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A multicenter study of nonmetastatic castration-resistant prostate cancer (nmCRPC) was conducted to identify the optimal cut-off value of prostate-specific antigen (PSA) doubling time (PSADT) that correlated with the prognosis in Japanese nmCRPC. Of the 515 patients diagnosed and treated for nmCRPC at 25 participating Japanese Urological Oncology Group centers, 450 patients with complete clinical information were included. The prognostic values of clinical factors were evaluated with respect to prostate specific antigen progression-free (PFS), cancer-specific survival (CSS), and overall survival (OS). The optimal cutoff value of PSADT was identified using survival tree analysis by Python. The Median PSA and PSADT at diagnosis of nmCRPC were 3.3 ng/ml, and 5.2 months, respectively. Patients treated with novel hormonal therapy (NHT) showed significantly longer PFS (HR: hazard ratio 0.38, p < 0.0001) and PFS2 (HR 0.45, p < 0.0001) than those treated with vintage nonsteroidal antiandrogen agent (Vintage). The survival tree identified 4.65 months as the most prognostic PSADT cutoff point. Among the clinical and pathological factors PSADT of < 4.65 months remained an independent prognostic factor for OS (HR 2.96, p = 0.0003) and CSS (HR 3.66, p < 0.0001). Current data represented optimal cut-off of PSADT 4.65 months for a Japanese nmCRPC.
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Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración , Humanos , Masculino , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/sangre , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Neoplasias de la Próstata Resistentes a la Castración/patología , Anciano , Persona de Mediana Edad , Japón/epidemiología , Pronóstico , Anciano de 80 o más Años , Pueblos del Este de AsiaRESUMEN
BACKGROUND: It remains unclear which patients with biochemical recurrence after prostatectomy are most suitable for salvage radiotherapy. We evaluated the parameters related to outcomes. METHODS: We retrospectively evaluated patients who underwent salvage therapy for biochemical recurrence after prostatectomy between 2005 and 2019. This study aimed to evaluate biochemical recurrence-free survival (bRFS) after salvage radiotherapy and elucidate the parameters associated with bRFS. The bRFS rate was calculated using the Kaplan-Meier method, and the parameters associated with bRFS were evaluated using Cox regression analysis. RESULTS: This study included 67 patients treated with salvage radiotherapy with a median age of 67 years at salvage radiotherapy. The median follow-up period after salvage radiotherapy was 7.3 years. The 5-year bRFS rate following salvage radiotherapy was 47.1%. Univariate analysis showed that PSA doubling time < 6 months, positive surgical margin, and pathological Gleason score ≥ 8 were significantly associated with shorter bRFS (p < 0.001, p = 0.036, p = 0.047, respectively). Multivariable analysis showed that a PSA doubling time < 6 months and positive surgical margins were significantly associated with shorter bRFS (p = 0.001 and p = 0.018, respectively). No serious adverse events were observed. CONCLUSIONS: In our hospital, approximately half of the patients are under long-term control with salvage radiotherapy. A PSA doubling time of < 6 months and positive surgical margins were suggested to be associated with poor outcomes of salvage radiotherapy.
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Recurrencia Local de Neoplasia , Antígeno Prostático Específico , Prostatectomía , Neoplasias de la Próstata , Terapia Recuperativa , Humanos , Masculino , Terapia Recuperativa/métodos , Prostatectomía/métodos , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/sangre , Anciano , Estudios Retrospectivos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/radioterapia , Antígeno Prostático Específico/sangre , Clasificación del Tumor , Supervivencia sin Enfermedad , Márgenes de EscisiónRESUMEN
Background: The benefits of novel androgen receptor axis-targeted agents (ARATs) on oncological outcomes in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) in real-world settings are unclear. Methods: This multi-institutional retrospective study included 178 patients with nmCRPC treated between September 2003 and August 2022. Patients were divided into two groups: those who were treated with any novel ARATs, including apalutamide, enzalutamide, darolutamide, and abiraterone acetate, during any line of nmCRPC treatment (novel ARATs group) and those who were not (control group). Multivariable Cox proportional hazards regression analyses were performed to evaluate the effects of novel ARATs on metastasis-free survival (MFS) and overall survival (OS). Results: The median age and follow-up period after nmCRPC diagnosis were 76 years and 37 months, respectively. Of the 178 patients, 122 (69%) were treated with novel ARATs after nmCRPC diagnosis. The MFS and OS in the novel ARATs group were significantly longer than those in the control group (P < 0.001 and P = 0.020, respectively). In multivariable analyses, a prostate-specific antigen doubling time (PSADT) of <3 months and novel ARATs were independently and significantly associated with MFS and OS. The effects of novel ARATs on MFS were consistently observed across subgroups stratified by age (<75 years or ≥75 years), history of radical treatment (no or yes), biopsy Gleason score (<9 or ≥9), clinical stage (≤cT3 and cN0, or cT4 or cN1), and PSADT (≥3 months or <3 months). Conclusion: Novel ARATs were significantly associated with improved oncological outcomes in patients with nmCRPC in a real-world setting, regardless of tumor aggressiveness.
