Active surveillance for favorable risk prostate cancer: what are the results, and how safe is it?

Active surveillance for favorable risk prostate cancer has become increasingly popular in populations in which prostate cancer screening is widespread because of evidence that prostate cancer screening results in the detection of disease that is not clinically significant in many patients (ie, untreated, would not pose a threat to health). The approach is supported by data showing that patients who fall into the category of clinically insignificant disease can be identified with reasonable accuracy and that patients who are initially classified as low risk who reclassify over time as higher risk and are treated radically are still cured in most cases. This means (1) identifying patients who have a low likelihood of disease progression during their lifetime based on clinical and pathologic features of the disease and patient age and comorbidity, (2) close monitoring over time, (3) reasonable criteria for intervention that will both identify more aggressive disease in a timely fashion and not result in excessive treatment, and (4) meeting the communication challenge to reduce the psychological burden of living with untreated cancer. The results of active surveillance, the criteria for patient selection, and the appropriate triggers for intervention are reviewed.     

Active surveillance for favorable-risk prostate cancer: who, how and why?

Active surveillance for favorable-risk prostate cancer has become increasingly common in populations in which screening for prostate cancer is widespread, owing to evidence that in many patients screening results in the detection of disease that is not clinically significant (i.e. untreated, it would not pose a threat to health). The approach is supported by data demonstrating that patients who have clinically insignificant disease can be identified with reasonable accuracy, and that patients who are initially classified as low risk but reclassified over time as higher risk and are treated radically are still cured in most cases. It is important to identify patients who have a low probability of disease progression during their lifetime according to clinical and pathologic features of the disease, patient age and comorbidity. Close monitoring of patients over time and availability of reasonable criteria for intervention, which will both identify more-aggressive disease in a timely fashion and not result in excessive treatment, are crucial. It is also important to communicate appropriately with the patient, to reduce the psychological burden of living with untreated cancer. The results of active surveillance, the criteria for patient selection and the appropriate thresholds for intervention are reviewed in this article.     

Active surveillance with selective radical treatment for localized prostate cancer

The challenge of managing localized prostate cancer is to distinguish patients with clinically relevant cancers, who may benefit from radical treatment, from the remainder who do not need any intervention. Active surveillance with selective radial intervention is a management strategy that offers patients the hope of avoiding "unnecessary" treatment without detriment to their long-term survival. Here we discuss the rationale for active surveillance, and the early results. There is no consensus on the optimum active surveillance protocol, with uncertainty regarding the interpretation of PSA kinetics, repeat biopsy results and prostate imaging. In the future, it is likely that molecular markers will revolutionize our ability to select patients who will benefit from definitive treatment. In the meantime, active surveillance provides an attractive way of reducing over treatment.     

Active surveillance for prostate cancer: for whom?

Prostate-specific antigen (PSA) -based prostate cancer screening results in the diagnosis of prostate cancer in many men who are not destined to have clinical progression during their lifetime. Good-risk prostate cancer, defined as a Gleason score of 6 or less, PSA < 10, and T1c to T2a, now constitutes 50% of newly diagnosed prostate cancer. In most of these patients, the disease is indolent and slow growing. The challenge is to identify those patients who are unlikely to experience significant progression while offering radical therapy to those who are at risk. The approach to favorable-risk prostate cancer described in this article uses estimation of PSA doubling time (PSA DT) to stratify patients according to the risk of progression. Patients who select this approach are managed initially with active surveillance. Those who have a PSA DT of 3 years or less (based on a minimum of three determinations over 6 months) are offered radical intervention. The remainder are closely monitored with serial PSA and periodic prostate rebiopsies (at 2, 5, and 10 years). In this series of 299 patients, the median DT was 7 years. Forty-two percent had a PSA DT > 10 years, and 20% had a PSA DT > 100 years. The majority of patients on this study remain under surveillance. The approach of active surveillance with selective delayed intervention based on PSA DT represents a practical compromise between radical therapy for all (which results in overtreatment for patients with indolent disease) and watchful waiting with palliative therapy only (which results in undertreatment for those with aggressive disease).     

Modern Active Surveillance in Prostate Cancer: A Narrative Review

The use of PSA screening has led to downstaging and downgrading of prostate cancer at diagnosis, increasing detection of indolent disease. Active surveillance aims to reduce over-treatment by delaying or avoiding radical treatment and its associated morbidity. However, there is not a consensus on the selection criteria and monitoring schedules that should be used. This article aims to summarize the evidence supporting the safety of active surveillance, the current selection criteria recommended and in use, the incidence of active surveillance, barriers existing to its uptake and future developments in patient selection.     

