Recent Advances in the Management of Hormone-Sensitive Oligometastatic Prostate Cancer.
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ABSTRACT:
SUBMITTER: Marvaso G
PROVIDER: S-EPMC8747627 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:With advancements in diagnostic techniques, including molecular and clinical imaging, that directly target cancer cells, oligometastatic prostate cancer (PCa) is being diagnosed in patients who were, in the past, considered to have localized disease. With accumulating evidence, there has been a paradigm shift in considering aggressive treatments targeted at both the primary tumor and metastatic lesions in an aim to avoid and delay the need for palliative treatments and, ultimately, to achieve survival benefits. However, many questions still remain unanswered regarding the understanding of oligometastatic PCa, from its definition to optimal treatment strategies for each individual. Limited retrospective studies have suggested that interventions, including local and/or metastasis-directed therapy using surgery and radiation therapy (RT), can improve survival outcomes with minimal risk of adverse effects. Such treatments have been shown to decrease the risks of subsequent palliative interventions and to delay the start of androgen-deprivation therapy. Nevertheless, available data are insufficient to draw a reliable conclusion regarding their effect on quality of life measures and overall survival. This comprehensive review overviews data from contemporary literature that have investigated treatments, including surgery and RT, for patients with oligometastatic PCa, namely pelvic lymph node positive disease and limited distant metastases, and summarizes ongoing trials that are evaluating the feasibility of aggressive multimodal treatments.
| S-EPMC5990677 | biostudies-literature
Project description:Probably, patients with de novo (synchronous) and recurrent (metachronous) oligometastatic hormone-sensitive prostate cancer have different oncologic outcomes. Thus, we are challenged with different scenarios in clinical practice, where different treatment options may apply. In the last years, several prospective studies have focused on the treatment of patients with de novo oligometastatic hormone-sensitive prostate cancer. Not only the addition of systemic therapeutic treatments, such as chemotherapy with docetaxel, abiraterone, enzalutamide, and apalutamide, next to androgen deprivation therapy, demonstrated to improve outcomes in these patients but also local therapy of the primary has been demonstrated to improve outcomes of low-volume metastatic disease. Next to radiotherapy, also radical prostatectomy has been reported as a feasible and safe treatment option. Additional metastasis-directed therapy in de novo metastatic disease is currently examined by four trials. In the recurrent metastatic setting, less data are available, and it remains uncertain if patients can be treated in the same way as synchronous oligometastatic disease. Metastasis-directed therapy has demonstrated to prolong outcomes, while data on survival are still missing.
| S-EPMC8498729 | biostudies-literature
Project description: Not available
| S-EPMC10493250 | biostudies-literature
Project description:The mainstay of treatment for men with three or fewer non-castrate metastatic lesions outside of the prostate remains morbid palliative androgen deprivation therapy. We believe there is now a significant body of retrospective literature to suggest a survival benefit if these men have radical treatment to their primary tumour alongside 'metastasis-directed therapy' to the metastatic deposits. However, this regimen should be reserved to high-volume centres with quality assurance programmes and excellent outcomes. Patients should be made clear as to the uncertainty of benefit for this multi-site treatment strategy, and we await the publication of randomised controlled trials reporting in the next 5 years.
| S-EPMC5083765 | biostudies-other
Project description:BackgroundMonotherapy with immune checkpoint inhibitors has generally been unsuccessful in men with advanced prostate cancer. Preclinical data support the notion that cryotherapy may improve immune-mediated and anti-tumor responses. The objective of this study was to assess the safety and feasibility of whole-prostate gland cryotherapy combined with pembrolizumab and androgen deprivation in men with oligometastatic hormone-sensitive prostate cancer.MethodsThis single-institution, pilot trial recruited 12 patients with newly diagnosed oligometastatic prostate cancer between 2015 and 2016. Patients underwent whole-prostate cryoablation combined with short-term androgen deprivation (eight months) and pembrolizumab (6 doses). The primary clinical endpoints were the number of patients with a PSA level of <0.6 ng/mL at one year and the frequency of adverse events. Other outcome measures included progression-free survival and systemic therapy-free survival. Exploratory analyses included PD-L1 protein expression.ResultsForty two percent (5/12) of patients had a PSAs of <0.6 ng/mL at one year though only 2 of these patients had recovered their testosterone at this time point. Median progression-free survival was 14 months, and median systemic therapy-free survival was 17.5 months. PD-L1 expression was not detectable by IHC in patients with evaluable tissue. All adverse events were grade ≤2, and there were no apparent complications from cryotherapy.ConclusionsWhole-prostate cryoablation combined with short-term androgen deprivation and pembrolizumab treatment was well tolerated and no safety concerns were observed in men with oligometastatic prostate cancer. Though local disease appeared effectively treated in the majority of men, the regimen only infrequency led to sustained disease control following testosterone recovery.