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In patients with prostate cancer (PCa), salvage radiotherapy (SRT) for biochemical progression (BP) after radical prostatectomy (RP) improves PCa-specific survival. However, no prospective randomized trials have compared the effect of SRT with untreated patients. In this analysis of 151 patients who received SRT for post-RP BP, we compared their overall survival (OS) with virtual, age-matched controls (n = 151,000) retrieved from government life tables. We also investigated the risk factors associated with BP and OS and compared the prostate-specific antigen (PSA) doubling times (DTs) before and after SRT for patients with BP. The median follow-up was 9.3 years for BP and 17.4 years for OS. The risk factors significantly affecting BP were Gleason score (p < 0.001), pre-SRT PSA (p = 0.003), and negative surgical margins (p = 0.003). None of these risk factors were associated with OS. In 93 patients with BP after SRT, the median PSADT was significantly prolonged compared with pre-SRT values (3.7 vs. 8.3 months, p < 0.001). The OS did not differ between patients and controls (p = 0.112), and life expectancy was similar, likely due to the survival benefit of SRT. The prolonged PSADT after SRT further supports the beneficial role of SRT in this patient population. However, subsequent treatments were not systematically recorded, which may have affected the results.
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BACKGROUND: Prostate cancer is a prevalent cancer in men worldwide, and castration-resistant prostate cancer (CRPC) is characterized by disease progression despite androgen deprivation therapy. While clinical and prognostic biomarkers have been identified in CRPC, the significance of serum inflammatory markers remains unclear. MATERIALS AND METHODS: This retrospective study included 79 CRPC patients treated with abiraterone or enzalutamide. Inflammatory markers, including the modified Glasgow prognostic score (mGPS), systemic immune-inflammation index (SII), and neutrophil-to-lymphocyte ratio (NLR), were assessed as predictive tools for treatment response. Patient data were obtained from medical charts, and statistical analyses were performed. RESULTS: The median age of the patients was 67 years, with most having a Gleason score of 8-10. The median values for NLR, PLR, and SII were 2.9, 168.5, and 713.5, respectively. The objective response rate (ORR) to abiraterone or enzalutamide therapy was 55.1%. mGPS showed a significant association with ORR, with the mGPS 0 group having the highest response rate (59.5%). Median progression-free survival (PFS) was 12.8 months, and median overall survival (OS) was 35.4 months. Palliative radiotherapy during therapy and PSA doubling time were independent prognostic factors for PFS. CONCLUSIONS: mGPS and PSA doubling time significantly impacted survival, and mGPS significantly predicted the treatment response in mCRPC, which may lead to further prospective studies.
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Androstenos , Benzamidas , Feniltiohidantoína , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Anciano , Neoplasias de la Próstata Resistentes a la Castración/patología , Antígeno Prostático Específico , Antagonistas de Andrógenos , Estudios Retrospectivos , Estudios Prospectivos , Nitrilos , Biomarcadores , Resultado del Tratamiento , Acetato de Abiraterona/uso terapéuticoRESUMEN
OBJECTIVE: To assess the influence of biochemical recurrence (BCR) risk groups and PSA kinetics on the outcomes of radioguided surgery against prostate-specific membrane antigen (PSMA-RGS). Currently, neither BCR risk group nor PSA doubling time (PSA-DT), or PSA velocity (PSA-V) are actively assigned or relevant for counseling prior to PSMA-RGS. METHODS: We retrospectively analyzed PSMA-RGS cases for oligorecurrent prostate cancer between 2014 and 2023. BCR risk groups, PSA-DT, and PSA-V were analyzed as predictors for complete biochemical response (cBR, PSA < 0.2 ng/mL), BCR-free, and therapy-free survival (BCRFS, TFS). RESULTS: Of 374 included patients, only 21/374 (6%) and 201/374 (54%) were classified as low- and high-risk BCR (no group assignment possible in 152/374, 41%). A total of 13/21 (62%) patients with low- and 120/201 (60%) with high-risk BCR achieved cBR (p = 1.0). BCR classification was no predictor for BCRFS (HR:1.61, CI: 0.70-3.71, p = 0.3) or subsequent TFS (HR:1.07, CI: 0.46-2.47, p = 0.9). A total of 47/76 (62%) patients with PSA-DT ≤ 6 mo and 50/84 (60%) with PSA-DT > 6 mo achieved cBR (p = 0.4). PSA-DT was not associated with cBR (OR: 0.99, CI: 0.95-1.03, p = 0.5), BCRFS (HR: 1.00, CI: 0.97-1.03, p = 0.9), or TFS (HR: 1.02, CI: 0.99-1.04, p = 0.2). Consistent negative findings were recorded for PSA-V. CONCLUSIONS: The BCR risk groups and PSA kinetics do not predict the oncological success of PSMA-RGS performed at low absolute PSA values. Indolent low-risk BCR is rarely treated by PSMA-RGS.
