Optimal timing for initiating androgen receptor signaling inhibitor therapy in patients with nonmetastatic castration-resistant prostate cancer: a multicenter collaborative study.

OBJECTIVE: We determined the optimal timing for initiating androgen receptor signaling inhibitor (ARSI) therapy in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) and assessed its impact on oncological outcomes. MATERIALS AND METHODS: This retrospective study included 145 nmCRPC patients who received enzalutamide, apalutamide or darolutamide at the Jikei University Hospital or its affiliated institutions between May 2014 and November 2022. Patients were stratified based on prostate-specific antigen (PSA) doubling time (PSADT) at CRPC diagnosis and PSA levels at ARSI initiation. Oncological outcomes, including progression-free survival (PFS), metastasis-free survival (MFS), cancer-specific survival and overall survival, were assessed using the Kaplan-Meier curve and Cox regression analysis. RESULTS: The median age of the patients was 73 (interquartile range [IQR]: 52-88) years, and the median follow-up duration was 36 (IQR: 2-104) months. The median PSA level at ARSI initiation was 5.4 (IQR: 2.2-48) ng/ml, and 44.8% of patients had a PSADT <3 months. Multivariate analysis revealed that PSADT and PSA levels at ARSI initiation were independent MFS predictors. Patients with a PSADT ≤3 months and a PSA level ≥5.4 ng/ml experienced significantly reduced PFS and MFS. Notably, ARSI initiation at a PSA level ≥5.4 ng/ml was associated with worse outcomes, suggesting the potential benefit of earlier intervention. CONCLUSIONS: Patients with rapid PSADT are at increased risk of early disease progression, suggesting that immediate treatment may be warranted. In addition, initiating therapy at a PSA level <5.4 ng/ml may be associated with improved patient outcomes in patients with low PSADT.

Cardiovascular events among men with prostate cancer treated with androgen receptor signaling inhibitors: a systematic review, meta-analysis, and network meta-analysis.

BACKGROUND: Androgen-receptor pathway inhibitors (ARPIs) have dramatically changed the management of advanced/metastatic prostate cancer (PCa). However, their cardiovascular toxicity remains to be clarified. OBJECTIVE: To analyze and compare the risks of cardiovascular events secondary to treatment of PCa patients with different ARPIs. METHODS: In August 2023, we queried PubMed, Scopus, and Web of Science databases to identify randomized controlled studies (RCTs) that analyze PCa patients treated with abiraterone, apalutamide, darolutamide, and enzalutamide. The primary outcomes of interest were the incidence of cardiac disorder, heart failure, ischemic heart disease (IHD), atrial fibrillation (AF), and hypertension. Network meta-analyses (NMAs) were conducted to compare the differential outcomes of each ARPI plus androgen deprivation therapy (ADT) compared to standard of care (SOC). RESULTS: Overall, 26 RCTs were included. ARPIs were associated with an increased risk of cardiac disorders (RR: 1.74, 95% CI: 1.13-2.68, p = 0.01), heart failure (RR: 2.49, 95% CI: 1.05-5.91, p = 0.04), AF (RR: 2.15, 95% CI: 1.14-4.07, p = 0.02), and hypertension (RR: 2.06, 95% CI: 1.67-2.54, p < 0.01) at grade ≥3. Based on NMAs, abiraterone increased the risk of grade ≥3 cardiac disorder (RR:2.40, 95% CI: 1.42-4.06) and hypertension (RR:2.19, 95% CI: 1.77-2.70). Enzalutamide was associated with the increase of grade ≥3 AF(RR: 3.17, 95% CI: 1.05-9.58) and hypertension (RR:2.30, 95% CI: 1.82-2.92). CONCLUSIONS: The addition of ARPIs to ADT increases the risk of cardiac disorders, including IHD and AF, as well as hypertension. Each ARPI exhibits a distinct cardiovascular event profile. Selecting patients carefully and vigilant monitoring for cardiovascular issues is imperative for those undergoing ARPI + ADT treatment.