Pros and cons of active surveillance for low-risk prostate cancer

Because of the recent increase of prostate specific antigen (PSA)-screening, potential risks of overdiagnosis and overtreatment are more easily pointed out for low-risk prostate cancer. Active surveillance is one of the therapeutic options for the management of patients with low-risk prostate cancer. Concerning the indication of active surveillance, candidates for it have been selected based on several clinical factors including clinical stage(T), PSA level, Gleason score, and the number of positive cores on prostatic biopsy, but the selection criteria have not yet been uniformly established. As for the observation method, PSA doubling time and results from repeated biopsies have been utilized to select a high-risk case for whom intervention by curative therapy will be recommended. However, there are still controversies concerned with which is the most appropriate method of follow-up during active surveillance. In addition, the psychological impact of active surveillance on both the patient and the health care staff needs to be taken into account. Since the efficacy and safety of active surveillance were demonstrated by the results of several clinical studies, it is regarded as one of the superior and acceptable therapeutic options for patients with low-risk prostate cancer. It is expected that both the patient and health care staff would choose active surveillance as a reliable option when the appropriate selection criteria and the suitable follow-up method are determined and established.     

Diet and Lifestyle Interventions in Active Surveillance Patients with Favorable-Risk Prostate Cancer

Opinion statement Active Surveillance (AS) is a viable, alternative option for patients who are diagnosed with favorable prognostic risk prostate cancer, and who are willing to undergo conservative, expectant management until treatment is warranted due to progression of the disease. Lifestyle interventions in patients who choose AS is an emerging area of research, and several studies are ongoing with results pending. New intervention studies will increase our knowledge of the etiology of prostate cancer and help determine whether dietary factors can influence prostate carcinogenesis after diagnosis in AS patients. The considerable amount of epidemiologic and experimental data relating components of the diet with prostate cancer risk suggest that diet or lifestyle interventions could potentially lengthen the period of active surveillance before treatment management is necessary, and further research is warranted to study the direct effects on secondary clinical outcomes.     

Active surveillance for early-stage prostate cancer: review of the current literature

The natural history of prostate cancer is remarkably heterogeneous and, at this time, not completely understood. The widespread adoption and application of prostate-specific antigen (PSA) screening has led to a dramatic shift toward the diagnosis of low-volume, nonpalpable, early-stage tumors. Autopsy and early observational studies have shown that approximately 1 in 3 men aged >50 years has histologic evidence of prostate cancer, with a significant portion of tumors being small and possibly clinically insignificant. Utilizing the power of improved contemporary risk stratification schema to better identify patients with a low risk of cancer progression, several centers are gaining considerable experience with active surveillance and delayed, selective, and curative therapy. A literature review was performed to evaluate the rationale behind active surveillance for prostate cancer and to describe the early experiences from surveillance protocols. It appears that a limited number of men on active surveillance have required treatment, with the majority of such men having good outcomes after delayed selective intervention for progressive disease. The best candidates for active surveillance are being defined, as are predictors of active treatment. The psychosocial ramifications of surveillance for prostate cancer can be profound and future needs and unmet goals will be discussed.     

Active surveillance: a potential strategy for select patients with small renal masses

Increased abdominal imaging has led to the significant incidental detection of clinically localized renal masses. While the gold standard remains surgical excision, mortality rates from kidney cancer remain relatively unchanged implying that a proportion of small renal masses may be indolent tumors that do not require surgical intervention. As a result, active surveillance has emerged as an alternative management strategy in select patients with significant competing risks. Although the contemporary literature characterizing the natural history of untreated small renal masses is limited, recent data demonstrate that many incidental renal masses demonstrate slow growth kinetics with a low rate of progression to metastatic disease over an intermediate time period. Prospective trials are necessary to define entry and intervention criteria for active surveillance protocols.     

