A pilot trial of pembrolizumab plus prostatic cryotherapy for men with newly diagnosed oligometastatic hormone-sensitive prostate cancer

Ross, Ashley E.; Hurley, Paula J.; Tran, Phuoc T.; Rowe, Steven P.; Benzon, Benjamin; Neal, Tanya O’; Chapman, Carolyn G.; Harb, Rana; Milman, Yelena; Trock, Bruce J.; Drake, Charles G.; Antonarakis, Emmanuel S.

doi:10.1038/s41391-019-0176-8

Cited by 42 publications

(38 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Median PFS was 14 months and median systemic therapy-free survival was 17.5 months. 34 There were no grade 3 adverse events, with grade 1 (non-pad, occasional) urinary incontinence in 16.7% (n=2). 34 This profile is in keeping with the favourable early functional outcomes from cryotherapy in patients with non-metastatic disease.…”

Section: Cytoreductive Radical Prostatectomymentioning

confidence: 83%

“… 34 There were no grade 3 adverse events, with grade 1 (non-pad, occasional) urinary incontinence in 16.7% (n=2). 34 This profile is in keeping with the favourable early functional outcomes from cryotherapy in patients with non-metastatic disease. 54 With regard to safety, there were no reported cases of rectal injury or fistulae in either study.…”

Section: Cytoreductive Radical Prostatectomymentioning

confidence: 83%

“… 34 In total, 12 men with oligometastatic disease initiated 8 months of ADT and pembrolizumab, with subsequent whole-gland cryotherapy. 34 Primary endpoint was PSA <0.6 ng/mL at 1 year, and this was met in 42% (n=5). Median PFS was 14 months and median systemic therapy-free survival was 17.5 months.…”

Section: Cytoreductive Radical Prostatectomymentioning

confidence: 99%

“… 54 With regard to safety, there were no reported cases of rectal injury or fistulae in either study. 34 53 In both studies, men did not receive prior systemic therapy escalation and thus the ‘additive’ value of cytoreductive cryotherapy in such a cohort remains unclear. 34 53 …”

Section: Cytoreductive Radical Prostatectomymentioning

confidence: 99%

“… 34 53 In both studies, men did not receive prior systemic therapy escalation and thus the ‘additive’ value of cytoreductive cryotherapy in such a cohort remains unclear. 34 53 …”

Section: Cytoreductive Radical Prostatectomymentioning

confidence: 99%

See 4 more Smart Citations

Additional Treatments to the Local tumour for metastatic prostate cancer-Assessment of Novel Treatment Algorithms (IP2-ATLANTA): protocol for a multicentre, phase II randomised controlled trial

et al. 2021

View full text Add to dashboard Cite

IntroductionSurvival in men diagnosed with de novo synchronous metastatic prostate cancer has increased following the use of upfront systemic treatment, using chemotherapy and other novel androgen receptor targeted agents, in addition to standard androgen deprivation therapy (ADT). Local cytoreductive and metastasis-directed interventions are hypothesised to confer additional survival benefit. In this setting, IP2-ATLANTA will explore progression-free survival (PFS) outcomes with the addition of sequential multimodal local and metastasis-directed treatments compared with standard care alone.MethodsA phase II, prospective, multicentre, three-arm randomised controlled trial incorporating an embedded feasibility pilot. All men with new histologically diagnosed, hormone-sensitive, metastatic prostate cancer, within 4 months of commencing ADT and of performance status 0 to 2 are eligible. Patients will be randomised to Control (standard of care (SOC)) OR Intervention 1 (minimally invasive ablative therapy to prostate±pelvic lymph node dissection (PLND)) OR Intervention 2 (cytoreductive radical prostatectomy±PLND OR prostate radiotherapy±pelvic lymph node radiotherapy (PLNRT)). Metastatic burden will be prespecified using the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease (CHAARTED) definition. Men with low burden disease in intervention arms are eligible for metastasis-directed therapy, in the form of stereotactic ablative body radiotherapy (SABR) or surgery. Standard systemic therapy will be administered in all arms with ADT±upfront systemic chemotherapy or androgen receptor agents. Patients will be followed-up for a minimum of 2 years. Primary outcome: PFS. Secondary outcomes include predictive factors for PFS and overall survival; urinary, sexual and rectal side effects. Embedded feasibility sample size is 80, with 918 patients required in the main phase II component. Study recruitment commenced in April 2019, with planned follow-up completed by April 2024.Ethics and disseminationApproved by the Health Research Authority (HRA) Research Ethics Committee Wales-5 (19/WA0005). Study results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03763253; ISCRTN58401737