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In biochemical recurrence of prostate cancer (BCR), prompt tumor localization guides early treatment, potentially improving patient outcomes. Gallium-68 prostate-specific membrane antigen-11 positron emission tomography/computed tomography (68Ga-PSMA-11 PET/CT) detection rates of lesions suspicious for prostate cancer are well known to rise along with prostate-specific antigen (PSA) concentration. However, published data are limited regarding very low values (≤0.2 ng/mL). We retrospectively analyzed ~7-year "real-world" experience in this setting in a large post-prostatectomy cohort (N = 115) from two academic clinics. Altogether 44 lesions were detected in 29/115 men (25.2%) (median [minimum-maximum] 1 [1-4]/positive scan). The apparent oligometastatic disease was found in nine patients (7.8%) at PSA as low as 0.03 ng/mL. Scan positivity rates were highest when PSA was >0.15 ng/mL, PSA doubling time was ≤12 months, or the Gleason score was ≥7b (in 83 and 107 patients, respectively, with available data); these findings were statistically significant (p ≤ 0.04), except regarding PSA level (p = 0.07). Given the benefits of promptly localizing recurrence, our observations suggest the potential value of 68Ga-PSMA-11 PET/CT in the very low PSA BCR setting, especially in cases with more rapid PSA doubling time or with high-risk histology.
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Background: In recent years, site-directed therapies (SDTs) targeting progressive lesions in patients with oligometastatic prostate cancer have attracted attention. However, whether they effectively treat oligoprogressive castration-resistant prostate cancer (CRPC) remains unclear. Here, we investigated the efficacy of SDT in patients with oligoprogressive CRPC and identified prognostic factors. Methods: We reviewed 59 patients with oligoprogressive CRPC who underwent SDT targeting prostate or metastatic lesions between April 2014 and March 2022. We evaluated the associations between several pretreatment clinical variables and treatment procedures and a >50% prostate-specific antigen (PSA) response, progression-free survival (PFS), and time to next treatment (TTNT). Results: A PSA response of >50% was observed in 66% of patients. The median PFS and TTNT were 8.3 months and 9.9 months, respectively. Patients with PSA doubling time ≥6 months showed a higher >50% PSA response rate (87% vs. 45%; P < 0.001), longer PFS (median, 15.0 vs. 5.0 months; P < 0.001), and longer TTNT (median, 16.3 vs. 5.9 months; P < 0.001) than patients with PSA doubling time <6 months. In multivariate analyses, a PSA doubling time of ≥6 months independently predicted a >50% PSA response, favorable PFS, and TTNT (P = 0.037, 0.025, and 0.017, respectively). Conclusion: PSA doubling time of ≥6 months may be a key indicator of the favorable efficacy of SDT for oligoprogressive CRPC.
