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Effectiveness of couple-based interventions for prostate cancer patients and their spouses on their quality of life: a systematic review and meta-analysis
Purpose
This systematic review and meta-analysis aimed to synthesize the evidence on the effect of couple-based interventions on quality of life (QOL) among prostate cancer patients and their spouses.
Method
Six English databases and two Chinese databases were systematically searched to identify relevant RCTs that examined the effect of couple-based interventions on QOL. The data from the included studies were extracted by two independent reviewers using a standardized data extraction form. Methodological quality was assessed by using the Cochrane Risk of Bias Tool. Meta-analysis was conducted among the suitable studies that the available data were sufficient.
Results
One thousand ninety-five studies were identified, and 11 studies met the inclusion criteria for qualitative synthesis and 7 studied for meta-analysis. Couple-based interventions involve different formats of physical and psychosocial interventions. Physical exercise-based interventions were popular among couples, and these interventions had the highest level of adherence among all interventions examined herein. However, the meta-analysis of total QOL and physical and mental health revealed a non-significant effect on both prostate cancer patients and their spouses. More RCTs examining couple-based interventions may be needed in developing countries, especially in Asian countries.
Conclusion
Couple-based interventions had non-significant effect on improving the total QOL and physical and mental health of prostate cancer patients and their spouses. However, the current evidence is limited because the sample size of the studies is small. Thus, more studies with large sample sizes need to be included to detect the efficacy of couple-based interventions on prostate cancer patients and their spouses.
Journal Article
CD46 targeted 212Pb alpha particle radioimmunotherapy for prostate cancer treatment
We recently identified CD46 as a novel prostate cancer cell surface antigen that shows lineage independent expression in both adenocarcinoma and small cell neuroendocrine subtypes of metastatic castration resistant prostate cancer (mCRPC), discovered an internalizing human monoclonal antibody YS5 that binds to a tumor selective CD46 epitope, and developed a microtubule inhibitor-based antibody drug conjugate that is in a multi-center phase I trial for mCRPC (NCT03575819). Here we report the development of a novel CD46-targeted alpha therapy based on YS5. We conjugated
212
Pb, an in vivo generator of alpha-emitting
212
Bi and
212
Po, to YS5 through the chelator TCMC to create the radioimmunoconjugate,
212
Pb-TCMC-YS5. We characterized
212
Pb-TCMC-YS5 in vitro and established a safe dose in vivo. We next studied therapeutic efficacy of a single dose of
212
Pb-TCMC-YS5 using three prostate cancer small animal models: a subcutaneous mCRPC cell line-derived xenograft (CDX) model (subcu-CDX), an orthotopically grafted mCRPC CDX model (ortho-CDX), and a prostate cancer patient-derived xenograft model (PDX). In all three models, a single dose of 0.74 MBq (20 µCi)
212
Pb-TCMC-YS5 was well tolerated and caused potent and sustained inhibition of established tumors, with significant increases of survival in treated animals. A lower dose (0.37 MBq or 10 µCi
212
Pb-TCMC-YS5) was also studied on the PDX model, which also showed a significant effect on tumor growth inhibition and prolongation of animal survival. These results demonstrate that
212
Pb-TCMC-YS5 has an excellent therapeutic window in preclinical models including PDXs, opening a direct path for clinical translation of this novel CD46-targeted alpha radioimmunotherapy for mCRPC treatment.
Journal Article
Chronic Treatment of an Advanced Prostate-cancer Patient With Oral Methioninase Resulted in Long-term Stabilization of Rapidly Rising PSA Levels
Background/Aim: Advanced prostate cancer is a recalcitrant disease with very limited treatment options. Our laboratory discovered methionine addiction, presumably a characteristic of all cancer types, including prostate cancer, which can be targeted by methionine restriction (MR), through treatment with oral recombinant methioninase (o-rMETase). Patients and Methods: o-rMETase was produced by fermentation of recombinant E. coli containing the Pseudomonas putida methioninase gene, and purified by column chromatography. An advanced prostate cancer patient received o-rMETase as a supplement, 500 units per day, divided into two oral doses of 250 units each. Results: Before treatment, the patient had a rapid rise in PSA levels, from 39 to 56 ng/ml, within 6 weeks. At the 15th week of o-rMETase administration, the PSA levels stabilized at 62 ng/ml. No overt side effects were observed. Conclusion: o-rMETase single treatment can be beneficial for advanced prostate cancer patients.
