A randomized controlled study on acupuncture for peri-operative pain after open radical prostatectomy.

OBJECTIVES: To evaluate the advantages of adding acupuncture to standard postoperative pain management for open radical prostatectomy (RP). MATERIALS AND METHODS: A randomized controlled trial (1:1:1) comparing routine postoperative analgesic care (control [CON]) vs the addition of press tack needle acupuncture (ACU) or press tack placebo acupressure (SHAM) for pain management after open RP was performed. A total of 126 patients were enrolled between February 2020 and April 2021. After open RP, the CON group received standard postoperative analgesia, the ACU group received long-term acupuncture with press tacks at specific points (P-6, Shenmen and SP-6) along with standard analgesia, and the SHAM group received placebo press tacks at the same acupuncture points alongside standard analgesia. The primary endpoint was postoperative pain measured on a numeric rating scale, the NRS-11, calculated as the area under the curve. The cumulative use of routine postoperative analgesics, time to first defaecation, and quality of life were analysed using the Kruskal-Wallis rank sum test, Fisher's exact test, and Pearson's chi-squared test. RESULTS: The ACU group reported significantly less postoperative pain compared to the SHAM (P = 0.007) and CON groups (P = 0.02). There were no significant difference in median (interquartile range) cumulative pain medication usage, time to first defaecation (CON: 37 [33, 44] h; SHAM: 37 [33, 42] h; ACU: 37 [33, 41] h; P > 0.9), or health status at discharge (EuroQol five-dimension, five-level general health assessment questionnaire: CON: 70 [65-83]; SHAM: 70 [60-80]; ACU: 70 [50-80]). CONCLUSION: Incorporating acupuncture into postoperative pain management can improve patient postoperative outcomes.

Circulating Vitamin D and Selenium Levels and Outcome in Prostate Cancer Patients: Lessons from the MARTINI-Lifestyle Cohort.

BACKGROUND: Dietary agents, in particular vitamin D (Vit D) and selenium, are widely used by prostate cancer (PCa) patients to improve cancer outcomes. OBJECTIVE: To investigate whether plasma Vit D and selenium levels prior to radical prostatectomy (RP) are associated with worse pathologic tumor characteristics and increased risk of disease recurrence. DESIGN, SETTING, AND PARTICIPANTS: A total of 3849 men with PCa scheduled for RP in the Martini-Klinik at the University Hospital Hamburg-Eppendorf, Hamburg, Germany, between January 2014 and December 2018 were included in this study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Age, and clinical and laboratory values were collected prior to RP. Biochemical recurrence (BCR) was defined as prostate-specific antigen (PSA) ≥0.2 µg/l and rising after RP. Kaplan-Meier plots depicted BCR-free survival. Cox regression models (adjusted for age, preoperative PSA, pT stage, pN stage, pGG, surgical margin status, and year of surgery) tested the relationship between oncologic outcomes and Vit D and selenium levels. RESULTS AND LIMITATIONS: Median plasma Vit D and selenium levels were 19.3 and 71 µg/l, respectively. Circulating Vit D and selenium levels correlated inversely with PSA values. Histologic grade, pT stage, and pN stage were not associated with Vit D and selenium levels at the time of RP. In the overall cohort, BCR-free survival at 3 yr of follow-up was 82.9%. When stratified according to median Vit D levels, BCR-free survival at 3 yr of follow-up was 82.7% and 83.0% (p ≤ 0.59). Upon stratification according to median selenium levels, BCR-free survival was 82.2% and 83.7% (p = 0.19). In a multivariable Cox regression model predicting BCR, lower Vit D and selenium levels were not independent predictors of BCR. CONCLUSIONS: Plasma Vit D and selenium levels prior to RP were not associated with BCR-free survival. PATIENT SUMMARY: The results of the MARTINI-Lifestyle cohort could not show a correlation between the occurrence of biochemical recurrence of prostate cancer after radical prostatectomy and the serum levels of vitamin D and selenium. A recommendation should therefore be made to compensate for a potential deficiency and not with the expectation of a reduction in the risk of progression.

Comparison of 11 Active Surveillance Protocols in Contemporary European Men Treated With Radical Prostatectomy.

BACKGROUND: The aim of this study was to compare 11 active surveillance (AS) protocols in contemporary European men treated with radical prostatectomy (RP) at the Martini-Clinic Prostate Cancer Center. PATIENTS AND METHODS: Analyzed were 3498 RP patients, from 2005 to 2016, who underwent ≥ 10 core biopsies and fulfilled at least 1 of 11 examined AS entry definitions. We tested proportions of AS eligibility, ineligibility, presence of primary Gleason 4/5, upstage, and combinations thereof at RP, as well as 5-year biochemical recurrence-free survival (BFS). RESULTS: The most and least stringent criteria were very low risk National Comprehensive Cancer Network and Royal Marsden with 18.8% and 96.1% of AS-eligible patients, respectively. Rates of primary Gleason 4/5 at RP, upstaging, or both features, respectively, ranged from 2.3% to 6.7%, 6.1% to 18.2%, and 7.1% to 21.0% for those 2 AS entry definitions. The range of individuals deemed AS-ineligible between the same 2 AS entry definitions, despite not harboring unfavorable pathology (primary Gleason pattern 4/5, upstage, or both), was 80.3% to 3.7%, 78.3% to 3.4%, and 77.8% to 3.4%, respectively. BFS rates showed narrow variability, with a range of 85.9% to 91.8%. CONCLUSION: Use of stringent AS entry definitions reduces the number of AS-eligible patients, which is related to a select range in individual entry parameters. Moreover, rates of unfavorable pathology at RP as much as tripled between most and least stringent AS entry definitions. However, less stringent AS entry definitions result in the lowest AS-ineligibility rates, in men without unfavorable pathology. BFS rates were virtually invariably high. Clinicians should know differences in key parameters underlying each AS entry definition, associated effect on rates of eligibility, and potential misclassification of individuals.

