Therapy In Oligometastatic Prostate Cancer Research Articles

Single Dose Radiotherapy (SDRT) With or Without Adjuvant Systemic Therapy for Oligometastatic Prostate Cancer

Single Dose Radiotherapy (SDRT) With or Without Adjuvant Systemic Therapy for Oligometastatic Prostate Cancer

Carbon 11-choline positron emission tomography/computed tomography and palliative local therapy for castration-resistant prostate cancer.

Carbon 11-choline positron emission tomography/computed tomography (11C-choline PET/CT) and subsequent local therapy for oligometastatic prostate cancer have been reported to be effective, but their effectiveness in castration-resistant prostate cancer (CRPC) remains unclear. Here, we evaluated the findings of 11C-choline PET/CT in CRPC patients and the efficacy of local treatments in correspondence of the pathologic choline uptake. We collected 12 cases of CRPC patients who underwent 11C-choline PET/CT between 2014 and 2016. The outcomes assessed included age, the prostate-specific antigen (PSA) value, the findings of 11C-choline PET/CT, the subsequent treatments, the PSA response following the treatments, and the progression-free survival (PFS). Seven of 12 cases (median PSA, 3.29ng/mL) had local prostate cancer and/or one or two metastatic lesions detected by the choline PET/CT. These localized lesions were treated with radiotherapy or lymphadenectomy. PSA decreased in all the seven cases and median PSA response was 86% (range, 23-100%). Median PFS was 8.5months (range, 2.8-25.3months). The other five cases (median PSA, 7.41ng/mL) had multiple metastases and systemic therapies were continued in those cases. 11C-choline PET/CT and the correspondent local treatments may play an important role in the treatment sequence of CRPC in selected patients.

Progressive Site-Directed Therapy for Castration-Resistant Prostate Cancer: Localization of the Progressive Site as a Prognostic Factor

Locoregional therapy for oligometastatic prostate cancer has generated great interest. However, its benefit for castration-resistant prostate cancer (CRPC) has not been fully demonstrated. Our objective was to evaluate the treatment outcome of progressive site-directed therapy (PSDT) for oligoprogressive CRPC (OP-CRPC). This study cohort consisted of 101 patients with CRPC who underwent whole-body diffusion-weighted magnetic resonance imaging between 2014 and 2018, when a new line of anticancer therapy was being considered. For OP-CRPC, PSDT with radiation therapy and unchanged continuation of systemic therapy were recommended. Thirty-eight patients received a diagnosis of OP-CRPC, and 23 (61%) underwent PSDT at a median prostate-specific antigen (PSA) level of 7.8 ng/mL. The regional radiation therapy targets were the prostate/pelvic lymph nodes (n = 7), bone (n = 15), or both (n=1). A decrease in PSA levels of at least 50% in response to PSDT (50% PSA decline) was observed in 16 cases (70%); the median time to PSA progression was 8.7 months. Intrapelvic localization of progressive lesions was a significant predictor of time to PSA progression (hazard ratio, 6.6; P = .007) as well as volumes of abnormal signal intensity on whole-body diffusion-weighted magnetic resonance imaging (hazard ratio, 0.5; P = .045). A 50% PSA decline was achieved in 16 of the 18 patients with intrapelvic OP-CRPC (89%) and in none of the 5 patients with non-intrapelvic OP-CRPC (P < .001). Intrapelvic OP-CRPC had a significantly longer time to PSA progression than non-intrapelvic OP-CRPC (10.1 vs 4.8 months, P = .0014). PSDT can be an effective treatment option for OP-CRPC. Progressive site localization was an important factor in good PSA response.

EP-1570 Stereotactic body radiation therapy for oligometastatic prostate cancer. Our experience.

EP-1570 Stereotactic body radiation therapy for oligometastatic prostate cancer. Our experience.