Active surveillance with selective delayed intervention: a biologically nuanced approach to favorable-risk prostate cancer

Prostate cancer is an indolent, slow-growing disease in many patients and may not pose a threat during a patient's lifetime. The challenge is to identify those patients who are not likely to experience significant progression while offering radical therapy to those who are at risk. To date, molecular markers have failed to provide sufficiently reliable predictive information to influence decision-making. The approach to favorable-risk prostate cancer described in this article uses estimation of prostate-specific antigen doubling time (PSA DT) to stratify patients according to the risk of progression. Patients who select this approach initially undergo management with active surveillance; those who have a PSA DT 10 years and 20% had a PSA DT > 100 years. The majority of patients in this study continue to undergo surveillance. The approach of active surveillance with selective delayed intervention based on PSA DT represents a practical compromise between radical therapy for all (which results in overtreatment of patients with indolent disease) and watchful waiting with palliative therapy only (which results in undertreatment of patients with aggressive disease).     

Counterpoint: the case for immediate active treatment

Active monitoring strategies recently have received attention as possible treatment options for men with low-risk prostate cancer who have a life expectancy of more than 10 years. However, no current criteria sufficiently predict outcomes for individuals with clinically localized disease and an otherwise long life expectancy who undergo either immediate or delayed treatment, or no treatment. This article describes the available evidence regarding treatment outcomes in men with low-risk prostate cancer and presents the case for immediate active treatment.     

Active surveillance versus radical treatment for favorable-risk localized prostate cancer

Opinion statement Widespread prostate-specific antigen (PSA) screening in North America has resulted in a profound stage migration and a marked increase in incidence. One in six men is now diagnosed, many with small-volume, low-grade cancer. This incidence is dramatically higher than the 3% lifetime risk of prostate cancer death that characterized the prescreening era. This article summarizes the case for active surveillance for “favorable-risk” prostate cancer with selective delayed intervention for rapid biochemical progression, assessed by increasing PSA levels, or grade progression. The results of a large phase II trial using this approach are reviewed. To date, this study has shown that virtually all men with favorable-risk prostate cancer managed in this fashion will die of unrelated causes. Based on the Swedish randomized trial of radical prostatectomy versus watchful waiting, the Connecticut observation series, and the Toronto active surveillance experience, a number needed to treat analysis of the benefit of radical treatment of all newly diagnosed favorable-risk prostate cancer patients, compared with a strategy of active surveillance with selective delayed intervention, is presented. This suggests that approximately 73 patients will require radical treatment for each prostate cancer death averted. This translates into a 3- to 4-week survival benefit, unadjusted for quality of life. This figure is confirmed based on an analysis of the 2004 D'Amico et al. PSA velocity data in favorable-risk disease. The approach of active surveillance with selective delayed intervention based on PSA doubling time and repeat biopsy represents a practical compromise between radical therapy for all patients (which results in overtreatment for patients with indolent disease) and watchful waiting with palliative therapy only (which results in undertreatment for those with aggressive disease).     

Active surveillance for the management of prostate cancer in a contemporary cohort

BACKGROUND: Active surveillance followed by selective treatment for men who have evidence of disease progression may be an option for select patients with early-stage prostate cancer. In this article, the authors report their experience in a contemporary cohort of men with prostate cancer who were managed with active surveillance. METHODS: All men who were managed initially with active surveillance were identified through the authors' institutional database. Selection criteria for active surveillance included: prostate-specific antigen (PSA)<10 ng/mL, biopsy Gleason sum 0.75 ng/mL per year), was a secondary outcome. Chi-square and log-rank tests were used to compare groups. The association between clinical characteristics and receipt of active treatment was analyzed by using Cox proportional hazards regression. RESULTS: Three hundred twenty-one men (mean age [+/-standard deviation]: 63.4+/-8.5 years) selected active surveillance as their initial management. The overall median follow-up was 3.6 years (range, 1-17 years). The initial mean PSA level was 6.5+/-3.9 ng/mL. One hundred twenty men (37%) met at least 1 criterion for progression. Overall, 38% of men had higher grade on repeat biopsy, and 26% of men had a PSA velocity>0.75 ng/mL per year. Seventy-eight men (24%) received secondary treatment at a median 3 years (range, 1-17 years) after diagnosis. Approximately 13% of patients with no disease progression elected to obtain treatment. PSA density at diagnosis and rise in Gleason score on repeat biopsy were associated significantly with receipt of secondary treatment. The disease-specific survival rate was 100%. CONCLUSIONS: Selected individuals with early-stage prostate cancer may be candidates for active surveillance. Specific criteria can be and need to be developed to select the most appropriate individuals for this form of management and to monitor disease progression. A small attrition rate can be expected because of men who are unable or unwilling to tolerate surveillance.     

