A Systematic Review and a Meta-analysis of Randomized Controlled Trials' Control Groups in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC).

PURPOSE OF REVIEW: Determining the risk for progression or survival after standard androgen deprivation treatment (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC) is essential for stratifying patients according to expected outcomes in future studies of treatment combination. This systematic review and meta-analysis aims to estimate the progression-free survival (PFS) and overall survival (OS) probabilities in the control group of randomized controlled trials (RCTs) of different regimens of standard androgen deprivation treatment (ADT) in mHSPC and to identify possible predictors of outcomes. RECENT FINDINGS: Studies reporting time-dependent outcomes (progression or death) after standard ADT treatment of mHSPC were searched in MEDLINE, CANCERLIT, the Cochrane Controlled Trials Register, and the Cochrane Library from inception through June 2021. Data on patient populations and outcomes were extracted from each study by three independent observers and combined using a distribution-free summary survival curve. Primary outcomes were actuarial probabilities of disease progression and survival. Fifteen studies met the inclusion criteria. The pooled estimate of the actuarial PFS rate was 35.2% at two years. The pooled actuarial OS rate was 62.5% at three years. Heterogeneity among studies was highly significant for all outcomes. By univariate meta-regression analyses, high-volume disease and the presence of visceral metastases were associated with shorter survival. Our findings show that PFS and OS are highly variable in patients with mHSPC treated with ADT, providing a helpful benchmark for indirect comparisons of the benefits of the combination of chemotherapy and second-generation hormonotherapy.

Moderately hypofractionated salvage radiotherapy in patients with biochemical recurrence of prostate cancer after prostatectomy: long-term results and comparative analysis of two schedules.

Hypofractionation in salvage radiotherapy (HSRT) for biochemical recurrence of prostatic cancer after prostatectomy is a debated issue and at present, it should be considered purely investigational because of the lack of evidence supporting its use. In this study, we report the outcomes of patients presenting with biochemical recurrence after radical prostatectomy who received HSRT. The additional aim of this study is to compare two moderately HSRT schedules. Patients treated to prostate bed with daily Image Guided-VMAT and a total dose of 65 Gy/26 fractions (Group A) or 66 Gy/30 fractions (Group B) were included in the study. Inclusion criteria were: pN0/pNx, pre-HSRT PSA ≥0.2 ng/ml and ≤1 ng/ml, no evidence of pelvic/extrapelvic disease at restaging, no pelvic irradiation or dose boost on macroscopic local recurrence, no neoadjuvant/concomitant Androgen Deprivation Therapy (ADT), follow-up ≥36 months, and available pre/post HSRT data. Genitourinary (GU) and gastrointestinal (GI) toxicities, early and late, were assessed using CTCAE Vers. 5.0. One hundred patients were retrospectively identified to 50 in each group. Median follow-up was 59 months. All patients completed the prescribed HSRT. 5-year biochemical failure-free survival, local control, distant relapse-free survival, and ADT- free survival were 52.1%, 85.9%, 63.7%, and 73.2%, respectively. No significant differences in these outcomes were found between the two groups. On multivariate analysis, a hypofractionation schedule was not associated with any outcome, but ISUP score ≥ 4 and pre-HSRT PSA were associated with worse biochemical failure-free survival while only ISUP score ≥ 4 was associated with worse distant relapse-free survival. No Grade 3 GU/GI acute event was reported; 6 (6%) and 2 (2%) patients experienced late Grade ≥ 2 GU and GI events, respectively. No difference was found between the two groups neither in acute nor in late GU/GI toxicities. Our findings demonstrate that HSRT is feasible, effective, and safe. Our analysis did not show any significant difference between the two hypofractionated schedules. Further studies and randomized controlled trials are required in order to confirm these results and to identify the optimal hypofractionated schedule in the salvage setting.

Sequencing radium 223 and other life-prolonging agents in castration-resistant prostate cancer patients.

