The following is adapted from a case presented in the New England
Journal of Medicine.
New England Journal of Medicine (2011) "Case 16-2011--A
67-Year-Old Man with Recurrent Prostate Cancer" 364:
2044-2051
A 67-year-old man was seen in the multidisciplinary genitourinary cancer clinic at this hospital because of recurrent prostate cancer.
Approximately 18 months earlier, needle biopsies of the prostate were performed because of an elevated level of prostate-specific antigen (PSA).
Is routine screening for prostate cancer by PSA testing recommended for all men?
Prostate cancer is the most frequently diagnosed cancer in men. Historically, prostate cancer was diagnosed through digital rectal examination, which mainly identified larger more advanced tumors. The digital rectal examination is not very sensitive or specific for prostate cancer and is no longer recommended for routine cancer screening.
Prostate specific antigen (PSA) is a protein that is produced by epithelial cells in the prostate gland, and is one of the prostatic secretions into semen. When the prostate gland is enlarged or diseased, the level of PSA in the blood increases. The PSA test revolutionized screening for prostate cancer because it was able to identify tumors at a much earlier stage.
However, there is a certain amount of controversy about PSA testing. Once PSA testing began to be widely used in the 1990's, there was a doubling in the rate of prostate cancer diagnosis, but a much smaller reduction in prostate cancer mortality. Thus, PSA testing has been linked to overdiagnosis of prostate cancer. Overdiagnosis occurs when a screening test leads to a diagnosis of cancer in a case that might not otherwise have clinical significance.
Prostate tumors can be slow-growing, and so even though a man may
have a prostate tumor, he may not die from prostate cancer.
Because of the location of the prostate, prostate cancer diagnosis
and treatment is associated with serious complications such as
impotence and urinary incontinence. Thus, in cases where
tumors are small, the best treatment approach may be no treatment
at all.
The United States Preventive Service Task Force (USPSTF) recommended against prostate cancer screening in 2012 because the harms of PSA testing appeared to outweigh the benefits. A re-evaluation of clinical trials has shown some benefit to early screening. As well, greater adoption of active surveillance, an approach in which small, slow-growing tumors are regularly monitored without treatment, has reduced the harms of overdiagnosis. The newest USPSTF recommendation statement published in 2018 recommends that men ages 55-69 should decide individually whether to have a PSA test after being informed about the potential benefits and harms of screening. (See the link at the bottom of the page to a video from the USPSTF, which provides an excellent summary of their position).
A diagnosis of adenocarcinoma of the prostate was made, with a Gleason score of 7 (grade 3 plus grade 4). (The Gleason score is the sum of the two most prevalent histologic grades in a prostate tumor, each of which is rated on a scale of 1 to 5, with 5 being the most cytologically aggressive.) Two months later, radical retropubic prostatectomy and bilateral lymph-node sampling were performed. Pathological examination of the tissue revealed adenocarcinoma with a Gleason score of 8 (4 plus 4) in the right and left posterior quadrants of the prostate (with capsular penetration), extending to within 0.1 cm of the inked resection margins...Three months after prostatectomy, the level of PSA was undetectable...Adjuvant external-beam radiation therapy was administered.
This patient had prostate cancer which was diagnosed following an
elevated PSA level and needle biopsies. The results of the biopsy
indicated that the prostate should be removed (prostatectomy). Because the tumor
extended to the capsule of the prostate gland, and based on its
histological appearance in the pathological examination following
prostatectomy, the patient was further treated with adjuvant
radiation. Adjuvant therapy
in cancer care is further treatment after all detectable disease
has been removed. The goal of adjuvant therapy is to reduce
the risk of recurrence due to undetected disease.
Eighteen months after prostatectomy, the serum PSA level of this patient was elevated, at 17.2 ng per milliliter, but a physical examination and radiographic imaging showed no evidence of local or distant disease...For men such as this patient, with a Gleason score of 8, 9, or 10 and less than a 2-year interval from prostatectomy to the first rise in the PSA level, the probability of metastases within 5 years after the first rise in the PSA level is 60% without additional therapy.
Androgen-deprivation therapy (ADT)...is the mainstay of treatment for metastatic prostate cancer and for the recurrence of high-risk PSA-only disease...He was treated with leuprolide.
The increased PSA level in this patient indicates that the prostate cancer has metastasized; that is, cancer cells have spread to other tissues. Androgen deprivation therapy (ADT) reduces testosterone to prepubertal levels.
What does the term "androgen" mean?
Why should androgen deprivation therapy reduce prostate tumor growth?
What type of drug is leuprolide?
How does leuprolide cause "androgen deprivation"?
ADT has been found to be effective in delaying disease progression and increasing survival. However, ADT causes loss of libido, hot flashes, osteoporosis, decreased muscle mass, and other symptoms related to hypogonadism. For this reason, ADT is mainly used to treat patients with metastatic disease, such as this patient.
Osteoporosis (loss of bone mass) is a side effect of androgen-deprivation therapy. Estrogen is the hormone that promotes bone health in both females and males. What is the source of the estrogen that maintains bone mass in men?
After 3 years, leuprolide was discontinued at the patient's request because of vasomotor flushing, loss of libido, fatigue, and subjective weakness. At the time of the discontinuation, the level of serum PSA was undetectable. After the discontinuation of leuprolide, the serum testosterone level promptly returned to a normal level and the patient's symptoms of vasomotor flushing, fatigue, and weakness improved. The administration of zoledronic acid every 6 months was begun for the treatment of osteoporosis. Two and a half years after the discontinuation of ADT, the serum PSA level was markedly elevated. Subsequent imaging studies showed multiple bone metastases. The patient was retreated with leuprolide and remained on continuous treatment.
The United States Preventive Services Task Force has an excellent 3-minute video explaining their recommendations for prostate cancer screening, which can be found at this link.
This link provides more detailed information from USPSTF regarding their recommendations concerning prostate cancer screening.
For those who are interested in reading the original paper, the
reference is: "Case 16-2011--A 67-Year-Old Man with Recurrent
Prostate Cancer" New England Journal of Medicine (2011)
364: 2044-2051 (link)