Henk, et al.
(författare)
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Role of active surveillance and focal therapy in low- and intermediate-risk prostate cancers
- 2015
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Ingår i: World Journal of Urology. - : Springer Science and Business Media LLC. - 0724-4983 .- 1433-8726. ; 33:7, s. 907-916
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Low-risk prostate cancer is found in about half of newly diagnosed men subjected to PSA screening. Methods: To define the role of active surveillance and focal therapy in low- and intermediate-risk prostate cancers, an invited international panel of practicing physicians in the field of localized prostate cancer discussed the available literature in three consecutive meetings to come to a broad interpretation of the available data. Results: The panel (“new prostate cancer management group,” npm) agreed on the following observations. In most men with a low-volume Gleason 6 tumor, initial conservative management is appropriate. In men with a larger unifocal Gleason score 6 or 3 + 4 lesion, focal therapy, although still considered an investigational approach, appears to be a suitable option in early non-randomized comparison studies. Furthermore, in patients with multifocal small satellite Gleason 6 lesions in the presence of a larger index lesion, focal therapy of the index lesion is an option. For patients with high-grade, large-volume disease, or in young men with evidence of high-volume multifocal low-grade prostate cancer, whole-gland treatment should be considered. Conclusion: Active surveillance is a preferred and safe option for low-risk prostate cancer. Focal therapy is still under investigation, but the available phase II data are promising. Clinical benefits must be shown in prospective trials. With improved imaging, focal therapy may be an option for patients not choosing active surveillance with low-risk disease, progression upon active surveillance or intermediate-risk cancers with a localizable lesion.
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| 9. |
- Yossepowitch, Ofer, et al.
(författare)
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Positive Surgical Margins in Radical Prostatectomy: Outlining the Problem and Its Long-Term Consequences
- 2009
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 55:1, s. 87-99
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Forskningsöversikt (refereegranskat)abstract
- Context: This review focuses on positive surgical margins (PSM) in radical prostatectomy (RP). Objective: To address the etiology, incidence, and oncologic impact of PSM and discuss technical points to help surgeons minimize their positive margin rate. An evidence-based approach to assist clinicians in counseling patients with a PSM is provided. Evidence acquisition: A literature search in English was performed using the National Library of Medicine database and the following key words: prostate cancer, surgical margins, and radical prostatectomy. Seven hundred sixty-eight references were scrutinized, and 73 were selected for rigorous review based on their pertinence, study size, and overall contribution to the field. Evidence synthesis: In contemporary series, PSM are reported in 11-38% of patients undergoing RP. Although variability exists in the pathologic interpretation of surgical margins, PSM are associated with an increased hazard of biochemical recurrence (BCR) and local disease recurrence as well as the need for secondary cancer treatment. A posterolateral PSM appears to confer the greatest risk of recurrence, whereas the prognostic significance of positive apical margins remains controversial. The role of preoperative imaging and intraoperative frozen section analysis are being investigated to reduce margin positivity rates. Level-1 evidence indicates that adjuvant radiotherapy (RT) in men with PSM reduces BCR rates and clinical progression and possibly improves overall survival (OS). Conclusions: PSM in RP specimens are uniformly considered an adverse outcome. Regardless of approach (open or laparoscopic), attention to surgical detail is essential to minimize rates. For patients with a PSM destined to experience a cancer recurrence, RT is the only established treatment with curative potential. A randomized trial in patients with PSM comparing immediate postoperative RT to salvage RT is critically needed before definitive recommendations can be made. (C) 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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