Background: Radium 223 (RA223) is currently administered as part of a therapeutic sequence with the other life-prolonging agents (LPAs) for metastatic castration-resistant prostate cancer (mCRPC). Patients & methods: We retrospectively reviewed the clinical records of patients who had received at least three LPAs including RA223. Results: Median overall survival (OS) from the start of first-line treatment was 39.8 months, with the patients who completed all six planned courses of RA223 having a longer OS than those who did not (53.2 vs 29.5 months; p < 0.0001). Conclusions: Our study confirms the activity of RA223 regardless of the treatment line in which it is administered and suggests that patient selection plays a central role in maximizing this activity.

Partial prostate re-irradiation for the treatment of isolated local recurrence of prostate cancer in patients previously treated with primary external beam radiotherapy: short-term results of a monocentric study.

Many different therapeutic options are available for locally recurrent prostate cancer (PCa). However, standard treatment has not yet been established. We conducted a partial prostate re-irradiation (PPR) program for the treatment of isolated and limited-size intraprostatic recurrences, in patients who previously underwent external beam radiation therapy (EBRT) as primary treatment for prostatic cancer (PCa). The analysis of this experience in terms of feasibility, toxicity, and efficacy is reported. The inclusion criteria of this retrospective analysis were: previous definitive EBRT, evidence of biochemical recurrence, radiological detection of isolated local relapse, and PPR as local salvage therapy. Gastrointestinal (GI) and genitourinary (GU) toxicities were registered according to the RTOG/EORTC criteria. Between July 2012 and May 2019, 44 patients were treated with PPR. All patients completed the planned treatment. The median follow-up was 25.4 months. Tumor progression was observed in 18 patients (40.9%). Two-year local control, biochemical failure-, and clinical relapse-free survival rates were 90.1%, 58.3%, and 67.9%, respectively. The occurrence of biochemical failure after PPR is lower for patients with the time interval between the primary EBRT and first biochemical failure >4 years; local control results strongly associated with a biologically effective dose (BED) at first EBRT >177 Gy. No acute grade 3 or greater toxic events were observed. Two late grade 3 GU toxicities were reported. Although retrospective in design, our study indicates that PPR appears as a feasible, well-tolerated, and effective salvage treatment for isolated local PCa recurrence. Long term data are required in order to confirm these results.

Interleukin-2 chronotherapy for metastatic renal cell carcinoma: Results of a phase I-II study.

BACKGROUND: Interleukin-2 (IL-2) was the cornerstone treatment for metastatic renal cell carcinoma (RCC) until the advent of tyrosine kinase inhibitors, but it still has therapeutic value. As a single bolus of IL-2 causes toxicity, there is interest in administration regimens with better tolerability and efficacy. Chronotherapy is the administration of therapy according to the circadian rhythm's influence on the immune and hormonal systems. This phase I-II trial evaluated the safety of IL-2 chronotherapy in metastatic RCC patients and determined the maximum tolerated dose. The secondary objective was to identify prognostic factors for survival. METHODS: Three chronomodulation schedules (5:00-13:00, 13:00-21:00, and 21:00-5:00) were tested. Each schedule was an 8-h IL-2 infusion, with a Gaussian distribution of drug concentration peaking at 4 h. To identify the maximum tolerated dose, the dose for different patients was escalated from 2 MIU/m2 (level I) to 18.6 MIU/m2 (level VI). RESULTS: Thirty patients were enrolled and completed treatment. Two patients were treated at 5:00-13:00, 15 at 13:00-21:00, and 13 at 21:00-5:00. Nine cases of grade 3 toxicity occurred in 7 patients at the highest dose (18.6 MIU/m2); no grade 4 toxicity occurred. The maximum tolerated dose was 14.0 MUI/m2. Patients were followed for a median of 16 months (range, 2-107). One patient was lost to follow-up, 3 patients were alive at last contact, and 26 patients died. Six patients achieved long-term survival (≥48 months). There was one complete response, four partial responses, 11 cases of stable disease and 14 of progressive disease. The response rate was 16% (5/30) and disease-control rate was 53% (16/30). Median progression-free survival was 4.5 months, and median overall survival was 14.5 months. Kaplan-Meier analyses revealed significant associations between overall survival and ECOG performance score (0 vs. 1-2), MSKCC score (0-2 vs. ≥ 3), IMDC risk score (0-2 vs. ≥ 3), IL-2 dose level (IV-VI vs. I-III), and prolactin (increase vs. no increase), and but not for chronotherapy schedule. CONCLUSION: IL-2 chronotherapy appears to be safe, moderately toxic and active in metastatic RCC. It may represent a new modality of IL-2 administration for these patients.

