Improved renal cancer prognosis among users of drugs targeting renin-angiotensin system.

PURPOSE: We explored renal cell cancer (RCC) survival among users of antihypertensive medication as hypertension is proposed to be a risk factor for RCC and ACE-inhibitors and angiotensin receptor blockers (ARBs) have been associated with improved prognosis of RCC. METHODS: Finnish cohort of 13,873 participants with RCC diagnosed between 1995-2012 was formed from three national databases. RCC cases were identified from Finnish Cancer Registry, medication usage from national prescription database and co-morbidities from Care Registry of Healthcare. Logistic regression was used to calculate odds ratios for metastatic tumor extent at the time of diagnosis. Risk of RCC specific death after diagnosis was analyzed using Cox regression adjusted for tumor clinical characteristics. RESULTS: A total of 5,179 participants died of RCC during the follow-up. No risk association was found for metastatic tumor extent for any drug group. ACE-inhibitors, but no other drug group were associated with decreased risk of RCC specific death overall (HR 0.88, 95% CI 0.82-0.95) compared to non-users. In time-dependent analysis high-dose use of ACE-inhibitors (392 Defined Daily Dose (DDD)/year), HR 0.54, 95% CI 0.45-0.66) and ARBs (786.1 DDD/year, HR 0.66, 95% CI 0.50-0.87) associated with improved RCC survival. No information of TNM-classification or tobacco smoking was available. CONCLUSION: ACE-inhibitors and ARBs in high dose associated with improved RCC specific survival. This may reflect overall benefit of treating hypertension with medication targeting renin-angiotensin system (RAS) system among RCC patients. Further studies are needed to explore the role of RAS in RCC.

Use of non-steroidal anti-inflammatory drugs and prostate cancer survival in the Finnish prostate cancer screening trial.

BACKGROUND: Growing evidence suggests that aspirin is associated with decreased prostate cancer (PCa) mortality. The effect of other NSAID use on risk of PCa death remains controversial. We examined prostate cancer survival among aspirin and other NSAID users in the Finnish Prostate Cancer Screening Trial. METHODS: A total of 6,537 men were diagnosed with prostate cancer in 1996-2009 among the 80,144 men in the trial and 617 died from prostate cancer during the median follow-up of 7.5 years after the diagnosis. Prescription drug purchases information was obtained from the national reimbursement database. We calculated hazard ratios and 95% confidence intervals for PCa-specific survival using multivariable-adjusted Cox regression analysis separately for NSAID and aspirin usage before and after the diagnosis. RESULTS: We observed an increased risk of PCa death associated with both pre- and post-diagnostic NSAID usage (HR 1.30, 95%CI 1.07-1.58 and HR 2.09, 95%CI 1.75-2.50, respectively). An increasing risk trend was observed by cumulative dose and intensity of NSAID use. When the last three years were excluded from the analysis, the death risk diminished to a protective level (HR 0.42, 95%CI 0.34-0.51 and HR 0.30 95%CI 0.24-0.39). Aspirin use was not significantly associated with prostate cancer survival. CONCLUSIONS: The survival decrease among NSAID users is likely explained by symptomatic treatment of metastatic pain in patients with advanced PCa. However, results of the lag time analysis support previous findings of a possible preventative action of NSAIDs.

Prognostic factors of renal cell cancer in elderly patients: a population-based cohort study.

Mortality in renal cell cancer (RCC) is high in the elderly population. Comorbidities have a greater impact on overall prognosis of RCC among elderly patients than in younger patients. All new RCC cases were collected in people over 74 years of age between 1995 and 2018 from the Finnish cancer registry. The comorbidities were identified from the Care Registry for Healthcare. Charlson Comorbidity Index (CCI) was used to evaluate the risk of death based on comorbidities. The overall risk of death was analyzed using the Cox regression model. The risk for RCC death was analyzed using Fine and Gray regression analysis. Individual prognostic role of CCI components was evaluated by adding each component separately into the multivariable Fine and Gray regression model. Using the most prognostic comorbidities we constructed a nomogram to predict RCC mortality. Statistically significant prognostic factors of RCC death were tumor morphology (clear cell, papillary and chromophobe), sex, operative treatment, age, primary tumor extent and CCI. The strongest prognostic factors for overall mortality were tumor extent, tumor morphology and operative treatment. Among the components of CCI, the most important comorbidities predicting mortality were dementia, heart failure and kidney disease. The limitation of this study is that the comorbidities have only been recorded at inpatient and outpatient hospital contacts, which is why the prevalence of comorbidities is probably underestimated. In addition, physical performance status was not available from registry data, but it significantly affects the treatment decisions. RCC mortality is high in the elderly population. Among comorbidities, dementia and heart failure have the greatest impact on the prognosis. Curative treatment in selected elderly patients is efficient and should be considered in patients who can tolerate it and have only limited comorbidities.

