| 61. |
- Jerlström, Tomas, 1969-, et al.
(författare)
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No increased risk of short-term complications after radical cystectomy for muscle-invasive bladder cancer among patients treated with preoperative chemotherapy : a nation-wide register-based study
- 2020
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Ingår i: World journal of urology. - : Springer. - 0724-4983 .- 1433-8726. ; 38:2, s. 381-388
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Preoperative chemotherapy is underused in conjunction with radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) due to concerns for complications and delay of surgery. Prospective data on short-term complications from population-based settings with frequent use of preoperative chemotherapy and standardised reporting of complications is lacking.METHODS: We identified 1,340 patients who underwent RC between 2011 and 2015 in Sweden due to MIBC according to the Swedish Cystectomy Register. These individuals were followed through linkages to several national registers. Propensity score adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for complications and death within 90 days of surgery, comparing patients receiving preoperative chemotherapy or not.RESULTS: Minimum two cycles of preoperative chemotherapy were given to 519 (39%) of the patients, who on average tended to be younger, have higher education, better physical status, and more advanced bladder cancer than patients not receiving chemotherapy. After adjusting for these and other parameters, there was no association between treatment with preoperative chemotherapy and short-term complications (OR 1.06 95% CI 0.82-1.39) or mortality (OR 0.75 95% CI 0.36-1.55). We observed a risk reduction for gastrointestinal complications among patients who received preoperative chemotherapy compared with those who did not (OR 0.49 95% CI 0.30-0.81).CONCLUSION: This nation-wide population-based observational study does not suggest that preoperative chemotherapy, in a setting with high utilisation of such treatment, is associated with an increased risk of short-term complications in MIBC patients treated with radical cystectomy.
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| 62. |
- Johansson, Jan-Erik, et al.
(författare)
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Natural history of early, localized prostate cancer
- 2004
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 291:22, s. 2713-2719
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Among men with early prostate cancer, the natural history without initial therapy determines the potential for survival benefit following radical local treatment. However, little is known about disease progression and mortality beyond 10 to 15 years of watchful waiting. OBJECTIVE: To examine the long-term natural history of untreated, early stage prostatic cancer. DESIGN: Population-based, cohort study with a mean observation period of 21 years. SETTING: Regionally well-defined catchment area in central Sweden (recruitment March 1977 through February 1984). PATIENTS: A consecutive sample of 223 patients (98% of all eligible) with early-stage (T0-T2 NX M0 classification), initially untreated prostatic cancer. Patients with tumor progression were hormonally treated (either by orchiectomy or estrogens) if they had symptoms. MAIN OUTCOME MEASURES: Progression-free, cause-specific, and overall survival. RESULTS: After complete follow-up, 39 (17%) of all patients experienced generalized disease. Most cancers had an indolent course during the first 10 to 15 years. However, further follow-up from 15 (when 49 patients were still alive) to 20 years revealed a substantial decrease in cumulative progression-free survival (from 45.0% to 36.0%), survival without metastases (from 76.9% to 51.2%), and prostate cancer-specific survival (from 78.7% to 54.4%). The prostate cancer mortality rate increased from 15 per 1000 person-years (95% confidence interval, 10-21) during the first 15 years to 44 per 1000 person-years (95% confidence interval, 22-88) beyond 15 years of follow-up (P =.01). CONCLUSION: Although most prostate cancers diagnosed at an early stage have an indolent course, local tumor progression and aggressive metastatic disease may develop in the long term. These findings would support early radical treatment, notably among patients with an estimated life expectancy exceeding 15 years.
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| 63. |
- Josefsson, Andreas, 1979-, et al.
