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Applying Key Insights from the PROCEED Real-World Registry to Clinical Practice

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Tremendous advances have been made in the field of immunotherapy in the last decade, changing treatment paradigms across a number of cancer types. Today there are nearly 4,000 immunotherapeutic drugs in the global development pipeline.1 Those of us who specialize in the treatment of cancer are excited about the pace of innovation. But the truth is that many of these novel agents will not be available for some time outside of clinical trials, and their effectiveness in solid tumors remains a clinical challenge.

Urology is the fortunate exception. Immunotherapy has been available to us as a treatment option for advanced prostate cancer since 2010. That year, the FDA approved sipuleucel-T (PROVENGE®) for the treatment of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). This was a paradigm shift in how this patient population was managed, and would mark the beginning of a cascade of treatment options that extend life for these men.

In many ways PROVENGE was before its time, in a period when few outside of immunology understood how immunotherapy worked. The product struggled to find its niche as a result. Nine years later we see the true potential as the large body of evidence clearly shows the benefit of immunotherapy when incorporated into the standard mCRPC treatment regimen.

Recently published results from the PROCEED registry (2011-2017) – the largest real-world study of immunotherapy – have shed new light on the potential of PROVENGE to extend survival in men with mCRPC when PSA levels are low.2 PSA levels at mCRPC diagnosis have declined steadily since the approval of PROVENGE in 2010 making these new findings particularly relevant to those of us who routinely see patients with early mCRPC.

Nearly 4 Year Median OS in Men with Low PSA
This PROCEED registry (NCT01306890) was a multicenter, open-label, observational registry conducted at urology and medical oncology clinics in private practice and academic sites. PROCEED enrolled nearly 2,000 men with mCRPC who received PROVENGE in everyday treatment settings between 2011 and 2014. Men in the registry were followed for a median of 46.6 months. Their median age was 72 years and their median baseline prostate-specific antigen (PSA) level was 15.0 ng/mL, a sharp contrast to the median PSA of 50 ng/mL observed in the Phase 3 pivotal IMPACT trial.

Findings from PROCEED were recently published in Cancer, and showed that men with mCRPC who were treated with PROVENGE when their PSA levels were low lived a median of nearly four years in a real-world treatment setting.

The analysis subdivided baseline PSA levels into quartiles to evaluate treatment effect patterns, and found that men with the lowest level PSA (≤5.27 ng/mL; n=472) had median survival of 47.7 months.3

These real-world findings are impressive, validating how urologists have been treating mCRPC patients in the “modern era” of prostate cancer. In the past decade, our treatment armamentarium has changed significantly with the addition of five agents with life-extending benefits. However, with this “embarrassment of riches” has come many important questions about when to administer each of these therapies and which sequence provides the greatest positive impact on survival. The key is to be able to use one therapy and reserve the others for later use to help patients live better and longer.

The PROCEED results also have provided useful information in that regard, showing that 44% of men in the lowest PSA quartile (≤5.27 ng/mL) did not receive another cancer treatment for at least a year. Of those patients, 95% were treated with sipuleucel-T as first-line therapy for mCRPC, as recommended by the National Comprehensive Cancer Network (NCCN). For urologists who treat patients with advanced prostate cancer, it is essential to follow recommended treatment guidelines and critically evaluate the appropriate treatment pathway for each individual patient. The availability of practical, real-world data that supplements clinical trial findings makes that decision-making process easier, as is the case with the PROCEED registry findings, which are consistent with survival and safety outcomes observed in the IMPACT trial.

Additionally, the PROCEED registry is consistent with results of a post hoc analysis published in Urology in 2013,4 demonstrating that treatment with sipuleucel-T when baseline PSA levels were lower was associated with longer OS.

Among patients with a baseline PSA ≤22.1 ng/mL, the median OS was 41.3 months (3.4 years) for those treated with sipuleucel-T vs. 28.3 months for those in the control arm – an improvement of 13 months.5

Taken together, these findings reinforce baseline PSA levels as a strong indicator of overall response with PROVENGE. It also underscores the importance of appropriately staging and monitoring patients who may benefit from immunotherapy for signs of metastatic disease, whether it’s new symptoms, rising PSA levels while on ADT, or evidence of disease on bone scans or CT.