show abstract

Section: Cytoreductive Radical Prostatectomymentioning

confidence: 83%

Section: Cytoreductive Radical Prostatectomymentioning

confidence: 83%

Section: Cytoreductive Radical Prostatectomymentioning

confidence: 99%

Section: Cytoreductive Radical Prostatectomymentioning

confidence: 99%

“… 34 53 In both studies, men did not receive prior systemic therapy escalation and thus the ‘additive’ value of cytoreductive cryotherapy in such a cohort remains unclear. 34 53 …”

Section: Cytoreductive Radical Prostatectomymentioning

confidence: 99%

See 3 more Smart Citations

Additional Treatments to the Local tumour for metastatic prostate cancer-Assessment of Novel Treatment Algorithms (IP2-ATLANTA): protocol for a multicentre, phase II randomised controlled trial

et al. 2021

View full text Add to dashboard Cite

show abstract

The Story of Breast and Prostate Cancer: Parallels and Common Controversies

Avolio,

Lughezzani,

Sanchez-Salas

2024

Imaging and Focal Therapy of Early Prostate Cancer

View full text Add to dashboard Cite

Immunotherapy in prostate cancer: new horizon of hurdles and hopes

et al. 2020

View full text Add to dashboard Cite

Purpose Prostate cancer (PCa) is the most common malignancy in men and the cause for the second most common cancer-related death in the western world. Despite ongoing development of novel approaches such as second generation androgen receptor targeted therapies, metastatic disease is still fatal. In PCa, immunotherapy (IT) has not reached a therapeutic breakthrough as compared to several other solid tumors yet. We aimed at highlighting the underlying cellular mechanisms crucial for IT in PCa and giving an update of the most essential past and ongoing clinical trials in the field. Methods We searched for relevant publications on molecular and cellular mechanisms involved in the PCa tumor microenvironment and response to IT as well as completed and ongoing IT studies and screened appropriate abstracts of international congresses. Results Tumor progression and patient outcomes depend on complex cellular and molecular interactions of the tumor with the host immune system, driven rather dormant in case of PCa. Sipuleucel-T and pembrolizumab are the only registered immune-oncology drugs to treat this malignancy. A plethora of studies assess combination of immunotherapy with other agents or treatment modalities like radiation therapy which might increase its antineoplastic activity. No robust and clinically relevant prognostic or predictive biomarkers have been established yet. Conclusion Despite immunosuppressive functional status of PCa microenvironment, current evidence, based on cellular and molecular conditions, encourages further research in this field.

show abstract

A pilot trial of pembrolizumab plus prostatic cryotherapy for men with newly diagnosed oligometastatic hormone-sensitive prostate cancer

Cited by 42 publications

References 38 publications

Additional Treatments to the Local tumour for metastatic prostate cancer-Assessment of Novel Treatment Algorithms (IP2-ATLANTA): protocol for a multicentre, phase II randomised controlled trial

Additional Treatments to the Local tumour for metastatic prostate cancer-Assessment of Novel Treatment Algorithms (IP2-ATLANTA): protocol for a multicentre, phase II randomised controlled trial

The Story of Breast and Prostate Cancer: Parallels and Common Controversies

Immunotherapy in prostate cancer: new horizon of hurdles and hopes

Contact Info

Product

Resources

About