Salvage therapies for biochemical recurrence after definitive local treatment: a systematic review, meta-analysis, and network meta-analysis.

PURPOSE: Recent advancements in the management of biochemical recurrence (BCR) following local treatment for prostate cancer (PCa), including the use of androgen receptor signaling inhibitors (ARSIs), have broadened the spectrum of therapeutic options. We aimed to compare salvage therapies in patients with BCR after definitive local treatment for clinically non-metastatic PCa with curative intent. METHODS: In October 2023, we queried PubMed, Scopus, and Web of Science databases to identify randomized controlled trials (RCTs) and prospective studies reporting data on the efficacy of salvage therapies in PCa patients with BCR after radical prostatectomy (RP) or radiation therapy (RT). The primary endpoint was metastatic-free survival (MFS), and secondary endpoints included progression-free survival (PFS) and overall survival (OS). RESULTS: We included 19 studies (n = 9117); six trials analyzed RT-based strategies following RP, ten trials analyzed hormone-based strategies following RP ± RT or RT alone, and three trials analyzed other agents. In a pairwise meta-analysis, adding hormone therapy to salvage RT significantly improved MFS (HR: 0.69, 95% CI: 0.57-0.84, p < 0.001) compared to RT alone. Based on treatment ranking analysis, among RT-based strategies, the addition of elective nodal RT and androgen deprivation therapy (ADT) was found to be the most effective in terms of MFS. On the other hand, among hormone-based strategies, enzalutamide + ADT showed the greatest benefit for both MFS and OS. CONCLUSIONS: The combination of prostate bed RT, elective pelvic irradiation, and ADT is the preferred treatment for eligible patients with post-RP BCR based on our analysis. In remaining patients, or in case of post-RT recurrence, especially for those with high-risk BCR, the combination of ADT and ARSI should be considered.

Real-world evidence of triplet therapy efficacy in patients with metastatic castration-sensitive prostate cancer: a Japanese multicenter study.

BACKGROUND: Two randomized trials demonstrated that the survival benefits afforded by triplet therapy were greater than those of doublet therapy, thus changing the treatment paradigm for metastatic castration-sensitive prostate cancer (mCSPC). This is the first study to assess the real-world use, performance, and safety of triplet therapy in Japanese patients. METHODS: This retrospective multicenter study included 45 consecutive mCSPC patients who received triplet therapy composed of androgen deprivation therapy (ADT), docetaxel, and darolutamide between January 2023 and June 2024. Baseline patient characteristics and their clinical parameters during triplet therapy were collected. Adverse events (AEs) were graded using Common Terminology Criteria for Adverse Events version 5.0, and imaging responses were evaluated following the RECIST criteria. The prostate-specific antigen (PSA) nadir was defined as the lowest PSA value during follow-up, and the PSA decrease was the initial PSA value minus the PSA nadir. RESULTS: The median patient age was 70 years and the median follow-up duration was 10 months. High-volume disease was present in 82.2% of patients. Concurrent administration of docetaxel and darolutamide was scheduled for 22.2% of cases. The incidence of any AE was 86.7%, with 55.5% of patients experiencing grade 3-4 AEs. Neutropenia was common, but prophylactic granulocyte colony-stimulating factor (G-CSF) significantly reduced the incidence of neutropenia of grade 3 or higher. Febrile neutropenia occurred in four patients (8.9%); these patients had not received prophylactic G-CSF. A decline in PSA of 90% was observed in 95.6% of patients, and an imaging response was seen in 97.8%. CONCLUSIONS: Triplet therapy with ADT, darolutamide, and docetaxel was highly efficacious and tolerable in Japanese mCSPC patients, particularly those with high-volume disease. Prophylactic G-CSF prescription is crucial to manage neutropenia effectively. Further studies with longer follow-ups are needed to confirm these findings and explore the long-term outcomes.

Urethral catheter entrapped in vesicourethral anastomotic sutures after laparoscopic radical prostatectomy successfully removed by transurethral approach.

