Progress in Oligometastatic Prostate Cancer: Emerging Imaging Innovations and Therapeutic Approaches.

Prostate cancer (PCa) exhibits a spectrum of heterogeneity, from indolent to highly aggressive forms, with approximately 10-20% of patients experiencing metastatic PCa. Oligometastatic PCa, characterized by a limited number of metastatic lesions in specific anatomical locations, has gained attention due to advanced imaging modalities. Although patients with metastatic PCa typically receive systemic therapy, personalized treatment approaches for oligometastatic PCa are emerging, including surgical and radiotherapeutic interventions. This comprehensive review explores the latest developments in the field of oligometastatic PCa, including its biological mechanisms, advanced imaging techniques, and relevant clinical studies. Oligometastatic PCa is distinct from widespread metastases and presents challenges in patient classification. Imaging plays a crucial role in identifying and characterizing oligometastatic lesions, with new techniques such as prostate-specific membrane antigen positron emission tomography demonstrating a remarkable efficacy. The management strategies encompass cytoreductive surgery, radiotherapy targeting the primary tumor, and metastasis-directed therapy for recurrent lesions. Ongoing clinical trials are evaluating the effectiveness of these approaches. Oligometastatic PCa occupies a unique position between locally advanced and high-volume metastatic diseases. While a universally accepted definition and standardized diagnostic criteria are still evolving, emerging imaging technologies and therapeutic strategies hold promise for improving the patient outcomes in this intermediate stage of PCa.

Laparoscopic adrenalectomy for adrenal tumors with endocrine activity: Perioperative management pathways for reduced complications and improved outcomes.

The major adrenal tumors with endocrine activity are primary aldosteronism, Cushing's syndrome/mild autonomous cortisol secretion, and pheochromocytoma/paraganglioma. Excessive aldosterone secretion in primary aldosteronism causes cardiovascular, renal, and other organ damage in addition to hypertension and hypokalemia. Cortisol hypersecretion in Cushing's syndrome/mild autonomous cortisol secretion causes obesity, hypertension, impaired glucose tolerance, and cardiometabolic syndrome. Massive secretion of catecholamines in pheochromocytoma/paraganglioma causes hypertension and cerebrocardiovascular disease due to rapid blood pressure fluctuation. Moreover, pheochromocytoma multi-system crisis is a feared and possibly fatal presentation of pheochromocytoma/paraganglioma. Thus, adrenal tumors with endocrine activity are considered an indication for adrenalectomy, and perioperative management is very important. They have a risk of perioperative complications, either due to direct hemodynamic effects of the hormone hypersecretion or due to hormone-related comorbidities. In the last decades, deliberate preoperative evaluation and advanced perioperative management have significantly reduced complications and improved outcomes. Furthermore, improvements in anesthesia and surgical techniques with the feasibility of laparoscopic adrenalectomy have contributed to reduced morbidity and mortality. However, there are still several challenges to be considered in the perioperative care of these patients. There are very few data available prospectively to guide clinical management, due to the rarity of adrenal tumors with endocrine activity. Therefore, most guidelines are based on retrospective data analyses or small case series. In this review, the latest knowledge is summarized, and practical pathways to reduce perioperative complications and improve outcomes in adrenal tumors with endocrine activity are presented.

Comparison of the medical costs between active surveillance and other treatments for early prostate cancer in Japan using data from the PRIAS-JAPAN study.

