Publications by authors named "Mark C Markowski"

Introduction: Non-castrating therapies are an unmet clinical need for patients with advanced prostate cancer. To maximize quality of life and prioritize cardiovascular health, we investigated SGLT2 inhibitors as a non-castrating therapy in patients with prostate cancer.

Materials And Methods: We conducted a retrospective analysis of patients with either local or biochemically recurrent prostate cancer who initiated therapy with an SGLT2 inhibitor without concurrent androgen deprivation therapy.

View Article and Find Full Text PDF

Background And Objective: Owing to the expansion of treatment options for metastatic hormone-sensitive prostate cancer (mHSPC) and an appreciation of clinical subgroups with differential prognosis and treatment responses, prognostic and predictive biomarkers are needed to personalize care in this setting. Our aim was to evaluate a multimodal artificial intelligence (MMAI) biomarker for prognostic ability in mHSPC.

Methods: We used data from the phase 3 CHAARTED trial; 456/790 patients with mHSPC had evaluable digital histopathology images and requisite clinical variables to generate MMAI scores for inclusion in our analysis.

View Article and Find Full Text PDF
Article Synopsis
  • Renal cell carcinoma (RCC) is a prevalent kidney cancer, and PSMA is a protein found in high levels in certain tumors, including metastatic RCC. This study investigates the effectiveness of PSMA-based imaging and treatment in preclinical models of RCC.
  • Researchers developed a PSMA-overexpressing murine cell line and used advanced imaging techniques (PET/CT and PET/MR) to assess the accumulation and treatment potential of tailored radiotheranostic agents (Ga-L1, Lu-L1, and Ac-L1) specifically targeting cancerous cells.
  • Results showed significantly higher uptake of the PSMA-targeted agents in cancerous cells compared to normal cells, indicating the specificity of these
View Article and Find Full Text PDF

[Lu]Lu-PSMA-617 was approved by the U.S. Food and Drug Administration for patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC).

View Article and Find Full Text PDF

Importance: Olaparib is a poly(adenosine diphosphate-ribose) polymerase inhibitor that provides benefit in combination with hormonal therapies in patients with metastatic prostate cancer who harbor homologous recombination repair (HRR) alterations. Its efficacy in the absence of androgen deprivation therapy has not been tested.

Objective: To determine the activity of olaparib monotherapy among patients with high-risk biochemically recurrent (BCR) prostate cancer after radical prostatectomy.

View Article and Find Full Text PDF
Article Synopsis
  • High-dose intravenous vitamin C (HDIVC) was tested alongside docetaxel in a clinical trial for patients with advanced prostate cancer, showing no significant benefit compared to docetaxel alone.
  • The trial involved 47 participants and measured effectiveness through PSA response rates, overall survival, and quality of life, with similar outcomes in both the HDIVC and placebo groups.
  • The study was halted early due to no evidence that HDIVC improved cancer treatment results, suggesting it shouldn’t be routinely used for metastatic castration-resistant prostate cancer.
View Article and Find Full Text PDF

Background: The activity of PARP inhibitors (PARPi) in patients with homologous recombination repair (HRR) mutations and metastatic castration-resistant prostate cancer has been established. We hypothesized that the benefit of PARPi can be maintained in the absence of androgen deprivation therapy (ADT) in an HRR-mutated population. We report the results of a phase II clinical trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer (mHSPC).

View Article and Find Full Text PDF

Background: Poly ADP-ribose polymerase (PARP) inhibitors are approved for the treatment of some men with advanced prostate cancer. Rare but serious side effects include myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The impact of PARP inhibitors on clonal hematopoiesis (CH), a potential precursor lesion associated with MDS and AML, is incompletely understood in prostate cancer.

View Article and Find Full Text PDF

Cyclic high-dose testosterone administration, known as bipolar androgen therapy (BAT), is a treatment strategy for patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we report the results of a multicenter, single arm Phase 2 study (NCT03554317) enrolling 45 patients with heavily pretreated mCRPC who received BAT (testosterone cypionate, 400 mg intramuscularly every 28 days) with the addition of nivolumab (480 mg intravenously every 28 days) following three cycles of BAT monotherapy. The primary endpoint of a confirmed PSA response rate was met and estimated at 40% (N = 18/45, 95% CI: 25.

View Article and Find Full Text PDF

Increased mitochondrial function may render some cancers vulnerable to mitochondrial inhibitors. Since mitochondrial function is regulated partly by mitochondrial DNA copy number (mtDNAcn), accurate measurements of mtDNAcn could help reveal which cancers are driven by increased mitochondrial function and may be candidates for mitochondrial inhibition. However, prior studies have employed bulk macrodissections that fail to account for cell type-specific or tumor cell heterogeneity in mtDNAcn.

View Article and Find Full Text PDF

Multiple studies have demonstrated prostate-specific membrane antigen (PSMA) expression in the neo-vasculature of non-prostate tumors including clear cell renal cell carcinoma (ccRCC). However, PSMA expression in rare renal tumors including MiTF family translocation renal cell carcinoma has not been previously characterized. We examined PSMA expression by immunohistochemistry in a series of MiTF family translocation renal cell carcinomas as well as in several genetically related tumors including alveolar soft part sarcoma and PEComas with TFE3 rearrangements.

View Article and Find Full Text PDF

Objectives: We evaluated F-DCFPyL test-retest repeatability of uptake in normal organs.