Intraoperative complications in kidney tumor surgery: critical grading for the European Association of Urology intraoperative adverse incident classification.

INTRODUCTION: The European Association of Urology committee in 2020 suggested a new classification, intraoperative adverse incident classification (EAUiaiC), to grade intraoperative adverse events (IAE) in urology. AIMS: We applied and validated EAUiaiC, for kidney tumor surgery. PATIENTS AND METHODS: A retrospective multicenter study was conducted based on chart review. The study group comprised 749 radical nephrectomies (RN) and 531 partial nephrectomies (PN) performed in 12 hospitals in Finland during 2016-2017. All IAEs were centrally graded for EAUiaiC. The classification was adapted to kidney tumor surgery by the inclusion of global bleeding as a transfusion of ≥3 units of blood (Grade 2) or as ≥5 units (Grade 3), and also by the exclusion of preemptive conversions. RESULTS: A total of 110 IAEs were recorded in 13.8% of patients undergoing RN, and 40 IAEs in 6.4% of patients with PN. Overall, bleeding injuries in major vessels, unspecified origin and parenchymal organs accounted for 29.3, 24.0, and 16.0% of all IEAs, respectively. Bowel (n = 10) and ureter (n = 3) injuries were rare. There was no intraoperative mortality. IAEs were associated with increased tumor size, tumor extent, age, comorbidity scores, surgical approach and indication, postoperative Clavien-Dindo (CD) complications and longer stay in hospital. 48% of conversions were reactive with more CD-complications after reactive than preemptive conversion (43 vs. 25%). CONCLUSIONS: The associations between IAEs and preoperative variables and postoperative outcome indicate good construct validity for EAUiaiC. Bleeding is the most important IAE in kidney tumor surgery and the inclusion of transfusions could provide increased objectivity.

Does every Clavien-Dindo complication matter? A national multi-center study in kidney cancer surgery.

BACKGROUND: There is huge variation in Clavien-Dindo (CD) complication rates in urology. We sought to optimize the use of the CD system in kidney tumor surgery. METHODS: We retrospectively analyzed 1,286 patients undergoing kidney tumor operations in 12 Finnish hospitals during 2016-2017. Primary CD assignments were made by site urologists. Data were centrally reviewed by two authors in consensus meetings. Consistency of the primary assignments was assessed by the number of cases requiring correction. Complication load was compared as different outcome rates between five university hospital regions. RESULTS: The overall complication rate in primary data was 40% (517/1286) and varied significantly from 32 to 62% (p < 0.001) between the regions. The need for corrections in central review was significantly greater for CD1 (54%) compared to CD2 (16%, p < 0.001) and CD3-5 (11%, p < 0.001) categories. The final data comprised 500 CD complications after 390 surgeries. The most frequent pathologies were bleeding (8.4%), urological complications (5.9%) and postoperative fever (4.7%). The overall CD2 complications rate was statistically (p < 0.001) higher in region D and that of CD3-5 was higher (p = 0.007) in region B. In multivariable analysis, university hospital region, male sex, BMI ≥ 27, ECOG ≥ 1, partial nephrectomy type and open surgery significantly increased the risk of complications. CONCLUSIONS: Comparative use of CD1 complications may be too inconsistent and only CD2-5 complications should be reported. Central review of the primary data and detailed guidelines are necessary.

Risk of urothelial cancer death among people using antihypertensive drugs-a cohort study from Finland.

