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European Urology Jun 2024Intensification of therapy may improve outcomes for patients with high-risk localized prostate cancer.
Corrigendum to "Androgen Deprivation and Radiotherapy with or Without Docetaxel for Localized High-risk Prostat Cancer: Long-term Follow-up from the Randomized NRG Oncology RTOG 0521 Trial" [Eur. Eurol. 84(2) (2023) 156-163].
BACKGROUND
Intensification of therapy may improve outcomes for patients with high-risk localized prostate cancer.
OBJECTIVE
To provide long-term follow-up data from phase III RTOG 0521, which compared a combination of androgen deprivation therapy (ADT) + external beam radiation therapy (EBRT) + docetaxel with ADT + EBRT.
DESIGN, SETTING, AND PARTICIPANTS
High-risk localized prostate cancer patients (>50% of patients had Gleason 9-10 disease) were prospectively randomized to 2 yr of ADT + EBRT or ADT + EBRT + six cycles of docetaxel. A total of 612 patients were accrued, and 563 were eligible and included in the modified intent-to-treat analysis.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
The primary endpoint was overall survival (OS). Analyses with Cox proportional hazards were performed as prespecified in the protocol; however, there was evidence of nonproportional hazards. Thus, a post hoc analysis was performed using the restricted mean survival time (RMST). The secondary endpoints included biochemical failure, distant metastasis (DM) as detected by conventional imaging, and disease-free survival (DFS).
RESULTS AND LIMITATIONS
After 10.4 yr of median follow-up among survivors, the hazard ratio (HR) for OS was 0.89 (90% confidence interval [CI] 0.70-1.14; one-sided log-rank p = 0.22). Survival at 10 yr was 64% for ADT + EBRT and 69% for ADT + EBRT + docetaxel. The RMST at 12 yr was 0.45 yr and not statistically significant (one-sided p = 0.053). No differences were detected in the incidence of DFS (HR = 0.92, 95% CI 0.73-1.14), DM (HR = 0.84, 95% CI 0.73-1.14), or prostate-specific antigen recurrence risk (HR = 0.97, 95% CI 0.74-1.29). Two patients had grade 5 toxicity in the chemotherapy arm and zero patients in the control arm.
CONCLUSIONS
After a median follow-up of 10.4 yr among surviving patients, no significant differences are observed in clinical outcomes between the experimental and control arms. These data suggest that docetaxel should not be used for high-risk localized prostate cancer. Additional research may be warranted using novel predictive biomarkers.
PATIENT SUMMARY
No significant differences in survival were noted after long-term follow-up for high-risk localized prostate cancer patients in a large prospective trial where patients were treated with androgen deprivation therapy + radiation to the prostate ± docetaxel.
PubMed: 38897867
DOI: 10.1016/j.eururo.2024.06.009 -
Canadian Urological Association Journal... Jun 2024Individuals at increased risk for prostate cancer (PCa) are inconsistently defined in national and international guidelines. The National Comprehensive Cancer Network... (Review)
Review
Individuals at increased risk for prostate cancer (PCa) are inconsistently defined in national and international guidelines. The National Comprehensive Cancer Network (NCCN) defines people at increased risk for PCa to include those with a concerning family history, Black/African American individuals, and those who have germline mutations in known PCa-related genes. Recommendations for screening are also inconsistently defined in national and international guidelines. The NCCN and American Urological Association state individuals at increased risk for PCa be screened with prostate-specific antigen and digital rectal exam starting at age 40. Defining increased risk groups and defining lifetime risk is an ongoing academic process that can be facilitated through patient registries of these cohorts at academic centers.
PubMed: 38896481
DOI: 10.5489/cuaj.8710 -
Abdominal Radiology (New York) Jun 2024To develop a deep learning (DL) zonal segmentation model of prostate MR from T2-weighted images and evaluate TZ-PSAD for prediction of the presence of csPCa (Gleason...
PURPOSE
To develop a deep learning (DL) zonal segmentation model of prostate MR from T2-weighted images and evaluate TZ-PSAD for prediction of the presence of csPCa (Gleason score of 7 or higher) compared to PSAD.