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Objectives: The objective of this study is to find clinical variables that predict the prognosis for men with castration-resistant prostate cancer (CRPC) in a Swedish real-life CRPC cohort, including a risk group classification to clarify the risk of succumbing to prostate cancer. This is a natural history cohort representing the premodern drug era before the introduction of novel hormonal drug therapies. Methods: PSA tests from the clinical chemistry laboratories serving health care in six regions of Sweden were retrieved and cross-linked to the National Prostate Cancer Registry (NPCR) to identify men with a prostate cancer diagnosis. Through further cross-linking with data sources at the Swedish Board of Health and Welfare, we retrieved other relevant information such as prescribed drugs, hospitalizations, and cause of death. Men entered the CRPC cohort at the first date of doubling of their PSA nadir value with the last value being >2 ng/ml, or an absolute increase of >5 ng/ml or more, whilst on 3 months of medical castration or if they had been surgically castrated (n = 4098). By combining the two variables with the largest C-statistics, "PSA at time of CRPC" and "PSA doubling time," a risk group classification was created. Results: PSA-DT and PSA at date of CRPC are the strongest variables associated with PC specific survival. At the end of follow-up, the proportion of men who died due to PC was 57%, 71%, 81%, 86%, and 89% for risk categories one through five, respectively. The median overall survival in our cohort of men with CRPC was 1.86 years (95% CI: 1.79-1.97). Conclusion: For a man with castration-resistant prostate cancer, there is a high probability that this will be the main cause contributing to his death. However, there is a significant difference in mortality that varies in relation to tumor burden assessed as PSA doubling time and PSA at time of CRCP. This information could be used in a clinical setting when deciding when to treat more or less aggressively once entering the CRPC phase of the disease.
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Optimal therapy of biochemically relapsed prostate cancer (BRPC) after local treatment is elusive. An established modified citrus pectin (PectaSol®, P-MCP), a dietary polysaccharide, is an established antagonist of galectin-3, a carbohydrate-binding protein involved in cancer pathogenesis. Based on PSA dynamics, we report on the safety and the primary outcome analysis of a prospective phase II study of P-MCP in non-metastatic BRPC based. Sixty patients were enrolled, and one patient withdrew after a month. Patients (n = 59) were given P-MCP, 4.8 grams X 3/day, for six months. The primary endpoint was the rate without PSA progression and improved PSA doubling time (PSADT). Secondary endpoints were the rate without radiologic progression and toxicity. Patients that did not progress by PSA and radiologically at six months continued for an additional twelve months. After six months, 78% (n = 46) responded to therapy, with a decreased/stable PSA in 58% (n = 34), or improvement of PSADT in 75% (n = 44), and with negative scans, and entered the second twelve months treatment phase. Median PSADT improved significantly (p = 0.003). Disease progression during the first 6 months was noted in only 22% (n = 13), with PSA progression in 17% (n = 10), and PSA and radiologic progression in 5% (n = 3). No patients developed grade 3 or 4 toxicity.
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Adenocarcinoma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Pectinas/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Adenocarcinoma/patología , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estudios Prospectivos , Neoplasias de la Próstata/patología , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of present study was to determine and compare the overall response rates, progression-free survival (PFS), overall survival (OS), and clinical toxicity of the combination of 177Lu-PSMA-617 radioligand therapy (PRLT) and abiraterone acetate (AA) versus 177Lu-PSMA-617 PRLT as monotherapy in metastatic castration-resistant prostate cancer (mCRPC) patients. MATERIALS AND METHODS: The mCRPC patients who received at least one cycle of 177 Lu-PSMA-617 PRLT with or without AA therapy, were included and analyzed in the present study. The patients were divided into two major groups. Group 1 received only 177 Lu-PSMA PRLT and Group 2 received combined 177 Lu-PSMA PRLT + AA therapy. Therapeutic dose of 177 Lu-PSMA-617 PRLT was 4.4-5.55 GBq per patient per cycle administered at intervals of 10-12 weeks in both groups. The Group 2 patients additionally received a dose of 1000 mg of AA once daily and 5 mg of prednisone twice daily. Treatment response in two groups was evaluated under four broad categories (a) symptomatic, (b) biochemical (serum prostate-specific antigen level), (c) objective molecular imaging (68 Ga-PSMA-11 and 18 F-FDG PET/CT), and (d) objective anatomical imaging (computed tomography). For assessing treatment response, patients in two groups were categorized into responders (complete response [CR], partial response [PR], and stable disease [SD]) and nonresponders (progressive disease [PD]). The Kaplan-Meier product-limit method was used to calculate PFS and OS following first 177 Lu-PSMA PRLT in the two groups. Univariate analysis was used to compare the patients' characteristics in two groups using a χ2 or Fisher exact test. The Kaplan-Meier curves of PFS and OS between two groups were compared by using the log-rank test (p < 0.05 significant). RESULTS: A total of 58 mCRPC patients (Group 1, 38 patients and Group 2, 20 patients) were included in this study analysis. The clinical and demographic characteristics of these patients (age, Gleason score, FDG avid disease, metastatic disease burden, and average number of 177 Lu-PSMA PRLT cycles) in two groups were compared and found to be similar (p > 0.05). Post-treatment, symptomatic, biochemical, molecular, and anatomic imaging responders were found in 22 patients (58%) and 17 patients (85%), 22 patients (58%) and 16 patients (80%), 19 patients (54%) and 14 patients (78%), and 19 patients (54%) and 14 patients (78%) in Group 1 and Group 2, respectively. The median PFS of 7 months and median OS of 8 months were documented in Group 1, whereas median PFS was not reached and median OS of 16 months registered in Group 2. Transient hematological toxicity of Grades 1 and 2 was found in total seven patients (five patients in Group 1 and two patients in Group 2). On comparison of the treatment outcome between two groups, significant p value was found for symptomatic responders (58% in Group 1 vs. 85% in Group 2), median PFS (7 months in Group 1 vs. not reached in Group 2), and median OS (8 months in Group 1 vs. 16 months in Group 2), with better outcome in Group 2 patients for these variables. CONCLUSION: In the present study, the combination of 177 Lu-PSMA-617 PRLT and AA therapy showed significant improvement in mCRPC patients' symptomatic response, PFS, and OS as compared to 177 Lu-PSMA-617 PRLT monotherapy.