Journal Article
Reminiscence therapy-based care program serves as an optional nursing modality in alleviating anxiety and depression, improving quality of life in surgical prostate cancer patients
PurposeReminiscence therapy is reported to attenuate the psychological disorders in cancer patients, such as colorectal and lung cancer patients. However, relevant report on surgical prostate cancer patients is scarce. This study put forward a reminiscence therapy-based care program (RTCP + UC) combing reminiscence therapy with usual care (UC), and aimed to evaluate the impact of RTCP + UC on anxiety, depression, quality of life and survival in surgical prostate cancer patients.MethodsTotally, 108 prostate cancer patients receiving surgical resection were enrolled, who were subsequently randomized and allocated to the RTCP + UC group (N = 55) and UC group (N = 53) at a 1:1 ratio. Hospital Anxiety and Depression Scale (HADS) and QLQ-C30 were assessed at month M0, M3, M6, M9 and M12 during the intervention period. After intervention, patients were followed up for another 24 months to calculate disease-free survival (DFS) and overall survival (OS).ResultsRTCP + UC decreased HADS-anxiety score at M9 and M12, declined HADS-depression score at M6, M9 and M12, reduced depression rate and the severity level of depression at M12, while did not affect these issues at other time points. Meanwhile, RTCP + UC enhanced the QLQ-C30 global health status score at M3, M6, M9 and M12, but did not influence the QLQ-C30 function score and QLQ-C30 symptom score at any time points. Meanwhile, RTCP + UC had no effect on the accumulating DFS and OS of surgical prostate cancer patients.ConclusionRTCP + UC serves as an optional nursing modality in alleviating anxiety and depression, improving quality of life in surgical prostate cancer patients.
Journal Article
Heterogeneity in regional changes in body composition induced by androgen deprivation therapy in prostate cancer patients: potential impact on bone health—the BLADE study
Background
It is not clear whether changes in body composition induced by androgen deprivation therapy (ADT) in prostate cancer (PC) patients are uniform or vary in the different body districts and whether regional lean body mass (LBM) and fat body mass (FBM) could have an impact on bone health.
Objective
To prospectively evaluate the regional changes in LBM and FBM in PC patients submitted to degarelix; to explore the relationship of regional body composition and bone mineral density (BMD) and bone turnover markers.
Design, setting, and participants
29 consecutive non metastatic PC patients enrolled from 2017 to 2019. FBM, LBM and bone mineral density (BMD) evaluated by dual-energy x-ray absorptiometry (DXA) at baseline and after 12-month of ADT. Alkaline phosphate (ALP) and C-terminal telopeptide of type I collagen (CTX) assessed at baseline, 6 and 12 months.
Intervention
All patients underwent degarelix administration.
Outcome measurements and statistical analysis
T
-test or sign test and Pearson or Spearman test for continuous variables were used when indicated.
Results and limitations
Median percent increase in FBM ranged from + 14.5% in trunk to + 25.4% in the left leg after degarelix. LBM changes varied from + 2% in the trunk to − 4.9% in the right arm. LBM in both arms and legs and their variations after degarelix directly correlated with ALP and inversely correlated with CTX. Lean mass of limbs, trunk and legs significantly correlated with BMD of the hip, lean mass of the trunk significantly correlated with spine BMD. These are post-hoc analysis of a prospective study and this is the main limitation.
Conclusions
an heterogeneous change in body composition among body district is observed after ADT and bone turnover is influenced by lean mass and its variation. A supervised physical activity is crucial to maintain general physical performance and preserving bone health.
Journal Article
Estrogen and Androgen Receptor Inhibitors: Unexpected Allies in the Fight Against COVID-19
Translational Relevance
No prophylactic treatments for COVID-19 have been clearly proven and found. In this pandemic context, cancer patients constitute a particularly fragile population that would benefit the best from such treatments, a present unmet need. TMPRSS2 is essential for COVID-19 replication cycle and it is under androgen control. Estrogen and androgen receptor dependent cues converge on TMPRSS2 regulation through different mechanisms of action that can be blocked by the use of hormonal therapies. We believe that there is enough body of evidence to foresee a prophylactic use of hormonal therapies against COVID-19 and this hypothesis can be easily tested on cohorts of breast and prostate cancer patients who follow those regimens. In case of pandemic, if the protective effect of hormonal therapies will be proven on cancer patients, the use of specific hormonal therapies could be extended to other oncological groups and to healthy individuals to decrease the overall risk of infection by SARS-CoV-2.
Given the COVID-19 coronavirus emergency, a special focus is needed on the impact of this rapidly spreading viral infection on cancer patients. Androgen receptor (AR) signaling in the transmembrane protease serine 2 (TMPRSS2) regulation is emerging as an important determinant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility. In our study, we analyzed AR and TMPRSS2 expression in 17,352 normal and 9,556 cancer tissues from public repositories and stratified data according to sex and age. The emerging picture is that some patient groups may be particularly susceptible to SARS-CoV-2 infection and may benefit from antiandrogen- or tamoxifen-based therapies. These findings are relevant to choose proper treatments in order to protect cancer patients from concomitant SARS-CoV-2 contagion and related symptoms and put forward the idea that hormonal therapies could be used as prophylactic agents against COVID-19.
