When to diagnose and how to treat prostate cancer in the not too fit elderly

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1 Critical Reviews in Oncology/Hematology 48 (2003) When to diagnose and how to treat prostate cancer in the not too fit elderly Philipp Dahm, Ari D. Silverstein, Alon Z. Weizer, Alfonso Crisci, Johannes Vieweg, David F. Paulson Division of Urology, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA Accepted 30 April 2003 Contents 1. Introduction Materials and methods Results Discussion Conservative management versus treatment with curative intent Relative advantages of surgery versus radiation Clinical outcomes of radical prostatectomy Study limitations Conclusions Reviewers References Biographies Abstract The appropriate management of elderly patients diagnosed with prostate cancer remains controversial. In order to provide guidelines as to when aggressive local treatment may be indicated, we provide estimates of the long-term probability of death from prostate cancer and other competing causes in patients of 70 years of age or older, who underwent radical surgery in the form of radical perineal prostatectomy for clinically non-metastatic disease. In this study, a total of 484 patients with an age of 70 or above who underwent radical perineal prostatectomy between 1970 and 2000 comprised a retrospective cohort of patients with clinically organ confined prostate cancer. Of these patients, 461 patients (95.3%) had a minimum follow-up of half a year and were included in the analysis. The median age was 73 years (range years) and the median follow-up was 5.4 years. Overall 115 men died during the follow-up period with 49.6% of deaths attributable to prostate cancer. The median time to cancer-associated death was 17.5 years and the median time to death of any cause 11.6 years. When the likelihood of death from prostate cancer as a function of Gleason score was estimated, the 10-year cancer-associated death rates of patients with Gleason scores of 2 6, 7 and 8 10, were 15.2, 25.2 and 40.2%, respectively. In the subset of patient with margin positive disease the estimated likelihood of a cancer-associated death was 45.3% after 10 years. While the median time to cancer-associated death for margin positive patients with a Gleason score of 2 6 was not reached, patients with a Gleason score of 7 and 8 10 experienced median cancer-associated survival times of 9.6 and 7.6 years, respectively. In conclusion, Gleason score is a strong predictor of the likelihood of prostate cancer related death in elderly Corresponding author. Tel.: ; fax: address: pauls002@mc.duke.edu (D.F. Paulson) /$ see front matter 2003 Elsevier Ireland Ltd. All rights reserved. doi: /j.critrevonc

2 124 P. Dahm et al. / Critical Reviews in Oncology/Hematology 48 (2003) patients. Patients with a given Gleason score and a projected life expectancy of at least 10 years may be at similar risk of dying of prostate cancer as younger patients Elsevier Ireland Ltd. All rights reserved. Keywords: Prostatic neoplasms; Prostatectomy; Aged; Outcome 1. Introduction The increasing statistical life expectancy of North America men as well as the introduction of the prostate specific antigen (PSA) as a screening tool have both contributed to a rising number of elderly men faced with a diagnosis of prostate cancer [1]. These patients will be offered a choice of treatments, or combinations thereof, ranging from observation or watchful waiting, early versus delayed hormonal therapy to control disease progression, or treatment modalities with curative intent such as full dose local radiation or radical prostatectomy. Unfortunately, the absence of data from large randomized trials limits the ability of patients and health care providers to directly compare most treatment alternatives directly, although a recently published, small, randomized trial between radical prostatectomy and watchful waiting did favor surgery with respect to disease specific mortality [2]. Recently, Albertsen et al. [3] reported the long-term outcomes of a large cohort of men who were treated expectantly or with hormonal therapy. This study demonstrated that men with high-grade disease (Gleason sum 7 10) faced a high risk of death from prostate cancer when