Patient K


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?

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Prostate cancer is the most frequently diagnosed cancer in men.  Prostate cancer was traditionally diagnosed through digital rectal examination, which mainly identified larger, more advanced tumors. The PSA test revolutionized screening for prostate cancer because it was able to identify tumors at a much earlier stage.

There is also 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. PSA testing has been linked to over-diagnosis of prostate cancer. Over-diagnosis 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.  Furthermore, 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.  More recently, the USPSTF has modified its approach.  The USPSTF draft recommendation on prostate cancer screening released in 2017 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.

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.

In the specimen from the radical prostatectomy, extensive cancer was identified in both lobes of the gland. The final Gleason score of 8 (4 plus 4) indicated that the tumor grade had been underestimated on the biopsy specimens. Because of tumor heterogeneity and sampling error, prostate cancer is upgraded at prostatectomy in approximately 40% of patients. In this patient's prostatectomy specimen, cancer invaded the perineural space, which is an indication of cancer aggression.

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 (the Gleason score), 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. Although the rising serum PSA level after prostatectomy and radiation therapy in this patient heralds the development of locally recurrent or metastatic disease, the natural history of the recurrence of such “PSA only” disease is variable...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.

What type of drug is leuprolide?

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How does leuprolide cause "androgen deprivation"?

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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. ADT prolongs patient survival because prostate tumor cells are stimulated to grow by androgens. 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.

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.

Optional

The United States Preventive Services Task Force Prostate Cancer Screening Draft Recommendations can be found at this link.

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)
[URL: http://www.nejm.org/doi/full/10.1056/NEJMcpc1011323]

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