Fracture risk and survival outcomes in metastatic castration-resistant prostate cancer patients sequentially treated with abiraterone acetate and RADIUM-223.

PURPOSE: To evaluate the fracture risk and survival outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) who received sequentially abiraterone acetate (AA) and radium 223 [223Ra]RaCl2 in the daily clinical practice. MATERIALS: We retrospectively reviewed the records of mCRPC patients who received [223Ra]RaCl2 immediately after progressing during an AA treatment line in everyday clinical practice. RESULTS: We reviewed data of a consecutive series of 94 mCRPC patients. Most of the patients (85.1%) received [223Ra]RaCl2 as second- or third-line treatment. [223Ra]RaCl2 treatment was well-tolerated; there were only four cases of grade 3 anaemia, two cases of grade 3 leukopenia and one case of grade 3 neutropenia. The overall fracture rate is 2.1%; one fracture was recorded during the course of [223Ra]RaCl2 treatment, and one was recorded 1 month after its end. The fractures both occurred at metastatic sites. Median OS from [223Ra]RaCl2 start was more than 14 months regardless of the treatment line when [223Ra]RaCl2 was administered. CONCLUSION: The findings of this study show that the treatment with [223Ra]RaCl2 immediately after AA was active and safe with a very low risk of a fracture. Thus, the present observational report makes a valuable contribution to the current debate concerning the risks and benefits of including [223Ra]RaCl2 in the therapeutic algorithm.

Metastasis-directed stereotactic radiotherapy for oligoprogressive castration-resistant prostate cancer: a multicenter study.

PURPOSE: Herein, we report the clinical outcomes of a multicenter study evaluating the role of SBRT in a cohort of patients affected by oligoprogressive castration-resistant prostate cancer (CRPC). MATERIALS AND METHODS: This is a retrospective multicenter observational study including eleven centers. Inclusion criteria of the current study were: (a) Karnofsky performance status > 80, (b) histologically proven diagnosis of PC, (c) 1-5 oligoprogressive metastases, defined as progressive disease at bone or nodes levels (detected by means of choline PET/CT or CT plus bone scan) during ADT, (d) serum testosterone level under 50 ng/ml during ADT, (e) controlled primary tumor, (f) patients treated with SBRT with a dose of at least 5 Gy per fraction to a biologically effective dose (BED) of at least 80 Gy using an alpha-to-beta ratio of 3 Gy, (g) at least 6 months of follow-up post-SBRT. RESULTS: Eighty-six patients for a total of 117 lesions were treated with SBRT. The median follow-up was 30.7 months (range 4-91 months). The median new metastasis-free survival after SBRT was 12.3 months (95% CI 5.5-19.1 months). One- and two-year distant progression-free survival was 52.3% and 33.7%, respectively. Twenty-six out of 86 patients underwent a second course of SBRT due to further oligoprogressive disease: This resulted in a median systemic treatment-free survival of 21.8 months (95% CI 17.8-25.8 months). One-year systemic treatment-free survival was 72.1%. CONCLUSION: SBRT appears to be a promising approach in oligoprogressive castration-resistant prostate cancer. Further investigations are warranted.

rs4143815-PDL1, a New Potential Immunogenetic Biomarker of Biochemical Recurrence in Locally Advanced Prostate Cancer after Radiotherapy.