METHODS
1020 patients with a prostate MRI were randomly selected to develop a DL zonal segmentation model. Test dataset included 20 cases in which 2 radiologists manually segmented both the peripheral zone (PZ) and TZ. Pair-wise Dice index was calculated for each zone. For the prediction of csPCa using PSAD and TZ-PSAD, we used 3461 consecutive MRI exams performed in patients without a history of prostate cancer, with pathological confirmation and available PSA values, but not used in the development of the segmentation model as internal test set and 1460 MRI exams from PI-CAI challenge as external test set. PSAD and TZ-PSAD were calculated from the segmentation model output. The area under the receiver operating curve (AUC) was compared between PSAD and TZ-PSAD using univariate and multivariate analysis (adjusts age) with the DeLong test.
RESULTS
Dice scores of the model against two radiologists were 0.87/0.87 and 0.74/0.72 for TZ and PZ, while those between the two radiologists were 0.88 for TZ and 0.75 for PZ. For the prediction of csPCa, the AUCs of TZPSAD were significantly higher than those of PSAD in both internal test set (univariate analysis, 0.75 vs. 0.73, p < 0.001; multivariate analysis, 0.80 vs. 0.78, p < 0.001) and external test set (univariate analysis, 0.76 vs. 0.74, p < 0.001; multivariate analysis, 0.77 vs. 0.75, p < 0.001 in external test set).
CONCLUSION
DL model-derived zonal segmentation facilitates the practical measurement of TZ-PSAD and shows it to be a slightly better predictor of csPCa compared to the conventional PSAD. Use of TZ-PSAD may increase the sensitivity of detecting csPCa by 2-5% for a commonly used specificity level.
PubMed: 38896250
DOI: 10.1007/s00261-024-04301-z -
Oncology Letters Aug 2024Despite the high prevalence of localised prostate cancer (LPC) and locally advanced prostate cancer (LAPC), evidence on the characteristics of patients, treatments and...
Despite the high prevalence of localised prostate cancer (LPC) and locally advanced prostate cancer (LAPC), evidence on the characteristics of patients, treatments and clinical outcomes stratified by disease risk is limited. The PEarlC study was conducted to characterise a cohort of patients with early-stage prostate cancer that included real-world clinical outcomes. Retrospective data from a cohort of patients diagnosed with LPC/LAPC between 2015 and 2017 and followed up until December 2020 at a Portuguese comprehensive cancer centre (IPO Porto) was analysed. Patients were classified as LPC (high- or non-high-risk) or LAPC according to European Association of Urology guidelines, were eligible if diagnosed at stage I-III and followed up in Urology, Medical Oncology or Radiation Oncology outpatient clinics of IPO Porto. Data was collected from the medical/administrative records database. Clinical outcomes included prostate-specific antigen (PSA) progression-free survival, metastasis-free survival, disease-free survival, progression-free survival, overall survival (OS), PSA response (palliative) and no evidence of residual tumour (prostatectomy). Time-to-event outcomes were compared between subgroups using the log-rank test. A total of 790 patients were included (54.8% non-high-risk LPC, 30.9% high-risk LPC, 14.3% LAPC) and the median follow-up was 46.7 months. Patients had a median age of 68.0 years. The majority of patients were stage II (52.9%) and Eastern Cooperative Oncology Group 0-1 (99.9%) and received treatment with curative intent (85.4%). The median was only achieved in progression-free survival (29.9 months; 95% CI, 26.5-41.0 months), as evaluated in palliative patients. At year 5, 82.9% were free of PSA progression (curative), 87.5% were metastasis-free, 83.7% were disease-free, all patients in palliative treatment progressed and the 5-year OS rate was 92.9% (CI 95%, 90.2-95.7%). Among patients with LPC, OS was worse in high-risk vs. non-high-risk patients (5-year OS rate, 88.8% vs. 96.8%; hazard ratio=3.34, CI 95%, 1.64-7.05; P=0.001). PSA response rate was 81.4% in the palliative setting. There was no evidence of residual tumour in 61.6% of patients who underwent prostatectomy. Although most patients with early-stage prostate cancer treated at IPO Porto showed positive 5-year real-world outcomes, patients with high-risk LPC showed worse OS compared with patients with non-high-risk LPC and therefore a poorer prognosis. The present large-sample real-world study is an important contribution to reducing the evidence gap on prostate cancer.
