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Therapeutic Advances in Medical Oncology 2024The COVID-19 pandemic affected cancer screening, diagnosis and treatments. Many surgeries were substituted with bridging therapies during the initial lockdown, yet...
BACKGROUND
The COVID-19 pandemic affected cancer screening, diagnosis and treatments. Many surgeries were substituted with bridging therapies during the initial lockdown, yet consideration of treatment side effects and their management was not a priority.
OBJECTIVES
To examine how the changing social restrictions imposed by the pandemic affected incidence and trends of endocrine treatment prescriptions in newly diagnosed (incident) breast and prostate cancer patients and, secondarily, endocrine treatment-related outcomes (including bisphosphonate prescriptions, osteopenia and osteoporosis), in UK clinical practice from March 2020 to June 2022.
DESIGN
Population-based cohort study using UK primary care Clinical Practice Research Datalink GOLD database.
METHODS
There were 13,701 newly diagnosed breast cancer patients and 12,221 prostate cancer patients with ⩾1-year data availability since diagnosis between January 2017 and June 2022. Incidence rates (IR) and incidence rate ratios (IRR) were calculated across multiple time periods before and after lockdown to examine the impact of changing social restrictions on endocrine treatments and treatment-related outcomes, including osteopenia, osteoporosis and bisphosphonate prescriptions.
RESULTS
In breast cancer patients, aromatase inhibitor (AI) prescriptions increased during lockdown pre-pandemic [IRR: 1.22 (95% confidence interval (CI): 1.11-1.34)], followed by a decrease post-first lockdown [IRR: 0.79 (95% CI: 0.69-0.89)]. In prostate cancer patients, first-generation antiandrogen prescriptions increased pre-pandemic [IRR: 1.23 (95% CI: 1.08-1.4)]. For breast cancer patients on AIs, diagnoses of osteopenia, osteoporosis and bisphosphonate prescriptions were reduced across all lockdown periods pre-pandemic (IRR range: 0.31-0.62).
CONCLUSION
During the first 2 years of the pandemic, newly diagnosed breast and prostate cancer patients were prescribed more endocrine treatments compared to pre-pandemic due to restrictions on hospital procedures replacing surgeries with bridging therapies. But breast cancer patients had fewer diagnoses of osteopenia and osteoporosis and bisphosphonate prescriptions. These patients should be followed up in the coming years for signs of bone thinning. Evidence of poorer management of treatment-related side effects will help assess resource allocation for patients at high risk for bone-related complications.
PubMed: 38832300
DOI: 10.1177/17588359241253115 -
Pharmacological Research Jul 2024After the initial androgen deprivation therapy (ADT), part of the prostate cancer may continuously deteriorate into castration-resistant prostate cancer (CRPC). The... (Review)
Review
After the initial androgen deprivation therapy (ADT), part of the prostate cancer may continuously deteriorate into castration-resistant prostate cancer (CRPC). The majority of patients suffer from the localized illness at primary diagnosis that could rapidly assault other organs. This disease stage is referred as metastatic castration-resistant prostate cancer (mCRPC). Surgery and radiation are still the treatment of CRPC, but have some adverse effects such as urinary symptoms and sexual dysfunction. Hormonal castration therapy interfering androgen receptor (AR) signaling pathway is indispensable for most advanced prostate cancer patients, and the first- and second-generation of novel AR inhibitors could effectively cure hormone sensitive prostate cancer (HSPC). However, the resistance to these chemical agents is inevitable, so many of patients may experience relapses. The resistance to AR inhibitor mainly involves AR mutation, splice variant formation and amplification, which indicates the important role in CRPC. Proteolysis-targeting chimera (PROTAC), a potent technique to degrade targeted protein, has recently undergone extensive development as a biological tool and therapeutic drug. This technique has the potential to become the next generation of antitumor therapeutics as it could overcome the shortcomings of conventional small molecule inhibitors. In this review, we summarize the molecular mechanisms on PROTACs targeting AR signaling for CRPC, hoping to provide insights into drug development and clinical medication.
Topics: Humans; Prostatic Neoplasms, Castration-Resistant; Male; Receptors, Androgen; Signal Transduction; Animals; Proteolysis; Androgen Receptor Antagonists; Antineoplastic Agents; Proteolysis Targeting Chimera
PubMed: 38815882
DOI: 10.1016/j.phrs.2024.107234 -
Acta Biochimica Polonica 2024To evaluate the clinical efficacy of different androgen deprivation therapies for prostate cancer (PCa) based on dynamic-contrast enhanced magnetic resonance imaging...