Background: To analyse the association between antihypertensive (anti-HT) drug use and risk of urothelial cancer (UC) death. UC occurs as bladder cancer (BCa) and upper tract urothelial carcinomas (UTUCs). Hypertension is a suggested risk factor for BCa and may impair disease prognosis. However, it's unclear if use of anti-HT drugs could improve the prognosis of UC.Materials and methods: This study evaluated the association between use of anti-HT drugs and UC survival among 14,065 participants diagnosed with BCa and 1080 with UTUC during 1995-2012 in Finland. It analyzed data using the multivariable adjusted conditional Cox regression model.Results: Angiotensin-receptor (ATR) blocker use before BCa diagnosis was associated with slightly decreased risk of BCa death (HR = .81, CI = .71-0.93). The association was dose-dependent and it decreased in association with elevated intensity of ATR-blocker use. Post-diagnostic use of ATR-blockers was similarly associated with better survival compared to non-users (HR = .81, CI = .71-0.92. Interestingly, use of calcium-channel blockers also associated with better survival and the risk of BCa death decreased with increasing intensity of use (HR = .67, CI = .52-0.86 for highest intensity).Conclusions: This large population-based cohort suggests decreased risk of BCa death among ATR-blocker and calcium-channel blocker users. The risk association among ATR-blockers and calcium-channel blockers was dose-dependent suggesting a causal explanation. Similar risk associations are not observed for other anti-HT drug users, which may suggest a direct effect of ATR blocker or calcium-channel blocker use. Further studies are needed to elucidate the potential anticancer mechanism.

Non-Steroidal Anti-Inflammatory Drugs and Cancer Death in the Finnish Prostate Cancer Screening Trial.

Non-steroidal anti-inflammatory drugs (NSAIDs), especially aspirin, have been associated with lowered cancer incidence and mortality. We examined overall cancer mortality and mortality from specific cancer sites among the 80,144 men in the Finnish Prostate Cancer Screening Trial. Information on prescription drug use was acquired from the national drug reimbursement database. Over-the-counter use information was gathered by a questionnaire. Hazard ratios (HR) and 95% confidence intervals (CI) by prescription and over-the-counter NSAID use for overall and specific cancer deaths were calculated using Cox regression. During the median follow-up time of 15 years, 7,008 men died from cancer. Men with prescription NSAID use had elevated cancer mortality (HR 2.02 95% CI 1.91-2.15) compared to non-users. The mortality risk was increased for lung, colorectal and pancreas cancer mortality (HR 2.68, 95%CI 2.40-2.99, HR 1.91, 95% CI 1.57-2.32 and HR 1.93, 95% CI 1.58-2.37, respectively). The increased risk remained in competing risks regression (HR 1.11, 95% CI 1.05-1.18). When the usage during the last three years of follow-up was excluded, the effect was reversed (HR 0.69, 95% CI 0.65-0.73). Cancer mortality was not decreased for prescription or over-the-counter aspirin use. However, in the competing risk regression analysis combined prescription and over-the-counter aspirin use was associated with decreased overall cancer mortality (HR 0.76, 95% CI 0.70-0.82). Cancer mortality was increased for NSAID users. However, the risk disappeared when the last 3 years were excluded.

Use of aspirin, but not other non-steroidal anti-inflammatory drugs is associated with decreased prostate cancer risk at the population level.

The cyclooxygenase 2 (COX-2) enzyme overexpression in prostate cancer has led to the hypothesis that COX-2 inhibition may reduce prostate cancer growth. Some previous studies have linked the usage of COX-2 inhibiting non-steroidal anti-inflammatory drugs (NSAIDs) with a decreased prostate cancer risk. We estimated the association between cumulative COX-2 inhibition by NSAID usage and prostate cancer risk at population level. All new prostate cancer cases in Finland during 1995-2002 and matched controls (24,657 case-control pairs) were identified from national registries. Detailed information on medication purchases was obtained from a national prescription database. A total cumulative COX-2 inhibition value was calculated based on total cumulative mg amount of each NSAID drug and the drug-specific COX-1/COX-2 inhibition ratio. Prostate cancer risk was analysed with propensity score-matched conditional logistic regression model. In total, 53.8% of the cases and 46.5% of the controls had any prescription-use of NSAIDs, while 8.1% and 7.9%, respectively, had used aspirin. Compared to the non-users, any NSAID use was associated with an elevated overall prostate cancer risk (46.4% versus 53.6%, respectively; odds ratio [OR] 1.3, 95% confidence interval [CI] 1.3, 1.4) and risk of advanced cancer (11.8% versus 14.1%; OR 1.6, 95% CI 1.5, 1.8). The risk remained elevated despite the amount of cumulative COX-2 inhibition. In a separate analysis, the risk increase was similar for each NSAID with the exception of aspirin, which was associated with a decreased overall prostate cancer risk (OR 0.90, 95% CI 0.84, 0.96) in a dose-dependent fashion. NSAID use is associated with an increased prostate cancer risk at the population level regardless of the COX-2 inhibition. This may be explained by systematic differences between prescription NSAID users and non-users. In contrast, aspirin use is associated with a decreased overall prostate cancer risk. Further studies on aspirin and prostate cancer will be needed.