OBJECTIVES: To compare the medical costs of active surveillance with those of robot-assisted laparoscopic prostatectomy, brachytherapy, intensity-modulated radiation therapy, and hormone therapy for low-risk prostate cancer. METHODS: The costs of protocol biopsies performed in the first year of surveillance (between January 2010 and June 2020) and those of brachytherapy and radiation therapy performed between May 2019 and June 2020 at the Kagawa University Hospital were analyzed. Hormone therapy costs were assumed to be the costs of luteinizing hormone-releasing hormone analogs for over 5 years. Active surveillance-eligible patients were defined based on the following: age <74 years, ≤T2, Gleason score ≤6, prostate-specific antigen level ≤10 ng/ml, and 1-2 positive cores. We estimated the total number of active surveillance-eligible patients in Japan based on the Japan Study Group of Prostate Cancer (J-CAP) study and the 2017 cancer statistical data. We then calculated the 5-year treatment costs of active surveillance-eligible patients using the J-CAP and PRIAS-JAPAN study data. RESULTS: In 2017, number of active surveillance-eligible patients in Japan was estimated to be 2808. The 5-year total costs of surveillance, prostatectomy, brachytherapy, radiation therapy, and hormone therapy were 1.65, 14.0, 4.61, 4.04, and 5.87 million United States dollar (USD), respectively. If 50% and 100% of the patients in each treatment group had opted for active surveillance as the initial treatment, the total treatment cost would have been reduced by USD 6.89 million (JPY 889 million) and USD 13.8 million (JPY 1.78 billion), respectively. CONCLUSION: Expanding active surveillance to eligible patients with prostate cancer helps save medical costs.

Risk assessment of multi-factorial complications after transrectal ultrasound-guided prostate biopsy: a single institutional retrospective cohort study.

BACKGROUND: Transrectal ultrasound-guided prostate biopsy (TRUSPB) is widely used to diagnose prostate cancer (PCa). The aim of this study was to evaluate the risk of multi-factorial complications (febrile genitourinary tract infection (GUTI), rectal bleeding, and urinary retention) after TRUSPB. METHODS: N = 2053 patients were Japanese patients undergoing transrectal or transperineal TRUSPB for suspicious of PCa. To assess risk of febrile GUTI adequately, the patients were divided into four groups: low-risk patients before starting a rectal culture, low-risk patients after starting a rectal culture, high-risk patients, and patients undergoing transperineal TRUSPB. Furthermore, to identify risk of rectal bleeding and urinary retention, patients were divided into transrectal and transperineal group. RESULTS: Febrile GUTI significantly decreased owing to risk classification. The frequency of rectal bleeding was 1.43% (transrectal: 25/1742), while it did not happen in transperineal group. The patients with rectal bleeding had a significantly lower body mass index (BMI) (P < 0.01). The frequency of urinary retention was 5.57% (transrectal: 97/1742), while it did not happen in transperineal group. The patients with urinary retention had a significantly higher prostate-specific antigen (PSA) (P = 0.01) in transrectal group. CONCLUSIONS: Risk classification, rectal swab culture, and selected antimicrobial prophylaxis for transrectal TRUSPB were extremely effective to reduce the risk of febrile GUTI. Furthermore, lower BMI and higher PSA were novel clinical predictors for rectal bleeding and urinary retention, respectively. When urologists perform transrectal TRUSPB to their patients, they can correctly understand and explain each complication risk to their patients based on these novel risk factors.

Impact of Lymphovascular Invasion on Prognosis in the Patients with Bladder Cancer-Comparison of Transurethral Resection and Radical Cystectomy.

(1) Background: This study aimed to evaluate the associations of lymphovascular invasion (LVI) at first transurethral resection of bladder (TURBT) and radical cystectomy (RC) with survival outcomes, and to evaluate the concordance between LVI at first TURBT and RC. (2) Methods: We analyzed 216 patients who underwent first TURBT and 64 patients who underwent RC at Toho University Sakura Medical Center. (3) Results: LVI was identified in 22.7% of patients who underwent first TURBT, and in 32.8% of patients who underwent RC. Univariate analysis identified ≥cT3, metastasis and LVI at first TURBT as factors significantly associated with overall survival (OS) and cancer-specific survival (CSS). Multivariate analysis identified metastasis (hazard ratio (HR) 6.560, p = 0.009) and LVI at first TURBT (HR 9.205, p = 0.003) as significant predictors of CSS. On the other hand, in patients who underwent RC, ≥pT3, presence of G3 and LVI was significantly associated with OS and CSS in univariate analysis. Multivariate analysis identified inclusion of G3 as a significant predictor of OS and CSS. The concordance rate between LVI at first TURBT and RC was 48.0%. Patients with positive results for LVI at first TURBT and RC displayed poorer prognosis than other patients (p < 0.05). (4) Conclusions: We found that the combination of LVI at first TURBT and RC was likely to provide a more significant prognostic factor.