Up to 30-50% of patients with locally advanced prostate cancer (PCa) undergoing radiotherapy (RT) experience biochemical recurrence (BCR). The immune system affects the RT response. Immunogenetics could define new biomarkers for personalization of PCa patients' treatment. The aim of this study is to define the immunogenetic biomarkers of 10 year BCR (primary aim), 10 year overall survival (OS) and 5 year BCR (secondary aims). In this mono-institutional retrospective study, 549 Caucasian patients (a discovery set n = 418; a replication set n = 131) were affected by locally advanced PCa and homogeneously treated with RT. In the training set, associations were made between 447 SNPs in 77 genes of the immune system; and 10 year BCR and 10 year OS were tested through a multivariate Cox proportional hazard model. Significant SNPs (p-value < 0.05, q-value < 0.15) were analyzed in the replication set. Replicated SNPs were tested for 5 year BCR in both sets of patients. A polymorphism in the PDL1 gene (rs4143815) was the unique potential genetic variant of 10 year BCR (training set: p = 0.003, HR (95% CI) = 0.58 (0.41-0.83); replication set: p = 0.063, HR (95% CI) = 0.52 (0.26-1.04)) that was significantly associated with 5 year BCR (training set: p = 0.009, HR (95% CI) = 0.59 (0.40-0.88); replication set: p = 0.036, HR (95% CI) = 0.39 (0.16-0.94)). No biomarkers of OS were replicated. rs4143815-PDL1 arose as a new immunogenetic biomarker of BCR in PCa, giving new insights into the RT/immune system interaction, which could be potentially useful in new approaches using anti-PDL1 therapies for PCa.

Diagnostic value of neutrophil gelatinase-associated lipocalin/matrix metalloproteinase-9 pathway in transitional cell carcinoma of the bladder.

Neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase (MMP)-9, and NGAL/MMP-9 complex have been evaluated as diagnostic markers of several cancers, but results for bladder cancer are scanty. We evaluated these proteins in urine and serum of 89 patients with histologically confirmed bladder cancer and 119 cancer-free controls from a case-control study. Urinary concentrations were standardized on creatinine level. The performance of these proteins as cancer biomarkers was evaluated through the receiver operating characteristic (ROC) analysis. Urinary level of NGAL, MMP-9, and NGAL/MMP-9 complex was higher in current smokers, whereas no impact of dietary habits was observed. After adjusting for tobacco smoking, urinary concentration of MMP-9 was independently associated with cancer invasiveness, grading, and histological subtype, with elevated concentrations among T2-T4 and non-papillary bladder cancers. Conversely, NGAL and NGAL/MMP-9 complex were significantly higher in non-papillary than in papillary subtype. The pattern was less clear in serum, but correlation between urinary and serum concentration was poor, especially for Ta/is-T1 tumors. The ROC analysis confirmed that MMP-9 was the best marker (area under the ROC curve (AUC) = 0.68). Performances were much greater for muscle-invasive bladder cancers (AUC = 0.90), with elevated negative predictive values (97 %). The present study suggests that NGAL/MMP-9 pathway is associated with an aggressive phenotype of bladder cancer. The elevated negative predictive value of MMP-9 and NGAL/MMP-9 complex makes them candidate markers of exclusion test for bladder cancer. These proteins may be integrated in the surveillance of bladder cancer, thus diminishing patients' discomfort and improving compliance.

Patterns of prescription and adherence to European Association of Urology guidelines on androgen deprivation therapy in prostate cancer: an Italian multicentre cross-sectional analysis from the Choosing Treatment for Prostate Cancer (CHOICE) study.

