{
  "abstract": "Background Grade group 5 (GG5) prostate cancer (PCa) carries a less favorable prognosis after standard-of-care (SOC) therapy, necessitating novel therapeutic approaches. High-dose rate brachytherapy (HDRBT) and androgen deprivation therapy (ADT) may modulate immune response in GG5 PCa, particularly in tumors with increased immune content. This study evaluated whether the addition of nivolumab to SOC was associated with improved disease control in patients with high-volume GG5 PCa, including those with oligometastatic disease.Methods In this non-randomized phase II trial, 31 patients with localized or oligometastatic GG5 PCa and >30% positive biopsy cores were evaluated between September 2018 and April 2021. Patients received four doses of nivolumab (240 mg every 2 weeks) beginning 4 weeks prior to HDRBT, alongside ADT, HDRBT, and external beam radiation. The primary endpoint was to evaluate whether the 2-year freedom from biochemical recurrence (FFBR) rate would exceed a prespecified historical control rate of 75%.Results Among the 31 patients, the median follow-up was 38.8 months (IQR 31.0–46.5 months). The addition of nivolumab to SOC RT with ADT was associated with a 2-year FFBR rate of 90.3% (95% CI 74.3% to 98.0%) (median FFBR not reached), exceeding the prespecified historical control rate of 75% (one-sided p value from binomial test=0.024). Definitive and probable nivolumab-related toxicity included 6.3% acute grade 2 and 6.3% acute grade 3 adverse events (AEs), with no grade 4+ AEs observed. A higher Decipher immunosuppression score at diagnosis correlated with early pathologic response (p=0.005) and was independently associated with time to metastatic failure (p=0.044).Conclusions Nivolumab combined with SOC was associated with encouraging FFBR in this high-risk GG5 PCa population and may represent a promising therapeutic intensification strategy. The Decipher immunosuppression score may serve as a predictive biomarker for response. These findings warrant further investigation in randomized trials.",
  "authors": [
    {
      "affiliations": [
        "Radiation Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA",
        "Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, USA"
      ],
      "name": "John Michael Bryant"
    },
    {
      "affiliations": [
        "Radiation Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Maria Sandoval"
    },
    {
      "affiliations": [
        "Biostatistics and Bioinformatics, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Ryan Putney"
    },
    {
      "affiliations": [
        "Cancer Epidemiology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Purvish Trivedi"
    },
    {
      "affiliations": [
        "Cancer Epidemiology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Esther N Katende"
    },
    {
      "affiliations": [
        "Cancer Epidemiology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Angelina Fink"
    },
    {
      "affiliations": [
        "Biostatistics and Bioinformatics, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Syeda Mahrukh Naqvi"
    },
    {
      "affiliations": [
        "Biostatistics and Bioinformatics, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Youngchul Kim"
    },
    {
      "affiliations": [
        "Biostatistics and Bioinformatics, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Vivian Yin"
    },
    {
      "affiliations": [
        "Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Jingsong Zhang"
    },
    {
      "affiliations": [
        "Cancer Epidemiology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Jong Y Park"
    },
    {
      "affiliations": [
        "Anatomic Pathology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Amparo Serna"
    },
    {
      "affiliations": [
        "Radiation Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Nghi Lam"
    },
    {
      "affiliations": [
        "Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Julio Pow-Sang"
    },
    {
      "affiliations": [
        "Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Michael Poch"
    },
    {
      "affiliations": [
        "Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Roger Li"
    },
    {
      "affiliations": [
        "Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Brandon J Manley"
    },
    {
      "affiliations": [
        "Radiation Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Arash Naghavi"
    },
    {
      "affiliations": [
        "Radiation Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Javier Torres-Roca"
    },
    {
      "affiliations": [
        "Radiation Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "G Daniel Grass"
    },
    {
      "affiliations": [
        "Radiation Oncology, Mayo Clinic Alix College of Medicine & Health Sciences, Jacksonville, Florida, USA"
      ],
      "name": "Sungjune Kim"
    },
    {
      "affiliations": [
        "Radiation Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Kujtim Latifi"
    },
    {
      "affiliations": [
        "Radiation Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Dylan Hunt"
    },
    {
      "affiliations": [
        "Radiation Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Peter Johnstone"
    },
    {
      "affiliations": [
        "Anatomic Pathology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Jasreman Dhillon"
    },
    {
      "affiliations": [
        "Immuno-Oncology Program, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Paulo C Rodriguez"
    },
    {
      "affiliations": [
        "Weill Cornell Medicine/NewYork-Presbyterian Hospital, New York, New York, USA"
      ],
      "name": "Rohit Jain"
    },
    {
      "affiliations": [
        "Radiation Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Daniel C Fernandez"
    },
    {
      "affiliations": [
        "Radiation Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"
      ],
      "name": "Kosj Yamoah"
    }
  ],
  "title": "Phase II trial of combination radiation, hormone, and immunotherapy in grade group 5 prostate cancer",
  "uid": "fae042a6-da7b-51ed-ac50-462090bf5870"
}