[SIGNIFICANCE OF IgG4 IN IDIOPATHIC RETROPERITONEAL FIBROSIS].

(Objective)Retroperitoneal fibrosis is largely divided into the idiopathic and secondary types. Some idiopathic cases include IgG4-related diseases, which are often similar to malignant diseases, such as lymphoma and sarcoma. The diagnostic criteria for IgG4-related disease are used and pathologic examination is necessary for a definitive diagnosis of IgG4-related retroperitoneal fibrosis. The first choice of treatment for IgG4-related retroperitoneal fibrosis is steroid administration, but no consensus has been established regarding its dose and tapering schedule. We investigated the significance of IgG4 in diagnosis and treatment of idiopathic retroperitoneal fibrosis. (Patients and methods)We examined 14 cases diagnosed as idiopathic retroperitoneal fibrosis between April 2013 and March 2019. Serum IgG4 was measured at the time of diagnosis in 13 cases, and changes over time in serum IgG4 before and after the induction of steroid therapy were measured in 6 cases. Computed tomography-guided biopsy was performed on 4 cases. (Results)Of all cases, 1 patient was diagnosed as IgG4-related retroperitoneal fibrosis and 5 patients were classified as possible group. Ten patients were administered steroid therapy. Percutaneous nephrostomy tube was placed in 3 patients and was removed in 2 of these patients after steroid therapy. The serum high levels of IgG4 were confirmed in all 4 patients who were classified into the possible group and who were treated with steroids. (Conclusion)Although histologic examination is necessary for the diagnosis of retroperitoneal fibrosis, tissue collection by open or laparoscopic surgery is highly invasive. CT-guided biopsy may be useful in high-risk cases, such as elderly patients on anticoagulation. After excluding other diseases in high-risk cases, response to empiric steroid therapy may be diagnostic. In the possible group, changes in serum IgG4 levels may reflect the disease condition and might be useful in determining the maintenance dose of steroids.

Preoperative Clinical Predictors of Lymphovascular Invasion of Bladder Tumors at Transurethral Resection Pathology.

BACKGROUND: The assessment of lymphovascular invasion (LVI) on the specimens of a transurethral resection of bladder tumors (TURBT) is very important for risk stratification and decision-making on further treatment for bladder cancer. OBJECTIVES: The present study aimed to identify clinical predictors associated with the risk of bladder cancer with LVI before a first TURBT. METHODS: A total of 291 patients underwent a first TURBT for bladder cancer at Toho University Sakura Medical Center between January 2012 and December 2016. We analyzed predictors of LVI based on data from 217 patients and predictors of high grade and ≥ pT1 tumors based on data from the medical records of 237 patients for comparison with LVI risk factors. RESULTS: Univariate analysis significantly associated LVI with episodes of gross hematuria, positive urinary cytology, and larger, non-papillary and sessile tumors. Multivariate analysis selected larger tumors [odds ratio (OR) 1.39; 95 % confidence interval (CI) 1.08-1.78; p = 0.01], and non-papillary (OR 10.05; 95% CI 3.75-26.91; p < 0.01) and sessile (OR 2.65; 95% CI 1.18-5.93; p = 0.02) tumors as significant predictors of LVI. Some predictors such as tumor size and non-papillary tumors overlapped between high-grade and ≥ pT1 bladder cancer. CONCLUSIONS: These predictors can help clinicians to identify patients with, or who are at high-risk for LVI before undergoing a first TURBT and to determine priorities for preoperative evaluation and scheduling consecutive treatments.

Quantitative evaluation of the relative apparent diffusion coefficient values on multiparametric magnetic resonance imaging to predict higher Gleason score prostate cancer.