treated conservatively, even when the cancer was diagnosed as late as age 75. Men with a Gleason score 5 6 disease faced a moderate risk of death from prostate cancer that increased slowly over at least 15 years of follow-up. Based upon these observations, one might question whether the current policy of using a 10-year projected life expectancy is reasonable when selecting current therapy [4]. In an attempt to provide guidelines as to when aggressive treatment may be indicated and in order to allow benchmark comparisons to alternative treatment modalities, the following study provides long-term outcome data of elderly patients treated with radical prostatectomy. All patients were at least 70 years of age, yet had a projected life expectancy of at least 10 years at the time of diagnosis. 2. Materials and methods The study group consisted of a total of 484 patients who underwent radical perineal prostatectomy between 1970 and 2000 for clinically organ confined prostate cancer and were at least 70 years of age at the time. Of these patients, 464 patients (95.3%) had a minimum follow-up of half a year and were included in the analysis. The prostatectomy specimens were processed in a standard manner and characterized pathologically by the Gleason grade and score, as well as the extent of disease using the categories organ confined, specimen confined and margin positive [5]. Organ confined includes disease into but not through the capsule, specimen confined encompasses all disease outside the anatomical limits of the prostate (includes through capsule and/or periprostatic tissue and/or base of seminal vesicle or perivesical tissue), and margin positive disease extends to the inked margin of the surgical specimen [6]. A bilateral pelvic lymph node dissection (BPLND) was routinely performed in all patients for staging purposes until January Thereafter, a BPLND was performed only if the preoperative PSA was 20 ng/ml and/or the Gleason score of the prostate biopsy was Prostatectomy was not performed if frozen section analysis documented metastatic and spread to the lymph. All node positive patients were excluded from this study. Patients were followed at 2 weeks, at 2 months and then at 6-month intervals for biochemical, physical and radiographic evidence of disease recurrence. Outcome was evaluated irrespective of any additional secondary treatment using cancer-associated survival as the endpoint. Cancer-associated death was defined as any death with a PSA 0.5 ng/ml or death in a patient receiving androgen deprivation therapy (with or without detectable PSA) independent of the actual cause of death. In the interest of a uniform outcome analysis based on a large cohort of patients with extended follow-up, of which approximately 1/3 predated the PSA-era, preoperative PSA values were not considered in the statistical analysis. Commercial computer software was used to calculate the time cancer-associated death using the Kaplan Meier method and compared using the log rank test. 3. Results The median age of the population was 73 years (range years) and the median follow-up 5.4 years (25th, 75th percentile range ). During follow-up 115 patients died, including 57 from prostate cancer and 58 from other causes (Table 1). Of the patients who died, 51% (29/57 patients) were operated on in the early part of the series prior to These patients were characterized by unfavorable prognostic features: 56.1% of patients had margin positive disease and 42.1% had poorly differentiated disease (Gleason score 8 10). Using Kaplan Meier survival estimates the overall 10-year cumulative rate of cancer-associated and death of other causes in all patients 70 years or older following radical prostatectomy was 25 and 21%, respectively.

