A 66-year-old Caucasian man with a history of hypertension, hyperlipidemia, and rheumatoid arthritis was diagnosed with prostate cancer. Transrectal ultrasound-guided biopsy revealed Gleason 3+4=7 disease in 1 of 12 cores and Gleason 3+3=6 disease in 2 of 12 cores. His prostate-specific antigen (PSA) level at biopsy was 3.5 ng/mL. The patient’s prostate cancer was asymptomatic: he had minimal lower urinary tract symptoms, was continent, and had erections sufficient for penetration without medical or mechanical assistance. He underwent open radical retropubic prostatectomy 6 months after diagnosis. His postoperative course was unremarkable and he was discharged on post-op day 1. His prostate specimen weighed 44 g and consisted of 9% adenocarcinoma tumor. Final surgical pathology revealed Gleason 4+3=7 disease with tertiary Gleason pattern 5 disease. There were positive margins (3 mm at the right periphery and 1 mm at the apex) and perineural invasion but no extracapsular extension, seminal vesicle invasion, or lymph node invasion. Final pathologic stage was pT2c.
Postoperatively, the patient’s PSA level was undetectable (< 0.1 ng/mL) for the first 19 months (Figure). His PSA level had risen above 0.1 ng/mL by 19 months postoperatively; it remained between 0.1 and 0.2 ng/mL until 31 months postoperation, at which time it reached 0.2 ng/mL. His PSA level had climbed to 0.22 ng/mL by 37 months, and to 0.33 ng/mL by 43 months; it then fell back to 0.25 ng/mL at 49 months postprostatectomy. After his PSA level became detectable, PSA doubling time was 24.3 months, with a velocity of 0.1 ng/mL/yr. The patient’s functional status was excellent. He did not require any pads by 7 months post-surgery; and he had an American Urological Association (AUA) symptom score of 6 and a bother score of 0. He eventually developed excellent urinary control. By 13 months postoperation, he reported that with a phosphodiesterase inhibitor he was able to sustain satisfactory erections for sexual activity (International Index of Erectile Function score = 18), and his erections slowly continued to improve. The ability to resume sexual activity was deeply gratifying to him.
The patient understands that his PSA level meets criteria for biochemical recurrence, which is justification for proceeding with further treatment of his prostate cancer. However, he feels very fortunate to have had excellent return of urinary and erectile functioning, and at age 70 years, he is still relatively healthy. Thus, he is loath to undergo treatment that might have a negative impact on his quality of life. He is very wary of the potential side effects and complications of radiation therapy and androgen deprivation therapy and he resists their implementation. He has already discussed such concerns with the care team, but remains paralyzed by the prospect of potential adverse effects and is having difficulty reaching a decision regarding his treatment. Very nervous, he returns to the clinic for a routine follow-up visit.
What would be the best next step in this patient’s management?
A. Proceed with radiation therapy, since his rising PSA level places him at risk for clinical recurrence.
B. Continue with periodic PSA surveillance.
C. Order a genetic biomarker test to determine cancer aggression.
D. Provide reassurance that this is likely a PSA elevation due to benign prostate tissue in situ.
1. Sim HG, Telesca D, Culp SH, et al. Tertiary Gleason pattern 5 in Gleason 7 prostate cancer predicts pathological stage and biochemical recurrence. J Urol. 2008;179:1775-9.
2. Patel AA, Chen MH, Renshaw AA, et al. PSA failure following definitive treatment of prostate cancer having biopsy Gleason score 7 with tertiary grade 5. JAMA. 2007;298:1533-8.
3. Freedland SJ, Humphreys EB, Mangold LA, et al. Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA. 2005;294:433-9.
4. Thompson IM, Valicenti RK, Albertsen P, et al. Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO guideline. J Urol. 2013;190:441-9.
5. Mohler JL, Armstrong AJ, Bahnson RR, et al. Prostate cancer. Version 1.2016. J Natl Compr Canc Netw. 2016;14:19-30.
6. Social Security Administration. Life expectancy calculator. https://www.ssa.gov/cgi-bin/longevity.cgi. Accessed July 23, 2016.
7. Lavery HJ, Levinson AW, Hobbs AR, et al. Baseline functional status may predict decisional regret following robotic prostatectomy. J Urol. 2012;188:2213-8.
8. Shah R, Bassily N, Wei J, et al. Benign prostatic glands at surgical margins of radical prostatectomy specimens: frequency and associated risk factors. Urology. 2000;56:721-5.
9. Paul R, Hoppmann M, van Randenborgh H, et al. Residual benign prostatic glands at the urethrovesical anastomosis after radical retropubic prostatectomy: prediction and impact on disease outcome. Eur Urol. 2004;46:321-6.
10. Valotto C, Falconieri G, Pizzolitto S, et al. Residual prostatic tumour in the surgical bed following radical prostatectomy in organ-confined prostate cancer: possible prognostic significance. Arch Ital Urol Androl. 2011;83:78-82.
11. Ross AE, D’Amico AV, Freedland SJ. Which, when and why? Rational use of tissue-based molecular testing in localized prostate cancer. Prostate Cancer Prostatic Dis. 2016;19:1-6.
12. Thompson I, Thrasher JB, Aus G, et al. Guideline for the management of clinically localized prostate cancer: 2007 update. J Urol. 2007;177:2106-31.
13. Erho N, Crisan A, Vergara IA, et al. Discovery and validation of a prostate cancer genomic classifier that predicts early metastasis following radical prostatectomy. PLoS One. 2013;8:e66855.
14. GenomeDx. Centers for Medicare and Medicaid Services publishes draft coverage decision to reimburse the Decipher® test for intermediate & high risk prostate cancer. 2014 Oct 16. https://genomedx.com/press-releases/centers-medicare-medicaid-services-publishes-draft-coverage-decision-reimburse-decipher-test-intermediate-high-risk-prostate-cancer. Accessed January 18, 2016.