Risk of colorectal cancer in men on long-term androgen deprivation therapy for prostate cancer

Background Androgen deprivation with gonadotropin-releasing hormone (GnRH) agonists or orchiectomy is a common but controversial treatment for prostate cancer. Uncertainties remain about its use, particularly with increasing recognition of serious side effects. In animal studies, androgens protect against colonic carcinogenesis, suggesting that androgen deprivation may increase the risk of colorectal cancer. Methods We identified 107 859 men in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database who were diagnosed with prostate cancer in 1993 through 2002, with follow-up available through 2004. The primary outcome was development of colorectal cancer, determined from SEER files on second primary cancers. Cox proportional hazards regression was used to assess the influence of androgen deprivation on the outcome, adjusted for patient and prostate cancer characteristics. All statistical tests were two-sided. Results Men who had orchiectomies had the highest unadjusted incidence rate of colorectal cancer (6.3 per 1000 person-years; 95% confidence interval [CI] = 5.3 to 7.5), followed by men who had GnRH agonist therapy (4.4 per 1000 person-years; 95% CI = 4.0 to 4.9), and men who had no androgen deprivation (3.7 per 1000 person-years; 95% CI = 3.5 to 3.9). After adjustment for patient and prostate cancer characteristics, there was a statistically significant dose-response effect (Ptrend = .010) with an increasing risk of colorectal cancer associated with increasing duration of androgen deprivation. Compared with the absence of these treatments, there was an increased risk of colorectal cancer associated with use of GnRH agonist therapy for 25 months or longer (hazard ratio [HR] = 1.31, 95% CI = 1.12 to 1.53) or with orchiectomy (HR = 1.37, 95% CI = 1.14 to 1.66). Conclusion Long-term androgen deprivation therapy for prostate cancer is associated with an increased risk of colorectal cance

Concordant colon tumors in monozygotic twins previously treated for prostate cancer

This report describes the quasi-simultaneous occurrence of colon cancers in monozygotic twin brothers (age 63years) who had undergone androgen deprivation therapy for prostate cancers 4years earlier. Concordance among male twins for both of these cancers has never been reported. Although the family history suggested possible genetic predispositions to both cancers, the twins have no evidence of the genetic alterations associated with hereditary colorectal tumors. We explore the possibility that colorectal tumorigenesis in these twins was fuelled by a combination of genetic and iatrogenic factors, in particular the androgen deprivation therapy used to treat their prostate cancer

Radium-223 in asymptomatic patients with castration-resistant prostate cancer and bone metastases treated in an international early access program

Radium-223; mCRPC, asymptomatic; Bone metastasesRadio-223; mCRPC, asintomático; Metástasis de huesoRadi-223; mCRPC, asimptomàtic; Metàstasis d'osBACKGROUND: Radium-223, a targeted alpha therapy, is used to treat symptomatic patients with castration-resistant prostate cancer (CRPC) and bone metastases. Data for radium-223 in asymptomatic CRPC patients with bone metastases are lacking. METHODS: This was a prospective, single-arm phase 3b study. Patients with metastatic CRPC (malignant lymphadenopathy not exceeding 6 cm was allowed, visceral disease was excluded) received radium-223, 55 kBq/kg intravenously, every 4 weeks for up to 6 cycles. Co-primary endpoints were safety and overall survival. Post hoc analyses were performed according to baseline asymptomatic or symptomatic disease status. Asymptomatic status was defined as no pain and no opioid use at baseline. RESULTS: Seven hundred eight patients received ≥1 radium-223 injection: 548 (77%) were symptomatic to various degrees, and 135 (19%) were asymptomatic. Asymptomatic patients had more favorable baseline disease characteristics than symptomatic. A lower proportion of asymptomatic versus symptomatic patients had received prior abiraterone (25% vs 35%) and prior docetaxel (52% vs 62%). A higher proportion of asymptomatic (71%) versus symptomatic (55%) patients completed radium-223 treatment. Overall survival (hazard ratio [HR] 0.486), time to disease progression (HR 0.722) and time to first symptomatic skeletal event (HR 0.328) were better in asymptomatic than symptomatic patients. Alkaline phosphatase (ALP) response rates were similar (46% vs 47%), and ALP normalization (44% vs 25%) and prostate-specific antigen response rates (21% vs 13%) were higher in asymptomatic than symptomatic patients. A lower proportion of asymptomatic patients reported treatment-emergent adverse events (TEAEs, 61% vs 79%), grade 3-4 TEAEs (29% vs 40%) and drug-related TEAEs (28% vs 44%). There were two treatment-related deaths, both in patients with baseline symptomatic disease. CONCLUSIONS: Using radium-223 earlier in the disease course, when patients are asymptomatic or minimally symptomatic, may enable patients to complete treatment and optimize treatment outcome compared to symptomatic patients, and therefore may allow sequencing with other life-prolonging therapie