3 Proportion of Patients Surviving P. Dahm et al. / Critical Reviews in Oncology/Hematology 48 (2003) Table 1 Survival status of patients age 70 years or older undergoing radical perineal prostatectomy (n = 464) between 1970 and 2000 grouped by time period of surgery. Time period Status Patients (%) Alive, NED a (%) (n) Alive, with disease (%) (n) Dead, NED (%) (n) Dead, with disease (%) (n) Dead, unknown (%) (n) Prior to (15) 8.0 (7) 39.8 (35) 33.0 (29) 2.3 (2) 88 (19.0) (12) 9.4 (3) 18.8 (6) 34.4 (11) 32 (6.9) (17) 14.6 (6) 19.5 (8) 22.0 (9) 2.4 (1) 41 (8.8) (47) 21.4 (15) 4.3 (3) 7.1 (5) 70 (15.1) (61) 8.3 (6) 2.8 (2) 4.2 (3) 72 (15.6) (53) 5.4 (3) 56 (12.2) (43) 12.0 (6) 2.0 (1) 50 (10.8) (54) 1.8 (1) 55 (11.9) Total 65.1 (302) 10.1 (47) 11.9 (55) 12.3 (57) 0.6 (3) 464 (100.0) a NED: no evidence of disease. The median time to cancer-associated death was 17.5 years and the median overall time to death of any cause 11.6 years (Fig. 1). Fig. 2 illustrates the distribution of pathologic disease extent in the prostatectomy specimen grouped by time period when surgery was performed. While only a little more than half the patients (51.1%) prior to 1987 were found to have organ confined disease, this number approximated 3/4 of the population (72.1%) in the time period of Fig. 3 demonstrates the distribution of Gleason scores over time. Overall a significant trend towards higher Gleason score disease (Gleason sum 7 10) was observed. Prior to 1987 approximately half the patients (49.4%) were found to have Gleason score 2 6 disease, compared to 38.3% in The proportion of Gleason score 7 disease accounted to the majority of this relative increase of higher score disease and approximately doubled from 24.7 to 53.2%, respectively in the same intervals. Deaths from prostate cancer were then analyzed as a function of the Gleason score. The estimated 10-year cancer-associated death rate of patients with Gleason scores of 2 6, 7 and 8 10, were calculated as 15.2, 25.2 and 40.2%, respectively. While patients with Gleason score 2 6 disease did not reach their median time to cancer-associated death during the follow-up period, patients with Gleason score 7 and 8 10 disease had cancer-associated survival times of 17.5 years and 12.3 years, respectively (Fig. 4). Meanwhile, the estimated 10-year death rates from all other causes but prostate cancer as a function of the same Gleason score categories were not significantly different with values of 18.6, 20.4 and 18.8%, respectively. A subset analysis was performed in those patients with margin positive disease. The overall estimated likelihood of Cancer Associated Survival Overall Survival Years Fig. 1. Time to cancer-associated death and time to death of any cause in patients of age 70 years or older (n = 461) undergoing radical perineal prostatectomy.

4 126 P. Dahm et al. / Critical Reviews in Oncology/Hematology 48 (2003) Fig. 2. Proportion of pathologic tumor stages (organ confined (OC); specimen confined (SC); margin positive (MP)) in patients of age 70 years or older undergoing radical perineal prostatectomy grouped by the year of surgery. cancer-associated death in this group of patients was 45.3% after 10 years. The calculated death rate from all other causes in comparison was only 15.7%. While the median time to cancer-associated death for margin positive patients with a Gleason score of 2 6 was once again not reached, patients with a Gleason score of 7 and 8 10 experienced median cancer-associated survival times of only 9.6 and 7.6 years, respectively (Fig. 5). 4. Discussion The reported analysis of the long-term outcome of elderly patients who underwent radical prostatectomy with curative intent provides a framework of reference for comparing alternative approaches to clinically organ confined prostate cancer. To our knowledge, it represents the first dedicated analysis of the long-term outcome of elderly patients treated surgically Conservative management versus treatment with curative intent The findings of this study may be compared to a recent study by Albertsen et al. [3] of 767 men with localized prostate cancer diagnosed between 1971 and 1984, aged years, treated with either immediate or delayed hormonal therapy and followed for years after diagnosis. This study demonstrated that men with prostate biopsy specimens showing Gleason score 2 4 disease faced a minimal risk of death from prostate cancer within 15 years of diagnosis. Conversely, men with prostate biopsy specimens showing Gleason score 7 10 disease faced a higher risk of prostate cancer when treated conservatively, even when the Fig. 3. Distribution of Gleason score categories [2 10] in patients of age 70 years or older undergoing radical perineal prostatectomy grouped by the year of surgery.