(författare)
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Effect of docetaxel added to bicalutamide in Hormone-Naïve non-metastatic prostate cancer with rising PSA, a randomized clinical trial (SPCG-14)
- 2023
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 62:4, s. 372-380
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Tidskriftsartikel (refereegranskat)abstract
- Background: Historically, endocrine therapy was used in a range of scenarios in patients with rising PSA, both as a treatment for locally advanced non-metastatic prostate cancer and PSA recurrence following curative intended therapy. In the present study the objective was to investigate if chemotherapy added to endocrine therapy could improve progression-free survival (PFS).Materials and Methods: Patients with hormone-naïve, non-metastatic prostate cancer and rising prostate-specific antigen (PSA), enrolled from Sweden, Denmark, the Netherlands, and Finland, were randomized to long-term bicalutamide (150 mg daily) or plus docetaxel (75 mg/m2, q3w, 8–10 cycles) without prednisone, after stratification for the site, prior local therapy or not, and PSA doubling time. The primary endpoint was 5-year PFS analyzed with a stratified Cox proportional hazards regression model on intention to treat basis.Results: Between 2009 and 2018, a total of 348 patients were randomized; 315 patients had PSA relapse after radical treatment, 33 patients had no prior local therapy. Median follow-up was 4.9 years (IQR 4.0–5.1). Adding docetaxel improved PFS (HR 0.68, 95% CI 0.50–0.93; p = 0.015). Docetaxel showed an advantage for patients with PSA relapse after prior local therapy (HR 0.67, 95% CI 0.49–0.94; p = 0.019). One event of neutropenic infection/fever occurred in 27% of the patients receiving docetaxel. Limitations were slow recruitment, lack of enrolling patients without radical local treatment, and too short follow-up for evaluation of overall survival in patients with PSA relapse.Conclusion: Docetaxel improved PFS in patients starting bicalutamide due to PSA relapse after local therapy or localized disease without local therapy. Confirmatory studies of the efficacy of docetaxel in the setting of PSA-only relapse in addition to endocrine therapies may be justified if longer follow-up will show increased metastatic-free survival.
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| 64. |
- Julin, B., et al.
(författare)
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Dietary cadmium exposure and prostate cancer incidence : a population-based prospective cohort study
- 2012
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Ingår i: British Journal of Cancer. - London, United Kingdom : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 21:5, s. 895-900
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Tidskriftsartikel (refereegranskat)abstract
- Background: Experimental data convincingly propose the toxic metal cadmium as a prostate carcinogen. Cadmium is widely dispersed into the environment and, consequently, food is contaminated.Methods: A population-based cohort of 41 089 Swedish men aged 45-79 years was followed prospectively from 1998 through 2009 to assess the association between food frequency questionnaire-based estimates of dietary cadmium exposure (at baseline, 1998) and incidence of prostate cancer (3085 cases, of which 894 were localised and 794 advanced) and through 2008 for prostate cancer mortality (326 fatal cases).Results: Mean dietary cadmium exposure was 19 μg per day±s.d. 3.7. Multivariable-adjusted dietary cadmium exposure was positively associated with overall prostate cancer, comparing extreme tertiles; rate ratio (RR) 1.13 (95% confidence interval (CI): 1.03-1.24). For subtypes of prostate cancer, the RR was 1.29 (95% CI: 1.08-1.53) for localised, 1.05 (95% CI: 0.87-1.25) for advanced, and 1.14 (95% CI: 0.86-1.51) for fatal cases. No statistically significant difference was observed in the multivariable-adjusted risk estimates between tumour subtypes (P(heterogeneity)=0.27). For localised prostate cancer, RR was 1.55 (1.16-2.08) among men with a small waist circumference and RR 1.45 (1.15, 1.83) among ever smokers.Conclusion: Our findings provide support that dietary cadmium exposure may have a role in prostate cancer development.
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| 65. |
- Kasperzyk, Julie L., et al.
(författare)
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One-carbon metabolism-related nutrients and prostate cancer survival
- 2009
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 90:3, s. 561-569
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Folate and other one-carbon metabolism nutrients may influence prostate cancer pathogenesis. Prior studies of these nutrients in relation to prostate cancer incidence have been inconclusive, and none have explored prostate cancer survival. OBJECTIVE: The objective was to assess whether dietary intakes of folate, riboflavin, vitamin B-6, vitamin B-12, and methionine measured around the time of prostate cancer diagnosis are associated with prostate cancer survival. DESIGN: This population-based prospective study comprised 525 men from Orebro, Sweden, who received a diagnosis of incident prostate cancer between 1989 and 1994 and completed a self-administered food-frequency questionnaire. Record linkages to the Swedish Death Registry enabled all cases to be followed for up to 20 y after diagnosis, and the cause of death was assigned via medical record review. Cox proportional hazards regression was used to calculate multivariable hazard ratios (HRs) and 95% CIs. During a median of 6.4 y of follow-up, 218 men (42%) died of prostate cancer and 257 (49%) of other causes. RESULTS: A comparison of the highest with the lowest quartile showed that vitamin B-6 intake was inversely associated with prostate cancer-specific death (HR: 0.71; 95% CI: 0.46, 1.10; P for trend = 0.08), especially in men with a diagnosis of localized-stage disease (HR; 0.05; 95% CI: 0.01, 0.26; P for trend = 0.0003). However, vitamin B-6 intake was not associated with improved prostate cancer survival among advanced-stage cases (HR: 1.04; 95% CI: 0.64, 1.72; P for trend = 0.87). Folate, riboflavin, vitamin B-12, and methionine intakes were not associated with prostate cancer survival. CONCLUSION: A high vitamin B-6 intake may improve prostate cancer survival among men with a diagnosis of localized-stage disease.