Management of Patients with Advanced Prostate Cancer. Part I: Intermediate-/High-risk and Locally Advanced Disease, Biochemical Relapse, and Side Effects of Hormonal Treatment: Report of the Advanced Prostate Cancer Consensus Conference 2022

Hormonal treatment; Prostate cancer; Side effectsTratamiento hormonal; Cáncer de próstata; Efectos secundariosTractament hormonal; Càncer de pròstata; Efectes secundarisBackground Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. Objective To present consensus voting results for select questions from APCCC 2022. Design, setting, and participants Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members (“panellists”) who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1–3. Outcome measurements and statistical analysis Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. Results and limitations The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. Conclusions These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers prioritise areas for future research. Diagnostic and treatment decisions should always be individualised based on patient and cancer characteristics (disease extent and location, treatment history, comorbidities, and patient preferences) and should incorporate current and emerging clinical evidence, therapeutic guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2022 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials

A phase II, open-label study of gefitinib (IRESSA) in patients with locally advanced, metastatic, or relapsed renal-cell carcinoma

Epidermal growth factor receptor (EGFR) expression has been associated with clinical outcome in some studies of renal-cell carcinoma (RCC). We investigated the efficacy and safety of gefitinib (IRESSA), an EGFR tyrosine kinase inhibitor, in RCC patients. This phase II trial recruited 28 patients with advanced, metastatic, or relapsed RCC. Patients received oral gefitinib 500mg/day. Objective responses (ORs) were assessed every 2months according to RECIST. Baseline tumor biopsies were analyzed immunohistochemically for EGFR expression. At trial closure (March 2003), no ORs were seen but 14 patients (53.8%) had stable disease. At extended analysis (August 2004), median time to progression was 110days (95% confidence interval [CI]: 55, 117); median overall survival was 303days (95% CI 180, 444). Gefitinib was generally well tolerated. Skin rash and diarrhea were the most common drug-related adverse events (AEs) [54 and 39% of patients, respectively] and the most common drug-related grade 3/4 AEs (both 11%). The majority of tumor biopsies (91%) had ≥70% of tumor cells expressing membrane EGFR. Despite the lack of ORs in this study, disease control was observed in 53.8% of patients. Gefitinib was generally well tolerated and no unexpected drug-related AEs were observe

Prostate Cancer and Sleep Disorders: A Systematic Review.

Prostate cancer (PCa) treatment involves multiple strategies depending on the disease's stage. Androgen deprivation therapy (ADT) remains the gold standard for advanced and metastatic stages. Sleep quality has been suggested as being additionally influenced also by local radiotherapy, prostatectomy and androgen-receptor (AR)-targeted agents. We performed a systematic review exploring the landscape of studies published between 1 January 1990 and 31 July 2021, investigating sleep disturbances in PCa patients receiving active treatments, including the influence of hormonal therapy on sleep quality as a factor affecting their quality of life. Out of 45 articles identified, 16 studies were selected, which recruited patients with PCa, undergoing active treatment in either a prospective longitudinal or cross-sectional study. Development of sleep disorders or changes in sleep quality were reported in 14 out of 16 trials included. Only five trials included objective measurements such as actigraphy, mostly at one time point and without a baseline assessment. Limitations to be addressed are the small number of existing trials, lack of randomized trials and heterogeneity of methodologies used. This systematic review outlines the lack of prospective trials investigating sleep disorders, with a rigorous methodology, in homogeneous cohorts of PCa patients. Future trials are needed to clarify the prevalence and impact of this side effect of PCa treatments

A phase I dose-escalation study of the immunocytokine EMD 521873 (Selectikine) in patients with advanced solid tumours

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Detecting BRAF Mutations in Formalin-Fixed Melanoma: Experiences with Two State-of-the-Art Techniques

BACKGROUND: Melanoma is characterized by a high frequency of BRAF mutations. It is unknown if the BRAF mutation status has any predictive value for therapeutic approaches such as angiogenesis inhibition. PATIENTS AND METHODS: We used 2 methods to analyze the BRAF mutation status in 52 of 62 melanoma patients. Method 1 (mutation-specific real-time PCR) specifically detects the most frequent BRAF mutations, V600E and V600K. Method 2 (denaturing gel gradient electrophoresis and direct sequencing) identifies any mutations affecting exons 11 and 15. RESULTS: Eighteen BRAF mutations and 15 wild-type mutations were identified with both methods. One tumor had a double mutation (GAA) in codon 600. Results of 3 samples were discrepant. Additional mutations (V600M, K601E) were detected using method 2. Sixteen DNA samples were analyzable with either method 1 or method 2. There was a significant association between BRAF V600E mutation and survival. CONCLUSION: Standardized tissue fixation protocols are needed to optimize BRAF mutation analysis in melanoma. For melanoma treatment decisions, the availability of a fast and reliable BRAF V600E screening method may be sufficient. If other BRAF mutations in exons 11 and 15 are found to be of predictive value, a combination of the 2 methods would be useful