INTRODUCTION: Apparent diffusion coefficient (ADC) values on multiparametric magnetic resonance imaging (mpMRI) have been reported to correlate with high-Gleason score (GS) prostate cancer. However, the relative ADC values between tumor lesions and normal tissue have been suggested as more suitable than the absolute ADC values for evaluation of diffusion abnormalities, because absolute ADC values are susceptible to differences in scanners or scanner settings. The present study evaluated the usefulness of the relative assessment of ADC values between tumor lesions and normal tissue on preoperative mpMRI for the prediction of high-risk prostate cancer on radical prostatectomy specimens. MATERIALS AND METHODS: A retrospective analysis of 48 men who underwent radical prostatectomy between January 2013 and December 2014 was conducted. MpMRI was performed with a 3.0-T scanner using b-values of 0 and 1500 s/mm2. ADC values of the tumor (ADCTUMOR) and normal prostate and the relative ADC tumor/normal ratio (ADCTNR) were evaluated by two radiologists. RESULTS: The inter-rater reliability between two radiologists for ADCTUMOR measurement was high, with Pearson's r = 0.982. There was no difference in ADCTUMOR between GS ≤7 and GS ≥8. In contrast, ADCTNR was significantly lower in GS ≥8 than in GS ≤7. ROC curves of ADCTNR to predict higher GS (≥8) showed better classification performance (AUC = 0.8243, p = .0012 by radiologist A and AUC = 0.7961, p = .0031 by radiologist B) than of ADCTUMOR. CONCLUSIONS: The relative assessment of ADC values between tumor lesions and normal tissue could improve the detection rate of high-risk prostate cancers.

Development and external validation of a nomogram to predict high-grade papillary bladder cancer before first-time transurethral resection of the bladder tumor.

BACKGROUND: The aim of this study was to identify the clinical predictors related to the risk of high-grade papillary bladder cancer before first-time transurethral resection of a bladder tumor (TUR-Bt), and to develop and validate a nomogram predicting the risk of high-grade papillary bladder cancer. METHODS: A retrospective clinical study of consecutive patients who underwent first-time TUR-Bt for papillary bladder cancer was performed. Medical records were reviewed uniformly, and the following data were collected: age, sex, episodes of urinary symptoms, tumor size, number of tumors, location of the largest tumor (lateral walls, base, posterior wall, dome, and anterior wall), tumor appearance (papillary or non-papillary, pedunculated or sessile), and urinary cytology. Data from 254 patients (Group A) were used for the development of a nomogram, while data from 170 patients (Group B) were used for its external validation. RESULTS: High-grade papillary bladder cancer was pathologically diagnosed in 51.6 and 74.6% of Group A and Group B patients, respectively. Based on univariable analyses in Group A, macrohematuria, tumor size, multiple tumors, appearance, and positive urinary cytology were selected as variables to incorporate into a nomogram. The AUC value was 0.81 for the internal validation (Group A), and 0.78 for the external validation (Group B). This novel nomogram can predict high-grade papillary bladder cancer accurately. CONCLUSIONS: The present nomogram can help clinicians calculate the probability in patients with bladder cancer before TUR-Bt and decide on earlier intervention and priorities for the treatment of patients diagnosed with bladder cancer.

External validation of two web-based postoperative nomograms predicting the probability of early biochemical recurrence after radical prostatectomy: a retrospective cohort study.

The present study aimed to validate and compare the predictive accuracies of the Memorial Sloan Kettering Cancer Center (MSKCC) and Johns Hopkins University (JHU) web-based postoperative nomograms for predicting early biochemical recurrence (BCR) after radical prostatectomy (RP) and to analyze clinicopathological factors to predict early BCR after RP using our dataset. The c-index was 0.72 (95% confidence (CI): 0.61-0.83) for the MSKCC nomogram and 0.71 (95% CI: 0.61-0.81) for the and JHU nomogram, demonstrating fair performance in the Japanese population. Furthermore, we statistically analyzed our 174 patients to elucidate prognostic factors for early BCR within 2 years. Lymphovascular invasion (LVI) including lymphatic vessel invasion (ly) was a significant predictor of early BCR in addition to common variables (pT stage, extraprostatic extension, positive surgical margin and seminal vesicle invasion). LVI, particularly ly, may provide a good predictor of early BCR after RP and improve the accuracy of the nomograms.

Abiraterone Followed by Enzalutamide Versus Enzalutamide Followed by Abiraterone in Chemotherapy-naive Patients With Metastatic Castration-resistant Prostate Cancer.

