FPIN's Clinical Inquiries

Testosterone Therapy and Risk of Recurrence After Treatment for Prostate Cancer

 

Am Fam Physician. 2013 Oct 15;88(8):online.

Clinical Question

In patients who are presumed cured of organ-confined prostate cancer, what are the benefits of testosterone replacement therapy, and what is the risk of cancer recurrence?

Evidence-Based Answer

Men with symptomatic androgen deprivation who have had clinically curative treatment for organ-confined prostate cancer may have symptomatic improvement with testosterone replacement therapy. (Strength of Recommendation [SOR]: C, based on two small case series.) There are no studies evaluating the risk of cancer recurrence in patients receiving testosterone replacement therapy. However, testosterone replacement therapy may be associated with increased prostate-specific antigen (PSA) levels. (SOR: C, based on one case report.) Some men discontinue therapy because their symptoms do not improve. (SOR: C, based on a small case series.)

Evidence Summary

Seven case series (n = 206 patients) describe symptomatic improvements in men with androgen deprivation syndrome who received testosterone replacement therapy.17 PSA levels were monitored over periods ranging from six months to 12 years. All of the case series included men who received clinically curative therapy for organ-confined prostate cancer; five used radical prostatectomy,15 one used brachytherapy,6 and one used external beam radiotherapy7 (Table 114,6,7).

View/Print Table

Table 1.

Case Series Using Testosterone Replacement Therapy After Clinically Curative Therapy for Organ-Confined Prostate Cancer

Case seriesDefinitive therapyBaseline Gleason scoreMean/median follow-up (range)Normal serum testosterone level achieved?OutcomesRecurrence (based on PSA level)
≤67≥8

Kaufman (2004)1 n = 7; mean age = 64 years

Radical prostatectomy

6

1

0

18 months (6 months to 12 years)

Yes: 6 Unknown: 1

3 participants reported symptom improvement

None

Agarwal (2005)2 n = 10; mean age = 54 years

Retroperitoneal radical prostatectomy

2

7

1

19 months (NA)

Yes: 10

Decreased hot flashes, increased energy

None

Nabulsi (2008)3 n = 22; mean age = 61 years

Radical prostatectomy

13

7

2

24 months (14 to 30 months)

Yes: 22

Not reported

1 (Gleason score = 8)

Khera (2009)4 n = 57; mean age = 64 years

Radical prostatectomy

24

26

4

13 months (7 to 17 months)

Yes: 57

Not reported

None

Sarosdy (2007)6 n = 36; mean age = 65 years

Brachytherapy (with or without external beam radiotherapy)

22

6

3

4.5 years (1.5 to 9 years)

Yes: 31

5 participants discontinued therapy because of no perceived benefit

None

Morales (2009)7 n = 5; mean age = 66 years

External beam radiotherapy

2

1

2

15 months (6 to 27 months)

Unknown: 5

4 participants reported decreased hot flashes, improved libido, and increased energy

Final PSA level < 1.5 ng per mL (1.5 μg per L)

2 participants had improved erectile function


NA = not available; PSA = prostate-specific antigen.

Information from references 1 through 4, 6, and 7.

Table 1.

Case Series Using Testosterone Replacement Therapy After Clinically Curative Therapy for Organ-Confined Prostate Cancer

Case seriesDefinitive therapyBaseline Gleason scoreMean/median follow-up (range)Normal serum testosterone level achieved?OutcomesRecurrence (based on PSA level)
≤67≥8

Kaufman (2004)1 n = 7; mean age = 64 years

Radical prostatectomy

6

1

0

18 months (6 months to 12 years)

Yes: 6 Unknown: 1

3 participants reported symptom improvement

None

Agarwal (2005)2 n = 10; mean age = 54 years

Retroperitoneal radical prostatectomy

2

7

1

19 months (NA)

Yes: 10

Decreased hot flashes, increased energy

None

Nabulsi (2008)3 n = 22; mean age = 61 years

Radical prostatectomy

13

7

2

24 months (14 to 30 months)

Yes: 22

Not reported

1 (Gleason score = 8)

Khera (2009)4 n = 57; mean age = 64 years

Radical prostatectomy

24

26

4

13 months (7 to 17 months)

Yes: 57

Not reported

None

Sarosdy (2007)6 n = 36; mean age = 65 years

Brachytherapy (with or without external beam radiotherapy)

22

6

3

4.5 years (1.5 to 9 years)

Yes: 31

5 participants discontinued therapy because of no perceived benefit

None

Morales (2009)7 n = 5; mean age = 66 years

External beam radiotherapy

2

1

2

15 months (6 to 27 months)

Unknown: 5

4 participants reported decreased hot flashes, improved libido, and increased energy

Final PSA level < 1.5 ng per mL (1.5 μg per L)

2 participants had improved erectile function


NA = not available; PSA = prostate-specific antigen.