Introduction: Urethral catheter entrapped in vesicourethral anastomotic sutures after radical prostatectomy is a relatively common complication. We herein present a novel and safe technique to remove urethral catheter. Case presentation: A 64-year-old man was diagnosed with prostate cancer. Subsequently he underwent laparoscopic radical prostatectomy. On postoperative Day 7, the patient experienced difficulty in removing the catheter, and entanglement of the suture with the urinary catheter was suspected. After conservative follow-up, a rigid endoscope was inserted into the urethra beside urethral catheter, identifying suture entanglement with the catheter. Finally, the suture was cut with scissor forceps. Conclusion: To the best of our knowledge, this is the first reported case in which scissor forceps were used to cut the entangled thread in such a complication. This case highlights a novel but simple method for difficult removal of an entrapped catheter.

Preoperative Tyrosine Kinase Inhibitors Before Percutaneous Cryoablation for Clinical T1b Renal Tumors.

Purpose To treat renal cell carcinoma, local ablative therapy is a viable alternative treatment option. Traditionally, cryoablation has been used for the treatment of T1a renal tumors. However, recent technological developments have expanded its application to encompass select T1b renal tumors. Here, we present a retrospective study of the utilization of preoperative tyrosine kinase inhibitors (TKIs) to induce tumor shrinkage and achieve favorable outcomes in percutaneous cryoablation (PCA). Methods We retrospectively evaluated the data from nine patients with clinical T1b renal tumors who underwent PCA. Six patients with TKI pretreatment at our institution between 2016 and 2018 were included in the study. We evaluated the safety and efficacy of preoperative TKIs prior to PCA. Results All patients received axitinib with a median treatment duration of 80.5 days (IQR: 49-85). All patients experienced tumor shrinkage (median: 13.5 mm; IQR: 7-16); five experienced downstaging to T1a following tumor shrinkage. There were no severe adverse events (common terminology criteria for adverse events (CTCAE) grade ≥ 3) in TKIs. After the discontinuation of TKIs for two weeks, all PCA procedures were performed successfully without any severe complications. During a median follow-up of 46 months, no local recurrence was observed in any of these cases. Conclusion In cases with large renal tumors, TKI pretreatment prior to PCA had potential benefits in terms of tumor shrinkage and long-term local control rate. Further well-designed studies in larger populations are needed to validate our findings.

The prognostic significance of additional localized treatment to primary lesion in patients undergoing hormone therapy for metastatic hormone-sensitive prostate cancer: A systematic review and meta-analysis.

BACKGROUND: We aimed to compare the prognostic values of 'localized treatment to the primary lesion (LT) plus hormone therapy (HT)' versus 'HT alone' in metastatic hormone-sensitive prostate cancer (mHSPC). METHODS: We conducted a systematic search through the databases of PubMed®, Web of Science®, and Cochrane library® in April 2023 based on the PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analyses) statement. A pooled meta-analysis was performed to assess the prognostic differences between LT + HT and HT alone according to randomized and non-randomized controlled studies (RCTs and NRCTs, respectively). RESULTS: The search identified three RCTs and eight NRCTs. In RCTs, LT did not show prognostic benefits regarding biochemical-failure free rate nor overall survival (OS), although in patients with low tumor burdens, the LT + HT group showed better OS (HR: 0.68, 95% CI: 0.54-0.86). In the NRCTs, the LT+HT group showed superior progression-free survival (hazard ratio (HR): 0.42, 95% confidence interval (CI): 0.21-0.87), cancer-specific survival (HR: 0.39, 95% CI: 0.20-0.76), and OS (HR: 0.63, 95% CI: 0.57-0.69) to the HT alone group. In addition, better OS was observed in the LT +HT group regardless of the type of treatment modality for LT; radical prostatectomy (HR: 0.52, 95% CI: 0.39-0.69), radiotherapy (HR: 0.63, 95% CI: 0.56-0.71) in NRCTs. CONCLUSIONS: LT to the primary lesion in metastatic hormone-sensitive prostate cancer may provide prognostic benefits and especially in patients with low tumor burden.

