Local Therapeutics for the Treatment of Oligo Metastatic Prostate Cancer.

PURPOSE OF REVIEW: Metastatic prostate cancer remains universally lethal. Although de-novo metastatic prostate cancer was historically managed with systemic therapy alone, local therapies are increasingly utilized in the early treatment of the disease, particularly in patients with oligometastatic prostate cancer (OMPC). OMPC represents an intermediate stage between clinically localized and widespread metastatic disease. Diseases classified within this stage present an opportunity for localized targeting of the disease prior to progression to widespread metastases. The purpose of this review is to discuss the contemporary and emerging local therapies for the treatment of OMPC. RECENT FINDINGS: To date, there are three utilized forms of local therapy for OMPC: cryoablation, radiation therapy, and cytoreductive prostatectomy. Cryoablation can be utilized for the total ablation of the prostate and has shown promising results in patients with OMPC either in combination with ADT or with ADT and systemic chemotherapy. Radiation therapy along with ADT has demonstrated improvement in progression-free survival. The STAMPEDE Arm G, PEACE-1, and the HORRAD clinical trials have investigated radiation therapy for mPCa compared to standard of care versus systemic therapy with varying results. Cytoreductive radical prostatectomy (CRP) in conjunction with ADT has also been proposed in the management of OPMC with promising results from case-control and retrospective studies. Currently there are larger controlled trials investigating CRP for OPMC including the SIMCAP, LoMP, TRoMbone, SWOG 1802, IP2-ATLANTA, g-RAMPP, and FUSCC-OMPCa trials. Given the novel nature of local treatments for OPMC, treatment selection is still controversial and requires long-term follow-up and randomized clinical trials to aid patient and clinician decision making.

Cytoreductive prostatectomy improves survival outcomes in patients with oligometastases: a systematic meta-analysis.

BACKGROUND: Whether cytoreductive prostatectomy (CRP) should be performed in patients with oligometastatic prostate cancer (OPC) remains controversial. The goal of this systematic meta-analysis was to assess the efficacy of CRP as a treatment for OPC. METHODS: This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. Data sources included publications in the PubMed, Embase, the Cochrane Library, EBSCO, and Web of Science (SCI) databases as of May 2022. Eligible articles included prospective studies comparing the efficacy of CRP to a lack of CRP in patients with OPC. RESULTS: In total, 10 publications incorporating 888 patients were analyzed. Tumor-reducing prostatectomy was found to have no significant effect on long-term or short-term OS [OR = 2.26, 95% CI (0.97, 5.28), P = 0.06] and [OR = 1.73, 95% CI (0.83, 3.58), P = 0.14], but it significantly improved patient long-term or short-term CSS [OR = 1.77, 95% CI (1.01, 310), P = 0.04] and [OR = 2.71, 95% CI (1.72, 4.29), P < 0.0001] and PFS [OR = 1.93, 95% CI (1.25, 2.97), P = 0.003]. CONCLUSION: These results suggest that cytoreductive prostatectomy can confer survival benefits to OPC patients. TRIAL REGISTRATION: INPLASY protocol 202260017 https://doi.org/10.37766/inplasy2022.6.0017 .

The cytoreductive prostatectomy in metastatic prostate cancer: what the individual trials are hoping to answer.

OBJECTIVE: To review the ongoing randomised trials of cytoreductive prostatectomy (CRP) in de novo hormone-sensitive metastatic prostate cancer (HSPC) in order to identify their goals and assess their strengths and weaknesses. METHODS: PubMed, MEDLINE and clinical trials websites searches were performed to identify currently ongoing trials of CRP in de novo HSPC. RESULTS: Nine randomised clinical trials in CRP were identified and included: Southwest Oncology Group (SWOG) 1802, Surgery in Metastatic Carcinoma of Prostate (SIMCAP), Adjuvant Treatments to the Local Tumour for Metastatic Prostate Cancer: Assessment of Novel Treatment Algorithms (IP2-ATLANTA), Testing Radical prostatectomy in men with prostate cancer and oligoMetastases to the bone (TRoMbone), Impact of Radical Prostatectomy as Primary Treatment in Patients with Prostate Cancer with Limited Bone Metastases (g-RAMPP), Cytoreductive Prostatectomy vs Cytoreductive Prostate Irradiation as a Local Treatment Option for Metastatic Prostate Cancer: a Multicentric Feasibility Trial (LoMP II), Androgen-Deprivation Therapy or Androgen-Deprivation Therapy Plus Definitive Treatment (Radiation or Surgery) (FUSCC-OMPCa), and the Testing Radical Prostatectomy in Chinese Men with Prostate Cancer and oligoMetastases to the Bone study. Each study was different; assessing various primary outcome measures including overall survival (OS), progression-free survival and feasibility to randomise between standard therapy and CRP or between radiation therapy and CRP in the metastatic setting. In the oligometastatic setting, the trials assess OS, feasibility to randomise and time to castration resistance. Similarly, a number of secondary endpoints ranging from cancer-specific outcomes to quality-of-life outcomes are being investigated. The inclusion criteria in these trials also varied in terms of volume of metastatic disease (oligometastatic to high-volume metastatic disease), diagnosis of metastases (imaging based vs biopsy confirmed), imaging modalities used (conventional to newer modalities), as well as outcomes and follow-up regimes. CONCLUSION: While there are differences in each protocol, each trial aims to address different aspects of CRP in de novo HSPC. Therefore, the specific goals of each study and the limitations have to be taken into consideration when interpreting the results of these trials.