Prospective randomized double-blind multicentre phase II study comparing gemcitabine and cisplatin plus sorafenib chemotherapy with gemcitabine and cisplatin plus placebo in locally advanced and/or metastasized urothelial cancer: SUSE (AUO-AB 31/05).

OBJECTIVE: To evaluate the efficacy and safety of gemcitabine and cisplatin in combination with sorafenib, a tyrosine-kinase inhibitor, compared with chemotherapy alone as first-line treatment in advanced urothelial cancer. PATIENTS AND METHODS: The study was a randomized phase II trial. Its primary aim was to show an improvement in progression-free survival (PFS) of 4.5 months by adding sorafenib to conventional chemotherapy. Secondary objectives were objective response rate (ORR), overall survival (OS) and toxicity. The patients included in the trial had histologically confirmed locally advanced and/or metastatic urothelial cancer of the bladder or upper urinary tract. Chemotherapy with gemcitabine (1250 mg/qm on days 1 and 8) and cisplatin (70 mg/qm on day 1) repeated every 21 days, was administered to all patients in a double-blind randomization of additional sorafenib (400 mg twice daily) vs placebo (two tablets twice daily) on days 3-21. Treatment continued until progression or unacceptable toxicity, the maximum number of cycles was limited to eight. The response assessment was repeated after every two cycles. RESULTS: Between October 2006 and October 2010, 98 of 132 planned patients were recruited. Nine patients were ineligible. The final analysis included 40 patients in the sorafenib and 49 patients in the placebo arm. There were no significant differences between the two arms concerning ORR (sorafenib: complete response [CR] 12.5%, partial response [PR] 40%; placebo: CR 12%, PR 35%), median PFS (sorafenib: 6.3 months, placebo: 6.1 months) or OS (sorafenib: 11.3 months, placebo: 10.6 months). Toxicity was moderately higher in the sorafenib arm. Diarrrhoea occurred significantly more often in the sorafenib arm and hand-foot syndrome occurred only in the sorafenib arm. The study was closed prematurely because of slow recruitment. CONCLUSION: Although the addition of sorafenib to standard chemotherapy showed acceptable toxicity, the trial failed to show a 4.5 months improvement in PFS.

Sorafenib for older patients with renal cell carcinoma: subset analysis from a randomized trial.

BACKGROUND: The perception that older cancer patients may be at higher risk than younger patients of toxic effects from cancer therapy but may obtain less clinical benefit from it may be based on the underrepresentation of older patients in clinical trials and the known toxic effects of cytotoxic chemotherapy. It is not known how older patients respond to targeted therapy. METHODS: This retrospective subgroup analysis of data from the phase 3, randomized Treatment Approach in Renal Cancer Global Evaluation Trial examined the safety and efficacy of sorafenib in older (age >or=70 years, n = 115) and younger patients (age <70 years, n = 787) who received treatment for advanced renal cell carcinoma. Patient demographics and progression-free survival were recorded. Best tumor response, clinical benefit rate (defined as complete response plus partial response plus stable disease), time to self-reported health status deterioration, and toxic effects were assessed by descriptive statistics. Health-related quality of life was assessed with a Cox proportional hazards model. Kaplan-Meier analyses were used to summarize time-to-event data. RESULTS: Median progression-free survival was similar in sorafenib-treated younger patients (23.9 weeks; hazard ratio [HR] for progression compared with placebo = 0.55, 95% confidence interval [CI] = 0.47 to 0.66) and older patients (26.3 weeks; HR = 0.43, 95% CI = 0.26 to 0.69). Clinical benefit rates among younger and older sorafenib-treated patients were also similar (83.5% and 84.3%, respectively) and were superior to those of younger and older placebo-treated patients (53.8% and 62.2%, respectively). Adverse events were predictable and manageable regardless of age. Sorafenib treatment delayed the time to self-reported health status deterioration among both older patients (121 days with sorafenib vs 85 days with placebo; HR = 0.66, 95% CI = 0.43 to 1.03) and younger patients (90 days with sorafenib vs 52 days with placebo; HR = 0.69, 95% CI = 0.59 to 0.81) and improved quality of life over that time. CONCLUSIONS: Among patients with advanced renal cell carcinoma receiving sorafenib treatment, outcomes of older (>or=70 years) and younger (<70 years) patients were similar.

Managing side effects of angiogenesis inhibitors in renal cell carcinoma.

Anti-angiogenetic agents are currently considered standard therapy for metastatic renal cell carcinoma (RCC) for the majority of the patients. In contrast to immuno- or chemotherapy, the inhibition of specific signaling pathways has been considered essentially non-toxic. The advance of these tyrosine kinase inhibitors into clinical practice has led to a more detailed understanding of their targets in both, the tumor and the patient. At the advent of targeted therapies, oncologists are in the process of developing surveillance strategies tailored for specific side effects of individual classes of agents to the individual needs of patients. In the current article, the significance of adverse events and their management in RCC patients is reviewed in order to guide the clinical oncologist through patient surveillance and treatment of adverse events.