PubMed: 38895053
DOI: 10.3892/ol.2024.14495 -
Cancers May 2024We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy...
Spatial Distribution of Recurrence and Long-Term Toxicity Following Dose Escalation to the Dominant Intra-Prostatic Nodule for Intermediate-High-Risk Prostate Cancer: Insights from a Phase I/II Study.
We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy (SBRT) to the dominant intra-prostatic nodule (DIN). In 33 patients with intermediate-high-risk prostate cancer (PCa), doses up to 50 Gy were administered to the DIN. Recurrence sites were determined and compared to the original tumor development sites through multiparametric MRI and Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (Ga-PSMA-PET/CT) images. Overlap rates, categorized as 75% or higher for full overlap, and 25-74% for partial overlap, were assessed. Long-term toxicity is reported. : All patients completed treatment, with only one receiving concomitant androgen deprivation therapy (ADT). Recurrences were diagnosed after a median of 33 months (range: 17-76 months), affecting 13 out of 33 patients (39.4%). Intra-prostatic recurrences occurred in 7 patients (21%), with ≥75% overlap in two, a partial overlap in another two, and no overlap in the remaining three patients. Notably, five patients with intra-prostatic recurrences had synchronous bone and/or lymph node metastases, while six patients had isolated bone or lymph node metastasis without intra-prostatic recurrences. Extended follow-up revealed late grade ≥ 2 GU and GI toxicity in 18% (n = 6) and 6% (n = 2) of the patients. : Among patients with intermediate-high-risk PCa undergoing focal dose-escalated SBRT without ADT, DIN recurrences were infrequent. When present, these recurrences were typically located at the original site or adjacent to the initial tumor. Conversely, relapses beyond the DIN and in extra-prostatic (metastatic) sites were prevalent, underscoring the significance of systemic ADT in managing this patient population. Focal dose-escalated prostate SBRT prevented recurrences in the dominant nodule; however, extra-prostatic recurrence sites were frequent.
PubMed: 38893216
DOI: 10.3390/cancers16112097 -
Cancers May 2024The objective of this retrospective study is to assess the effectiveness and safety of two beta-emitting prostate-specific membrane antigen (PSMA) radioligands, [Lu]Lu...
The objective of this retrospective study is to assess the effectiveness and safety of two beta-emitting prostate-specific membrane antigen (PSMA) radioligands, [Lu]Lu and [161Tb]Tb, in heavily treated patients with metastatic castration-resistant prostate cancer (mCRPC). A total of 148 cycles of beta-emitting PSMA radioligand therapy were given to 53 patients at a specialized cancer care center in Amman, Jordan. This treatment was offered following the exhaustion of all prior treatment modalities. Approximately half of the cases (n = 26) demonstrated an initial partial response to PSMA radioligand therapy. Moreover, roughly one-fourth of the patients (n = 13) exhibited a sustained satisfactory biochemical response, which qualified them to receive a total of six PSMA radioligand therapy cycles and maintain continued follow-up for additional treatment cycles. This was reflected by an adequate prostate-specific antigen (PSA) decline and a concomitant partial response evident on [Ga]Ga-PSMA positron emission tomography/computed tomography imaging. A minority of patients (n= 18; 34%) experienced side effects. Generally, these were low-grade and self-limiting toxicities. This study endorses previous research evidence about PSMA radioligand therapy's safety and efficacy. It also provides the first clinical insight from patients of Arab ethnicity. This should facilitate and promote further evidence, both regionally and internationally.
PubMed: 38893095
DOI: 10.3390/cancers16111974 -
International Journal of Molecular... May 2024Astatine (At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the At-labeled prostate-specific membrane antigen (PSMA)...
