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- Eriksson, Victoria, et al.
(författare)
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Adverse events during neoadjuvant chemotherapy for muscle invasive bladder cancer - a Swedish retrospective multicentre study of a clinical database
- 2022
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Ingår i: Translational Andrology and Urology. - : AME Publishing Company. - 2223-4683 .- 2223-4691. ; 11:8, s. 1105-1115
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adverse events (AEs) during neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer (MIBC) are known but insufficiently reported. Clinical implications include affected cardiac, pulmonary, urinary, vascular and haematological organ systems. The main purpose was to evaluate the incidence and severity of AEs for ascertaining possible clinical significance. Further investigating possible effects of AEs on downstaging outcomes-downstaging is considered a surrogate marker for overall survival (OS).Methods: A retrospective evaluation of AEs during ongoing NAC for MIBC patients analysing individual patient data in a clinical database. We identified 687 cystectomies between 2009-2020 at four Swedish urological centres. Inclusion criteria were cT2-4aN0M0 in 261 NAC patients undergoing radical cystectomy (RC). Medical files were reviewed and AEs were assessed and graded, including detailed measurements by the Common Terminology Criteria for Adverse Events (CTCAE) v.5. Data were retrospectively analysed in SPSS statistics 27.0 with Spearman rank-order correlation coefficient and Mann-Whitney U-test (MWU).Results: A total of 251/261 patients [95% confidence interval (CI), 93-98%] experienced AEs during NAC pre-RC (mean two AEs/patient). In total, 208 (80%) patients received methotrexate, vinblastine, adriamycin (doxorubicin) and cisplatin (MVAC). In the total cohort, 200 (76.6%) received all pre-planned NAC-cycles. Most common AEs were anaemia (88.9%), thrombocytopenia (44.8%) and acute kidney injury (40.6%). Patients with prematurely terminated cycles had higher AE-grades (P=0.042 MWU). A correlation between higher AE-grades and decrease in downstaging existed, in the entire cohort (-0.133; P=0.033) and in patients undergoing all pre-planned NAC-cycles (-0.148; P=0.038). Anaemia and acute kidney injury were individually associated with decreased downstaging (-0.360, P=0.025 and -0.183, P=0.010, respectively).Conclusion: NAC in MIBC poses a significant risk for AEs before RC with clinical implications. For instance, patients terminating chemotherapy prematurely, have higher AE-grades and decreased downstaging. Further, acute kidney injury and anaemia are individually associated with decreased downstaging. We propose that early detection and prevention of AEs may increase downstaging of the primary tumour.
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| 3. |
- Hugosson, Jonas, 1955
(författare)
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Stopping screening, when and how?
- 2018
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Ingår i: Translational Andrology and Urology. - : AME Publishing Company. - 2223-4683 .- 2223-4691. ; 7:1, s. 46-53
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Tidskriftsartikel (refereegranskat)abstract
- Screening for prostate cancer (PC) is still controversial despite randomized trials has found that PC mortality is decreased. The major concern is the high rate of over-diagnosis and subsequent harms that may follow in many men who never would have had any symptoms during life-time if not screened. The high rate of over-diagnosis is driven by the large reservoir of small non-significant cancers that increases with age and found in more than half of men over 70 years, the low specificity of prostate specific antigen (PSA) but also by current "blind" biopsy technique that risk accidentally to hit these small non-significant cancers. The risk of over-diagnosis is increasing with age and the trade-off by screening men in high age is probably higher. At what age harms exceeds benefits is not established but modelling studies has demonstrated that after 65-70 years the quality adjusted life-years (QALYs) gained are decreasing but still on the positive side if screening is continued up to 75 years. A dilemma is that most PC deaths occur in men after the age 80 and the effect of screening seems not to last as long as was thought, already 10 years after termination of screening PC mortality has caught up in the screening arm to a level similar to that in the control group. In the European Randomised Study of Screening for Prostate Cancer (ERSPC) screening was terminated between 71 and 75 years and the first effect of screening on mortality was discernible after 7 years and has been relatively stable around 20% since 9 years after study start. It seems questionable from any standpoint to invite men for screening with an expected life length below 10 years, which is the expected life-length of an averaged 78-year-old man in 2018. However, the balance between harms and benefits specifically in the age 70-80 need more attention as also costs need. Permanent side-effects from (unnecessary) treatments and their impact on quality of life must be evaluated better and related to age and individual variations. In future better screening methods with more specific markers and introduction of imaging will hopefully decrease the present large risk of over-diagnosis in elderly men and thereby expand efficient screening to men in the age group > 70 who actually is the high risk group of dying from PC. © Translational Andrology and Urology.