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Acetato de Abiraterona/uso terapéutico , Antineoplásicos/uso terapéutico , Lutecio/uso terapéutico , Antígeno Prostático Específico/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Radiofármacos/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Supervivencia sin Progresión , Neoplasias de la Próstata Resistentes a la Castración/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Routine use of neoadjuvant hormonal therapy (NHT) before radical prostatectomy (RP) is not recommended, but it is sometimes performed to reduce the prostate size and tumor volume or to prevent tumor progression during the wait times for surgery in clinical practice. On the other hand, the impact of NHT on the pattern of biochemical recurrence (BCR) is unknown. METHODS: We retrospectively examined 1749 consecutive patients who underwent RP between 1996 and 2017. Among the patients who met the inclusion criteria, BCR developed in 240 of non-NHT patients and in 120 of NHT patients during the mean follow-up period of 6.9 years. We examined the impact of NHT on the PSA-doubling time (DT) following BCR at different times after RP. RESULTS: The median PSA-DTs in non-NHT patients who experienced BCR in the first year after surgery, between 1 and 2 years, between 2 and 3 years, between 3 and 4 years, between 4 and 5 years, and at > 5 years were 5.5, 8.8, 11.3, 17.7, 18.2, and 18.4 months, respectively. On the other hand, those in NHT patients were 1.4, 4.1, 9.1, 13.4, 27.2, and 19.3 months, respectively. The differences of PSA-DTs in the first year after surgery (p < 0.001) and between 1 and 2 years (p = 0.005) were significant between non-NHT and NHT patients. CONCLUSION: Patients who received NHT had a higher risk of a rapid PSA increase when they experienced BCR, especially within 2 years after RP. In order to not miss the optimal timing of salvage treatment for BCR, intensive PSA follow-up is necessary.
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PURPOSE: 18F-Fluciclovine PET imaging has been increasingly used in the restaging of prostate cancer patients with biochemical recurrence (BCR); however, its clinical utility in patients with low prostate-specific antigen (PSA) levels following primary radiation therapy has not been well-studied. This study aims to determine the detection rate and diagnostic accuracy of 18F-fluciclovine PET and the patterns of prostate cancer recurrence in patients with rising PSA after initial radiation therapy, particularly in patients with PSA levels below the accepted Phoenix definition of BCR (PSA nadir +2 ng/mL). METHODS: This retrospective study included patients from two tertiary institutions who underwent 18F-fluciclovine PET scans for elevated PSA level following initial external beam radiation therapy, brachytherapy, and/or proton therapy. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to determine the diagnostic accuracy of 18F-fluciclovine PET and associations of PSA kinetic parameters with 18F-fluciclovine PET outcome. RESULTS: One hundred patients were included in this study. The overall detection rate on a patient-level was 79% (79/100). 18F-Fluciclovine PET was positive in 62% (23/37) of cases with PSA below the Phoenix criteria. The positive predictive value of 18F-fluciclovine PET was 89% (95% CI: 80-94%). In patients with PSA below the Phoenix criteria, the PSA velocity had the highest predictive value of 18F-fluciclovine PET outcome. PSA doubling time (PSADT) and PSA velocity were associated with the presence of extra-pelvic metastatic disease. CONCLUSION: 18F-Fluciclovine PET can identify recurrent disease at low PSA level and PSA rise below accepted Phoenix criteria in patients with suspected BCR after primary radiation therapy, particularly in patients with low PSADT or high PSA velocity. In patients with low PSADT or high PSA velocity, there is an increased probability of extra-pelvic metastases. Therefore, these patients are more likely to benefit from PET/CT or PET/MRI than pelvic MRI alone.