Does age impact clinical outcomes of radical nephroureterectomy in the elderly?-results from a multicenter retrospective study.

Background: Few studies have addressed the efficacy of nephroureterectomy for managing upper tract urothelial carcinoma (UTUC) in very elderly patients (those aged 85 years and older). We aimed to elucidate the association between age and clinical outcomes in patients with UTUC who underwent radical nephroureterectomy. Methods: We retrospectively analyzed data from 847 patients who underwent nephroureterectomy for UTUC. These patients were classified into four age brackets: young (≤64 years, n=177), intermediate (65-74 years, n=300), elderly (75-84 years, n=312), and very elderly (≥85 years, n=58). We applied logistic regression models to ascertain predictors of postoperative complications. Cox's proportional hazards models were used to evaluate key prognostic factors affecting non-urothelial tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). Results: In all, 56 patients reported postoperative complications. An Eastern Cooperative Oncology Group performance status ≥2 was identified as a significant predictor for postoperative complications whereas age did not show a noteworthy correlation. Kaplan-Meier survival analyses indicated that very elderly patients had notably poorer OS than younger groups. Nevertheless, the differences in NUTRFS and CSS across the age brackets were not statistically significant. In multivariable analyses, very elderly age was a substantial independent determinant of OS but not NUTRFS or CSS. Conclusions: The therapeutic benefits of surgical procedures are relatively consistent across age groups. This underscores the potential of considering surgical treatment for UTUC in patients aged 85 and above, provided they are deemed fit to withstand the surgical rigors and associated invasiveness.

Perioperative renal function change and oncological outcomes of radical nephroureterectomy in patients with upper tract urothelial carcinoma: A multicenter retrospective study.

BACKGROUND: The effect of radical nephroureterectomy (RNUx) on postoperative renal function in patients diagnosed with upper tract urothelial carcinoma (UTUC) has not been thoroughly explored. METHODS: We conducted a retrospective analysis including 785 patients who underwent RNUx for UTUC. We assessed the preoperative and postoperative estimated glomerular filtration rates (eGFRs) and factors related to the decline in eGFR. Additionally, we examined the effect of comorbidities (diabetes or hypertension) on the postoperative eGFR at 1 year. Cox proportional hazard models were employed to investigate the clinical effect of RNUx on oncological outcomes, including non-urothelial tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: The median preoperative and postoperative eGFR levels were 54.7 and 40.6 ml/min/1.73 m2 respectively. The proportions of patients with preoperative and postoperative eGFR ≥60 mL/min/1.73 m2 were 35.9% and 5.1%, respectively. The median decline in the eGFR after surgery was 26.8%. Patients with preoperative eGFR <60 ml/min/1.73 m2 demonstrated significantly lower odds of a postoperative decline in eGFR of 25% or more. The effect of comorbidities on postoperative eGFR at 1 year was significant (P = 0.048). The 3-year NUTRFS, CSS, and OS rates were 72.9%, 85.2%, and 81.5%, respectively. Preoperative chronic kidney disease was an independent factor associated with inferior NUTRFS, CSS, and OS. CONCLUSION: Different degrees of impairment of renal function occur among UTUC patients. Only 5.1% of patients retain a postoperative eGFR ≥60 ml/min/1.73 m2. Preoperative renal impairment was linked to reduced odds of postoperative eGFR decrease and associated with survival. In addition, the presence of comorbidities had a significant effect on the decline in eGFR. These findings emphasize the importance of developing evidence-based perioperative treatment strategies for UTUC patients with impaired renal function.

Site-Specific Differences of Eligibility for Adjuvant Immunotherapy Among Urothelial Carcinoma Patients Treated With Radical Surgery: Results From a Multicenter Cohort Study.