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| 4. |
- Kinsella, N., et al.
(författare)
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Active surveillance for prostate cancer: A systematic review of contemporary worldwide practices
- 2018
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Ingår i: Translational Andrology and Urology. - : AME Publishing Company. - 2223-4683 .- 2223-4691. ; 7:1, s. 83-97
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Tidskriftsartikel (refereegranskat)abstract
- In the last decade, active surveillance (AS) has emerged as an acceptable choice for low-risk prostate cancer (PC), however there is discordance amongst large AS cohort studies with respect to entry and monitoring protocols. We systematically reviewed worldwide AS practices in studies reporting =5 years follow-up. We searched PubMed and Medline 2000-now and identified 13 AS cohorts. Three key areas were identified: (I) patient selection; (II) monitoring protocols; (III) triggers for intervention-(I) all studies defined clinically localised PC diagnosis as T2b disease or less and most agreed on prostate-specific antigen (PSA) threshold ( < 10 μg/L) and Gleason score threshold (3+3). Inconsistency was most notable regarding pathologic factors (e.g., number of positive cores); (II) all agreed on PSA surveillance as crucial for monitoring, and most agreed that confirmatory biopsy was required within 12 months of initiation. No consensus was reached on optimal timing of digital rectal examination (DRE), general health assessment or re-biopsy strategies thereafter; (III) there was no universal agreement for intervention triggers, although Gleason score, number or percentage of positive cancer cores, maximum cancer length (MCL) and PSA doubling time were used by several studies. Some also used imaging or re-biopsy. Despite consistent high progression-free/cancer-free survival and conversion-to-treatment rates, heterogeneity exists amongst these large AS cohorts. Combining existing evidence and gathering more long-term evidence [e.g., the Movember's Global AS database or additional information on use of magnetic resonance imaging (MRI)] is needed to derive a broadly supported guideline to reduce variation in clinical practice. © Translational Andrology and Urology.
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| 5. |
- Kohestani, Kimia, et al.
(författare)
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Prostate cancer screening-when to start and how to screen?
- 2018
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Ingår i: Translational Andrology and Urology. - : AME Publishing Company. - 2223-4683 .- 2223-4691. ; 7:1, s. 34-45
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Tidskriftsartikel (refereegranskat)abstract
- Prostate-specific antigen (PSA) screening reduces prostate cancer (PCa) mortality; however such screening may lead to harm in terms of overdiagnosis and overtreatment. Therefore, upfront shared decision making involving a discussion about pros and cons between a physician and a patient is crucial. Total PSA remains the most commonly used screening tool and is a strong predictor of future life-threatening PCa. Currently there is no strong consensus on the age at which to start PSA screening. Most guidelines recommend PSA screening to start no later than at age 55 and involve well-informed men in good health and a life expectancy of at least 10-15 years. Some suggest to start screening in early midlife for men with familial predisposition and men of African- American descent. Others suggest starting conversations at age 45 for all men. Re-screening intervals can be risk-stratified as guided by the man's age, general health and PSA-value; longer intervals for those at lower risk and shorter intervals for those at higher risk. Overdiagnosis and unnecessary biopsies can be reduced using reflex tests. Magnetic resonance imaging in the pre-diagnostic setting holds promise in pilot studies and large-scale prospective studies are ongoing. © Translational Andrology and Urology.
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| 7. |
- Mogos, Haben, et al.