OBJECTIVE
To evaluate the clinical efficacy of different androgen deprivation therapies for prostate cancer (PCa) based on dynamic-contrast enhanced magnetic resonance imaging (DCE-MRI).
METHODS
104 patients with PCa were studied, all of whom were treated with androgen deprivation therapy. The patients were divided into a continuous group (continuous androgen deprivation therapy) and an intermittent group (intermittent androgen deprivation therapy) by random number table method, 52 cases/group. The therapeutic effect and DCE-MRI indices were compared and the relationship between DCE-MRI indices and clinical efficacy and the evaluation value of therapeutic efficacy were analyzed.
RESULTS
The objective response rate (ORR) of the intermittent group was higher than that of the continuous group ( < 0.05), and there was no significant difference in disease control rate (DCR) between the two groups ( > 0.05). After treatment, volume transfer coefficient (K), reverse transfer constant (K), volume fraction (Ve), blood volume (BV), and blood flow (BF) in both groups were lowered, and those in the intermittent group were lower than the continuous group ( < 0.05). K, K, Ve, BF, and BV in the ORR group were lower than those in the non-ORR group ( < 0.05). K, K, Ve, BF, and BV were correlated with the therapeutic effect of PCa ( < 0.05). The AUC value of the combined detection of DCE-MRI indices in evaluating the therapeutic effect of PCa was greater than that of each index alone ( < 0.05).
CONCLUSION
Compared with continuous androgen deprivation therapy, intermittent androgen deprivation therapy has better clinical efficacy in the treatment of PCa, and DCE-MRI indices are related to the treatment efficacy of PCa and have an evaluation value.
Topics: Humans; Male; Prostatic Neoplasms; Magnetic Resonance Imaging; Androgen Antagonists; Aged; Middle Aged; Contrast Media; Treatment Outcome
PubMed: 38812492
DOI: 10.3389/abp.2024.12473 -
BMC Cancer May 2024The proposed trial is to examine the feasibility of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-guided...
Protocol for CHAMPION study: a prospective study of maximal-cytoreductive therapies for patients with de novo metastatic hormone-sensitive prostate cancer who achieve oligopersistent metastases during systemic treatment with apalutamide plus androgen deprivation therapy.
BACKGROUND
The proposed trial is to examine the feasibility of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-guided cytoreduction plus apalutamide and androgen deprivation therapy (ADT) for newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) at oligometastatic state.
METHODS
CHAMPION (NCT05717582) is an open-label, single-arm, phase II trial, planning to enroll newly diagnosed mHSPC cases with oligometastases (≤ 10 distant metastatic sites in conventional imaging). Patients will receive 6 cycles of apalutamide plus ADT. Patients with oligometastatic disease at PSMA PET/CT after 3 treatment cycles will receive cytoreductive radical prostatectomy. PSMA PET/CT-guided metastasis-directed external radiation therapy will be determined by the investigators. Apalutamide plus ADT will be continued for 2 weeks postoperatively. The primary endpoint is the proportion of patients with undetectable prostate-specific antigen (PSA), no disease progression, and no symptom deterioration after 6 cycles of apalutamide plus ADT. Secondary endpoints include the percentage of patients with PSA ≤ 0.2 ng/mL and oligometastases by the end of 3 treatment cycles, PSA response rate, and safety. Fleming's two-stage group sequential design will be adopted in the study, where the null hypothesis is that the rate of patients with an undetectable PSA is ≤ 40% after 6 cycles of treatment, while the alternate hypothesis is an undetectable PSA of > 60%; with one-sided α = 0.05, power = 0.80, and an assumed dropout rate of 10%, the required number of patients for an effective analysis is 47. Enrolment in the study commenced in May 2023.
DISCUSSION
The multi-modal therapy based on treatment response may improve the prognosis of newly diagnosed mHSPC patients with oligometastases.
TRIAL REGISTRATION
The study is registered with Clinical Trials.Gov (NCT05717582). Registered on 8th February 2023.