Active surveillance: towards a new paradigm in the management of early prostate cancer

Prostate cancer is the only human cancer that is curable but which commonly does not need to be cured. Active surveillance is a new strategy that aims to individualise therapy by selecting only those men with significant cancers for curative therapy. Patients with favourable tumour characteristics are closely monitored using serum prostate specific antigen (PSA) concentrations and repeat prostate biopsies. The choice between radical treatment and continued observation is based on evidence of disease progression, defined in terms of the PSA doubling time, and "upgrading" at repeat biopsy. Active surveillance provides an excellent opportunity for studies to identify markers of prostate-cancer behaviour. Knowledge of prostate cancer biomarkers would have an immediate effect on clinical decision-making and would also identify targets for the development of novel therapeutic strategies. In the longer term, active surveillance may accelerate progress towards a new treatment paradigm for early prostate cancer based on the selective use of therapies designed, not to eradicate the disease, but to alter its natural history.     

Active Surveillance for Intermediate-Risk Prostate Cancer: Systematic Review and Meta-analysis of Current Protocols and Outcomes

IntroductionCurrent guidelines allow active surveillance for intermediate-risk prostate cancer patients but do not provide comprehensive recommendations for selection. We performed a systematic review and meta-analysis of outcomes for active surveillance in intermediate- and low-risk groups.MethodsWe performed a systematic literature search of intermediate-risk localized prostate cancer patients undergoing active surveillance using 3 literature search engines (Medline, Web of Science, and Scopus) over the past 10 years. The primary outcome was the percentage of patients who remain under surveillance. Secondary outcomes included cancer-specific survival, overall survival, and metastasis-free survival. For articles including both low- and intermediate-risk patients undergoing active surveillance, comparisons between the two groups were made.ResultsThe proportion of patients who remained on active surveillance was comparable between the low- and intermediate-risk groups after 10 and 15 years’ follow-up (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.83–1.14; and OR, 0.86; 95% CI, 0.65–1.13). Cancer-specific survival was worse in the intermediate-risk group after 10 years (OR, 0.47; 95% CI, 0.31–0.69) and 15 years (OR, 0.34; 95% CI, 0.2–0.58). The overall survival rate showed no statistical difference at 5 years’ follow-up (OR, 0.84; 95% CI, 0.45–1.57) but was worse in the intermediate-risk group after 10 years (OR, 0.43; 95% CI, 0.35–0.53). Metastases-free survival did not significantly differ after 5 years (OR, 0.55; 95% CI, 0.2–1.53) and was worse in the intermediate-risk group after 10 years (OR, 0.46; 95% CI, 0.28–0.77).ConclusionActive surveillance could be offered to patients with intermediate-risk prostate cancer. However, they should be informed of the need for regular monitoring and the possibility of discontinuation as a result of a higher rate of progression. Available data indicate that 5-year survival rates between intermediate- and low-risk patients do not differ; 10-year survival rates are worse. To assess the long-term effectiveness and safety of active surveillance, it is necessary to develop unified algorithms for patient selection and management, and to prospectively conduct studies with long-term surveillance.     