(författare)
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Computerized tomography before the final treatment cycle of neoadjuvant chemotherapy or induction chemotherapy in muscle-invasive urinary bladder cancer, cannot predict pathoanatomical outcomes and does not reflect prognosis-results of a single centre retrospective prognostic study
- 2020
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Ingår i: Translational Andrology and Urology. - : AME Publishing Company. - 2223-4683 .- 2223-4691. ; 9:3, s. 1062-1072
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evaluating the routine of using control computer tomography (cCT) for determining the response status of muscle-invasive bladder cancer (MIBC) prior to final cycle of neoadjuvant chemotherapy (NAC) or induction chemotherapy (IC), in terms of predicting histopathological pTNM-staging and pathoanatomical responses/non-responses. Secondly, predicting two and three-year overall survival (OS).Methods: Seventy-seven patients with localized MIBC (cT2-4aN0M0) and 3 patients with minimal nodal dissemination (cN1-2), undergoing NAC or IC and radical cystectomy (RC), the years 2006–2014 at Norrland university hospital in Umeå, Sweden. Baseline pre-cystectomy CTs and cCTs prior to final chemotherapy-cycle, were reviewed and underwent attempted RECIST-criteria categorization, into five response/non-response related subgroups (n=71). The diagnostic accuracy of cCT in comparison with pTNM was assessed using sensitivity, specificity, positive- and negative likelihood ratios. OS for 2 and 3 years was calculated, both in relation to histopathological pTNM-stages in all patients (n=80) and for the patients with cCT-evaluated categories (n=71). Multivariable analysis for OS, was performed in correlation to pTNM-stages firstly, and to radiological staging secondly.Results: The sensitivity of cCT to predict non-responders according to pTMN was 64% and specificity 36%. The positive likelihood ratio=1 and the negative likelihood ratio =1. CT-evaluations couldn’t accurately predict pTNM-stages in terms of response/non-response. No statistically significant results were found in correlating cCTs with two and three-year OS.Conclusions: cCT prior to planned final preoperative chemotherapy-cycle in MIBC patients undergoing NAC or IC, has a poor correlation with pTNM and cannot predict pathoanatomical responses. Prediction of OS based on cCTs is unfeasible.Keywords: Computed X ray tomography; cystectomy interdisciplinary health team; neoadjuvant therapy; urinary bladder neoplasms
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| 10. |
- Shill, D. K., et al.
(författare)
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Active surveillance for prostate cancer
- 2021
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Ingår i: Translational Andrology and Urology. - : AME Publishing Company. - 2223-4683 .- 2223-4691. ; 10:6, s. 2809-2819
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Tidskriftsartikel (refereegranskat)abstract
- Many men diagnosed with localized prostate cancer can postpone definitive treatment without raising their risk of metastasis or death from disease. Active surveillance (AS) is a method of monitoring select men, with the option of switching to active treatment upon signs of progression, thereby avoiding the well-known side-effects of surgery and radiotherapy. This review analyzes the data from long-running AS cohorts to determine the safety and efficacy of AS. We conducted a narrative review of recently published data, including 14 articles from 13 AS cohorts. The cohorts used varying inclusion criteria, with reported differences in clinical T stage and Gleason Score (Grade Group), among other features. Some studies (n=5) limited their cohorts to low-risk patients, while others (n=8) also included intermediate-risk patients. The heterogeneity of the cohorts produced mixed results, with the risk of prostate cancer metastasis ranging from 0.1-1.0% at 10 years and the risk of prostate cancer mortality ranging from 0-1.9% at 10 years. However, the majority of studies reported risks of less than 0.5% at 10 years for both metastasis and death. For most cohorts, half of men remained untreated for 5-10 years, with estimates ranging from 37% receiving active treatment in the Toronto cohort to 73% in the Prostate Cancer Research International AS (PRIAS) study. Current data do not support the use of negative magnetic resonance imaging (MRI) to avoid scheduled biopsy. Taken together, the data collected from these AS cohorts suggests that AS is a safe approach for men with low-grade prostate cancer and some men with intermediate risk disease. AS should be more broadly implemented for eligible patients to avoid the decreases in quality of life from undergoing active treatment. Studies expanding the inclusion criteria and further defining a subset of men with favorable intermediate-risk prostate cancer who might safely benefit from AS are needed to assess the long-term outcomes of using AS in intermediate-risk groups.
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