Advanced Prostate Cancer – State of Care
The state of Prostate Cancer management in the U.S. can only be described as complete failure. In the U.S. alone, there are over 3.3 million prostate cancer “survivors.”[1] Approximately 90% of these men have been treated for the disease. They are not alone, a recent article reported an “estimated 15.5 million cancer survivors in the U.S. …this number is expected to rise 35% by 2022. Prostate cancers account for about 20%,”[2] an additional 42,000 men each year. Conservatively, 1.1 million men are living with the burden or recurrent prostate cancer.[3] They have been diagnosed to have “castrate-resistant prostate cancer,” or CRPC. For those men that have not abandoned medical treatments, which includes chemotherapy, radiation and vaccines, are told by their oncologists to “try another drug.” These patients have been classified as having a terminal disease, no opportunity for cure.
“…more than 50% of men receiving ADT had at least one adverse event – heart attack, stroke, congestive heart failure, diabetes.”[4]
After initial definitive treatment, a significant percentage patients experience recurrence of the disease. These patients, almost universally, are prescribed androgen deprivation therapy, ADT. Recent research of clinical experience is beginning to present a disturbing reality. The following paragraph reveals unintended results of ADT drugs. It was discovered that early ADT treatments actually caused patients die sooner, an average of 10 years earlier. Instead of suppressing cancer progression, anti-androgen chemotherapeutic drugs were shown to enhance prostate cancer cell invasion.
“The recurrence of prostate cancer (Pca)[2] with metastases … was more significant when ADT was applied to patients in an earlier stage of PCa, which was correlated with a 10-year decreased survival rate[4].”[5]
“…we found currently used anti-androgens, MDV3100 (enzalutamide) or Casodex (bicalutamide), promoted macrophage migration to PCa cells that consequently led to enhanced PCa cell invasion.”[6]
As devastating as it is, many patients do not consider the additional implications of the classification, “terminal CRPC.” If the patient is considered to be terminal, their oncologist is now only concerned with treating the patient to “extend survival” and provide palliative care. For example, in addition to the known ADT side effect, dramatic bone loss is also common side effect of chemotherapeutic drugs in the treatment of CRPC patients. Since the patient is facing a terminal disease with limited time to live, bone loss is not considered to be a priority. This serious side effect is left untreated and, according to published reviews[6], this consequence and numerous other debilitating side effects erode the patient’s health and quality of life. In the face of these serious problems, the growing number of terminal patients that are “living longer” with the disease, the medical community claims to have made great strides in the treatment of Prostate Cancer.
“For patients with prostate cancer we have a nearly 100 percent five-year survival rate…”[8]
Unfortunately, the underwhelming claims, 5 years of “improved survival,” are further undermined by the reality that prostate cancer is overtreated. Patients are treated even though they are diagnosed with non-life-threatening cancers. A lot of patients. A study published by Johns Hopkins in 2011, reported that 85% of men with PSA less than 4.0ng/ml with “favorable-risk” cancers were treated.[9] Consider that each year, about 138,000 radical prostatectomies alone are performed in the U.S.[3]
Experience has demonstrated that drugs that received accelerated FDA approvals have not provided the outcomes that were originally claimed. These drugs are prescribed sequentially to patients. As the patient develops resistance to each drug, another drug is “tried.” The patient’s cancer becomes more and more aggressive as the patient’s health and quality of life continues to erode.
“… the benefits of antiangiogenic agents for the treatment of cancer are controversial; increased formation of metastases was recently demonstrated with these therapies[4–6], and progression-free survival (PFS) benefits are often not translated into long-term overall survival (OS) gain.”
“One well-accepted explanation for this apparent contradiction is that tumours can develop resistance to anti-VEGF therapy. Indeed, a complete lack of effect in refractory tumours or tumour rebound after an initial effect have been descibed.[3].”
“… recently VEGFsignalling inhibitors have been introduced into clinical protocols for the treatment of several types of tumours [2]. Nevertheless, transitory effects of these agents and the promotion of tumour aggressiveness have been reported [3–6].”
“Other stromal alterations in the production of such factors in the stroma inevitably modify the behaviour of tumour cells leading to acquired resistance and thus the initial antitumour effects can be overcome.[14,16]”[10]
Studies also revealed that FDA-approved, chemotherapeutic drugs for CRPC, docetaxel, prednisone, bevacizumab and aflibercept did not improve overall survival in patients studied.[11] Interestingly, some provided “progression-free survival (PFS), while not improving “overall survival (OS).” What is disturbing about this observation is that after initial benefit the cancer must acquire resistance to the drug. The cancer must become more aggressive than it was before taking the drug to the extent that it did not improve survival as compared to patients who did not take the drug.
The results of these and other recent studies portend an uncertain future for current the state of care for prostate cancer:
Androgen deprivation therapy – “10 year treatment costs $81,000.[12]”
Androgen deprivation therapy (GnRH) – “reduces survival, accelerates resistance and metastases[13]”
Anti-androgen therapy (AR) – “enhances cell invasion and metastases[13]”
Anti-angiogenic drugs – “acquired resistance and increased formation of metastases[11]”
Chemotherapeutic drugs (first-line therapy) – “did not improve overall survival[11]”
There are over 3.3 million men, many with very little time (and remaining health), waiting for the medical community to change course. Men, their spouses and families are still waiting for improvement over the delivery of serial drug therapies with increasing cancer aggressiveness and diminishing health of the patient. Similar to other cancers, there are several new drugs in development which are undergoing accelerated FDA-approval. Unfortunately, not a single one of these drugs have sufficient historical data to confirm that they will not provide similar outcomes. These drugs are very expensive and are approved even though they extend survival, if only a few weeks.
“The (FDA) approval was based on a large, randomized clinical trial in patients with metastatic CRPC who experienced a statistically significant improvement in overall survival with 223Ra-dichloride compared with placebo, 14 months vs 11.2 months.”[14]
Needless to say, if the patient is informed of this outcome, it presents a very difficult decision to the patient and his family. For patients treated for prostate cancer, the future landscape is only of uncertainty, living with the hope and fear that their cancer will not return, or that their resistant, metastatic cancer will somehow be cured. Current research reveals that there are no drugs in the pipeline that actually intend to cure prostate cancer.