OBJECTIVE: To evaluate both the patterns of prescription of androgen deprivation therapy (ADT) in patients with prostate cancer (PCa) and the adherence to European Association of Urology (EAU) guidelines for ADT prescription. METHODS: The Choosing Treatment for Prostate Cancer (CHOICE) study was an Italian multicentre cross-sectional study conducted between December 2010 and January 2012. A total of 1 386 patients, treated with ADT for PCa (first prescription or renewal of ADT), were selected. With regard to the EAU guidelines on ADT, the cohort was categorized into discordant ADT (Group A) and concordant ADT (Group B). RESULTS: The final cohort included 1 075 patients with a geographical distribution including North Italy (n = 627, 58.3%), Central Italy (n = 233, 21.7%) and South Italy (n = 215, 20.0%). In the category of patients treated with primary ADT, a total of 125 patients (56.3%) were classified as low risk according to D'Amico classification. With regard to the EAU guidelines, 285 (26.51%) and 790 patients (73.49%) were classified as discordant (Group A) and concordant (Group B), respectively. In Group A, patients were more likely to receive primary ADT (57.5%, 164/285 patients) than radical prostatectomy (RP; 30.9%, 88/285 patients), radiation therapy (RT; 6.7%, 19/285 patients) or RP + RT (17.7%, 14/285 patients; P < 0.01). Multivariate logistic regression analysis, adjusted for clinical and pathological variables, showed that patients from Central Italy (odds ratio [OR] 2.86; P < 0.05) and South Italy (OR 2.65; P < 0.05) were more likely to receive discordant ADT. CONCLUSION: EAU guideline adherence for ADT was low in Italy and was influenced by geographic area. Healthcare providers and urologists should consider these results in order to quantify the inadequate use of ADT and to set policy strategies to overcome this risk.

Clinical outcomes in octogenarians treated with docetaxel as first-line chemotherapy for castration-resistant prostate cancer.

AIM: To assess clinical outcomes in octogenarians treated with docetaxel (DOC) for metastatic castration-resistant prostate cancer. PATIENTS & METHODS: The multicenter retrospective study was based on a review of the pre- and post-DOC clinical history, DOC treatment and outcomes. RESULTS: We reviewed the records of 123 patients (median age: 82 years) who received DOC every 3 weeks or weekly, without significant grade 3-4 toxicities. Median progression-free survival was 7 months; median overall survival from the start of DOC was 20 months, but post-progression treatments significantly prolonged overall survival. CONCLUSION: The findings of this study suggest that toxicity is acceptable, survival is independent of patient's age and survival can be significantly prolonged by the use of new agents.

Real-world cabazitaxel safety: the Italian early-access program in metastatic castration-resistant prostate cancer.

AIM: Cabazitaxel is a novel taxane that is approved for use in metastatic castration-resistant prostate cancer based on the Phase III TROPIC study, which showed improved overall survival with cabazitaxel/prednisone versus mitoxantrone/prednisone. A global early-access program was initiated in order to provide early access to cabazitaxel in docetaxel-pretreated patients and to obtain real-world data. PATIENTS & METHODS: We report interim safety results from an Italian prospective, single-arm, multicenter, open-label trial of 218 patients receiving cabazitaxel 25 mg/m2 every 3 weeks plus prednisolone 10 mg/day, until disease progression, unacceptable toxicity, investigator's decision or death. RESULTS: Patients completing treatment received a median of six cabazitaxel cycles. The most common grade 3/4 adverse events were neutropenia (33.9%), leukopenia (15.6%), anemia (6%) and asthenia (6%). No peripheral neuropathy or nail disorders were observed. CONCLUSION: These results confirm that cabazitaxel has a manageable safety profile in daily clinical practice and support its use in patients with prostate cancer who progress during or after a docetaxel-based therapy.

Navigating the evolving diagnostic and therapeutic landscape of low- and intermediate-risk prostate cancer.

ABSTRACT: In this nonsystematic review of the literature, we explored the changing landscape of detection and treatment of low- and intermediate-risk prostate cancer (PCa). Through emphasizing improved cancer assessment with histology classification and genomics, we investigated key developments in PCa detection and risk stratification. The pivotal role of prostate magnetic resonance imaging (MRI) in the novel diagnostic pathway is examined, alongside the benefits and drawbacks of MRI-targeted biopsies for detection and tumor characterization. We also delved into treatment options, particularly active surveillance for intermediate-risk PCa. Outcomes are compared between intermediate- and low-risk patients, offering insights into tailored management. Surgical techniques, including Retzius-sparing surgery, precision prostatectomy, and partial prostatectomy for anterior cancer, are appraised. Each technique has the potential to enhance outcomes and minimize complications. Advancements in technology and radiobiology, including computed tomography (CT)/MRI imaging and positron emission tomography (PET) fusion, allow for precise dose adjustment and daily target monitoring with imaging-guided radiotherapy, opening new ways of tailoring patients' treatments. Finally, experimental therapeutic approaches such as focal therapy open new treatment frontiers, although they create new needs in tumor identification and tracking during and after the procedure.