Methods: Twenty-two prostate cancer (PC) patients underwent two F-DCFPyL PET scans within 7 days within a prospective clinical trial (NCT03793543). In both PET scans, uptake in normal organs (kidneys, spleen, liver, and salivary and lacrimal glands) was quantified.

View Article and Find Full Text PDF

Objective: Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has revolutionized the treatment of patients with many tumor histologies. Simultaneously, stereotactic body radiotherapy (SBRT) provides excellent local control (LC) and plays an important role in the management of spine metastasis. Promising preclinical work suggests the potential therapeutic benefit of combining SBRT with ICI therapy, but the safety profile of combined therapy is unclear.

View Article and Find Full Text PDF

Inhibition of androgen receptor (AR) signaling has been the mainstay of treatment of advanced prostate cancer (PCa) for the past 80 years. Combination and sequential AR-inhibiting therapies are highly effective palliative therapy, but they are not curative. All patients eventually develop resistance to primary castrating therapy [ie, castration-resistant PCa (CRPC)].

View Article and Find Full Text PDF

Increased mitochondrial function may render some cancers vulnerable to mitochondrial inhibitors. Since mitochondrial function is regulated partly by mitochondrial DNA copy number (mtDNAcn), accurate measurements of mtDNAcn could help reveal which cancers are driven by increased mitochondrial function and may be candidates for mitochondrial inhibition. However, prior studies have employed bulk macrodissections that fail to account for cell type-specific or tumor cell heterogeneity in mtDNAcn.

View Article and Find Full Text PDF

Introduction: The bromodomain and extraterminal (BET) family of proteins are epigenetic readers of acetylated histones and are critical activators of oncogenic networks across many cancers. Therapeutic targeting of BET proteins has been an attractive area of clinical development for metastatic castration-resistant prostate cancer. In recent years, many structurally diverse BET inhibitors have been discovered and tested.

View Article and Find Full Text PDF

Objective: The aims of this study were to investigate the utility of [F]F-Florastamin, a novel prostate-specific membrane antigen (PSMA)-targeted PET radiotracer with facile radiochemistry, relative to the conventional imaging for the detection of sties of disease and evaluate the effect of multi-timepoint imaging with [F]F-Florastamin PET on lesion detectability.

Methods: Eight prostate cancer patients with known or suspected recurrence who underwent [F]F-Florastamin PET/CT at 1-h and 2-h imaging time-points were included in this prospective pilot study. [F]F-Florastamin PET images were interpreted visually and quantitatively at both time points and compared with CIM.

View Article and Find Full Text PDF

Objectives: PET-based radiomic metrics are increasingly utilized as predictive image biomarkers. However, the repeatability of radiomic features on PET has not been assessed in a test-retest setting. The prostate-specific membrane antigen-targeted compound F-DCFPyL is a high-affinity, high-contrast PET agent that we utilized in a test-retest cohort of men with metastatic prostate cancer (PC).

View Article and Find Full Text PDF

Testosterone is the canonical growth factor of prostate cancer but can paradoxically suppress its growth when present at supraphysiological levels. We have previously demonstrated that the cyclical administration of supraphysiological androgen (SPA), termed bipolar androgen therapy (BAT), can result in tumor regression and clinical benefit for patients with castration-resistant prostate cancer. However, predictors and mechanisms of response and resistance have been ill defined.

View Article and Find Full Text PDF

The treatment landscape of renal cell carcinoma is rapidly evolving, especially with the introduction and approval of immune checkpoint inhibitor combination therapies. Clinical trial data show substantial improvements in patient outcomes, and now results in the real-world setting support the use of these combinations.

View Article and Find Full Text PDF

Introduction: 10-year outcomes in patients living with HIV who are diagnosed with prostate cancer are unknown.

Methods: 52 patients living with HIV were diagnosed with prostate cancer. Disease-free survival stratified by clinical, pathologic, and HIV characteristics were examined.

View Article and Find Full Text PDF

Unlabelled: Bipolar androgen therapy (BAT) relies on oscillating levels of serum testosterone as a way to treat patients with metastatic castration-resistant prostate cancer (mCRPC). Aggressive-variant prostate cancers typically require combination chemotherapy and are frequently associated with loss-of-function mutations in tumor suppressor genes. Here we report clinical outcomes after BAT among patients with mCRPC harboring pathogenic alterations in at least two of three genes: , and In this setting, BAT induced a meaningful PSA response rate, progression-free survival and overall survival, particularly in patients without prior chemotherapy.

View Article and Find Full Text PDF

Purpose: Sabizabulin, an oral cytoskeleton disruptor, was tested in a phase Ib/II clinical study in men with metastatic castration-resistant prostate cancer (mCRPC).

Patients And Methods: The phase Ib portion utilized a 3+3 design with escalating daily oral doses of 4.5-81 mg and increasing schedule in 39 patients with mCRPC treated with one or more androgen receptor-targeting agents.

View Article and Find Full Text PDF

Bipolar androgen therapy (BAT) is a new treatment concept for men whose prostate cancer has become resistant to standard hormone-blocking therapy. Over the past decade, we have performed a series of clinical studies testing BAT in asymptomatic men with castration-resistant prostate cancer. The key findings from these clinical studies are that BAT (a) can be safely administered to asymptomatic patients with metastatic castrate-resistant prostate cancer; (b) does not produce symptomatic disease progression; (c) produces sustained prostate-specific antigen and objective responses in 30%-40% of patients; and (d) can resensitize and prolong response to subsequent antiandrogen therapy.

View Article and Find Full Text PDF