What’s Next for a 69-Year-Old Man With Prostate Cancer?

Answer: C, there is very little difference between prostatectomy and observation in all-cause or prostate cancer mortality.

The most difficult part of preparing this What’s the “Take Home”? case was comparing the patient data with the preponderance of published characteristics such that there would be minimal protest from involved parties (internists, family practice, oncologists, and the American Cancer Society). I believe that I have done so with the presented patient’s demographics and clinical data—specifically, he is white, older than 65, and has a PSA level less than 10 ng/mL and a Gleason score of 6. The significance of these will be discussed below.

This patient’s story can serve to initiate a discussion and review of the current literature on two very controversial topics: the current role of and recommendations for PSA screening, and the current data and recommendations for the management of subsequently discovered prostate carcinomas.

First, where are we regarding PSA screening? In its newest recommendation statement, the US Preventive Services Task Force (USPSTF) concludes “with moderate certainty that the net benefit of PSA-based screening for prostate cancer in men aged 55 to 69 years is small for some men,”¹ and thus PSA screening should be offered selectively based on demographics (eg, African American, positive family history), physician judgment (eg, comorbidities), and patient values. For men older than 70, the USPSTF recommended against routine testing.¹ Seems simple and clean, yet editorials quickly appeared. A prominent urologist pointed out that more recent data analysis shows increased absolute reduction in prostate cancer mortality from 7 per 10,000 at 9 years to 13 per 10,000 at 13 years and assured us that the data will only get better.² Note that in absolute terms, that is 1.3 fewer prostate cancer deaths per 1000 screened men at 13 years—in this author’s opinion, not a raging public health milestone. Conversely, an oncologist authority just as strongly posited that the minimal benefit demonstrated does not justify the morbidity and fiscal expense in the proposed beneficiaries on its face, and that the overall mortality between screened and unscreened groups is not different at 10 years’ median follow-up.³ The two schools of thought may never agree. More data to select demographics for targeted screening will continue to evolve. For now, the guidelines are the guidelines and will be, unfortunately, variably interpreted, but we’ll leave it there.

Next to be considered is management of a prostate carcinoma once it is diagnosed. A body of data, including a well-done recent study,⁴ provides some current guidance. In this study, the therapeutic maneuvers were either radical prostatectomy within 12 months of diagnosis or observation with palliative, noncurative interventions as indicated, with 364 patients randomly assigned to early prostatectomy and 367 to observation.⁴ Strict criteria for entry included age 75 or younger, PSA level less than 50 ng/mL, histologically confirmed clinically localized prostate cancer, and life expectancy greater than 10 years. The risk stratification scheme included PSA level and Gleason score. (Note that our index case is low risk across all presented parameters.) 

At 19.5 years’ follow-up, the results were clear: Small absolute percentage-point differences (5.5 points for all-cause mortality and 4.0 points for prostate cancer–related mortality) were seen in the prostatectomy group, but none of the differences were statistically significant. 

When one probes subgroup analysis—a dangerous maneuver that is useful in pointing the direction of further study but not for making firm clinical conclusions—patients with intermediate-risk disease may have benefited from prostatectomy, whereas low-risk and high-risk subgroups did not benefit. 

On the other side of the ledger, very high-percentage differences in adverse events (erectile dysfunction, 53% vs 20%; urinary incontinence, 63% vs 16%) were seen in the prostatectomy group. When disease progression occurred in the observation cohort (68.4% vs 40.9% in the prostatectomy group), it was most commonly local or biochemical in nature and amenable to subsequent treatment. Essentially, no difference in low-risk cases was found in systematic progressions. The conclusion reached averred that there is at most a minimal absolute and nonsignificant difference in prostate cancer–related and all-cause mortality between early surgery or observation, while large, long-term differences are seen in the adverse events of erectile dysfunction and urinary incontinence. The authors believe low-risk patients can avoid surgery with PSA-based and active clinical surveillance biopsy–based schemes and delayed radical intervention.⁴ Moreover, another recent paper⁵ has found that a biennial biopsy scheme seems acceptable for biopsy upgrading in surveillance groups and can accurately and timely demonstrate when surgery is indicated.

Regarding the presented case, the patient is low-risk by all criteria available in the literature, and therefore Answers A and D—the immediate use of ablative modalities—would not be expected to provide statistically significant survival benefit. The most accurate is Answer C—there is very little difference between observation and prostatectomy with regard to mortality. There is, however, large difference in adverse events, making Answer B an incorrect statement.

PATIENT FOLLOW-UP

The patient elected observation with surveillance. At 2-year follow-up, his PSA level remained under 10 ng/mL, and biopsy results showed the carcinoma to have remained localized (T1), with a Gleason score of 6.

TAKE-HOME MESSAGE

Controversy continues about screening and management schemes for prostate cancer. The most current guidelines suggest screening using PSA should be an individual choice in men aged 55 to 69 years, capable of preventing 1.3 deaths in 1000 men screened over 13 years—quite modest at best in this author’s view, considering the associated potential harms. In men older than 70, the harms outweigh the benefits, and screening is not recommended. Regarding management, long-term follow-up (approximately 20 years) has shown effective surveillance and observation has statistical equality to early prostatectomy (or radiation) in most studies and populations. However, decades’ worth of other theories and methodologies in screening and therapy are very difficult to displace, despite newer studies and guidelines. Decisions are very often individual choices, to be sure, for both the patient and the physician.

Ronald N. Rubin, MD, is a professor of medicine at the Lewis Katz School of Medicine at Temple University and is chief of clinical hematology in the Department of Medicine at Temple University Hospital in Philadelphia, Pennsylvania.

REFERENCES:

1. US Preventive Services Task Force. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018;​319(18):1901-1913. doi:10.1001/jama.2018.3710
2. Carter HB. Prostate-specific antigen (PSA) screening for prostate cancer: revisiting the evidence. JAMA. 2018;319(18):1866-1868. doi:10.1001/jama.2018.4914
3. Raghavan D. Schrödinger’s cat: PSA screening is alive and dead. HemOnc Today. March 25, 2018:11. https://www.healio.com/hematology-oncology/prostate-cancer/news/print/hemonc-today/%7B8caefce1-8b28-473e-b088-b457f23d39bb%7D/schrdingers-cat-psa-screening-is-alive-and-dead. Accessed February 20, 2020.
4. Wilt TJ, Jones KM, Barry MJ, et al. Follow-up of prostatectomy versus observation for early prostate cancer. N Engl J Med. 2017;377(2):132-142. doi:10.1056/NEJMoa1615869
5. Inoue LYT, Lin DW, Newcomb LF, et al. Comparative analysis of biopsy upgrading in four prostate cancer active surveillance cohorts. Ann Intern Med. 2018;168(1):1-9. doi:10.7326/M17-0548