BACKGROUND: Abiraterone (AA) and enzalutamide (ENZA) are increasingly being used in chemotherapy-naive patients with metastatic castration-resistant prostate cancer owing to efficacy and favorable toxicity. However, the order in which they should be administered has not been determined. PATIENTS AND METHODS: We retrospectively reviewed the records of chemotherapy-naive patients with metastatic castration-resistant prostate cancer who had received sequential treatment with either AA followed by ENZA (AA-ENZA) or the converse (ENZA-AA). Prostate-specific antigen (PSA) response rates (defined as ≥ 50% PSA decline from baseline), first-line progression-free survival (PFS), second-line PFS, combined PFS (defined as first-line PFS plus second-line PFS), and overall survival are compared between the 2 sequence groups. RESULTS: A total of 97 patients received sequential treatment with AA and ENZA; 50 patients were in the AA-ENZA group, and 47 patients were in the ENZA-AA group. The PSA response rate to first-line treatment was not significantly different between AA (48%) and ENZA (51%) (P = .840). However, a significant difference was observed in the PSA response rate to second-line treatment (AA, 6.4% vs. ENZA, 30%; P = .004). The median combined PFS was not significantly different between sequence groups (hazard ratio, 0.71; 95% confidence interval, 0.46-1.08; log-rank P = .105). The order of addition also had no significant effect on median overall survival (hazard ratio, 0.98; 95% confidence interval, 0.64-1.52; log-rank P = .834). CONCLUSION: With the exception of the second-line PSA response, there was no significant difference in clinical outcomes between the AA-ENZA and ENZA-AA groups. Our results might be useful reference in daily practice, especially for patients who do not have a suitable general condition for chemotherapy.

Comparison of Sequential Treatment With Androgen Receptor-Targeted Agent Followed by Another Androgen Receptor-Targeted Agent Versus Androgen Receptor-Targeted Agent Followed by Docetaxel in Chemotherapy-Naive Patients With Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: An important clinical question of great interest to clinicians is how to best sequence androgen receptor targeted agents (ARTAs) and chemotherapy for metastatic castration-resistant prostate cancer (mCRPC), but the answer is still unclear. MATERIALS AND METHODS: To evaluate and compare the clinical outcomes of ARTA and docetaxel (DTX) as second-line treatment in the post first-line ARTA, we conducted a retrospective analysis of chemotherapy-naive mCRPC patients who had received sequential treatment with ARTA followed by another ARTA (ARTA-ARTA) or ARTA followed by DTX (ARTA-DTX). RESULTS: A total of 97 patients were treated with the ARTA-ARTA sequence and 42 with the ARTA-DTX sequence. A prostate-specific antigen (PSA) response to the second-line treatment was observed in 18.6% in the ARTA-ARTA and in 33.3% in the ARTA-DTX sequence, but the difference in PSA response was not statistically significant (P = .057). The median progression-free survival (PFS) was significantly different between ARTA and DTX in the second-line treatment (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.24-0.59; P < .001). The favorable outcome in the ARTA-DTX sequence compared with the ARTA-ARTA sequence remained (HR, 0.51, 95% CI, 0.33-0.80; P = .004) in the combined PFS (first-line PFS + second-line PFS). However, no statistically significant difference in overall survival (OS) between the 2 groups was observed (HR, 0.60; 95% CI, 0.34-1.09; P = .095). In multivariate analysis, the ARTA-DTX sequence was identified as an independent prognostic factor for combined PFS, but not OS. CONCLUSION: ARTA-DTX might improve clinical outcomes in terms of second-line PFS and combined PFS, compared with the ARTA-ARTA sequence. However, this significance was not observed for OS.

Development of novel nomograms to predict renal functional outcomes after laparoscopic adrenalectomy in patients with primary aldosteronism.

