Abstract
A 52-year-old male with elevated serum prostate-specific antigen (PSA) level, moderate lower urinary tract symptoms (LUTS), and negative family history of prostate cancer is found to have adenocarcinoma of the prostate with negative bone scan. Following radical retropubic prostatectomy and satisfactory postoperative recovery, heretofore undetectable serum PSA level rose 35 months later. Digital rectal examination (DRE) and bone scan were negative. Adjuvant external beam radiation preceded by a 3-month injection of goserelin was initiated. Radiation was well tolerated, although the patient reported significant loss of libido, hot flashes, and depression warranting antidepressant medication. Failure to respond to this intervention led to initiation of supplemental testosterone; 1 month later, the patient reported significant relief of symptoms. The patient is currently successfully tapering use of supplemental testosterone in order to decrease andropause symptoms and to permit restoration of intrinsic testosterone.
Key words: Prostate, Prostate-specific antigen, Radiation, Testosterone
In November 1998, a 52-year-old male presented to a local urologist with a serum prostate-specific antigen (PSA) level of 7.9 ng/mL. He denied symptoms suggestive of prostatic carcinoma, but did have moderate lower urinary tract symptoms (LUTS) with an International Prostate Symptoms Score (IPSS) of 14. There was no family history of prostate cancer. Rectal examination revealed a nodule on the right side of the prostate, which was consistent with clinical stage T2B carcinoma. Ultrasound-guided prostate needle biopsy was performed; 6 cores were obtained. Analysis revealed adenocarcinoma of prostate (5.2 cm), with Gleason 4+3 in 3 of 3 cores from the right and Gleason 3+3 in 1 core from the left. Radionuclide bone scan was negative for metastatic disease.
After a number of consultations, the patient elected to undergo radical retropubic prostatectomy. There was significant induration on the right side of the prostate; therefore, nerve-sparing was performed only on the left. Pathology revealed Gleason 4+4 adenocarcinoma. The tumor extended microscopically to the surgical margin on the right (PT3A) lymph nodes; seminal vesicles were negative. Tumor volume was 7.2 cc.
The patient did exceedingly well postoperatively and had rapid restoration of urinary control and maintenance of good erections. Serum PSA level remained undetectable until 35 months postoperative when the total serum PSA level rose to 0.3 ng/mL with a complex of 0.19. Repeat serum PSA testing confirmed these findings. There was no evidence of recurrence on rectal examination and repeat bone scan was negative. After counseling, it was elected to proceed with adjuvant external beam radiation therapy. A 3-month injection of goserelin was administered prior to initiation of this therapy. The patient tolerated radiation well; however, he complained of significant loss of libido and hot flashes.
The patient reported significant depression, sought psychiatric intervention, and was subsequently placed on antidepressants, with his depression progressing to the level of suicidal ideation. These symptoms persisted and he again sought consultation. Sixteen months following the single 3-month goserelin injection, his serum testosterone level was 150 ng/dL, while his serum PSA level remained undetectable.
After careful consultation, it became apparent that the patient’s depression and lack of libido (which had been only moderately helped by the antidepressant regimen) as well as his fatigability and erectile dysfunction (ED), were significantly impacting his life and willingness to live. It was elected to administer supplemental testosterone.
Testim® (Auxilium Pharmaceuticals, Inc., Norristown, PA) 5 g qd was administered; 1 month later, serum testosterone had risen to 583 ng/dL. PSA remained undetectable. Serial serum PSAs and testosterone levels are shown in Figure 1. The patient noted marked relief of his psychological symptoms, prompt restoration of libido, and began enjoying sexual activity.
Figure 1.
Serum testosterone levels for patient undergoing supplemental testosterone therapy.
In December 2003, it was decided to wean the patient off supplemental testosterone. One week after discontinuation, he began having significant hot flashes and diminution of libido. Serum testosterone level was 164 ng/dL. The patient resumed using Testim and 1 month later the serum testosterone level was 517 ng/dL.
It was then elected to taper the use of Testim in order to decrease the andropause symptoms and to allow restoration of the intrinsic testosterone. The patient began weaning himself off Testim by administrating 75% of a 5 g tube qd. Serum testosterone level decreased to 222 ng/dL. One month later, with continuing reduction to half a tube qd of Testim, serum testosterone rose to 312 ng/dL. The patient also experienced lessening of andropause symptoms, less frequent hot flashes, and almost complete restoration to his normal level of libido and sexual activity. Serum PSA level remained undetectable.
At this time, the patient continues to taper the use of Testim, and it is hoped that in the near future he will have restoration of his intrinsic testosterone.
This case illustrates a number of important points. Adjuvant external beam radiation therapy in men with biochemical failure several years following prostatectomy does provide curative therapy in many men. In light of this patient’s relatively young age, this course was indicated. Adjuvant hormonal therapy in this setting remains debatable. However, the impressive results using long-term hormonal therapy in advanced prostate cancer with external beam therapy make this the preferred approach.
Hypogonadal status following luteinizing hormone-releasing hormone antagonist has been well documented. In my experience, this has been a problem primarily in older patients, and I have never seen such a prolonged and symptomatic hypogonadal presentation in such a relatively young man. The clinical use of androgen supplementation in men without prostate cancer has been widely accepted for those suffering from andropause or other hypogonadal symptoms. In general, it is felt that supplemental androgen replacement in men with established prostate cancer is contraindicated. Such therapy should be administrated for the patient only in the context of clinical therapy with curative intent, and it is imperative to include careful discussion with the patient and documentation in the record.
In this case, the administration of Testim did result in significant improvement in quality of life for this patient. It is hoped that he will continue to show progressive restoration of his intrinsic testosterone and will eventually be able to discontinue supplemental androgen.
Main Points.
Adjuvant external beam radiation therapy in men with biochemical failure several years following prostatectomy appears to provide curative therapy in many men.
Impressive results have been seen using a combination of long-term hormonal therapy in advanced prostate cancer with external beam therapy, making it the preferred approach.
The clinical use of androgen supplementation in men without prostate cancer has been widely accepted in those suffering from andropause or other hypogonadal symptoms.
It is generally agreed that supplemental androgen replacement in men with established prostate cancer is contraindicated.