Clinical Use of a Commercial Artificial Intelligence-Based Software for Autocontouring in Radiation Therapy: Geometric Performance and Dosimetric Impact.

PURPOSE: When autocontouring based on artificial intelligence (AI) is used in the radiotherapy (RT) workflow, the contours are reviewed and eventually adjusted by a radiation oncologist before an RT treatment plan is generated, with the purpose of improving dosimetry and reducing both interobserver variability and time for contouring. The purpose of this study was to evaluate the results of application of a commercial AI-based autocontouring for RT, assessing both geometric accuracies and the influence on optimized dose from automatically generated contours after review by human operator. MATERIALS AND METHODS: A commercial autocontouring system was applied to a retrospective database of 40 patients, of which 20 were treated with radiotherapy for prostate cancer (PCa) and 20 for head and neck cancer (HNC). Contours resulting from AI were compared against AI contours reviewed by human operator and human-only contours using Dice similarity coefficient (DSC), Hausdorff distance (HD), and relative volume difference (RVD). Dosimetric indices such as Dmean, D0.03cc, and normalized plan quality metrics were used to compare dose distributions from RT plans generated from structure sets contoured by humans assisted by AI against plans from manual contours. The reduction in contouring time obtained by using automated tools was also assessed. A Wilcoxon rank sum test was computed to assess the significance of differences. Interobserver variability of the comparison of manual vs. AI-assisted contours was also assessed among two radiation oncologists for PCa. RESULTS: For PCa, AI-assisted segmentation showed good agreement with expert radiation oncologist structures with average DSC among patients ≥ 0.7 for all structures, and minimal radiation oncology adjustment of structures (DSC of adjusted versus AI structures ≥ 0.91). For HNC, results of comparison between manual and AI contouring varied considerably e.g., 0.77 for oral cavity and 0.11-0.13 for brachial plexus, but again, adjustment was generally minimal (DSC of adjusted against AI contours 0.97 for oral cavity, 0.92-0.93 for brachial plexus). The difference in dose for the target and organs at risk were not statistically significant between human and AI-assisted, with the only exceptions of D0.03cc to the anal canal and Dmean to the brachial plexus. The observed average differences in plan quality for PCa and HNC cases were 8% and 6.7%, respectively. The dose parameter changes due to interobserver variability in PCa were small, with the exception of the anal canal, where large dose variations were observed. The reduction in time required for contouring was 72% for PCa and 84% for HNC. CONCLUSIONS: When an autocontouring system is used in combination with human review, the time of the RT workflow is significantly reduced without affecting dose distribution and plan quality.

Central nervous system metastases from castration-resistant prostate cancer in the docetaxel era.

Central nervous system (brain or leptomeningeal) metastases (BLm) are considered rare in castration-resistant prostate cancer (CRPC) patients. Now that docetaxel has become the reference drug for first-line treatment of CRPC, patients whose disease is not controlled by hormonal manipulations may live much longer than before and have higher risk of developing BLm. We retrospectively reviewed the records of all patients with CRPC attending our centres from 2002 to 2010, and identified all of those who were diagnosed as having BLm and received (or were considered to have been eligible to receive) docetaxel-based treatment. We identified 31 cases of BLm (22 brain metastases and 9 leptomeningeal metastases) with an incidence of 3.3%. BLm-free survival was 43.5 months, and survival after BLm discovery was 4 months. With six patients surviving for more than 1 year after developing BLm, the projected 1-year BL-S rate was 25.8%. The findings of our study may be relevant in clinical practice as they indicate that incidence of BLm in CRPC patients in the docetaxel era seems to be higher than in historical reports, meaning that special attention should be paid to the appearance of neurological symptoms in long-term CRPC survivors because they may be related to BLm.