Call it cancer

The findings of the National Institutes of Health State-of-the-Science Conference on the role of active surveillance in the management of men with localized prostate cancer are examined.In the opening statement of Herman Melville''s Moby Dick, the narrator unambiguously declares his identity with the words, “Call me Ishmael” [1]. It would serve us well to remember this injunction as we ponder the ambiguous status of prostate cancer. Consensus panels have offered us important advice about the management of prostate cancer in recent weeks, with the latest coming from a National Institutes of Health (NIH) panel convened to consider whether or not active surveillance is appropriate for low-grade (Gleason score ≤ 6), low-volume (prostate-specific antigen [PSA] <10 ng/mL) disease [2]. Their conclusion, that active surveillance is an acceptable strategy for many patients in this category, is eminently reasonable advice, particularly for elderly men with significant comorbidity and limited life expectancy. The majority of men currently diagnosed with prostate cancer have low-grade and low-volume disease, and many are advanced in age and will never experience morbidity or mortality as a result of this disease. However, the panel does advise us that a diagnosis of prostate cancer in any patient entails, at a minimum, active surveillance: careful follow-up with monitoring of PSA on an annual basis, or more frequently, and potentially, repeat biopsies, depending on the clinical setting. For the younger patient, active surveillance entails accepting some risk for later disease-related morbidity or mortality. This depends on the accuracy of the Gleason score (subject, of course, to sampling error and reader interpretation) and on patient compliance with the required surveillance. The advantages of active surveillance are obvious: it postpones or avoids costly, morbid, and potentially unnecessary treatment. A number of urologists and radiation oncologists participated in this panel, and one would have a hard time arguing with their conclusion.A more controversial aspect of the NIH panel''s report was the statement that it may be a mistake to call low-grade low-volume prostate cancer a “cancer” in these patients. The panel''s opinion is that the term causes unnecessary anxiety, and may prompt patients to take unnecessary action. Although we agree that the connotation of lethality for some patients is unfortunate, the diagnosis of cancer depends on pathological findings, specifically, pathological appearance and invasive behavior. Indolent cancers occur as part of the spectrum of breast cancers, lymphoma, and other forms of malignancy, and those will continue to be called cancer. Prostate cancer, in all its manifestations, is a real cancer. It is the second leading killer of men in the U.S., with incidence and mortality rates little different from those of breast cancer (2]. However, for patients aged <70 years, with a life expectancy >15 years, the outcome of active surveillance is less certain. Much will depend on the judgment of the individual oncologist following the patient as to when to rebiopsy and when to intervene with treatment. The actual benefits of active surveillance, compared with aggressive intervention, in this younger age group remain to be proven by a clinical trial. An unknown number, perhaps 10%–20%, of such younger men with favorable findings at presentation if untreated will live long enough to develop metastatic disease, and some will die as a result of its dissemination. Because of this uncertainty, many younger patients will choose to proceed with treatment.

Table 1.

Cancer mortality rates, 1990 and 2007: Disease-specific death rates per 100,000 peopleOpen in a separate windowA further ambiguity is posed by the lack of consistency of these recommendations with those of the U.S. Preventive Services Task Force, which, after reviewing available prospective trials, recently pronounced PSA measurement as having unproven value as a screening test for men aged <75 years and of no proven value for men aged ≥75 years [3]. Most oncologists agree that PSA screening is of unproven value for men aged ≥75 years. However, for younger men, without a PSA test, how will doctors detect the higher-grade prostate cancers, and how will physicians proceed with active surveillance for low-grade tumors? The active surveillance strategy itself depends on identifying patients early in the course of their disease and tailoring treatment decisions to the biopsy results. Urologists, radiation oncologists, and medical oncologists know that the digital rectal exam is not a tool for early detection of disease and is able to detect locally advanced disease, which in most cases is no longer curable. Some will argue that low-grade disease does not ever require treatment whereas advanced disease is unaffected by treatment, but if this is so, why undertake active surveillance at all? The fact is that prostate cancer treatment is effective in eradicating disease and delaying its progression, and early treatment is very likely contributing to the steady 4% yearly decline in mortality in the U.S. since the introduction of widespread PSA screening [4]. It is true that there is limited evidence from prospective clinical trials to prove that the decline in mortality is directly related to screening and early institution of therapy. The European screening trial did show a significantly higher prostate cancer-specific survival rate for men aged 55–69 years with regular PSA screening, but the Prostate, Lung, Colorectal, and Ovarian Cancer trial did not show this advantage [5, 6]. Both trials have been criticized for methodological flaws, and further prospective trials are warranted.Meanwhile, the oncologist (surgeon, radiation oncologist, medical oncologist) and primary care physician must sort out these conflicting messages and provide sensible advice for men at risk for prostate cancer. Prostate cancer is cancer. It has the potential to kill, and decisions to screen or not to screen, to treat or not to treat, may well affect an individual''s survival and quality of life. Patients deserve to know this uncertainty, and to make informed decisions. Ignoring the fact that it is cancer, or renaming it something else, does not help the discussion.     

Expectant management for men with early stage prostate cancer

Answer questions and earn CME/CNE Since the dissemination of prostate‐specific antigen screening, most men with prostate cancer are now diagnosed with localized, low‐risk prostate cancer that is unlikely to be lethal. Nevertheless, nearly all of these men undergo primary treatment with surgery or radiation, placing them at risk for longstanding side effects, including erectile dysfunction and impaired urinary function. Active surveillance and other observational strategies (ie, expectant management) have produced excellent long‐term disease‐specific survival and minimal morbidity for men with prostate cancer. Despite this, expectant management remains underused for men with localized prostate cancer. In this review, various approaches to the expectant management of men with prostate cancer are summarized, including watchful waiting and active surveillance strategies. Contemporary cancer‐specific and health care quality‐of‐life outcomes are described for each of these approaches. Finally, contemporary patterns of use, potential disparities in care, and ongoing research and controversies surrounding expectant management of men with localized prostate cancer are discussed. CA Cancer J Clin 2015;65:264–282. © 2015 American Cancer Society.     