PURPOSE: Most patients with primary aldosteronism (PA) show a significant decrease in kidney function after surgery. Glomerular hyperfiltration peculiar to PA can mask mild renal failure before surgery. The aim of this retrospective study was to investigate postoperative renal functional outcomes in PA patients from different viewpoints and to develop novel nomograms that can predict renal functional outcomes in PA patients after surgery. METHODS: 130 Japanese PA patients treated by unilateral laparoscopic adrenalectomy were retrospectively surveyed. Pre- and postoperative changes of estimated glomerular filtration rates (eGFRs) and the distribution of eGFR classification were compared. Furthermore, predictors of the following renal functional outcomes were investigated: (I) the percentage decrease >25% in eGFR and (II) the presence of new-onset eGFR <45 ml/min/1.73 m2. Finally, two nomograms that predicted postoperative renal functional outcomes were developed and internally validated. RESULTS: At 6 months, the average decrease in eGFR was 16.7 mL/min/1.73 m2 (corresponding percent decrease: 19.7%). Upstaging of eGFR classification was observed in 54.6% of patients. Age, potassium, plasma aldosterone concentration, and initial eGFR were incorporated into a nomogram predicting a >25% postoperative decrease in eGFR. Duration of hypertension and initial eGFR were incorporated into a nomogram predicting new-onset eGFR <45 ml/min/1.73 m2. The value of the area under the receiver operating characteristics curve for each nomogram was 0.82 and 0.74, respectively. CONCLUSION: The first nomograms that can predict postoperative renal outcomes in PA patients were developed. They will help clinicians calculate the probability of renal dysfunction in PA patients after laparoscopic adrenalectomy.

Clinical outcomes of second transurethral resection in non-muscle invasive high-grade bladder cancer: a retrospective, multi-institutional, collaborative study.

BACKGROUND: A retrospective, multi-institutional collaborative study was conducted to evaluate the impact of second transurethral resection (TUR) on the clinical outcome of non-muscle invasive high-grade bladder cancer and to identify predictors of invasion to the lamina propria (pT1) or deeper and residual tumor at the second TUR. METHODS: The clinical and pathological features of 198 patients with non-muscle invasive high-grade bladder cancer treated in five medical institutions from April 1990 to March 2013 were reviewed retrospectively. All patients underwent a second TUR within a mean of 1.5 months after the first resection. Clinicopathological findings of the first and second TURs were compared. Cancer-specific survival and recurrence-free survival were evaluated. Univariate and multivariate analyses for predictors of residual cancer at the second TUR were performed using a logistic regression model. RESULTS: At the second TUR, no tumor was found in 111 (56 %) patients, and 87 (44 %) had residual cancer. At the first TUR, five pT1 patients (3 %) were upstaged to pT2, one pTa patient (1 %) was upstaged to pT1, and 12 G2 patients (6 %) had their tumor upgraded to G3. Patients the group with less than stage pT1 cancer at the second TUR had significantly better survival than those in the group with stage pT1 or deeper cancer. Tumor multiplicity at the first resection was an independent risk factor for pT1 or deeper tumor at the second TUR. CONCLUSION: A second TUR is a valuable diagnostic procedure for accurate staging of non-muscle invasive high-grade bladder cancer. Tumor multiplicity at the first TUR was a significant independent predictor of pT1 or deeper tumor at the second TUR.

Hypertension Cure Following Laparoscopic Adrenalectomy for Hyperaldosteronism is not Universal: Trends Over Two Decades.

BACKGROUND: Laparoscopic adrenalectomy has been established as a standard surgical method for unilateral primary aldosteronism. Meanwhile, the background characteristics of the patients undergoing adrenalectomy have changed over the last 20 years. The aim of this study was to investigate the changes in hypertension cure rates after laparoscopic adrenalectomy during the last two decades. METHODS: This retrospective clinical study included 176 patients who underwent unilateral laparoscopic adrenalectomy for primary aldosteronism from 1995 to 2015. The patients were divided into two groups by decade. The patients' baseline characteristics and the hypertension cure rates were compared between the two groups. Additionally, the values were re-examined based on predictive model predicting postoperative hypertension cure. RESULTS: The hypertension cure rate decreased significantly from 51.8 to 31.1%. The following variables were significantly different between the two groups: age, sex, body mass index, history of diabetes mellitus, preoperative systolic and diastolic blood pressures, potassium level, and plasma renin activity. CONCLUSIONS: This study showed that the number of patients with unfavorable conditions for hypertension cure after adrenalectomy has recently increased. The treatment goal for primary aldosteronism is not only to cure the hypertension but also to prevent organ disorders due to inappropriate aldosterone levels. Therefore, we recommend laparoscopic adrenalectomy for unilateral primary aldosteronism, even if hypertension is not always cured postoperatively. However, clinicians need to fully explain the postoperative hypertension outcomes to primary aldosteronism patients.