Predicting Local Failure after Partial Prostate Re-Irradiation Using a Dosiomic-Based Machine Learning Model.

The aim of this study is to predict local failure after partial prostate re-irradiation for the treatment of isolated locally recurrent prostate cancer by using a machine learning classifier based on radiomic features from pre-treatment computed tomography (CT), positron-emission tomography (PET) and biological effective dose distribution (BED) of the radiotherapy plan. The analysis was conducted on a monocentric dataset of 43 patients with evidence of isolated intraprostatic recurrence of prostate cancer after primary external beam radiotherapy. All patients received partial prostate re-irradiation delivered by volumetric modulated arc therapy. The gross tumor volume (GTV) of each patient was manually contoured from planning CT, choline-PET and dose maps. An ensemble machine learning pipeline including unbalanced data correction and feature selection was trained using the radiomic and dosiomic features as input for predicting occurrence of local failure. The model performance was assessed using sensitivity, specificity, accuracy and area under receiver operating characteristic curves of the score function in 10-fold cross validation repeated 100 times. Local failure was observed in 13 patients (30%), with a median time to recurrence of 36.7 months (range = 6.1-102.4 months). A four variables ensemble machine learning model resulted in accuracy of 0.62 and AUC 0.65. According to our results, a dosiomic machine learning classifier can predict local failure after partial prostate re-irradiation.

Upfront metastasis-directed therapy in oligorecurrent prostate cancer does not decrease the time from initiation of androgen deprivation therapy to castration resistance.

The aim of the present study was to explore the potential impact of upfront metastases-directed therapy (MDT) in terms of prolongation of castration-sensitive phase in a series of oligorecurrent castration-sensitive prostate cancer (PC) patients. The present article is a multicenter retrospective study. The population of interest was castrate-sensitive oligorecurrent PC, defined as the presence of 1-3 uptakes in non-visceral sites such as bones or nodes detected by means of 18F-Choline PET/CT or 68-Gallium PSMA PET/CT. Primary endpoint was the time to castration resistance. Secondary endpoints were ADT-free survival, local progression-free survival, and overall survival. Eighty-two patients and 118 lesions were analyzed. The median time to castration resistance for the entire population of the study was 49 months (95% CI 43.6-54.4 months). The 1- and 2-year TTCR-free survival rates were 94% and 82%, respectively. At the time of analysis, 52 patients were still in the castration-sensitive phase of the disease. In this cohort of patients, the median ADT-free survival was 20 months (range 3-69 months). On the other hand, during follow-up 30 patients switched to the castration-resistant phase of disease. In this last group of patients, the median ADT-free survival was 20 months (range 4-50 months). After the ADT administration, the median castration-sensitive phase was 29 months (range 5-71 months). Castration resistance generally occurs at a median follow-up of 24-36 months following ADT. In the current study, upfront MDT does not decrease the time from initiation of ADT to castration resistance.

The role of stereotactic body radiation therapy and its integration with systemic therapies in metastatic kidney cancer: a multicenter study on behalf of the AIRO (Italian Association of Radiotherapy and Clinical Oncology) genitourinary study group.

Although systemic therapy represents the standard of care for polymetastatic kidney cancer, stereotactic body radiation therapy (SBRT) may play a relevant role in the oligometastatic setting. We conducted a multicenter study including oligometastatic kidney cancer treated with SBRT. We retrospectively analyzed 207 patients who underwent 245 SBRT treatments on 385 lesions, including 165 (42.9%) oligorecurrent (OR) and 220 (57.1%) oligoprogressive (OP) lesions. Most common sites were lung (30.9%) for OR group, and bone (32.7%) for OP group. Among 78 (31.8%) patients receiving concomitant systemic therapy, sunitinib (61.5%) and pazopanib (15.4%) were the most common for OR patients, while sunitinib (49.2%) and nivolumab (20.0%) for OP patients. End points were local control (LC), progression free survival (PFS), overall survival (OS), time to next systemic therapy (TTNS) and toxicity. Median follow-up was 18.6 months. 1, 2 and 3-year LC rates were 89.4%, 80.1% and 76.6% in OR patients, and 82.7%, 76.9% and 64.3% in those with OP, respectively. LC for OP group was influenced by clear cell histology (p = 0.000), total number of lesions (p = 0.004), systemic therapy during SBRT (p = 0.012), and SBRT dose (p = 0.012). Median PFS was 37.9 months. 1, 2- and 3-year OS was 92.7%, 86.4% and 81.8%, respectively. Median TTNS was 15.8 months for OR patients, and 13.9 months for OP patients. No grade 3 or higher toxicities were reported for both groups. SBRT may be considered an effective safe option in the multidisciplinary management of both OR and OP metastases from kidney cancer.