BACKGROUND: The CheckMate274 trial has reported enhanced disease-free survival rates in patients with stage pT3-4/ypT2-4 or pN+ urothelial carcinoma (UC) undergoing adjuvant nivolumab therapy. This study compares prognostic differences between urothelial carcinoma of the bladder (UCB) and upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively analyzed data from 719 patients with UC who underwent radical surgery, stratifying to patients at stage pT3-4 and/or pN+ without neoadjuvant chemotherapy (NAC) or at ypT2-4 and/or ypN+ with NAC (potential candidates for adjuvant immunotherapy), and to those who were not candidates for adjuvant immunotherapy. We used Kaplan-Meier curves to assess oncological outcomes, particularly nonurothelial tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). Risk factors were identified by Cox regression analysis. RESULTS: Kaplan-Meier curves showed significantly lower NUTRFS, CSS, and OS for potential adjuvant immunotherapy candidates than for noncandidates in each UCB and UTUC group. NUTRFS, CSS, and OS did not differ significantly between adjuvant immunotherapy candidates with UBC or UTUC. Trends were similar among patients ineligible for adjuvant immunotherapy. Pathological T stage (pT3-4 or ypT2-4), pathological N stage, and lymphovascular invasion (LVI) were independent predictors of oncological outcomes on multivariate analysis. CONCLUSION: The criteria for adjuvant immunotherapy candidates from the CheckMate 274 trial can also effectively stratify UC patients after radical surgery. Substantial clinical significance is attached to LVI status as well as to pathological T and N status, suggesting that LVI status should be considered when selecting suitable candidates for adjuvant immunotherapy.

Radiographic Progression at Castration-Resistant Prostate Cancer Diagnosis: A Prognostic Indicator of Metastatic Hormone-Sensitive Prostate Cancer.

BACKGROUND: The critical role of radiographic assessment at the time of castration-resistant prostate cancer (CRPC) diagnosis is underscored by this study. We performed a retrospective analysis of radiographic changes in metastasis from the time of diagnosis of metastatic hormone-sensitive prostate cancer (mHSPC) to CRPC diagnosis. We also explored its impact on prognosis post-CRPC. MATERIALS AND METHODS: We retrospectively analyzed 98 men who underwent radiographic examinations (bone scans and computed tomography [CT]) at the time of CRPC diagnosis. When radiographic studies demonstrated progression at CRPC diagnosis, patients were assigned to the radiographic progressive disease (rPD) group. The remaining patients were placed in the "non-rPD" group. The overall survival (OS) post-CRPC was compared between the 2 groups. RESULTS: The median OS post-CRPC was significantly shorter in the rPD group (n = 50) compared to the non-rPD group (n = 48) (32 months vs. not reached, P = .0124). Multivariate analysis showed that radiographic progression and shorter time to CRPC were associated with a shorter OS post-CRPC (hazard ratio [HR] = 3.14; 95% confidence interval [CI], 1.21-8.12, P = .019). CONCLUSION: Radiographic progression at the point of CRPC diagnosis independently predicts a shorter OS post-CRPC in patients with mHSPC. Therefore, assessing radiographic changes at the time of CRPC diagnosis could be instrumental in managing CRPC in patients with mHSPC.

Extracellular vesicles and prostate cancer management: a narrative review.

Background and Objective: Prostate cancer (PCa) is the second most common male cancer in the United States. Although new drugs have recently been approved, clinical challenges remain, notably the precise detection and prognostic implications of drug-resistant PCa. Extracellular vesicles (EVs), nanoscale lipid membrane vesicles, are actively secreted into the extracellular milieu by a variety of cell types. Over the past decade, interest in EVs has grown, and emerging evidence suggests that EVs play pivotal roles in cancer biology. In this review, we would like to summarize recent reports on EVs in PCa and discuss the potential clinical applications. Methods: We performed a non-systematic literature review using the PubMed database to identify articles specifically related to EVs and PCa management. Key Content and Findings: EVs contain pathogenic components, such as proteins, DNA fragments, mRNA, non-coding RNA, and lipids, all of which can trigger intercellular signaling within tumor microenvironments. Thereby, EVs exert significant effects on several stages of cancer progression, influencing the immune system, angiogenesis, and the establishment of pre-metastatic niches. Furthermore, as EVs are encapsulated, their contents are stable in bodily fluids, and thus EVs have recently attracted attention as a novel kind of liquid biopsy. Conclusions: We have summarized recent research on how EVs may aid PCa management. To date, we have discovered only the tip of the iceberg. We anticipate that further research will yield innovative therapeutic modalities, thereby aiding all PCa patients.

