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Immunotherapy: Personalized Treatment for Advanced Prostate Cancer

Sandra Kelly, RN, MS, NP, Nurse Practitioner, Brigham & Women’s Hospital
Allison Tyler, RN, BSN, OCN®, CCRP, Staff Nurse, Cleveland Clinic
Published: Wednesday, Sep 19, 2012

In 2000, Dr. Howard Scher published the then-current practice algorithm for the various stages of prostate cancer. Healthcare practitioners used that algorithm almost exclusively and virtually unchanged for the ensuing 10 years. Then, in the spring of 2010, the algorithm changed substantially for patients with advanced prostate cancer. Two new therapies were approved for use in patients with post-docetaxel, metastatic, castration-resistant, progressive prostate cancer, and something happened that scientists had long worked toward. In April 2010, the US Food and Drug Administration approved sipuleucel-T (Provenge®, Dendreon Corporation), an immune therapy and the first treatment for pre-chemotherapy use. Patients with castration-resistant and metastatic disease now had a treatment that would help the body fight its own cancer. This white paper focuses on the new immunotherapy, Provenge.
Prostate cancer is the second most common cancer in men worldwide, with an estimated 903,500 new cases and 258,400 deaths in 2008.1 In 2012, about 241,740 men will be newly diagnosed with prostate cancer in the United States alone.2 Widespread use of screening with digital rectal examination and prostate-specific antigen (PSA) testing has led to an increasing proportion of prostate cancers that are localized at diagnosis, and fewer patients present initially with metastatic disease. In 1998, a retrospective data analysis suggested that 6.4% of presenting cases were stage 4. Most newly diagnosed patients with prostate carcinoma are asymptomatic and have moderately differentiated and organ-confined disease.3,4 However, about one-third of men who have undergone primary treatment with either prostatectomy or radiation therapy need additional therapy because of progressive disease.5

The standard systemic therapy for patients who progress after primary treatment is androgen deprivation.6 Currently, androgen-deprivation therapy (ADT), luteinizing hormonereleasing hormone (LHRH) agonists in combination with anti-androgen, is used for palliative treatment of advanced carcinoma of the prostate and as adjuvant therapy with radiation therapy.6 ADT tends to be used widely in other patient scenarios, including biochemical recurrence, locally advanced disease, lymph node metastasis, and asymptomatic metastatic disease, despite the fact that overall survival has not been demonstrated in clinical trials for ADT in metastatic disease.6 The median duration of response to ADT is about 10 years; however, almost all men on ADT eventually develop disease that is resistant to some hormonal regimens, which classifies a patient as having hormone-refrectory disease. Some men respond to secondary hormonal treatments, but when their disease is resistant to all hormonal manipulations, they have castration-resistant prostate cancer (CRPC).6,7,8

Clinical trials have demonstrated that a substantial proportion of men with CRPC go on to develop metastases. One study showed that 84% of men with CRPC had bone metastases at diagnosis; in another, 95% did. Men with no metastases at diagnosis commonly also develop metastases after diagnosis.8 Prostate cancer still remains the second most common cause of death in men in the United States.2

Castration-resistant disease is manifested in several ways.8

  • Rising PSA values despite hormonal therapy
  • New sites of metastatic disease on radiographic imaging
  • Clinical symptoms of the disease, such as fatigue, anorexia, or bone pain (with radiographic confirmation of metastatic disease)
CRPC is aggressive, with median bone metastasis–free survival of 25 months (bone is the most common site of metastasis).8 Until recently, the initial treatment approach has been ADT to control PSA with an anti-androgen drug and LHRH agonist.9 Upon further disease progression, chemotherapy often is used to control symptoms and extend survival.10

In most patients with prostate cancer, clinical prognostic factors are used to identify patients at risk for metastatic disease.11,12 One such prognostic tool is the Gleason score. A Gleason grade predicts how fast cancer might spread on a scale of 1–5. One biopsy sample may have two Gleason grades, which are added together to provide a Gleason score. The higher a Gleason score, the more likely the cancer is to spread.2

Patients at high risk for the development of metastatic disease are those with Gleason score of 8 and higher, PSA greater than 20, and clinical stage T3-4.11 High serum PSA, rapid PSA doubling time, higher clinical stage, and the presence of extracapsular extension or seminal vesicle invasion of the tumor are other indicators that a patient is more likely to develop metastatic disease.13 Once patients become castration resistant, the time to development of bone metastases is impacted by a baseline PSA higher than 10 and a rapid PSA velocity.14 These two factors have been significantly associated with shorter time to first bone metastasis and also predicted overall survival and bone metastasis–free survival.14

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Clinical Interchange™: Translating Research to Inform Changing Paradigms: Assessment of Emerging Immuno-Oncology Strategies and Combinations across Lung, Head and Neck, and Bladder CancersOct 31, 20182.0
35th Annual Chemotherapy Foundation Symposium: Innovative Cancer Therapy for Tomorrow® Clinical Vignette SeriesJan 31, 20192.0
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