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Antígeno Prostático Específico , Neoplasias de la Próstata , Humanos , Masculino , Recurrencia Local de Neoplasia/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/radioterapia , Estudios RetrospectivosRESUMEN
BACKGROUND: Radium-223 (Ra-223) is a targeted alpha therapy that has been shown to prolong overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases. However, prognosis after Ra-223 administration varies among patients. The aim of the present study was to assess risk factors associated with the poor prognosis of patients treated with Ra-223. METHODS: We retrospectively reviewed patients' records of treatment with Ra-223 between October 2016 and December 2019. All patients had mCRPC, bone metastasis, and no known visceral metastases, and received up to six cycles of Ra-223 (55 kBq/kg). Prognostic factors for OS were analyzed by Cox proportional hazards model and log-rank test. RESULTS: We identified 42 patients who received at least one cycle of Ra-223 (median six cycles, range 1-6). Approximately two-thirds of patients had received at least two lines of therapy for mCRPC. The median age was 74 years, and the median follow-up duration was 13.6 months. The median OS time was 16.6 months. On multivariate analysis, PSA doubling time (PSADT) (0-3 months) at baseline, number of bone metastases (≥ 20), and treatment line of Ra-223 (4th-5th line) remained significantly correlated with the poor OS (HR 4.354, P = 0.003; HR 2.855, P = 0.020; and HR 4.871, P = 0.001, respectively). CONCLUSIONS: Our study demonstrated that a shorter PSADT, a heavier volume of bone metastases, and a later treatment line before Ra-223 are poor prognostic factors for mCRPC patients. These newly discovered risk factors may help select patients who potentially have long-term OS after Ra-223 treatment.
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Neoplasias Óseas , Neoplasias de la Próstata Resistentes a la Castración , Radio (Elemento) , Anciano , Neoplasias Óseas/radioterapia , Humanos , Masculino , Pronóstico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Radio (Elemento)/uso terapéutico , Estudios RetrospectivosRESUMEN
Current guidelines recommend a repeat biopsy within 3-6 months after an initial diagnosis of atypical small acinar proliferation (ASAP) due to the high incidence of cancer detection on repeat biopsy. The current study sought to investigate practice patterns after a diagnosis of ASAP in a real-world setting and examine the clinicopathological outcomes of repeat biopsy. The departmental database of the Hyogo Prefectural Nishinomiya Hospital identified 97 of 1,218 patients with a diagnosis of ASAP on initial biopsy from 2011 to 2016. Clinical and pathological data were retrospectively analyzed. Of the 97 patients, 34 (35.1%) underwent a repeat biopsy. Patients with a repeat biopsy had a significantly higher prostate-specific antigen (PSA) velocity and shorter PSA doubling time than patients without a repeat biopsy (P=0.0002), and of these 34 patients with a repeat biopsy, 16 (47.1%) were diagnosed as having cancer. Multivariate logistic regression analysis revealed that a small prostate (P=0.0250) and advanced age (P=0.0297) were associated with cancer detection on repeat biopsy. Of the 16 cancers identified, 13 (81.6%) were diagnosed with a Gleason score >6. The results indicated that the implementation of a repeat biopsy for patients with ASAP could be affected by clinical characteristics in real-world settings, despite the current recommendation of guidelines endorsing immediate repeat biopsy. Prostate volume and age would aid in the decision-making process to perform repeat biopsy in patients with high PSA velocity and short PSA doubling time after a diagnosis of ASAP.