Kerosene condenses in the trachea following inhalation.

PURPOSE: We have investigated the absorption dynamics of petroleum fuel components from the analytical results of autopsy samples. METHODS: Post-mortem samples of the severely burned case, including femoral blood, intratracheal contents (mucus) and intratracheal gas-phase samples were collected, and analysed by gas chromatography-mass spectrometer with head-space solid-phase microextraction. RESULTS: The composition of flammable substances in the tracheal gas phase differed slightly from that in mucus. CONCLUSION: High-boiling point components are retained in the trachea, whereas relatively lower-boiling point components are detected predominantly in the tracheal gas phase and blood.

Association between comorbidities and survival in patients with metastatic urothelial carcinoma treated with pembrolizumab.

BACKGROUND: This study aims to investigate the relationship between comorbidities and survival in patients with mUC treated with pembrolizumab as a second-line treatment. METHODS: From February 2018 to October 2021, we analyzed the data of 185 consecutive patients with metastatic UC who received pembrolizumab as second-line therapy at The Jikei University Hospital and five affiliated hospitals. We used the Charlson Comorbidity Index (CCI) to assess the comorbidities. The outcomes of interest were progression-free survival (PFS) and overall survival (OS). To compare the survival differences, inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and the IPTW-adjusted Cox regression hazards model were used. RESULTS: After IPTW adjustment, patient characteristics were well-balanced between patients with high CCI and those with low CCI. The IPTW-adjusted Kaplan-Meier curves of PFS and OS based on CCI revealed that the patients with high CCI (2 or more) had a shorter PFS (median, 1.6 vs. 2.8 months) and a shorter OS (median, 12.4 vs. 18.8 months) (0-1). Similarly, in the IPTW-adjusted Cox regression hazards model, patients with high CCI had significantly shorter PFS [HR, 1.84 (95% CI 1.26-2.68; p = 0.002)] and OS [HR, 1.98 (95% CI 1.20-3.27; p = 0.008)] than those with lower CCI. CONCLUSIONS: High CCI was associated with a higher risk of disease progression as well as overall mortality in mUC patients treated with second-line pembrolizumab.

Effectiveness and safety of primary prophylaxis of granulocyte colony-stimulating factor during dose-dense chemotherapy for urothelial cancer: Clinical Practice Guidelines for the Use of G-CSF 2022.

Granulocyte colony-stimulating factor (G-CSF) decreases the incidence, duration, and severity of febrile neutropenia (FN); however, dose reduction or withdrawal is often preferred in the management of adverse events in the treatment of urothelial cancer. It is also important to maintain therapeutic intensity in order to control disease progression and thereby relieve symptoms, such as hematuria, infection, bleeding, and pain, as well as to prolong the survival. In this clinical question, we compared treatment with primary prophylactic administration of G-CSF to maintain therapeutic intensity with conventional standard therapy without G-CSF and examined the benefits and risks as major outcomes. A detailed literature search for relevant studies was performed using PubMed, Ichu-shi Web, and Cochrane Library. Data were extracted and evaluated independently by two reviewers. A qualitative analysis of the pooled data was performed, and the risk ratios with corresponding confidence intervals were calculated and summarized in a meta-analysis. Seven studies were included in the qualitative analysis, two of which were reviewed in the meta-analysis of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) therapy, and one randomized controlled study showed a reduction in the incidence of FN. Primary prophylactic administration of G-CSF may be beneficial, as shown in a randomized controlled study of dose-dense MVAC therapy. However, there are no studies on other regimens, and we made a "weak recommendation to perform" with an annotation of the relevant regimen (dose-dense MVAC).