Evidence and emerging trends in local therapy for metastatic hormone-sensitive prostate cancer: a narrative review.

Introduction: Metastatic hormone-sensitive prostate cancer (mHSPC) displays both simultaneous and sequential patterns of metastasis, emphasizing a comprehensive treatment approach that integrates both local therapy and systemic treatment strategies. The increasing use of molecular imaging has led to a rise in mHSPC diagnoses, underscoring the importance of identifying the right patient population and effective treatment concepts for this disease state. Results: Two prospective trials, HORRAD and STAMP EDE, investigated prostate radiotherapy (RT) for mHSPC; however, they did not show an overall survival (OS) benefit in the unselected cohort. Nonetheless, RT showed favorable outcomes in patients with fewer than five bone metastases, resulting in a 7% 3-year survival improvement and supporting the integration of RT in multimodal treatment for men with oligometastatic mHSPC. Regarding cytoreductive prostatectomy (cRP), the TRoMbone Trial confirmed its feasibility and safety. In addition, findings from the FUSCC-OMPCa Trial demonstrated improved 3-year radiographic progression-free survival and OS rates with acceptable rates of complications and incontinence. Recent data from the LoMP registry have further supported superior OS and cancer-specific survival (CSS) in patients undergoing cRP compared to systemic therapy alone. Notably, no significant differences in OS and CSS were observed between the cRP and RT groups. However, cRP-treated patients exhibited superior 2-year local event-free survival when compared to those treated with RT. Conclusion: RT in combination with systemic therapy remains the established first-line treatment for low-burden mHSPC, though the exact definition of low metastatic burden remains contentious. Precise assessment of metastatic burden is vital to identify patients who would derive the greatest benefit from RT. As treatment paradigms evolve, embracing multimodal approaches holds potential for optimizing outcomes in patients with mHSPC. Further research is needed to solidify the role of cRP as a standard therapeutic approach and to refine treatment strategies for improved patient outcomes.

A systematic review of cytoreductive prostatectomy outcomes and complications in oligometastatic disease.

Objective: To analyze outcomes and complications of cytoreductive prostatectomy (CRP) for oligometastatic prostate cancer (PCa) in order to elucidate its role in this space. Methods: We performed a systematic literature search using three databases (Medline, Scopus, and Web of Science). The primary endpoints were oncologic outcomes. The secondary endpoints were complication rates and functional results. Results: In all studies, overall survival was better or at least comparable variable in the groups with CRP compared to no local treatment. The greatest benefit from CRP in 5-year overall survival in one study was 67.4% for CRP versus 22.5% for no local treatment. Cancer-specific survival (CSS) showed the same trend. Several authors found significant benefits from CSS in the CRP group: from 79% vs. 46% to 100% vs. 61%. CRP was a predictor of better CSS (hazard ratio 0.264, p=0.004). Positive surgical margin rates differed widely from 28.6% to 100.0%. Urinary continence in CRP versus RP for localized PCa was significantly lower (57.4% vs. 90.8%, p<0.0001). Severe incontinence occurred seldom (2.5%-18.6%). Total complication rates after CRP differed widely, from 7.0% to 43.6%. Rates of grades 1 and 2 events prevailed. Patients on ADT alone also showed a considerable number of complications varying from 5.9% to 57.7%. Conclusion: CRP improves medium-term cancer control in patients with oligometastatic PCa. The morbidity and complication rates of this surgery are comparable with other approaches, but postoperative incontinence rate is higher compared with RP for localized disease.