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BACKGROUND: To best employ radium-223 dichloride (Ra-223) for patients with castration-resistant prostate cancer (CRPC) and bone metastasis, we investigated the bone-predominant status in patients treated with Ra-223. METHODS: We retrospectively evaluated 127 CRPC patients who underwent treatment with Ra-223. The patients were divided into three groups based on the types of dynamic changes of bone metastasis between diagnosis and just before Ra-223: (a) only known lesions; (b) de novo lesions; (c) new progressive lesions. We developed the risk assessment using predictive factors based on progression-free survival (PFS). RESULTS: During the median follow-up period of 10.4 months, the median PFS in the only known lesions group was 11.3 months compared to 8.1 months in the de novo lesions group and 5.1 months in the new progressive lesions group (P < .001). In multivariate analysis, the type of the new progressive lesions in bone metastasis (HR 1.45, 95% CI 1.13-1.66, P = .003), performance status of >1 (HR 1.74, 95% CI 1.04-2.89, P = .034), PSA value of >100 ng/mL (HR 1.59, 95% CI 1.02-2.50, P = .043), and PSA doubling time (PSADT) of <3 months (HR 1.53, 95% CI 1.11-2.03, P = .007) were independent unfavorable predictive factors for PFS. The risk assessment for PFS was highlighted when the type of dynamic changes of bone metastasis was combined with PSADT just before Ra-223 treatment. This was associated with non-bone metastasis progression, especially visceral metastasis, and overall survival. CONCLUSIONS: Risk assessment in combination with dynamic changes of bone metastasis and PSADT determines the bone-predominant metastasis type to benefit from Ra-223.
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Neoplasias Óseas/radioterapia , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Radiofármacos/uso terapéutico , Radio (Elemento)/uso terapéutico , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/secundario , Toma de Decisiones Clínicas , Humanos , Masculino , Supervivencia sin Progresión , Neoplasias de la Próstata Resistentes a la Castración/patología , Radioisótopos/efectos adversos , Radioisótopos/uso terapéutico , Radiofármacos/efectos adversos , Radio (Elemento)/efectos adversos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
BACKGROUND: Biochemical recurrence (BCR) after radical prostatectomy (RP) is most commonly diagnosed by detecting an increase in asymptomatic prostate-specific antigen (PSA). We previously reported the "optimal PSA follow-up schedule after RP". The aim of this study was to confirm the usefulness and safety of that follow-up schedule in another cohort. METHODS: We retrospectively reviewed the clinicopathological data of 798 consecutive patients who underwent radical prostatectomy between 2009 and 2017. We examined all PSA values measured during follow-up. Furthermore, we estimated the PSA value when we observed the "optimal PSA follow-up schedule" at each timing in the virtual follow-up. BCR was defined as an elevation of PSA to greater than 0.2 ng/ml, and the ideal PSA range for detection of BCR was regarded to be 0.2-0.4 ng/ml. RESULTS: During the mean follow-up period of 5.8 years, BCR occurred in 115 (14.9%) patients and the frequency of virtual follow-up was significantly lower than the actual frequency. However, overlooking of BCR (detecting BCR when PSA exceeded 0.4 ng/ml) was observed in 17 patients, which is higher than the actual frequency of overlooking (12 patients). Therefore, we modified the follow-up schedule, which could achieve the lower follow-up frequency and a limited number of overlooking of BCR (7 patients). CONCLUSION: This external validation study revealed that the "modified optimal PSA follow-up schedule after RP" can reduce the frequency of PSA measurement with a limited risk of overlooking BCR.
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Calicreínas/sangre , Antígeno Prostático Específico/sangre , Prostatectomía/métodos , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Biomarcadores de Tumor/sangre , Estudios de Seguimiento , Humanos , Masculino , Recurrencia Local de Neoplasia/patología , Estudios RetrospectivosRESUMEN
PURPOSE: To examine the prognosis after BCR with and without salvage therapy, including radiation and/or androgen deprivation. METHODS: The study population consisted of 431 patients, all of whom underwent radical prostatectomy and developed BCR (PSA > 0.2 ng/mL). According to the two risk factors [Gleason score ≥ 8 and PSA-doubling time (DT) < 6 months], we divided the patients into two groups. The high/intermediate-risk group consisted of patients with both or one risk factor. On the other hand, patients with neither factor were in the low-risk group. We set the starting point at the timing of BCR, and the endpoints were development to castration-resistant prostate cancer (CRPC) and cancer-specific death. RESULTS: During the mean follow-up period of 8.3 years after BCR, CRPC was observed in 49 patients (11.4%), and 21 patients (4.9%) died due to prostate cancer. We first divided the 191 high/intermediate-risk patients according to the PSA level (PSA < 1.0 ng/mL, PSA 1.0-4.0, and PSA > 4.0 or no therapy) at the initiation of salvage therapy, including radiation and/or androgen deprivation. We found that delayed (PSA > 4.0 ng/mL) or no salvage therapy was significantly associated with CRPC and cancer-specific death. In the 240 low-risk patients, Kaplan-Meier curves demonstrated no significant difference in CRPC-free survival or cancer-specific survival within 10 years from the timing of BCR. CONCLUSIONS: Observation after BCR without salvage therapy or delayed administration may be an option for low-risk patients with a Gleason score ≤ 7 and PSA-DT ≥ 6 months when their life expectancy is within 10 years.