Topics: Humans; Male; Thiohydantoins; Androgen Antagonists; Prostatic Neoplasms; Prospective Studies; Neoplasm Metastasis; Positron Emission Tomography Computed Tomography; Antineoplastic Combined Chemotherapy Protocols; Aged; Prostate-Specific Antigen; Middle Aged; Clinical Trials, Phase II as Topic; Prostatectomy
PubMed: 38796422
DOI: 10.1186/s12885-024-12395-3 -
Journal of Personalized Medicine May 2024Although metastatic hormone-sensitive prostate cancer (mHSPC) treatments have evolved, androgen deprivation therapy (ADT) remains a widely used regimen. Therefore, this...
BACKGROUND
Although metastatic hormone-sensitive prostate cancer (mHSPC) treatments have evolved, androgen deprivation therapy (ADT) remains a widely used regimen. Therefore, this study sought patients who did not progress to castration-resistant prostate cancer (CRPC) but received ADT monotherapy and factors affecting overall survival (OS) in de novo mHSPC.
METHODS
De novo mHSPC patients who received ADT treatment were included. ADT included luteinizing hormone-releasing hormone agonists with or without anti-androgen. The total cohort was divided into two groups relative to CRPC progression within two years. Logistic analysis was used to identify factors that did not progress CRPC within two years. Cox regression was used to assess the independent predictors for OS.
RESULTS
The total cohort was divided into the no-CRPC within two years group ( = 135) and the CRPC within two years group ( = 126). Through multivariate logistic analysis, the life expectancy (odds ratio [OR] 0.95, 95% CI 0.91-0.99, = 0.014) and Gleason scores (≥9 vs. ≤8; OR 0.43, 95% CI 0.24-0.75, = 0.003) were associated with the group without castration-resistant prostate cancer progression within two years. The multivariate Cox model revealed that life expectancy (hazard ratio [HR] 0.951, 95% CI 0.904-0.999, = 0.0491), BMI (HR 0.870, 95% CI 0.783-0.967, = 0.0101), and CCI (≥2 vs. <2; HR 2.018, 95% CI 1.103-3.693, = 0.0227) were significant predictive factors for OS.
CONCLUSIONS
Patients with long life expectancy and a Gleason score of 9 or more were more likely to develop mCRPC while alive. Patients with short life expectancy, low BMI, and worsening comorbidity were more likely to die before progressing to CRPC. Although intensified treatment is essential for oncologic outcomes in mHSPC, shared decision making is integral for patients who may not benefit from this treatment.
PubMed: 38793099
DOI: 10.3390/jpm14050517 -
Trials May 2024The oral gonadotropin-releasing hormone antagonist relugolix, which temporarily stops menstruation, is used to treat heavy menstrual bleeding, pelvic pressure, and low...
The effectiveness of relugolix compared with leuprorelin for preoperative therapy before laparoscopic myomectomy in premenopausal women, diagnosed with uterine fibroids: protocol for a randomized controlled study (MyLacR study).
BACKGROUND
The oral gonadotropin-releasing hormone antagonist relugolix, which temporarily stops menstruation, is used to treat heavy menstrual bleeding, pelvic pressure, and low back pain in women with uterine fibroids. Treatment can also help women recover from low hemoglobin levels and possibly shrink the fibroids. However, evidence of preoperative use of relugolix before laparoscopic myomectomy is limited. Nevertheless, the treatment could reduce interoperative blood loss, decrease the risk of developing postoperative anemia, and shorten the operative time. Thus, we aim to test whether 12-week preoperative treatment with relugolix (40 mg orally, once daily) is similar to or not worse than leuprorelin (one injection every 4 weeks) to reduce intraoperative blood loss.
METHODS
Efficacy and safety of preoperative administration of drugs will be studied in a multi-center, randomized, open-label, parallel-group, noninferiority trial enrolling premenopausal women ≥ 20 years of age, diagnosed with uterine fibroids and scheduled for laparoscopic myomectomy. Participants (n = 80) will be recruited in the clinical setting of participating institutions. The minimization method (predefined factors: presence or absence of fibroids ≥ 9 cm and the International Federation of Gynecology and Obstetrics [FIGO] type 1-5 fibroids) with randomization is used in a 1:1 allocation. Relugolix is a 40-mg oral tablet taken once a day before a meal, for 12 weeks, up to the day before surgery. Leuprorelin is a 1.88 mg, or 3.75 mg subcutaneous injection, given in three 4-week intervals during patient visits before the surgery. For the primary outcome measure of intraoperative bleeding, the blood flow is collected from the body cavity, surgical sponges, and collection bag and measured in milliliters. Secondary outcome measures are hemoglobin levels, myoma size, other surgical outcomes, and quality-of-life questionnaire responses (Kupperman Konenki Shogai Index and Uterine Fibroid Symptoms-Quality of Life).