Systemic and tumor-directed therapy for oligometastatic prostate cancer: study protocol for a phase II trial for veterans with de novo oligometastatic disease

BackgroundThe treatment paradigm for metastatic hormone-sensitive prostate cancer (mHSPC) patients is evolving. PET/CT now offers improved sensitivity and accuracy in staging. Recent randomized trial data supports escalated hormone therapy, local primary tumor therapy, and metastasis-directed therapy. The impact of combining such therapies into a multimodal approach is unknown. This Phase II single-arm clinical trial sponsored and funded by Veterans Affairs combines local, metastasis-directed, and systemic therapies to durably render patients free of detectable disease off active therapy.MethodsPatients with newly-diagnosed M1a/b prostate cancer (PSMA PET/CT staging is permitted) and 1–5 radiographically visible metastases (excluding pelvic lymph nodes) are undergoing local treatment with radical prostatectomy, limited duration systemic therapy for a total of six months (leuprolide, abiraterone acetate with prednisone, and apalutamide), metastasis-directed stereotactic body radiotherapy (SBRT), and post-operative fractionated radiotherapy if pT ≥ 3a, N1, or positive margins are present. The primary endpoint is the percent of patients achieving a serum PSA of < 0.05 ng/mL six months after recovery of serum testosterone ≥150 ng/dL. Secondary endpoints include time to biochemical progression, time to radiographic progression, time to initiation of alternative antineoplastic therapy, prostate cancer specific survival, health related quality-of-life, safety and tolerability.DiscussionTo our knowledge, this is the first trial that tests a comprehensive systemic and tumor directed therapeutic strategy for patients with newly diagnosed oligometastatic prostate cancer. This trial, and others like it, represent the critical first step towards curative intent therapy for a patient population where palliation has been the norm.Trial registrationClinicaltrials.gov identifier: NCT03298087 (registration date: September 29, 2017).

Yes or no to local therapy for oligometastatic prostate cancer?

Metastatic prostate cancer has traditionally been treated with systemic therapy alone, but the issue of oligometastatic disease raises the question of whether local therapy — radical prostatectomy or prostate radiotherapy — should be performed. A number of phase III trials should improve our understanding of metastatic disease and lead to better care of our patients.

Recent advances in radiation oncology: multimodal targeting of high risk and recurrent prostate cancer.

The overview summarizes recent developments in radiation oncology for high risk and recurrent prostate cancer. A number of well known phase III prostate hypofractionated radiation therapy (HFxRT) trials were finally published with long-term follow-ups. These trials demonstrate patterns of equivalent tumor control with several showing worse toxicity rates. The ASCENDE-RT randomized trial demonstrated the superiority of brachytherapy boost in intermediate and high-risk prostate cancer. Important randomized trials show a clear benefit to androgen deprivation therapy (ADT) in both intermediate-risk prostate cancer and postprostatectomy patients with rising PSA. Finally, the first randomized trial of metastasis-directed therapy showed a delay in time to ADT and biochemical failures in oligometastatic prostate cancer. The use of brachytherapy boost in high-risk disease and ADT in locally recurrent cancer after prostatectomy are practice changing given the magnitude of benefit seen in the randomized trials. The benefit of metastasis-directed therapy in oligometastatic prostate cancer must be validated in a larger randomized trial. However, hypofractionated radiation therapy requires further long-term follow-up so that late toxicity risk can be accurately assessed before it becomes a standard of care in prostate cancer.

Radiotherapy as metastasis-directed therapy for oligometastatic prostate cancer.

To summarize the available literature regarding radiotherapy as a metastasis-directed therapy (MDT) in the treatment of oligometastatic prostate cancer (PCa). Three different clinical scenarios of oligometastatic PCa exist in which MDT can be applied: de novo oligometastatic PCa, oligorecurrent PCa, and oligoprogressive PCa. A cut off of three to five metastatic lesions is most often used in these settings. Data from retrospective studies, treating over 1000 patients in total, have been reported. The median progression-free survival ranges between 1 and 3 years, but is influenced by a heterogeneous use of androgen deprivation therapy. For lymph node metastases, a propensity scored matched analysis suggests that cancer specific and overall survival is improved with MDT over standard of care. MDT treatment regimens vary with different radiotherapy techniques, doses, and volumes. Adverse events are limited to grade 1-2 and only rarely grade 3 events are reported. Based on data from retrospective studies, progression-free survival following MDT for oligometastatic PCa is promising with few adverse events. Comparative prospective studies are under way and will shed light on the future of MDT.

The role of metastasis-directed therapy and local therapy of the primary tumor in the management of oligometastatic prostate cancer.