Sequencing Life-Prolonging Agents in Castration-Resistant Prostate Cancer Patients: Comparison of Sequences With and Without 223Ra.

Background: The retrospective studies that have so far described the outcomes of the sequential use of life-prolonging agents (LPAs) did not include metastatic castration-resistant prostate cancer (mCRPC) patients who received radium-223 (223Ra) as part of their treatment. Consequently, it is not known whether including 223Ra in the therapeutic sequence has an impact on cumulative survival. The aim of this study was to evaluate this impact by comparing the cumulative overall survival (OS) in two series of mCRPC patients sequentially treated with two or three LPAs after first-line docetaxel (DOC), including 223Ra and not. Materials and Methods: The authors retrospectively reviewed the records of mCRPC patients with bone involvement alone who received two or three LPAs (including 223Ra) after first-line DOC. The control group was a contemporary series of mCRPC patients with bone involvement alone treated with sequences of two or three LPAs other than 223Ra after first-line DOC. Results: Median cumulative OS was 40.6 months in the 223Ra group of 78 patients and 36.2 months in the non-223Ra group of 186 patients (p = 0.08). OS outcomes were significantly influenced by the number of treatment lines, and baseline Eastern Cooperative Oncology Group performance status (PS) and prostate-specific antigen levels. Conclusions: To the best of the authors' knowledge, this is the first study designed to evaluate the impact of introducing 223Ra in the treatment sequences for mCRPC patients, and the results show that its use does not negatively affect cumulative OS.

Incidence and outcomes of severe acute respiratory syndrome coronavirus 2 infection in patients with metastatic castration-resistant prostate cancer.

BACKGROUND: Patients with cancer are at increased risk of complicated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, but it is still unclear if the risk of mortality is influenced by cancer type or ongoing anti-cancer treatments. An interesting debate concerning the potential relationship between androgen deprivation therapy (ADT) and SARS-CoV-2 infection has recently been opened in the case of prostate cancer (PC), and the aim of this multi-centre cohort study was to investigate the incidence and outcomes of SARS-CoV-2 infection in patients with metastatic castration-resistant prostrate cancer (mCRPC). PATIENTS AND METHODS: We retrospectively reviewed the clinical records of patients with mCRPC who developed SARS-CoV-2 infection, and recorded their baseline clinical characteristics, their history of PC and SARS-CoV-2 infection, and their oncological status and treatment at the time of infection. The primary study end point was the death rate and the possible impact of the patients' PC-related history and treatments on mortality. RESULTS: Thirty-four of the 1433 patients with mCRPC attending the participating centres (2.3%) developed SARS-CoV-2 infection, 22 (64.7%) of whom were hospitalised. Most of the patients were symptomatic, the most frequent symptoms being fever (70.6%), dyspnoea (61.8%), cough (52.9%) and fatigue (38.2%). After a median follow-up of 21 days (interquartile range: 13-41), 13 patients had died (38.2%), 17 recovered (50.0%) and four (11.7%) were still infected. The number of treatments previously administered for mCRPC had a significant impact on mortality (p = 0.004). CONCLUSIONS: Our findings contribute additional data to the current debate concerning the postulated protective role of ADT, which seems to be less in patients with metastatic PC.