DISCUSSION
Real-world evidence will be collected in a clinical setting to use pre-treatment with an oral gonadotropin-releasing hormone antagonist to reduce intraoperative bleeding in women who undergo laparoscopic myomectomy.
TRIAL REGISTRATION
jRCTs031210564 was registered on 19 January 2022 in the Japan Registry of Clinical Trials ( https://jrct.niph.go.jp ).
Topics: Humans; Female; Leiomyoma; Leuprolide; Uterine Myomectomy; Laparoscopy; Uterine Neoplasms; Premenopause; Treatment Outcome; Multicenter Studies as Topic; Preoperative Care; Equivalence Trials as Topic; Antineoplastic Agents, Hormonal; Adult; Blood Loss, Surgical; Gonadotropin-Releasing Hormone; Time Factors; Randomized Controlled Trials as Topic; Phenylurea Compounds; Pyrimidinones
PubMed: 38790029
DOI: 10.1186/s13063-024-08170-1 -
American Society of Clinical Oncology... Jun 2024Androgen-deprivation therapy (ADT) is well established as the standard of care in metastatic prostate cancer (PCa) management; however, ADT has significant adverse... (Review)
Review
Androgen-deprivation therapy (ADT) is well established as the standard of care in metastatic prostate cancer (PCa) management; however, ADT has significant adverse effects (AEs) that must be addressed. This review aims to highlight opportunities to mitigate AEs of ADT and explore alternatives in PCa management. Specifically, we discuss behavioral and pharmacologic strategies for mitigating ADT AEs as well as ADT-sparing approaches for hormone-sensitive and castration-resistant PCa. Equipped with effective mitigation strategies and possible alternatives, clinicians and researchers can optimize health-related quality of life for patients currently receiving ADT for PCa and consider treatments that spare patients from AEs of ADT.
Topics: Humans; Male; Androgen Antagonists; Prostatic Neoplasms; Quality of Life; Antineoplastic Agents, Hormonal; Disease Management
PubMed: 38788186
DOI: 10.1200/EDBK_433126 -
Cirugia Y Cirujanos 2024To assess and compare the functional and quality of life results in patients treated with curative intent for localized prostate cancer during 2015 in our hospital. (Comparative Study)
Comparative Study
OBJECTIVE
To assess and compare the functional and quality of life results in patients treated with curative intent for localized prostate cancer during 2015 in our hospital.
METHOD
77 patients treated by radical prostatectomy or external radiotherapy with androgen deprivation were prospective enrolled. Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) questionnaire at 3-year follow-up and Spanish Questionnaire on Quality of Life in Patients with Prostate Cancer (CAVIPRES-30) at diagnosis and at 3-year follow-up were registered.
RESULTS
68 patients were included, 39 patients treated by radical prostatectomy and 29 received external radiotherapy with androgen deprivation. Among the operated patients, 61.5% were dry and 17.9% use three or more daily pads, compared to 72.4% and 6.8%, respectively, in the radiotherapy group. 48.7% of prostatectomized patients reported very poor or no capacity to have a sufficiently rigid erection, compared to 69% of the radiated group. After surgery, 43.6% considered bad or very bad quality-of-life, compared to 68.9% in the radiotherapy group. In the comparison of the data of the pre- and post-treatment questionnaire can be seen that the patients had a superior perception before the procedure.
CONCLUSIONS
Patients treated by surgery have a better perception of quality-of-life compared to those treated by radiotherapy.
Topics: Humans; Male; Quality of Life; Prostatectomy; Prostatic Neoplasms; Aged; Prospective Studies; Middle Aged; Androgen Antagonists; Surveys and Questionnaires; Erectile Dysfunction; Follow-Up Studies
PubMed: 38782388
DOI: 10.24875/CIRU.22000249 -
BMJ Open May 2024Androgen deprivation therapy (ADT), a common treatment for prostate cancer, has debilitating impacts on physical and psychological quality of life. While some...