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| 66. |
- Kirrander, Peter, 1978-, et al.
(författare)
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Dynamic sentinel node biopsy in penile cancer : initial experiences at a Swedish referral centre
- 2013
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Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 111:3B, s. E48-E53
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Tidskriftsartikel (refereegranskat)abstract
- Study Type Therapy (case series) Level of Evidence4 What's known on the subject? and What does the study add? According to the current European Association of Urology Guidelines, dynamic sentinel node biopsy is the recommended approach to assess lymph node status in men with cN0 intermediate and high risk penile cancer. Nevertheless, most encouraging results derive from a limited number of studies. The present study shows a false-negative rate of 15%, comparable with or better than several previous studies. Nevertheless, the aim should be a false-negative rate of no more than 5%. We conclude that increased overall experience and the use of the complete modern dynamic sentinel node biopsy protocol are paramount to improve results.OBJECTIVE center dot To evaluate the false-negative rate and complication rate of dynamic sentinel node biopsy (DSNB) in penile cancer.PATIENTS AND METHODS center dot In this retrospective study, 58 unilaterally or bilaterally clinically lymph node negative (cN0) patients with penile cancer (57 squamous cell carcinomas and one malignant melanoma), scheduled for DSNB at the orebro University Hospital, Sweden, between 1999 and 2011, were analysed. center dot Preoperative ultrasonography and fine-needle aspiration cytology of suspicious nodes were not introduced until 2008. center dot Patients were assessed by lymphoscintigraphy using 99mtechnetium nanocolloid on the day before surgery and the dissection of sentinel nodes was aided by the lymphoscintigraphic images and intraoperative detection of radiotracer and patent blue dye. center dot The false-negative rate and complication rate were calculated per groin.RESULTS center dot Of the 58 patients, 32 (55%) underwent preoperative ultrasonography. center dot Two patients had positive fine-needle aspiration cytology and discontinued further DSNB protocol. Of the remaining 56 patients, all but one were bilaterally cN0 and hence 111 cN0 groins were assessed by lymphoscintigraphy. center dot In the 55 bilaterally cN0 patients, lymphoscintigraphy visualized a bilateral sentinel node in 34 (62%). center dot At surgery, all excised sentinel nodes were radioactive while 43% were additionally blue. In total, at least one sentinel node was harvested in 96 (86%) of the DSNB staged groins. center dot A positive sentinel node was found in 11 groins (bilaterally in three patients). During a median follow-up of 21 months, two false-negative cases emerged, producing a false-negative rate of 15%. Both false-negative cases occurred during the first half of the study. The complication rate was 10%. The majority of complications were minor and transient.CONCLUSIONS center dot DSNB is a minimally invasive staging tool in men with cN0 penile cancer, enabling early detection of metastatic disease and thus optimal care. center dot Our false-negative rate of 15% is comparable or even favourable in comparison with several previous studies, but far from the 5% or less that we aim for. The complication rate found is somewhat higher than previously reported. center dot With increased overall experience and the continued use of the complete DSNB protocol, we believe our results will improve and the complication rate will decrease.
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| 67. |
- Kirrander, Peter, 1978-, et al.
(författare)
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Human papillomavirus prevalence, distribution and correlation to histopathological parameters in a large Swedish cohort of men with penile carcinoma
- 2011
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Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 108:3, s. 355-359
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To analyse the overall and type-specific human papillomavirus (HPV) prevalence and distribution in penile carcinoma and determine the correlation to histopathological parameters.PATIENTS AND METHODS: In this retrospective study, we analysed HPV status in 241 patients with penile carcinoma, treated at Örebro University Hospital, Örebro, Sweden, between 1984 and 2008. Age and date at diagnosis was recorded. The tumour specimens were categorized according to the UICC 2002 TNM classification. A subset of patients was operatively staged with regard to lymph node status. A commercially available Real Time PCR was used to detect 13 different types of HPV (6,11,16,18,31,33,35,45,51,52,56,58 and 59).RESULTS: We excluded 25 patients due to low DNA quality. Of the remaining 216, 179 (82.9%) tumour specimens were HPV infected. The majority of cases positive for HPV (70.4%) were infected by a single-type. The most frequent type was HPV 16 followed by HPV 18. No significant association between HPV status and pathological tumour stage, grade or lymph node status was found.CONCLUSION: The HPV prevalence found is higher than in most other studies, further strengthening HPV as an etiological agent in penile carcinoma. Furthermore, the high prevalence of HPV 16 and 18 raises the question of what potential impact current HPV vaccines that target these specific HPV types might have on penile carcinoma. No significant association between HPV status and histopathological parameters was found in the present study. Additional investigations are needed to draw final conclusions on the prognostic value of HPV status in penile carcinoma.