Prostate-Specific Antigen Flare Phenomenon Induced by Abiraterone Acetate in Chemotherapy-Naive Patients With Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: Prostate-specific antigen (PSA) flare is a well-known phenomenon in patients with prostate cancer treated with luteinizing hormone-releasing hormone agonist and chemotherapy. However, its incidence and the significance for the clinical outcomes of patients treated with abiraterone acetate (AA) are uncertain. PATIENTS AND METHODS: A multicenter retrospective analysis of chemotherapy-naive patients treated with AA for metastatic castration-resistant prostate cancer (mCRPC) was conducted. The baseline characteristics, treatment history of mCRPC, and serum PSA kinetics during AA treatment were collected. The log-rank test was applied to compare progression-free survival (PFS) between patient groups with a PSA flare according to the different definitions and immediate PSA declines. RESULTS: The data from 83 patients were analyzed. An immediate PSA decline of any amount was observed in 59 patients (71.1%). According to the various definitions of PSA flare, its incidence ranged from 6.0% to 10.8%. Although the median interval to the peak PSA level was 0.95 month, regardless of the PSA flare definition, the interval to the PSA nadir showed a wide range of 2.8 to 7.6 months. In PSA flare subgroup, the median PFS in patients with any PSA decline to less than the baseline and > 30% decline from the baseline was 12.4 months. The PFS duration of PSA flare patients did not significantly differ from that of patients with an immediate PSA decline of any amount and immediate > 30% decline without PSA flare. CONCLUSION: The PSA flare phenomenon is not rare event during AA treatment. A PSA decline during AA treatment, with or without a PSA flare, was associated with favorable clinical outcomes. Thus, AA should not be withdrawn early in patients with mCRPC in whom an initial, isolated PSA increase has been observed.

Abiraterone acetate after progression with enzalutamide in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer: a multi-center retrospective analysis.

BACKGROUND: Both abiraterone acetate (AA) and enzalutamide are promising agents for patients with pre- and post-chemotherapy metastatic castration-resistant prostate cancer (mCRPC). Several retrospective analysis suggested clinical cross-resistance between these agents in patients previously treated with docetaxel. However, data on the antitumor activity of AA as a second androgen receptor-targeting new agent after the failure of enzalutamide in chemotherapy-naive mCRPC patients is unavailable. METHODS: Patients with chemotherapy-naïve mCRPC who were treated with AA after disease progression with enzalutamide, were retrospectively reviewed at five institutions. Primary outcome measure was the rate of any prostate-specific antigen (PSA) decline. Secondary outcome measures were progression-free survival (PFS) and overall survival (OS) with subsequent AA treatment. We also performed correlation analysis between previous PSA response, PFS duration to enzalutamide and subsequent PSA response, PFS duration to AA. RESULTS: A total of 14 patients were identified. Any PSA declines and PSA decline ≥50 % with AA treatment, were observed in 36 and 7 % of patients, respectively. Median PFS with initial enzalutamide was 5.0 months (95 % CI 3.7-6.4 months), and for subsequent AA treatment was 3.4 months (95 % CI 0.8-6.0 months). Median OS from initiation of AA was 9.1 months (95 % CI 5.6-12.5 months). No significant correlations were observed between these PSA responses (Pearson r = -0.67, p = 0.82) and PFS duration (Kendall tau r = 0.33, p = 0.87). CONCLUSIONS: The PSA decline with subsequent AA treatment in chemotherapy-naive mCRPC patients after a failure of enzalutamide was modest, however, the PFS and OS with subsequent AA treatment were comparable to those of enzalutamide previously reported as a second androgen receptor-targeting new agent after AA failure. The PSA response and PFS duration to previous enzalutamide treatment did not predict those of subsequent AA treatment.