An Updated Systematic and Comprehensive Review of Cytoreductive Prostatectomy for Metastatic Prostate Cancer.

(1) Background: Local therapy is highly promising in a multimodal approach strategy for patients with low-volume metastatic prostate cancer (mPCa). We aimed to systematically assess and summarize the safety, oncologic, and functional outcomes of cytoreductive prostatectomy (cRP) in mPCa. (2) Methods: Three databases were queried in September 2022 for publications that analyzed mPCa patients treated with cytoreductive prostatectomy without restrictions. The outcomes of interest were progression-free survival (PFS), cancer-specific survival (CSS), overall survival (OS), perioperative complication rates, and functional outcomes following cRP. (3) Results: Overall, 26 studies were included in this systematic review. Among eight population-based studies, cRP was associated with a reduced risk of CSS and OS compared with no local therapy (NLT) after adjusting for the effects of possible confounders. Furthermore, one population-based study showed that cRP reduced the risk of CSS even when compared with radiotherapy (RT) of the prostate after adjusting for the effects of possible confounders. In addition, one randomized controlled trial (RCT) demonstrated that local therapy (comprising 85% of cRP) significantly improved the prostate-specific antigen (PSA)-PFS and OS. Overall, cRP had acceptable perioperative complication rates and functional outcomes. (4) Conclusions: Mounting evidence suggests that cRP offers promising oncological and functional outcomes and technical feasibility and that it is associated with limited complications. Well-designed RCTs that limit selection bias in patients treated with cRP are warranted.

Current Controversy and Developments Regarding the Cytoreductive Prostatectomy for Oligometastatic Prostate Cancer.

Oligometastatic prostate cancer is a term that is most often used to refer to limited sites of disseminated tumor growth following primary radical prostatectomy (RP) or radiotherapy (RT), while de novo oligometastatic is a term that is used to refer to prostate tumors that have disseminated to limited sites before definitive treatment. In patients with de novo oligometastatic prostate cancer, treatment planning must thus consider the need to manage the primary tumor and the associated distant lesions. Traditionally, resectioning primary metastatic tumors is not thought to offer significant benefits to affected patients while increasing their risk of surgery-related complications. Recent clinical evidence indicates that patients undergoing cytoreductive prostatectomy (CRP) may observe substantial enhancements in overall survival rates while not experiencing a noticeable decline in their quality of life. Nevertheless, based on the current body of evidence, it is deemed inadequate to justify revising clinical guidelines. Consequently, it is not advisable to propose CRP for patients with oligometastatic prostate cancer. The present review was compiled to summarize available data regarding the indications, functional outcomes, and oncological outcomes associated with cytoreductive radical prostatectomy to provide a robust and objective foundation that can be used to better assess the value of this interventional strategy from a clinical perspective.

The cytoreductive radical prostatectomy in metastatic prostate cancer.

BACKGROUND: In metastatic prostate cancer (mPCa), the standard treatment involves systemic treatment including androgen deprivation therapy (ADT), possibly in combination with new drugs called androgen receptor targeting agents (ARTA) or docetaxel. The treatment of the prostate itself in mPCa represents a new paradigm in the so-called oligometastatic prostate cancer (OMPCa), which is considered to be a kind of intermediate stage between localized disease and extensive metastatic disease. Thanks to new dia-gnostic methods, OMPCa is an increasingly frequently dia-gnosed stage of mPCa. In addition to improving local control of the disease, aggressive local therapy could lower the need for ADT, or improve survival. Radiotherapy has already demonstrated the oncological benefit of OMPCa in a randomized study and is now part of the guidelines for the treatment of low volume de novo mPCa. Cytoreductive prostatectomy (CP) is still awaiting the results of randomized trials; however, retrospective data already exist to support this treatment modality. Several population-based studies have been published that have demonstrated the benefit of CP. Minor retrospective works have demonstrated the safety of CP in clinical practice. Several prospective randomized trials investigating this treatment modality are currently underway. However, the whole concept of CP in OMPCa is still shrouded in many unresolved issues such as the definition of a suitable patient and the role of another form of local therapy targeted to metastases. PURPOSE: This article aims to provide an overview of key published or ongoing studies related to CP in relation not only to functional and oncological results but also to the indication criteria and design of individual studies.