5 Proportion of Patients Surviving P. Dahm et al. / Critical Reviews in Oncology/Hematology 48 (2003) Gleason score 2-6 (n=200).8.7 Gleason score 7 (n=157).6.5 p = Gleason score 8-10 (n=96) Years Fig. 4. Time to cancer-associated death in patients of age 70 years or older undergoing radical perineal prostatectomy grouped by Gleason score categories [2 10]. cancer was diagnosed as late as age 75. Men with Gleason score 5 6 disease faced a moderate risk of death from prostate cancer that increased slowly over at least 15 years of follow-up. When addressing the subset of patients in the age group years, only 7 and 11% of patients with a Gleason score of 2 4 and 5 died of prostate cancer. Meanwhile, 32, 40 and 60% of patients with biopsy Gleason scores of 6, 7, and 8 10 died of prostate cancer. In fact, men with Gleason scores of 7, and 8 10 experienced very high rates of death from prostate cancer regardless of their age at diagnosis. These findings are in accordance with our series and highlight the importance of not only age when discussing treatment, but also Gleason score as a measure of the biological aggressiveness of the underlying disease. Further ev- idence on the outcome of prostate cancer patients treated by radical prostatectomy and bilateral pelvic lymph node dissection stems from a recent study by Sweat et al. [7]. These authors found that age and Charlson co-morbidity score were independent predictors of death from other causes, while only Gleason score was significant for prostate cancer death. The high death rates observed in series of expectant management as reported by Albertsen et al. [3] are particularly worrisome in face of the methodology used to determine the cause of death from death certificates. It is likely that if the definition of cancer-associated death were to be applied, the observed number of deaths attributed to prostate cancer would have been even higher. It this context it appears important to account for the potential bias that derives from Gleason score 2-6 (n=23) Proportion of Patients Surviving p = Gleason score 7 (n=42) Gleason score 8-10 (n=47) Years Fig. 5. Time to cancer-associated death in patients of age 70 years or older and margin positive disease grouped by Gleason score categories [2 10].

6 128 P. Dahm et al. / Critical Reviews in Oncology/Hematology 48 (2003) the discrepancy between biopsy and prostatectomy Gleason score. The biopsy grade underestimates the final Gleason score by at least 1 Gleason score point in over 40% of the time [8], and by 2 Gleason score points in 20% of cases. It has been suggested that increasing the number of cores may improve concordance between the pretreatment biopsy and the true (prostatectomy) Gleason score [9]. A further critical aspect relates to the trend towards a greater percentage of patients with moderately to poorly differentiated tumors over the course of the study period. While it is possible that both a selection bias and altered tumor biology play a role, it has been successfully argued that the trend towards higher Gleason scores may have its basis in the different interpretation of pathologists today compared to earlier [10]. In consequence, it is rare for contemporary patients to be diagnosed with Gleason score 2 4 prostate cancer and in this series there was only been a single case (0.4%) among the last 250 radical prostatectomies performed. Among other treatment modalities, radical prostatectomy is one potentially curative therapy. Only recently, the results of a so far unique, prospective randomized trial comparing radical prostatectomy and watchful waiting were published by Holmberg et al. [2] providing strong evidence for the benefit of radical surgery. In this study with a median follow-up time of 6.2 years, the men assigned to radical prostatectomy (n = 53) had a significantly lower risk of death from prostate cancer (4.6%) than patients assigned to the watchful waiting group (n = 62; 8.9%). In addition, the men assigned to surgery had a significantly lower relative risk of developing distant metastasis. In comparison, men 70 years of age or older that elected radical surgery in this study, had an estimated 5- and 10-year cancer-associated survival of 98.8 and 78.5%. When deaths from prostate cancer were subsequently examined as a function of Gleason sum, it was noted that there are very few deaths in the Gleason score 2 6 group at 10 years of observation. The death rate of prostate cancer in this subset of patient of 15.2% was less than that of all other causes calculated as 18.6%. This data suggests that cancer of Gleason sum 6 or less provides very little biological risk in the patient with a life expectancy of 10 years or less. Meanwhile in patients with Gleason score 7 diseases, more patients died of prostate cancer at 10 years of follow-up than of other reasons. In patients with Gleason score 8 10 prostate cancer, the likelihood of dying of prostate cancer was 40.2% and more than twice than that of other competing causes. Therefore, when facing an elderly population that may be frail, the benefits of observation, radiation therapy, hormonal therapy, and radical prostatectomy over the competing risks of death are relative to the severity of the competing risks. The large percentage of patients with high-grade disease that die of prostate cancer despite aggressive management raise