| S-EPMC7031012 | biostudies-literature
Project description:The treatment landscape of metastatic hormone-sensitive prostate cancer (mHSPC) has changed radically in recent years. Androgen deprivation therapy (ADT) alone was for decades the standard of care for treating mHSPC. This changed when studies showed that the addition of docetaxel chemotherapy or abiraterone acetate to ADT significantly increases overall survival of patients with mHSPC, followed by more recent evidence showing the efficacy of androgen receptor antagonists, such as enzalutamide and apalutamide, in this setting. While this rapid therapeutic evolution is welcome, it presents clinicians with a crucial challenge: the choice of treatment selection and sequencing. In the first-line setting there are no comparative data currently available to guide treatment choice between the different available regimens, and no prospective data to guide clinical decision after progression. Decisions on treatment will now need to be personalised based on indirect comparison of the available efficacy data from multiple phase 3 studies, together with considerations of disease volume, comorbidities, treatment aims, toxicity profile and cost reimbursement within the healthcare setting. Here, we provide an overview of the clinical trial data to date and propose some biological and clinical insights which may be helpful in making decisions on treatment selection and sequencing.
| S-EPMC7683690 | biostudies-literature
Project description:BackgroundIn recent years, there is increasing evidence showing a beneficial outcome (e.g. progression free survival; PFS) after metastases-directed therapy (MDT) with external beam radiotherapy (EBRT) or targeted surgery for oligometastatic hormone sensitive prostate cancer (oHSPC). However, many patients do not qualify for these treatments due to prior interventions or tumor location. Such oligometastatic patients could benefit from radioligand therapy (RLT) with 177Lu-PSMA; a novel tumor targeting therapy for end-stage metastatic castration-resistant prostate cancer (mCRPC). Especially because RLT could be more effective in low volume disease, such as the oligometastatic status, due to high uptake of radioligands in smaller lesions. To test the hypothesis that 177Lu-PSMA is an effective treatment in oHSPC to prolong PFS and postpone the need for androgen deprivation therapy (ADT), we initiated a multicenter randomized clinical trial. This is globally, the first prospective study using 177Lu-PSMA-I&T in a randomized multicenter setting.Methods & designThis study compares 177Lu-PSMA-I&T MDT to the current standard of care (SOC); deferred ADT. Fifty-eight patients with oHSPC (≤5 metastases on PSMA PET) and high PSMA uptake (SUVmax > 15, partial volume corrected) on 18F-PSMA PET after prior surgery and/or EBRT and a PSA doubling time of < 6 months, will be randomized in a 1:1 ratio. The patients randomized to the interventional arm will be eligible for two cycles of 7.4GBq 177Lu-PSMA-I&T at a 6-week interval. After both cycles, patients are monitored every 3 weeks (including adverse events, QoL- and xerostomia questionnaires and laboratory testing) at the outpatient clinic. Twenty-four weeks after cycle two an end of study evaluation is planned together with another 18F-PSMA PET and (whole body) MRI. Patients in the SOC arm are eligible to receive 177Lu-PSMA-I&T after meeting the primary study objective, which is the fraction of patients who show disease progression during the study follow up. A second primary objective is the time to disease progression. Disease progression is defined as a 100% increase in PSA from baseline or clinical progression.DiscussionThis is the first prospective randomized clinical study assessing the therapeutic efficacy and toxicity of 177Lu-PSMA-I&T for patients with oHSPC.Trial registrationClinicaltrials.gov identifier: NCT04443062 .
| S-EPMC7490874 | biostudies-literature
Project description:Oligometastatic disease was proposed by Hellman and Weichselbaum in 1995 as an intermediate tumour state between localised lesions and widespread metastases, characterised by the limited number and size of metastases in specific organs such as lung, liver, bone or even brain. The oligometastatic state has increasingly been recognised as a unique clinical state during which local ablative treatment can be effective in several types of cancer, including prostate cancer. However, the role of systemic therapy, such as hormone therapy and chemotherapy, is not yet well known. Some promising data for local ablative therapy have emerged, but it remains unclear whether local therapy can eliminate the need for, androgen-deprivation therapy (ADT), or reduce the required duration. In addition, several randomised phase III trials have demonstrated survival benefits from the addition of docetaxel or abiraterone to ADT in patients with metastatic hormone-sensitive prostate cancer. These findings suggest that such aggressive treatments may improve clinical outcomes for patients with oligometastatic prostate cancer. However, the efficacy of these treatments may depend on the volume of metastases, with higher efficacy for high-volume disease. Therefore, further investigation including stratification by disease volume is warranted. This review will discuss the current evidence and controversies surrounding the role of systemic therapy in patients with oligometastatic prostate cancer.
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Project description:The incidence and mortality of squamous cell carcinoma of the anus (SCCA) is on the rise, which highlights the unmet need for advances in treatment options. The landscape of treatment for this cancer is rapidly evolving with novel combination strategies including immunotherapy, radiation therapy and biomarker-guided therapy. This review article features an overview of recent advancements in both locoregional and metastatic SCCA. The recent focus on locoregional SCCA management is to tailor treatment according to tumor burden and minimize treatment-related toxicities. Mitomycin plus either infusional 5-fluorouracil (5-FU) or capecitabine is used for first-line chemoradiotherapy (CRT), and intensity-modulated radiotherapy (IMRT) is the preferred modality for radiation for locoregional anal cancer. Locally recurrent disease is managed with surgical resection. Systemic treatment is first-line for metastatic SCCA and immunotherapy with nivolumab and pembrolizumab being included as second-line agents. Current and future clinical trials are evaluating treatments for SCCA including immunotherapy alone or in combination regimens, radiotherapies, targeted treatments and novel agents. Another critical aspect of current research in SCCA is the personalization of CRT and immunotherapies based on molecular characterization and biomarkers such as the programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR) and circulating tumor DNA.
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