Effectiveness and safety of primary prophylaxis of G-CSF during chemotherapy for prostate cancer, Japanese clinical guideline for appropriate use of G-CSF: clinical practice guidelines for the use of G-CSF 2022.

BACKGROUND: Docetaxel (DTX) is commonly used as a primary chemotherapy, and cabazitaxel (CBZ) has shown efficacy in patients who are DTX resistant. Primary prophylactic granulocyte colony stimulating factor (G-CSF) therapy is currently used with CBZ treatment in routine clinical care in Japan. METHODS: In this study, we performed a systematic review following the Minds guidelines to investigate the effectiveness and safety of primary prophylaxis with G-CSF during chemotherapy for prostate cancer and to construct G-CSF guidelines for primary prophylaxis use during chemotherapy. A comprehensive literature search of various electronic databases (PubMed, Cochrane Library, and Ichushi) was performed on January 10, 2020, to identify studies published between January 1990 and December 31, 2019 that investigate the impact of primary prophylaxis with G-CSF during CBZ administration on clinical outcomes. RESULTS: Ultimately, nine articles were included in the qualitative systematic review. Primary G-CSF prophylaxis during CBZ administration for metastatic castration-resistant prostate cancer was difficult to assess in terms of correlation with overall survival, mortality from infection, and patients' quality of life. These difficulties were owing to the lack of randomized controlled trials comparing patients with and without primary prophylaxis of G-CSF during CBZ administration. However, some retrospective studies have suggested that it may reduce the incidence of febrile neutropenia. CONCLUSION: G-CSF may be beneficial as primary prophylaxis during CBZ administration for metastatic castration resistant prostate cancer, and we made a "weak recommendation to perform" with an annotation of the relevant regimen.

Nonsurgical Interventions to Prevent Disease Progression in Prostate Cancer Patients on Active Surveillance: A Systematic Review and Meta-analysis.

CONTEXT: Active surveillance (AS) is a standard of care for patients with low-risk and selected intermediate-risk prostate cancer (PCa). Nevertheless, there is a lack of summary evidence on how to impact disease trajectory during AS. OBJECTIVE: To assess which interventions prevent PCa progression effectively during AS. EVIDENCE ACQUISITION: We queried PubMed, Scopus, and Web of Science databases to identify studies examining the impact of interventions aimed at slowing disease progression during AS. The primary endpoint was PCa progression, the definition of which must have included pathological upgrading. The secondary endpoint included treatment toxicities. EVIDENCE SYNTHESIS: We identified 22 studies, six randomized controlled trials and 16 observational studies, which analyzed the association between different interventions and PCa progression during AS. The interventions considered in the studies included 5-alpha reductase inhibitors (5-ARIs), statins, diet, exercise, chlormadinone, fexapotide triflutate (FT), enzalutamide, coffee, vitamin D3, and PROSTVAC. We found that administration of 5-ARIs was associated with improved progression-free survival (PFS; hazard ratio: 0.59; 95% confidence interval 0.48-0.72), with no increased toxicity signals. Therapies such as vitamin D3, chlormadinone, FT, and enzalutamide have shown some efficacy. However, these anticancer drugs have been associated with treatment-related adverse events in up to 88% of patients. CONCLUSIONS: The use of 5-ARIs in PCa patients on AS is associated with longer PFS. However, for the other interventions, it is difficult to draw clear conclusions based on the weak available evidence. PATIENT SUMMARY: Patients with prostate cancer managed with active surveillance (AS) who are treated with 5-alpha reductase inhibitors have a lower risk of disease progression, with minimal adverse events. Other interventions require more studies to determine their efficacy and safety profile in men on AS.