the question whether local treatment has any impact on disease progression in the setting of a biologically aggressive malignancy [11]. A recent study by Egevad et al. analyzed a series of 305 elderly patients with prostate cancer diagnosed by transurethral resection [12]. These patients had a mean patient mean age of 74 years and treatment in the form of hormonal treatment was deferred until the time of clinical symptoms, local progression or evidence of metastatic disease. The mean disease specific survival decreased significantly with every increment in Gleason score except Gleason score 4 and 5, and 8 10, which overlapped considerably. The reported mean disease specific survival rates for Gleason scores 4 5 ranged from 14.3 to 18.2 years, for Gleason scores 6 and 7 were 14.3 and 10.4 years, respectively, and for Gleason scores 8 10 ranged from 6.8 to 4.7 years. These survival estimates for patients managed with deferred androgen ablation were consistently lower than those observed in our series of patients who initially underwent radical surgery (Fig. 6). While a direct comparison of outcomes is hampered for many methodical reasons, the cancer-associated survival time of 12.4 years in this series of patients with a Gleason score of eight does support the concept that radical surgery impacts on the progression of even high-grade prostate cancer [13] and may result in significantly prolonged survival in the elderly patient. Even patients with the combination of adverse prognosticators in the form of Gleason 8 10 disease who were margin positive after radical surgery experienced an extended survival with a median of 7.6 years, when managed expectantly until disease progression was noted Relative advantages of surgery versus radiation In examining the relative advantages of radiation therapy versus surgery, we find it necessary to go to a series that has observation periods of greater than 5 years since no significant difference between the two therapies can be identified at 5 years. In addition, any difference in outcome will be the most apparent in patients with biologically aggressive disease. A review of outcome data of patients with high-grade prostate cancer from the Surveillance, Epidemiology and End Results (SEER) Program database demonstrated a survival advantage of surgery over radiation: Perrotti et al. [14] found the 12-year actuarial survival rates for patients with clinically organ confined prostate cancer and Gleason 8 10 disease treated with radiation versus radical surgery to be 46.3 and 67.6%, respectively. This difference in survival in favor of surgery for high-grade disease was statistically significant and presumably, could be carried into Gleason sum 7 disease. While inherent biases in this nonrandomized tumor registry deserve consideration, this data does support the long-term efficacy of radical surgery in establishing cancer control. While contemporary forms of radiation may yield improved results over historical series, such long-term outcome data is pending Clinical outcomes of radical prostatectomy Over the last decade modern radical prostatectomy has made significant advances in terms of improved clinical outcomes and decreased morbidity [15]. Two surgical

7 P. Dahm et al. / Critical Reviews in Oncology/Hematology 48 (2003) GS Years Fig. 6. Time to cancer-associated death with 95% confidence intervals in patients of age 70 years or older undergoing radical perineal prostatectomy grouped by Gleason scores [4 10]. approaches are most commonly performed referred to as radical retropubic and perineal prostatectomy. Of these two, radical retropubic offers the advantage of allowing a bilateral pelvic lymph node dissection (BPLND) through the same incision. While this may have had conceptual advantages prior to the PSA-era, the availability of accurate staging nomograms [16,17] as well as the outlined stage shift towards earlier pathologic stages has made a BPLND unnecessary in many cases. In addition, the perineal approach does offer some distinct advantages, which may be of particular relevance in elderly patients. These include low transfusion requirements, short operating times and fast recovery [15,18 20]. While outpatient radical prostatectomy has been reported [21], it is our practice to routinely keep patients in the hospital for 2 days. A review of our experience of over 2000 cases was favorable with a perioperative mortality of less than 1% and no case of acute pulmonary embolism. Aside from cancer control, urinary continence may be regarded as one of the most relevant outcome parameter [22]. In general, continence rates achieved by modern prostatectomy may be regarded as highly satisfactory to the patient. The percentage of patients that achieved total urinary continence within 1 year postoperatively has been reported to range between 92 and 96%, depending on the definition used [18,23,24]. Continence following RPP is typically achieved early in the postoperative course, which has been suggested to constitute a potential advantage over RRP [25]. In a retrospective analysis, Weldon et al. reported a return of continence with no routine pad use in 23% of patients at 1 month, 56% by 3 months, and 90% by 6 months [24]. Our own experience has been similar: in an ongoing prospective quality of life study only 8% of patients reported to still require up to a single