The role of radical prostatectomy for the treatment of metastatic prostate cancer: a systematic review and meta-analysis.

The recommended therapy by EAU guidelines for metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT) with or without chemotherapy. The role of radical prostatectomy (RP) in the treatment of mPCa is still controversial. Hence, a meta-analysis was conducted by comprehensively searching the databases PubMed, EMBASE and Web of Science for the relevant studies published before September 1st, 2017. Our results successfully shed light on the relationship that RP for mPCa was associated with decreased cancer-specific mortality (CSM) (pooled HR = 0.41, 95%CI = 0.36-0.47) and enhanced overall survival (OS) (pooled HR = 0.49, 95%CI = 0.44-0.55). Subsequent stratified analysis demonstrated that no matter how RP compared with no local therapy (NLT) or radiation therapy (RT), it was linked to a lower CSM (pooled HR = 0.36, 95%CI = 0.30-0.43 and pooled HR = 0.56, 95%CI 0.43-0.73, respectively) and a higher OS (pooled HR = 0.49, 95%CI = 0.44-0.56 and pooled HR = 0.46, 95%CI 0.33-0.65, separately). When comparing different levels of Gleason score, M-stage or N-stage, our results indicated that high level of Gleason score, M-stage or N-stage was associated with increased CSM. In summary, the outcomes of the present meta-analysis demonstrated that RP for mPCa was correlated with decreased CSM and enhanced OS in eligible patients of involved studies. In addition, patients with less aggressive tumors and good general health seemed to benefit the most. Moreover, no matter compared with NLT or RT, RP showed significant superiority in OS or CSM. Upcoming prospective randomized controlled trials were warranted to provide more high-quality data.

Cytoreductive prostatectomy in metastatic prostate cancer: a systematic review.

The impact of cytoreductive radical prostatectomy on oncological outcome in patients with prostate cancer and limited number of bone metastases is unclear. Data from cancer registries, multi-institutional databases and a single institutional case-control study indicate a possible benefit of combined cytoreduction and hormonal therapy compared to hormonal therapy alone. However, the results may be biased by a number of factors. The evidence from studies on cytoreductive prostatectomy is reviewed.

Local Therapy Improves Survival in Metastatic Prostate Cancer.

BACKGROUND: Treatment of the primary, termed local therapy (LT), may improve survival in metastatic prostate cancer (mPCa) versus no local therapy (NLT). OBJECTIVE: To assess cancer-specific mortality (CSM) after LT versus NLT in mPCa. DESIGN, SETTING, AND PARTICIPANTS: Within the Surveillance, Epidemiology and End Results database (2004-2013), 13 692 mPCa patients were treated with LT (radical prostatectomy [RP] or radiation therapy [RT]) or NLT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable competing risk regression analyses (MVA CRR) tested CSM after propensity score matching (PSM) in two analyses, (1) NLT versus LT and (2) RP versus RT, and were complemented with interaction, sensitivity, unmeasured confounder, and landmark analyses. RESULTS AND LIMITATIONS: Of 13 692 mPCa patients, 474 received LT: 313 underwent RP and 161 RT. In MVA CRR, after PSM, LT (n=474) results in lower CSM (subhazard ratio [SHR] 0.40, 95% confidence interval [CI] 0.32-0.50) versus NLT (n=1896). In MVA CRR after PSM, RP (n=161) results in lower CSM (SHR 0.59, 95% CI 0.35-0.99) versus RT (n=161). Invariably, lowest CSM rates were recorded for Gleason ≤7, ≤cT3, and M1a substage. Interaction and sensitivity analyses confirmed the robustness of results, and landmark analyses rejected the bias favouring LT. A strong unmeasured confounder (HR=5), affecting 30% of NLT patients, could obliterate LT benefit. Data were retrospective. CONCLUSIONS: In mPCa, LT results in lower mortality relative to NLT. Within LT, lower mortality is recorded after RP than RT. Patients with most favourable grade, local stage, and metastatic substage derive most benefit from LT. They also derive most benefit from RP, when LT types are compared (RP vs RT). It is important to consider study limitations until ongoing clinical trials confirm the proposed benefits. PATIENT SUMMARY: Individuals with prostate cancer that spreads outside of the prostate might still benefit from prostate-directed treatments, such as radiation or surgery, in addition to receiving androgen deprivation therapy.