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Recurrencia Local de Neoplasia/sangre , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/cirugía , Terapia Recuperativa , Anciano , Antagonistas de Andrógenos/uso terapéutico , Terapia Combinada , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/terapia , Pronóstico , Prostatectomía , Neoplasias de la Próstata/clasificación , Neoplasias de la Próstata/terapia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Serum prostate-specific antigen (PSA) may predict the risk of positive positron emission tomography/computed tomography with radiolabelled prostate-specific membrane antigen (PSMA-PET/CT) in patients with biochemical recurrent prostate cancer (BRPCa). However, to date, there are no clear data regarding the correlation between PSA kinetics and PSMA-PET findings. We performed a systematic review and meta-analysis to provide evidence-based data in this setting. METHODS: A comprehensive literature search of studies published through October 2018 in PubMed/MEDLINE, EMBASE and Cochrane library databases was performed. A meta-analysis to establish the detection rate (DR) of PSMA-PET using different cut-off values of PSA doubling time (PSAdt) and a pooled analysis to establish whether shorter PSAdt may predict positive PSMA-PET results was performed in patients with BRPCa. RESULTS: Twelve articles were included in the systematic review, and eight articles (including about 1400 patients) were selected for the meta-analysis. The pooled DR including 95% confidence intervals (95%CI) of PSMA-PET in restaging prostate cancer (PCa) patients was 72% (95%CI:60%-82%), increasing to 83% (95%CI:75%-90%) when PSAdt was ≤6 months and decreasing to 60% (95%CI:37%-80%) when PSAdt was >6 months, without a statistical significant difference. PSAdt ≤6 months may predict the positive result of PSMA-PET (pooled odds ratio: 3.22; 95%CI:1.17-8.88). Statistical heterogeneity among the included studies was found. CONCLUSIONS: PSA kinetics, and in particular shorter PSAdt, may be predictor of PSMA-PET positivity in patients with BRPCa. Further larger studies in this setting are warranted.
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Antígenos de Superficie/metabolismo , Glutamato Carboxipeptidasa II/metabolismo , Antígeno Prostático Específico/metabolismo , Neoplasias de la Próstata/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de PositronesRESUMEN
BACKGROUND: 68Ga-PSMA Positron Emission Tomography/Computerized Tomography (PET/CT) has shown promising results for the detection of recurrent prostate cancer (RPCa). However, the diagnostic value of this method is yet to be validated. The aim of this study was to determine the influence of clinical and biochemical variables on the detection rate of 68Ga-PSMA PET/CT in patients with RPCa. METHODS: This is a prospective study of 121 patients who underwent 68Ga-PSMA-PET/CT and conventional imaging (CI) for RPCa. Detection rates were analyzed and correlated with various clinical and biochemical variables such as Gleason score GS), androgen deprivation therapy (ADT), trigger PSA (tPSA), PSA doubling-time (PSAdt) and PSA velocity (PSAv). RESULTS: 68Ga-PSMA-PET/CT showed at least one focus of pathological 68Ga-PSMA uptake in 92/121 (76%) of patients. Nodal metastases (in 47% of patients) were the most common site of recurrent disease followed by bones (36%) and prostate (32%). Out of 121 patients, 57 (47%) had only positive findings on PSMA scan verified by biopsy or follow-up. The majority of these lesion were located in the lymph nodes (31/57, 54,5%), which were below the detection limit of CT. Univariate analysis showed higher detection rate of PET/CT with increasing tPSA, PSAv and short PSAdt. Best cutoff for tPSA, PSAv and PSAdt was 0.5 ng/ml, 2.25 ng/ml/year and 8.65 months, respectively. The detection rate of PSMA-PET/CT was higher in patients with high grade tumors (GS > 7, 23.7% vs 76.3%) and in patients who were on ADT during of PSMA scan (76.3% vs 96%). In multiple logistic regression analysis, PSAdt and concurrent ADT were identified as predictors of positive 68Ga-PSMA-PET/CT. CONCLUSION: 68Ga-PSMA-PET/CT is useful for re-staging patients with RPCa and has improved performance compared with CI for disease detection. Detection rates are improved in patients on ADT and with short PSAdt.