Astatine (At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the At-labeled prostate-specific membrane antigen (PSMA) compound ([At]PSMA-5) exhibited excellent tumor growth suppression in a xenograft model. We conducted preclinical biodistribution and toxicity studies for the first-in-human clinical trial. [At]PSMA-5 was administered to both normal male ICR mice ( = 85) and cynomolgus monkeys ( = 2). The mice were divided into four groups for the toxicity study: 5 MBq/kg, 12 MBq/kg, 35 MBq/kg, and vehicle control, with follow-ups at 1 day ( = 10 per group) and 14 days ( = 5 per group). Monkeys were observed 24 h post-administration of [At]PSMA-5 (9 MBq/kg). Blood tests and histopathological examinations were performed at the end of the observation period. Blood tests in mice indicated no significant myelosuppression or renal dysfunction. However, the monkeys displayed mild leukopenia 24 h post-administration. Despite the high accumulation in the kidneys and thyroid, histological analysis revealed no abnormalities. On day 1, dose-dependent single-cell necrosis/apoptosis was observed in the salivary glands of mice and intestinal tracts of both mice and monkeys. Additionally, tingible body macrophages in the spleen and lymph nodes indicated phagocytosis of apoptotic B lymphocytes. Cortical lymphopenia (2/10) in the thymus and a decrease in the bone marrow cells (9/10) were observed in the 35 MBq/kg group in mice. These changes were transient, with no irreversible toxicity observed in mice 14 days post-administration. This study identified no severe toxicities associated with [At]PSMA-5, highlighting its potential as a next-generation targeted alpha therapy for prostate cancer. The sustainable production of At using a cyclotron supports its applicability for clinical use.
Topics: Animals; Male; Prostatic Neoplasms; Mice; Tissue Distribution; Mice, Inbred ICR; Astatine; Alpha Particles; Humans; Macaca fascicularis; Glutamate Carboxypeptidase II; Radiopharmaceuticals
PubMed: 38891856
DOI: 10.3390/ijms25115667 -
Healthcare (Basel, Switzerland) May 2024Globally, prostate cancer is the second leading cause of cancer deaths among males. It is the most commonly diagnosed cancer in Australia. The quality of life of...
BACKGROUND
Globally, prostate cancer is the second leading cause of cancer deaths among males. It is the most commonly diagnosed cancer in Australia. The quality of life of prostate cancer patients is poorer when compared to the general population due to the disease itself and its related complications. However, there is limited research on the geographic pattern of quality of life and its risk factors in Victoria. Therefore, an examination of the spatio-temporal pattern and risk factors of poor quality of life, along with the impact of spatial weight matrices on estimates and model performance, was conducted.
METHOD
A retrospective study was undertaken based on the Prostate Cancer Outcome Registry-Victoria data. Patient data ( = 5238) were extracted from the Prostate Cancer Outcome Registry, a population-based clinical quality outcome assessment from 2015 to 2021. A Bayesian spatio-temporal multilevel model was fitted to identify risk factors for poor quality of life. This study also evaluated the impact of distance- and adjacency-based spatial weight matrices. Model convergence was assessed using Gelman-Rubin statistical plots, and model comparison was based on the Watanabe-Akaike Information Criterion.
RESULTS
A total of 1906 (36.38%) prostate cancer patients who had undergone surgery experienced poor quality of life in our study. Belonging to the age group between 76 and 85 years (adjusted odds ratio (AOR) = 2.90, 95% credible interval (CrI): 1.39, 2.08), having a prostate-specific antigen level between 10.1 and 20.0 (AOR = 1.33, 95% CrI: 1.12, 1.58), and being treated in a public hospital (AOR = 1.35, 95% CrI: 1.17, 1.53) were significantly associated with higher odds of poor quality of life. Conversely, residing in highly accessible areas (AOR = 0.60, 95% CrI: 0.38, 0.94) was significantly associated with lower odds of poor prostate-specific antigen levels. Variations in estimates and model performance were observed depending on the choice of spatial weight matrices.
CONCLUSION
Belonging to an older age group, having a high prostate-specific antigen level, receiving treatment in public hospitals, and remoteness were statistically significant factors linked to poor quality of life. Substantial spatio-temporal variations in poor quality of life were observed in Victoria across local government areas. The distance-based weight matrix performed better than the adjacency-based matrix. This research finding highlights the need to reduce geographical disparities in quality of life. The statistical methods developed in this study may also be useful to apply to other population-based clinical registry settings.
