Because of heightened awareness and media attention directed at high-profile celebrity cases, prostate cancer is one of the most commonly discussed diseases in both the scientific and lay literature. Moreover, debates regarding the diagnosis and treatment of this common malignancy have generated heated discussions and have polarized both urologists and family practitioners. Nowhere is this more evident than the current controversy regarding prostate cancer screening. Since the test for serum levels of prostate-specific antigen (PSA) became widely available, prostate cancer screening is practiced both on a yearly basis (associated with Prostate Cancer Awareness Week) and throughout the year at select institutions.

In this issue of American Family Physician, LeFevre presents a case against support of widespread prostate cancer screening.¹ The pillars of this argument are: (1) that the natural history of prostate cancer is not well understood; and (2) that treatment of asymptomatic prostate cancer has not been shown to alter the natural history of the disease. With the current increase in data relating to these two critical issues, these conclusions warrant further consideration.

A series of Scandinavian studies on the conservative management of prostate cancer have provided conflicting results. However, the majority of patients in these studies who did not stand to benefit from radical prostatectomy were older than 70 years and had low-grade and low-stage disease. Furthermore, under current standards of care, these patients would not be surgical candidates in the United States.^2,3 Two recent studies have explored the long-term results of conservative treatment of clinically localized prostate cancer.

Significantly, Chodak and colleagues⁴ documented that men with moderately and poorly differentiated tumors had a 42 percent and a 74 percent risk, respectively, of developing metastatic disease within 10 years. Perhaps more importantly, Albertsen and associates⁵ showed that even men 70 and 75 years old would realize a significant benefit, in terms of quality life years, from surgical treatment of moderately and poorly differentiated prostate cancer. Albertsen's study also shows that men with low-grade and low-stage disease may derive little benefit from aggressive treatment, but make up a small proportion of patients with clinically evident prostate cancer. While I believe that patients with low-grade disease are the best candidates for cure, modern decision analysis demonstrates that patients with moderate or poorly differentiated disease actually have the most to gain from aggressive therapy.^6,7

Prostate cancer is a heterogeneous disease, and many men have clinically insignificant cancers that do not merit treatment. However, these insignificant tumors have been identified during autopsy studies, and their relevance to prostate cancers diagnosed during screening studies is uncertain. In addition to autopsy studies, clinically insignificant prostate cancer has been demonstrated in approximately 25 percent of cystoprostatectomy specimens in which the prostate was clinically benign.

To estimate the potential for diagnosing clinically insignificant prostate cancer during screening, Ohori and associates⁸ compared the pathologic features of clinical stage T1C prostate cancers to clinical stage T2A and B cancers and to cancers identified at the time of cystoprostatectomy. The results of this study show that the pathologic spectrum of T1C cancers much more closely resembles the pathology of T2 disease than that of prostate cancer seen at the time of cystoprostatectomy.⁸

In the Baylor College of Medicine radical prostatectomy series, it has been consistently noted that less than 10 percent of radical prostatectomies are performed in men with clinically insignificant disease. Furthermore, in a review of the literature, Brendler⁹ found that clinically insignificant prostate cancer accounted for 17 percent or fewer of all cases diagnosed in early detection programs. While the diagnosis of a large number of clinically insignificant prostate cancers is a theoretical consequence of PSA screening, in practice this does not appear to be the case.

If one accepts that the natural history of prostate cancer diagnosed in early detection programs warrants treatment, then the efficacy of treatments for clinically localized prostate cancer must be demonstrated. There is mounting evidence that radical prostatectomy is efficacious in the treatment of clinically localized prostate cancer. Long-term, disease-free survival has been shown in patients with clinical stage T2 prostate cancer.¹⁰ Moreover, men with nonmetastatic, poorly differentiated disease who are treated with radical prostatectomy have significantly improved long-term survival when compared with men who receive nonoperative therapy.^11,12 Importantly, between 1991 and 1995, the age-adjusted prostate cancer mortality rate decreased by 6.3 percent overall and by 7.4 percent in men less than 75 years.¹³ Not coincidently, this reduction in prostate cancer mortality coincides with increased deployment of early detection and aggressive treatment of clinically localized disease.

Some experts believe that early detection and aggressive treatment of clinically localized prostate cancer are promising strategies to reduce mortality associated with this disease.¹⁴ Although unequivocal evidence supporting this hypothesis is lacking, there are ongoing trials that address the diagnostic and treatment dilemmas associated with prostate cancer screening. Once these trials are completed, we will have the prospective data necessary to make firm recommendations regarding both prostate cancer screening and radical prostatectomy.