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| 68. |
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| 69. |
- Klaff, Rami, 1971-
(författare)
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Disease-Specific Survival in Prostate Cancer Patients : Results from the Scandinavian Prostate Cancer Group (SPCG) Trial No. 5 and Regional Cancer Register Data
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- IntroductionProstate cancer (PCa) is the most common cancer among men in Sweden. The clinical course varies considerably, which makes it difficult to predict the prognosis in the individual case. In order to explore the early as well as the late course of the disease, large study groups and population-based cohorts are necessary.AimsTo explore factors that influence the long-term outcome of men with low-risk tumours in a population-based register, to predict the long-term course, and to assess the mortality rate for men with prostate cancer (Paper I)To analyse long-term outcome and to investigate factors associated with long-term survival in patients with metastases to the skeleton (Paper II)To analyse early androgen deprivation treatment (ADT) failure and to define clinical predictors associated with short survival due to early ADT failure in prostate cancer patients with bone metastases (Paper III)To analyse the prognostic significance of the extent of bone metastases in relation to other pretreatment variables in prostate cancer patients, and to explore the impact of bone metastases on quality-of-life (Paper IV)Material and methodsThe study groups were assembled from The South East Region Prostate Cancer Register (SERPCR), and The Scandinavian Prostate Cancer Group (SPCG) Trial No. 5. In the first study, prognostic factors and long-term disease-specific mortality rates of low-risk prostate cancer patients from the early PSA era were analysed. In the second study, patient-related factors, quality-of-life (QoL) and long-term survival in 915 PCa patients with bone metastases (M1b) under ADT, were analysed. In Study III factors predicting primary failure to respond to ADT were identified. Study IV explored the impact of the extent of bone metastases on survival and QoL for these men.Result and conclusionsThe long-term disease-specific mortality of low-risk localised PCa is low, but the annual mortality rate gradually increases. This indicates that some tumours slowly develop into lethal cancer, particularly in men 70 years or older and with a PSA level ≥ 4 μg/L. From the SPCG Trial No. 5, a subgroup of patients with M1b disease and favourable set of predictive factors survived more than 10 years under ADT with an acceptable QoL. Independent predictors of long-term survival were identified as performance status (PS) < 2, limited extent of bone metastases, and a PSA level < 231 μg/L at the time of enrolment in the trial. However, four independent clinical predictors of early ADT failure could be defined. Men exhibiting these features should be considered for an alternative treatment. Patient grouping based on three categories of extent of bone metastases related to PS, haemoglobin, and QoL at presentation, as independent predictors of mortality, may provide improved accuracy of prognosis.
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| 70. |
- Lehmann, S, et al.
(författare)
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Targeting p53 in vivo : a first-in-man study with the p53-targeting compound APR-246 in refractory hematologic malignancies and prostate cancer
- 2012
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 30:29, s. 3633-3639
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: APR-246 (PRIMA-1MET) is a novel drug that restores transcriptional activity of unfolded wild-type or mutant p53. The main aims of this first-in-human trial were to determine maximum-tolerated dose (MTD), safety, dose-limiting toxicities (DLTs), and pharmacokinetics (PK) of APR-246.PATIENTS AND METHODS: APR-246 was administered as a 2-hour intravenous infusion once per day for 4 consecutive days in 22 patients with hematologic malignancies and prostate cancer. Acute myeloid leukemia (AML; n = 7) and prostate cancer (n = 7) were the most frequent diagnoses. Starting dose was 2 mg/kg with dose escalations up to 90 mg/kg.RESULTS: MTD was defined as 60 mg/kg. The drug was well tolerated, and the most common adverse effects were fatigue, dizziness, headache, and confusion. DLTs were increased ALT/AST (n = 1), dizziness, confusion, and sensory disturbances (n = 2). PK showed little interindividual variation and were neither dose nor time dependent; terminal half-life was 4 to 5 hours. Tumor cells showed cell cycle arrest, increased apoptosis, and upregulation of p53 target genes in several patients. Global gene expression analysis revealed changes in genes regulating proliferation and cell death. One patient with AML who had a p53 core domain mutation showed a reduction of blast percentage from 46% to 26% in the bone marrow, and one patient with non-Hodgkin's lymphoma with a p53 splice site mutation showed a minor response.CONCLUSION: We conclude that APR-246 is safe at predicted therapeutic plasma levels, shows a favorable pharmacokinetic profile, and can induce p53-dependent biologic effects in tumor cells in vivo.
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