PubMed: 38891168
DOI: 10.3390/healthcare12111093 -
Abdominal Radiology (New York) Jun 2024Rising prostate-specific antigen (PSA) levels following radical prostatectomy are indicative of a poor prognosis, which may associate with periprostatic adipose tissue...
BACKGROUND
Rising prostate-specific antigen (PSA) levels following radical prostatectomy are indicative of a poor prognosis, which may associate with periprostatic adipose tissue (PPAT). Accordingly, we aimed to construct a dynamic online nomogram to predict tumor short-term prognosis based on F-PSMA-1007 PET/CT of PPAT.
METHODS
Data from 268 prostate cancer (PCa) patients who underwent F-PSMA-1007 PET/CT before prostatectomy were analyzed retrospectively for model construction and validation (training cohort: n = 156; internal validation cohort: n = 65; external validation cohort: n = 47). Radiomics features (RFs) from PET and CT were extracted. Then, the Rad-score was constructed using logistic regression analysis based on the 25 optimal RFs selected through maximal relevance and minimal redundancy, as well as the least absolute shrinkage and selection operator. A nomogram was constructed to predict short-term prognosis which determined by persistent PSA.
RESULTS
The Rad-score consisting of 25 RFs showed good discrimination for classifying persistent PSA in all cohorts (all P < 0.05). Based on the logistic analysis, the radiomics-clinical combined model, which contained the optimal RFs and the predictive clinical variables, demonstrated optimal performance at an AUC of 0.85 (95% CI: 0.78-0.91), 0.77 (95% CI: 0.62-0.91) and 0.84 (95% CI: 0.70-0.93) in the training, internal validation and external validation cohorts. In all cohorts, the calibration curve was well-calibrated. Analysis of decision curves revealed greater clinical utility for the radiomics-clinical combined nomogram.
CONCLUSION
The radiomics-clinical combined nomogram serves as a novel tool for preoperative individualized prediction of short-term prognosis among PCa patients.
PubMed: 38890216
DOI: 10.1007/s00261-024-04421-6 -
EBioMedicine Jun 2024The accuracy of blood-based early tumour recognition is compromised by signal production at non-tumoral sites, low amount of signal produced by small tumours, and...
BACKGROUND
The accuracy of blood-based early tumour recognition is compromised by signal production at non-tumoral sites, low amount of signal produced by small tumours, and variable tumour production. Here we examined whether tumour-specific enhancement of vascular permeability by the particular tumour homing peptide, iRGD, which carries dual function of binding to integrin receptors overexpressed in the tumour vasculature and is known to promote extravasation via neuropilin-1 receptor upon site-specific cleavage, might be useful to improve blood-based tumour detection by inducing a yet unrecognised vice versa tumour-to-blood transport.
METHODS
To detect an iRGD-induced tumour-to-blood transport, we examined the effect of intravenously injected iRGD on blood levels of α-fetoprotein (AFP) and autotaxin in several mouse models of hepatocellular carcinoma (HCC) or in mice with chronic liver injury without HCC, and on prostate-specific antigen (PSA) levels in mice with prostate cancer.
FINDINGS
Intravenously injected iRGD rapidly and robustly elevated the blood levels of AFP in several mouse models of HCC, but not in mice with chronic liver injury. The effect was primarily seen in mice with small tumours and normal basal blood AFP levels, was attenuated by an anti-neuropilin-1 antibody, and depended on the concentration gradient between tumour and blood. iRGD treatment was also able to increase blood levels of autotaxin in HCC mice, and of PSA in mice with prostate cancer.
INTERPRETATION
We conclude that iRGD induces a tumour-to-blood transport in a tumour-specific fashion that has potential of improving diagnosis of early stage cancer.
FUNDING
Deutsche Krebshilfe, DKTK, LOEWE-Frankfurt Cancer Institute.
PubMed: 38889481
DOI: 10.1016/j.ebiom.2024.105178