A Promising Future with Improved Survival
Urologists and others treating prostate cancer are living in a prostate cancer “revolution”. Five to seven years ago, it didn’t seem possible that men with mCRPC could live two years after their diagnosis, and now real-world data is showing us it may be as long as four years or longer if immunotherapy is used when PSA levels are lower and likely to offer the most benefit.

The future is bright in mCRPC – for patients and those of us that treat them. The introduction of PROVENGE in 2010 was certainly a game changer, but the game is certainly far from over. As we continue to collect real-world data and better understand outcomes in clinical practice, we can improve how we sequence currently available therapies to benefit our patients. We also are just beginning to gain a deeper understanding of the role genetics play in prostate cancer and better predicting which patients will respond to treatment, allowing us to treat with even more precision in the future.

Jason M. Hafron, M.D., is a partner and Director of Research at the Michigan Institute of Urology, P.C.; an Associate Professor of Urology at the William Beaumont School of Medicine, Oakland University; and the Director of Robotic Surgery at William Beaumont Hospital in Royal Oak, Mich. He specializes in the minimally invasive treatment of cancers involving the prostate, kidney and bladder utilizing laparoscopic and robotic surgery. He is board certified by the American Board of Urology. He is on the editorial board of International Urology and Nephrology and Advances in Urology, and on the Board of Directors of United Physicians Organization. He has published numerous peer-reviewed journal articles and presented at many national and international scientific meetings.

    PROVENGE® (sipuleucel-T) is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer.

  • IMPORTANT SAFETY INFORMATIONAcute Infusion Reactions: Acute infusion reactions (reported within 1 day of infusion) may occur and include nausea, vomiting, fatigue, fever, rigor or chills, respiratory events (dyspnea, hypoxia, and bronchospasm), syncope, hypotension, hypertension, and tachycardia.

  • Thromboembolic Events: Thromboembolic events, including deep venous thrombosis and pulmonary embolism, can occur following infusion of PROVENGE. The clinical significance and causal relationship are uncertain. Most patients had multiple risk factors for these events. PROVENGE should be used with caution in patients with risk factors for thromboembolic events.

  • Vascular Disorders: Cerebrovascular events (hemorrhagic/ischemic strokes and transient ischemic attacks) and cardiovascular disorders (myocardial infarctions) have been reported following infusion of PROVENGE. The clinical significance and causal relationship are uncertain. Most patients had multiple risk factors for these events.

  • Handling Precautions: PROVENGE is not tested for transmissible infectious diseases.

  • Concomitant Chemotherapy or Immunosuppressive Therapy: Chemotherapy or immunosuppressive agents (such as systemic corticosteroids) given concurrently with the leukapheresis procedure or PROVENGE has not been studied. Concurrent use of immune-suppressive agents may alter the efficacy and/or safety of PROVENGE.

  • Adverse Reactions: The most common adverse reactions reported in clinical trials (≥ 15% of patients receiving PROVENGE) were chills, fatigue, fever, back pain, nausea, joint ache, and headache.


  • 2. Higano CS, Armstrong AJ, Sartor AO, et al. Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration resistant prostate cancer. Cancer. 2019.

  • PROCEED evaluated the expected safety and survival profile of PROVENGE (sipuleucel-T) in a real-world treatment setting. PROCEED was a registry without a control group where all patients received PROVENGE, and patients may have received subsequent anti-cancer interventions per the local investigator’s standard of care.

  • 3. Media OS by Quartile: ≤5.27 ng/mL (47.7 months) >5.27-<15.08 ng/mL (33.2 months) >15.08-<46 ng/mL (27.2 months) >46 ng/mL (18.4)

  • 4. Schellhammer PF, Chodak G, Whitmore JB, Sims R, Frohlich MW, Kantoff PW. Lower baseline prostate-specific antigen is associated with a greater overall survival benefit from sipuleucel-T in the Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) trial. Urology. 2013;81(6):1297-1302.

  • This post hoc analysis was not powered for statistical significance, and the population within the subgroups was not randomized. Therefore, the findings are limited by their exploratory nature.

  • 5. Media OS by Quartile: ≤22.1ng/mL (41.3 months), >22.1-50.1ng/mL (27.1), >50.1-134.1ng/mL (20.4), >134.1ng/mL (18.4)

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