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Clinical Crossroads | Clinician's Corner

A 64-Year-Old Man With Low-Risk Prostate Cancer Review of Prostate Cancer Treatment

Martin G. Sanda, MD; Irving D. Kaplan, MD, Discussants
JAMA. 2009;301(20):2141-2151. doi:10.1001/jama.2009.674.
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Earlier detection of prostate cancer in the past decade has been accompanied by greater reduction in US prostate cancer mortality than that seen with any other cancer. Prostate cancer is usually diagnosed at early stages and is most commonly treated by prostatectomy, radiotherapy, or brachytherapy. For intermediate- and high-risk prostate cancers, randomized clinical trials have shown survival benefit subsequent to prostatectomy or to combined radiation with androgen-suppressive therapy. However, prostatectomy, radiotherapy, and brachytherapy each can lead to distinct adverse effects. Moreover, for the lowest-risk categories of early stage prostate cancer, evidence supporting an intervention is only indirect. New approaches to surveillance of prostate cancer have consequently emerged that do not eschew treatment altogether. Instead “active” surveillance aims to implement definitive intervention effectively for those low-risk cancers that show a propensity for progression as evidenced by histopathological or serological change during the surveillance interval.

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Figure. Prostate Biopsy Histopathology of Mr D
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Scattered acini are seen with round, rigid outlines that are lined by epithelial cells with mildly eosinophilic cytoplasm, enlarged nuclei, and prominent nucleoli that are consistent with Gleason score 6 (low grade) prostatic adenocarcinoma. The absence of basal cells that typically line the acinar spaces and rigid contours of the acini are clues to the histologic diagnosis. A, Box indicates area of detail in panel B (hematoxylin-eosin, original magnification ×200). B, High-powered view (hematoxylin-eosin, original magnification ×400).




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Informed decision making for prostate cancer treatment
Posted on May 21, 2009
Richard M. Hoffman, MD, MPH
University of New Mexico School of Medicine
Conflict of Interest: None Declared
The first step in managing Mr. D's case is to clarify his treatment options and their potential risks and benefits. He uses the phrase "watchful waiting" which actually connotes a palliative approach to prostate cancer, where the intention is to offer symptomatic relief if and when cancer progresses. Given the often indolent course of prostate cancer, this approach makes most sense for men with limited life expectancies due to advanced age or comorbidities. However, Mr. D is young and fairly healthy, so watchful waiting is not necessarily an appropriate option. Even though his cancer is moderately differentiated, population-based survival data suggest that, without treatment, he has over a 20% chance of dying from prostate cancer in 20 years (1). At the same time, he might be one of the estimated 23% to 42% of men with PSA-detected cancers who never have clinical problems with prostate cancer (2)-other than those associated with diagnosis and treatment. Many men with an early-stage cancer who share Mr. D's concerns about treatment complications--but are uncomfortable with foregoing treatment-- have opted for androgen deprivation therapy (ADT)(3). However, ADT is not really an acceptable compromise for these men because it also has many potential complications, does not cure cancer, and is expensive. So, are there any other options for Mr. D? He could consider active surveillance (AS). This strategy, which is recommended for men with less than a 10- to 15-year life expectancy, PSA ≤ 10 ng/mL, low tumor burden, and no worse than a moderately differentiated cancer, involves serial PSA testing, digital rectal examinations, and prostate biopsies (4). Engaging in AS means that a future decision for curative treatment would be based on evidence that cancer is progressing—rising PSA, changing DRE, or worsening Gleason score. This may strike a reasonable balance for men who want to avoid complications from unnecessary treatment but do not want to ignore their cancer. Recent observational data from a small multi-institutional cohort study found that 75% of subjects remained on active surveillance after a median follow-up of 29 months--and only one developed skeletal metastases (5). So while a cancer could progress under active surveillance and become incurable, the chance of this seems small.
Admittedly, Mr. D may not quite fit the guideline indications for AS; the foci of atypia and high-grade intraepithelial neoplasia suggest that his tumor volume could have been underestimated and he has a long life expectancy. Whether or not he opts for active surveillance, Mr. D should be fully educated about the natural history of prostate cancer and the potential risks and benefits associated with various treatment options. He should also understand that radiotherapies (external beam and brachytherapy), unlike radical prostatectomy, have never been evaluated in controlled trials of men with early-stage cancer. Thus, there is no evidence-based consensus on the optimal treatment. Given this uncertainty about treatment selection and the risks for overdiagnosis, the most important recommendation for Mr. D is that he be involved in an informed/shared decision-making process regarding his treatment.
References 1. Albertsen PC, Hanley JA, Fine J. 20-year outcomes following conservative management of clinically localized prostate cancer. Jama. May 4 2005;293(17):2095-2101. 2. Draisma G, Etzioni R, Tsodikov A, et al. Lead time and overdiagnosis in prostate-specific antigen screening: importance of methods and context. J Natl Cancer Inst. Mar 18 2009;101(6):374-383. 3. Cooperberg MR, Moul JW, Carroll PR. The changing face of prostate cancer. J Clin Oncol. Nov 10 2005;23(32):8146-8151. 4. Thompson I, Thrasher JB, Aus G, et al. Guideline for the management of clinically localized prostate cancer: 2007 update. J Urol. Jun 2007;177(6):2106-2131. 5. Eggener SE, Mueller A, Berglund RK, et al. A multi-institutional evaluation of active surveillance for low risk prostate cancer. J Urol. Apr 2009;181(4):1635-1641; discussion 1641.
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