Oligometastasis has been proposed as an intermediate stage of cancer spread between localized disease and widespread metastasis. Oligometastatic malignancy is now being diagnosed more frequently as the result of improvements in diagnostic modalities such as functional imaging. The importance of oligometastasis in managing metastatic prostate cancer is that it is possible to treat with a curative aim by metastasis-directed or local therapy in selected patients. Many studies have shown that these aggressive treatments lead to improved survival in other oligometastatic malignancies. However, few studies have shown definitive benefits of metastasis-directed or local therapy in oligometastatic prostate cancer. Review of the available studies suggests that stereotactic radiotherapy (RT) of metastatic lesions in oligorecurrent disease is a feasible and safe modality for managing oligometastatic prostate cancer. Also, stereotactic RT can delay the start of androgen deprivation therapy. Many retrospective studies of metastatic prostate cancer have shown that patients undergoing local therapy seem to have superior overall and cancer-specific survival compared with patients not receiving local therapy. Ongoing prospective randomized trials would be helpful to evaluate the role of local therapy in oligometastatic prostate cancer.

Stereotactic Body Radiation Therapy for Oligometastatic Prostate Cancer

To review outcomes of patients with oligometastatic prostate cancer (PCa) treated with stereotactic body radiation therapy (SBRT) and to identify variables associated with local failure. We retrospectively reviewed records of patients treated with SBRT for oligometastatic PCa. Metastasis control (ie, control of the treated lesion, MC), biochemical progression-free survival, distant progression-free survival, and overall survival were estimated with the Kaplan-Meier method. Sixty-six men with 81 metastatic PCa lesions, 50 of which were castrate-resistant, were included in the analysis. Lesions were in bone (n=74), lymph nodes (n=6), or liver (n=1). Stereotactic body radiation therapy was delivered in 1 fraction to 71 lesions (88%), at a median dose of 16Gy (range, 16-24Gy). The remaining lesions received 30Gy in 3 fractions (n=6) or 50Gy in 5 fractions (n=4). Median follow-up was 16months (range, 3-49months). Estimated MC at 2years was 82%. Biochemical progression-free survival, distant progression-free survival, and overall survival were 54%, 45%, and 83%, respectively. On multivariate analysis, only the dose of SBRT was significantly associated with MC; lesions treated with 16Gy had 58% MC, and those treated with ≥18Gy had 95% MC at 2years (P≤.001). At 2years, MC for lesions treated with 18Gy (n=21) was 88%. No patient treated with ≥18Gy in a single fraction or with any multifraction regimen had local failure. Six patients (9%) had grade 1 pain flare, and 2 (3%) had grade 2 pain flare. No grade 2 or greater late toxicities were reported. Stereotactic body radiation therapy for patients with oligometastatic prostate cancer provided optimal metastasis control and acceptable toxicity with doses ≥18Gy. Biochemical progression-free survival was 54% at 16months with the inclusion of SBRT in the treatment regimen. Stereotactic body radiation therapy should be considered in patients with castration-refractory, oligometastatic prostate cancer who have limited options for systemic therapy.

Progression-free Survival Following Stereotactic Body Radiotherapy for Oligometastatic Prostate Cancer Treatment-naive Recurrence: A Multi-institutional Analysis

The literature on metastasis-directed therapy for oligometastatic prostate cancer (PCa) recurrence consists of small heterogeneous studies. This study aimed to reduce the heterogeneity by pooling individual patient data from different institutions treating oligometastatic PCa recurrence with stereotactic body radiotherapy (SBRT). We focussed on patients who were treatment naive, with the aim of determining if SBRT could delay disease progression. We included patients with three or fewer metastases. The Kaplan-Meier method was used to estimate distant progression-free survival (DPFS) and local progression-free survival (LPFS). Toxicity was scored using the Common Terminology Criteria for Adverse Events. In total, 163 metastases were treated in 119 patients. The median DPFS was 21 mo (95% confidence interval, 15–26 mo). A lower radiotherapy dose predicted a higher local recurrence rate with a 3-yr LPFS of 79% for patients treated with a biologically effective dose ≤100Gy versus 99% for patients treated with >100Gy (p=0.01). Seventeen patients (14%) developed toxicity classified as grade 1, and three patients (3%) developed grade 2 toxicity. No grade ≥3 toxicity occurred. These results should serve as a benchmark for future prospective trials. Patient summaryThis multi-institutional study pools all of the available data on the use of stereotactic body radiotherapy for limited prostate cancer metastases. We concluded that this approach is safe and associated with a prolonged treatment progression-free survival.

Targeted local therapy in oligometastatic prostate cancer: a promising potential opportunity after failed primary treatment.

Targeted local therapy in oligometastatic prostate cancer: a promising potential opportunity after failed primary treatment.