Effectiveness of educational and psychological survivorship interventions to improve health-related quality of life outcomes for men with prostate cancer on androgen deprivation therapy: a systematic review.
OBJECTIVES
Androgen deprivation therapy (ADT), a common treatment for prostate cancer, has debilitating impacts on physical and psychological quality of life. While some interventions focus on managing the physical side effects of ADT, there is a paucity of interventions that also address psychosocial and educational needs. The objective of this systematic review was to identify psychological and educational survivorship interventions targeting health-related quality of life (HRQoL) outcomes in men on ADT.
DESIGN
A systematic review of randomised controlled trials.
DATA SOURCES
Web of Science, Cochrane, EBSCO Host, PubMed, SCOPUS from inception (1984) to 28 January 2023.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Psychological and/or educational survivorship interventions targeting HRQoL outcomes for men on ADT; minimum 80% of participants on ADT; used a validated HRQoL outcome measure; published in English in a peer-reviewed journal.
DATA EXTRACTION AND SYNTHESIS
Data extraction using pre-specified study criteria was conducted. Heterogeneity of eligible studies precluded a meta-analysis.
RESULTS
A total of 3381 publications were identified with eight meeting the criteria. Interventions were either psychological with a cognitive behavioural approach (n=4), or educational with (n=2) or without (n=2) psychoeducational components.Two studies reported a statistically significant improvement using a specific HRQoL measure. Most studies were not adequately powered and/or included small sample sizes limiting the conclusions that can be drawn on effectiveness. The most effective interventions were (i) individually based, (ii) educational with a psychoeducational component, (iii) supplemented with information packages and/or homework and (iv) included personalised needs assessments.
CONCLUSION
There is a paucity of literature reporting psychological and educational survivorship interventions targeting HRQoL outcomes for men on ADT. What is urgently needed are person-centred survivorship interventions that are flexible enough to identify and address individual needs, taking into account the impact ADT has on both physical and psychological quality of life.
PROSPERO REGISTRATION NUMBER
CRD4202230809.
Topics: Humans; Male; Quality of Life; Prostatic Neoplasms; Androgen Antagonists; Patient Education as Topic; Cancer Survivors; Survivorship; Randomized Controlled Trials as Topic
PubMed: 38777593
DOI: 10.1136/bmjopen-2023-080310 -
JU Open Plus Apr 2024Management strategies for metastatic castration-resistant prostate cancer (mCRPC) have rapidly shifted in recent years. As novel imaging and therapeutic approaches have...
Expert Perspectives on Controversies in Metastatic Castration-Resistant Prostate Cancer Management: Narrative Review and Report of the First US Prostate Cancer Conference Part 2.
BACKGROUND
Management strategies for metastatic castration-resistant prostate cancer (mCRPC) have rapidly shifted in recent years. As novel imaging and therapeutic approaches have made their way to the clinic, providers are encountering increasingly challenging clinical scenarios, with limited guidance from the current literature.
MATERIALS AND METHODS
The US Prostate Cancer Conference (USPCC) is a multidisciplinary meeting of prostate cancer experts intended to address the many challenges of prostate cancer management. At the first annual USPCC meeting, areas of controversy and consensus were identified during a 2-day meeting that included expert presentations, full-panel discussions, and postdiscussion responses to questions developed by the USPCC cochairs and session moderators.
RESULTS
This narrative review covers the USPCC expert discussion and perspectives relevant to mCRPC, including neuroendocrine/aggressive-variant prostate cancer (NEPC/AVPC). Areas of broad agreement identified among USPCC experts include the benefits of poly (ADP-ribose) polymerase (PARP) inhibitors for patients with mutations, the use of radioligand therapy in patients with prostate-specific membrane antigen (PSMA)-positive mCRPC, and the need for clinical trials that address real-world clinical questions, including the performance of novel therapies when compared with modern standard-of-care treatment. Ongoing areas of controversy and uncertainty included the appropriateness of PARP inhibitors in patients with non- mutations, the optimal definition of PSMA positivity, and systemic therapies for patients with NEPC/AVPC after progression on platinum-based therapies.
CONCLUSIONS
The first annual USPCC meeting identified several areas of controversy in the management of mCRPC, highlighting the urgent need for clinical trials designed to facilitate treatment selection and sequencing in this heterogeneous disease state.
PubMed: 38774467
DOI: 10.1097/ju9.0000000000000138