1. Radical Prostatectomy versus Watchful Waiting in Early Prostate Cancer Anna Bill-Axelson, M.D., Lars Holmberg, M.D., Ph.D., Mirja Ruutu, M.D., Ph.D., Michael Häggman, M.D., Ph.D., Ph.D., Jan-Erik Jo for the Scandinavian Prostate Cancer Group Study No. 4 NEJM 352:19 MAY 12,2005

2. Background  Prostate cancer  Incidence 200,600,900/10 5 men (50-59,60-69,70-over)  Even without initial treatment, only a small proportion of all patients with cancer at an early clinical stage die from prostate cancer within 10 to 15 years following diagnosis.  mortality due to prostate cancer among men with grade 1 or grade 2 disease - 13 % at 10 years  maximize the possibilities for survival without extensive overtreatment.

3. Results of Conservative Management of Clinically Localized Prostate Cancer initial conservative management and delayed hormone therapy - reasonable choice for some men with grade 1 or 2 clinically localized prostate cancer, particularly for those who have an average life expectancy of 10 years or less Gerald W. Chodak et al. NEJM Vol 330;4 1997

4. A RANDOMIZED TRIAL COMPARING RADICAL PROSTATECTOMY WITH WATCHFUL WAITING IN EARLY PROSTATE CANCER Lars Holmberg et al. NEJM Vol 347;11 2002

6. Copyright restrictions may apply. Natural History of Early, Localized Prostate Cancer, Johansson, J.-E. et al. JAMA 2004;291 Survival of Prostate Cancer Patients (n = 223)

7. Radical prostatectomy one of the most common major surgical procedures In the US alone, an estimated 60,000 men each year Radical prostatectomy Vs watchful waiting in the management of early prostate cancer Main purpose Relative reduction in the risk of death due to prostate cancer after surgery increases over time because removal of the primary tumor prevents metastasis Radical prostatectomy significantly improves over all survival

8. Methods Study Design From 1989 to 1999, 695 men from 14 centers in Sweden, Finland, and Iceland The eligibility criteria under 75 years the presence of newly diagnosed, untreated, localized prostate cancer, as verified by cytologic or histologic examination a tumor stage of T0d (later changed to T1b), T1, or T2 (T1c was included in 1994) a health status that would permit radical prostatectomy a life expectancy of more than 10 years well differentiated to moderately well differentiated bone scan that showed no abnormalities prostate-specific antigen (PSA) level of less than 50 ng per milliliter randomly assigned to undergo either radical prostatectomy or watchful waiting

9. Result

14. 2.0 %  5.3 % 1.7 %  10.2 % Metastasis Death

15. Conclusion Radical prostatectomy reduces disease-specific mortality, overall mortality, and the risk of metastasis and local progression. The absolute reduction in the risk of death after 10 year is small, but the reduction in the risks of metastasis and local tumor progression are substantial.

20. The strategy of initial conservative management and delayed hormone therapy is a reasonable choice for some men with grade 1 or 2 clinically localized prostate cancer, particularly for those who have an average life expectancy of 10 years or less. New treatment strategies are needed for men with grade 3 prostate cancer.

21. Natural History of Early, Localized Prostate Cancer JAMA. 2004;291:2713-2719. Design Population-based, cohort study with a mean observation period of 21 years Setting Regionally well-defined catchment area in central Sweden (recruitment March 1977 through February 1984). Patients A consecutive sample of 223 patients (98% of all eligible) with early-stage (T0-T2 NX M0 classification), initially untreated prostatic cancer. Patients with tumor progression were hormonally treated (either by orchiectomy or estrogens) if they had symptoms. Main Outcome Measures Progression-free, cause-specific, and overall survival. Results After complete follow-up, 39 (17%) of all patients experienced generalized disease. Most cancers had an indolent course during the first 10 to 15 years. However, further follow-up from 15 (when 49 patients were still alive) to 20 years revealed a substantial decrease in cumulative progression-free survival (from 45.0% to 36.0%), survival without metastases (from 76.9% to 51.2%), and prostate cancer–specific survival (from 78.7% to 54.4%). The prostate cancer mortality rate increased from 15 per 1000 person-years (95% confidence interval, 10-21) during the first 15 years to 44 per 1000 person-years (95% confidence interval, 22-88) beyond 15 years of follow-up (P =.01). Conclusion Although most prostate cancers diagnosed at an early stage have an indolent course, local tumor progression and aggressive metastatic disease may develop in the long term. These findings would support early radical treatment, notably among patients with an estimated life expectancy exceeding 15 years.

24. the radical-prostatectomy group surgery with dissection of the pelvic lymph nodes. retropubic radical prostatectomy. The men in the watchful-waiting group no initial treatment other than the transurethral resection Hormonal Treatment for men with symptomatic local progression in the radicalprostatectomy group for those with disseminated disease in both groups. Transurethral resection initial treatment for men with urinary obstruction in the watchful-waiting group.

25. six categories of cause of death: prostate cancer another main cause but with distant metastases, regardless of local status Another main cause but with local progression, without distant metastases; another main cause, but with local progression and unknown status concerning distant metastases another main cause, with no evidence of tumor recurrence, tumor progression, or metastases another main cause within the first month after randomization. In the radical-prostatectomy group, local progression was defined as the presence of a histologically confirmed local tumor. In the watchful-waiting group, men with palpable transcapsular tumor growth or with symptoms of urinary obstruction that necessitated intervention were classified as having local progression. Distant metastases were considered present when bone scans, skeletal radiographs, computed tomographic scans, or chest radiographs revealed metastases or if lymph nodes at sites other than the regional sites showed cytologic or histologic evidence of prostate cancer.