Prostatakarzinom

Prostate cancer is a malignancy of higher age groups, and because of demographic changes it will become more significant in the future. Radical prostatectomy and radiotherapy are curative treatment options. Further options are androgen deprivation, chemotherapy, and active surveillance. However, a patient’s chronological age is not sufficient for making decisions about therapy; the risk of the cancer’s progression and the patient’s life expectancy as determined by preexisting comorbidities must be considered. Considerations regarding the consequences of therapy should take precedence over the diagnostics or early detection; especially for older patients, frequently the most reasonable alternative is active surveillance. These patients would profit in their quality of life by not being confronted with the diagnosis of “prostate cancer.”     

Ten-year survival after radical prostatectomy: specimen Gleason score is the predictor in organ-confined prostate cancer

Pathologic stage is a major prognostic factor in patients with clinically localized prostate cancer. However, disease recurrence occurs even in patients with organ-confined disease. With the advent of prostate-specific antigen (PSA) testing, the percentage of patients with pathologically organ-confined tumors has increased significantly. We studied clinical/pathologic factors that will predict disease recurrence in patients with pathologically organ-confined tumors. Patients with clinically localized newly diagnosed prostate cancer who had not received prior therapeutic intervention but who underwent radical prostatectomy as definitive treatment between 1990 and 1999, were included in this study. Clinical/pathologic parameters including age, race, clinical stage, preoperative PSA, and biopsy and specimen Gleason scores (grouped as 2-6, 7, and 8-10) were correlated with disease-free survival in patients with organ-confined disease. Metastasis-free and cancer-specific survival for the cohort was also assessed. A total of 1045 patients fulfilled our inclusion criteria. Overall, the 10-year estimates of PSA progression-free, metastasis-free, and cancer-specific survival were 75%, 91%, and 92%, respectively. Cancer was confined to the prostate in 532 of 1045 patients (51%), of whom 96% (511 of 532) remain PSA progression-free, compared to 65% (335 of 513) with extraprostatic disease (P = 0.0001). Interestingly, in patients with organ-confined disease, the specimen Gleason score was the only prognostic factor for disease recurrence after multivariable analysis. Radical prostatectomy provided excellent cancer control. For patients with pathologically organ-confined tumors, the specimen Gleason score is the only factor predictive of disease-free survival. Of note, Gleason scores of 8-10 are uncommon in these patients.     

Ten-Year Survival After Radical Prostatectomy: Specimen Gleason Score Is the Predictor in Organ-Confined Prostate Cancer

Pathologic stage is a major prognostic factor in patients with clinically localized prostate cancer. However, disease recurrence occurs even in patients with organ-confined disease. With the advent of prostate-specific antigen (PSA) testing, the percentage of patients with pathologically organ-confined tumors has increased significantly. We studied clinical/pathologic factors that will predict disease recurrence in patients with pathologically organ-confined tumors. Patients with clinically localized newly diagnosed prostate cancer who had not received prior therapeutic intervention but who underwent radical prostatectomy as definitive treatment between 1990 and 1999, were included in this study. Clinical/pathologic parameters including age, race, clinical stage, preoperative PSA, and biopsy and specimen Gleason scores (grouped as 2-6, 7, and 8-10) were correlated with disease-free survival in patients with organ-confined disease. Metastasis-free and cancer-specific survival for the cohort was also assessed. A total of 1045 patients fulfilled our inclusion criteria. Overall, the 10-year estimates of PSA progression-free, metastasis-free, and cancer-specific survival were 75%, 91%, and 92%, respectively. Cancer was confined to the prostate in 532 of 1045 patients (51%), of whom 96% (511 of 532) remain PSA progression-free, compared to 65% (335 of 513) with extraprostatic disease (P = 0.0001). Interestingly, in patients with organ-confined disease, the specimen Gleason score was the only prognostic factor for disease recurrence after multivariable analysis. Radical prostatectomy provided excellent cancer control. For patients with pathologically organ-confined tumors, the specimen Gleason score is the only factor predictive of disease-free survival. Of note, Gleason scores of 8-10 are uncommon in these patients.