Information from references 1 through 4, 6, and 7.

Two case series evaluated androgen deprivation symptoms in patients receiving testosterone replacement therapy.2,7 The first study included 10 men (average age = 54 years) who used the hormonal assessment subscale of the Expanded Prostate Cancer Index Composite.2 This self-administered quality-of-life questionnaire measures hot flashes, breast tenderness, depression, low energy, and weight change. On a scale of 0 (no improvement) to 100 (maximum improvement), scores for patients receiving testosterone replacement therapy improved from 38 (95% confidence interval [CI], 32 to 46) to 49 (95% CI, 46 to 54). The second study described five men (average age = 66 years) who had 30 androgen-related symptoms (e.g., hot flashes, decreased libido, erectile dysfunction, lack of ejaculation, fatigue, muscle aches, depressed mood).7 After testosterone replacement therapy, the men had only 14 symptoms.

No studies have evaluated the risk of cancer recurrence after testosterone replacement therapy. The seven case series discussed above monitored PSA levels and found one patient with an unexpected increase.17 The authors did not describe a clinical recurrence of cancer in that case. In one case series, five of 36 patients discontinued therapy because of a lack of perceived symptomatic benefit, and one patient reported headache.6

Recommendations from Others

A 2008 consensus guideline from the International Society of Andrology, International Society for the Study of the Aging Male, European Association of Urology, European Academy of Andrology, and American Society of Andrology states that men successfully treated for prostate cancer who have confirmed symptomatic hypogonadism are candidates for testosterone replacement therapy if there is no clinical or laboratory evidence of residual cancer. It states that physicians should discuss the risks and benefits of therapy with the patient and ensure close follow-up.8 The Endocrine Society recommends against initiating testosterone replacement therapy in this population.9

Author disclosure: No relevant financial affiliations.

Address correspondence to James Meza, MD, at jmeza@med.wayne.edu. Reprints are not available from the authors.


Copyright Family Physicians Inquiries Network. Used with permission.

REFERENCES

show all references

1. Kaufman J, Graydon RJ. Androgen replacement after curative radical prostatectomy for prostrate cancer in hypogonadal men. J Urol. 2004;172(3):920–922....

2. Agarwal PK, Oefelein MG. Testosteron replacement therapy after primary treatment for prostate cancer. J Urol. 2005;173(2):533–536.

3. Nabulsi O, Tal R, Gotto G, Narus J, Goldenberg L, Mulhall JP. Outcomes analysis of testosterone supplementation in hypogonadal men following radical prostatectomy. In: Abstracts of the American Urological Association Annual Meeting. May 17–22, 2008. Orlando, Florida, USA. J Urol. 2008;179(4 suppl):426–427.

4. Khera M, Grober ED, Najari B, et al. Testosterone replacement therapy following radical prostatectomy. J Sex Med. 2009;6(4):1165–1170.

5. Isbarn H, Fisch M, Huland H, Graefen M, Sommer F. Testosterone treatment after radical prostatectomy for pathologically organ-confined prostate cancer; results from a multi-institutional study. In: Abstracts of the American Urological Association Annual Meeting. May 29–June 3, 2010. San Francisco, California, USA. J Urol. 2010;183(4 suppl):e576–e577.

6. Sarosdy MF. Testosterone replacement for hypogonadism after treatment of early prostate cancer with brachytherapy. Cancer. 2007;109(3):536–541.

7. Morales A, Black AM, Emerson LE. Teststrone administration to men with testosterone deficiency syndrome after external beam radiotherapy for localized prostate cancer: preliminary observations. BJU Int. 2009;103(1):62–64.

8. Wang C, Nieschlag E, Swerdloff R, et al. Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA recommendations. Eur J Endocrinol. 2008;159(5):507–514.

9. Bhasin S, Cunningham GR, Hayes FJ, et al.; Endocrine Society Task Force. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(6):2536–2559.

Clinical Inquiries provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recommendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group (http://www.cebm.net/?o=1025).

The complete database of evidence-based questions and answers is copyrighted by FPIN. If interested in submitting questions or writing answers for this series, go to http://www.fpin.org or email: questions@fpin.org.

A collection of FPIN's Clinical Inquiries published in AFP is available at http://www.aafp.org/afp/fpin.


 

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