Journal Article
Real‐World Treatment Patterns Before and After Metastatic Castration–Resistant Prostate Cancer in Japan: Retrospective Analysis Using a Hospital‐Based, Multicenter Database
Although treatment options for metastatic castration-resistant prostate cancer (mCRPC) have been increasing since 2014, the actual treatment sequences of each drug in clinical practice in Japan have only been reported in a limited number of patients and facilities. The primary objective of this database study was to investigate the general situation and the transition of prior and post-mCRPC treatments.
Using Medical Data Vision's medical record database across Japan, patients diagnosed with mCRPC from January 2015 to December 2022 based on defined criteria were extracted. Treatment sequences before and after mCRPC diagnosis were analyzed.
Analysis of 4967 patients revealed that the most common pretreatment for mCRPC was classical vintage hormone therapy (77.1%), followed by androgen receptor signaling inhibitors (ARSI), including enzalutamide (7.8%) and abiraterone (7.4%). The most common treatments for first-line mCRPC were enzalutamide (43.1%), abiraterone (28.3%), and docetaxel (10.7%). When the treatment prior to mCRPC was ARSI, docetaxel was the most common first-line treatment for mCRPC, but another ARSI that had not been used as treatment prior to mCRPC was also selected as first-line mCRPC treatment at a similar rate to docetaxel. Regarding annual changes, the proportion of vintage hormone therapy for mCRPC has been decreasing annually, and there has been a trend to replace it with ARSIs.
In terms of the treatment sequence for mCRPC in Japan, vintage hormone therapy was the most common pretreatment for mCRPC, and ARSIs were the most common first-line treatments for mCRPC.
Journal Article
Glyoxalase 1 Expression as a Novel Diagnostic Marker of High-Grade Prostatic Intraepithelial Neoplasia in Prostate Cancer
Glyoxalase 1 (GLO1) is an enzyme involved in the detoxification of methylglyoxal (MG), a reactive oncometabolite formed in the context of energy metabolism as a result of high glycolytic flux. Prior clinical evidence has documented GLO1 upregulation in various tumor types including prostate cancer (PCa). However, GLO1 expression has not been explored in the context of PCa progression with a focus on high-grade prostatic intraepithelial neoplasia (HGPIN), a frequent precursor to invasive cancer. Here, we have evaluated GLO1 expression by immunohistochemistry in archival tumor samples from 187 PCa patients (stage 2 and 3). Immunohistochemical analysis revealed GLO1 upregulation during tumor progression, observable in HGPIN and PCa versus normal prostatic tissue. GLO1 upregulation was identified as a novel hallmark of HGPIN lesions, displaying the highest staining intensity in all clinical patient specimens. GLO1 expression correlated with intermediate–high risk Gleason grade but not with patient age, biochemical recurrence, or pathological stage. Our data identify upregulated GLO1 expression as a molecular hallmark of HGPIN lesions detectable by immunohistochemical analysis. Since current pathological assessment of HGPIN status solely depends on morphological features, GLO1 may serve as a novel diagnostic marker that identifies this precancerous lesion.
Journal Article
Transperineal prostate biopsies for diagnosis of prostate cancer are well tolerated： a prospective study using patient-reported outcome measures
We aimed to determine short-term patient-reported outcomes in men having general anesthetic transperineal （TP） prostate biopsies. A prospective cohort study was performed in men having a diagnostic TP biopsy. This was done using a validated and adapted questionnaire immediately post-biopsy and at follow-up of between 7 and 14 days across three tertiary referral hospitals with a response rate of 51.6%. Immediately after biopsy 43/201 （21.4%） of men felt light-headed, syncopal, or suffered syncope. Fifty-three percent of men felt discomfort after biopsy （with 95% scoring 〈5 in a 0-10 scale）. Twelve out of 196 men （6.1%） felt pain immediately after the procedure. Despite a high incidence of symptoms （e.g., up to 75% had some hematuria, 47% suffered some pain）, it was not a moderate or serious problem for most, apart from hemoejaculate which 31 men suffered. Eleven men needed catheterization （5.5%）. There were no inpatient admissions due to complications （hematuria, sepsis）. On repeat questioning at a later time point, only 25/199 （12.6%） of men said repeat biopsy would be a significant problem despite a significant and marked reduction in erectile function after the procedure. From this study, we conclude that TP biopsy is well tolerated with similar side effect profiles and attitudes of men to repeat biopsy to men having TRUS biopsies. These data allow informed counseling of men prior to TP biopsy and a benchmark for tolerability with local anesthetic TP biopsies being developed for clinical use.
Journal Article