at 6 months after RPP. By this point in time the patient s subjective quality of life in regards to urinary function and bother had returned to at least baseline levels. Patients may, however, expect a further improvement of their continence up to 1 year following surgery. While the results of an ongoing prospective study at our institution would suggest that the return of continence in patients of 70 years or older may be delayed, the ultimate degree of continence appears to be similar. Although one group [25] has suggested an increased incidence of fecal incontinence following perineal prostatectomy, and to some extent the retropubic prostatectomy, a review of our own experience with perineal prostatectomy indicated that any bowel related problems are transient in nature and resolve within 3 6 months of follow-up. The incidence of bowel related problems was not significantly increased in the subset of patients aged 70 or older compared to baseline. All forms of treatment for prostate cancer significantly affect erectile function [26]. While a nerve-sparing prostatectomy may be performed in appropriately selected and motivated candidates of any age group [27], one of the most important insights made over the last decade, is that of a strong inverse correlation of the rate of success in sparing potency and increasing age: In series of RPP patients reported by Weldon [24], potency returned in all patients less than 50 years of age, but only 29% of patients 70 years or older. With respect to elderly men, it appears most important to communicate realistic expectations: not only is the achieved erectile function in patients 70 years or older after nerve-sparing surgery relatively poor, but also recovery may be delayed to up to 1.5 years [28]. Meanwhile, in appropriately selected patients with good preoperative erectile function and realistic expectations, nerve-sparing RPP may preserve some erectile function and retain valuable quality of life.

8 130 P. Dahm et al. / Critical Reviews in Oncology/Hematology 48 (2003) Study limitations Several limitations of this study deserve careful consideration. First, preoperative PSA levels were unavailable in approximately 1/3 of patients in this series for which reason this variable was not evaluated as a prognosticator of outcome. As studies in non-aged prostatectomy patients indicate, preoperative PSA levels represent an important independent predictor both of the risk for biochemical failure as well as long-term survival [29]. Second, outcome in this study is reported as cancer-associated survival which may overestimate the number of patients suffering a prostate cancer related death. In contrast, survival analyses based on death certificates may underestimate the number of patients dying from prostate cancer. Until the controversy as to how best to determine the cause of death in a prostate cancer patient with biologically active disease is resolved [5,30,31] our long-term outcome estimates may be interpreted as conservative, yet valid. Finally, the dynamic impact of both an increasing life expectancy and an increasing lead time introduced by PSA screening may force us to reconsider our treatment guidelines ever so often. Based on the available data though, it does appear that PSA screening and curative treatment should not be deferred based on age alone and that a projected life expectancy of at least 10 years represents an appropriate benchmark when considering treatment with curative intent. 5. Conclusions Prostate cancer constitutes a health care issue of increasing importance in the aging male. Based on the potentially detrimental impact aggressive prostate cancer may have, overall healthy elderly men should be routinely followed with PSA measurements and undergo biopsy when elevated. A projected life expectancy of approximately 10 years may serve as a guideline as to when prostate cancer screening may be indicated. The Gleason score of prostate cancer is a strong predictor of the natural history of the disease and should be emphasized in the decision-making process between the patient and health care provider. A biopsy Gleason score of six or less may carry little biological risk in the aging patient with an expected survival of 10 years; meanwhile, patients with poorly differentiated prostate cancer are at high risk for death by prostate cancer even when 70 or more years of age. While treatment must be tailored to the individual, aggressive cancers should be treated aggressively. Treatment without curative intent may deprive even the frail patient of years of life. When considering local treatment, strong consideration should be given to radical surgery. Modern radical prostatectomy is associated with low perioperative morbidity, excellent clinical outcomes as well as documented long-term disease control. The short convalescence associated with the perineal approach may find particular appeal in the frail elderly patient. Longer follow-up of men who undergoing radical surgery in the PSA-era is needed to determine the impact of PSA testing in terms of cancer-associated survival. Reviewers Mark S. Soloway, MD, Department of Urology, University of Miami School of Medicine, Miami, FL , USA. Ralph De Vere White, MD, Department of Urology, Director, UC Davis Cancer Center, Sacramento, CA 95817, USA. Cora Sternberg, MD, FACP, Department of Medical Oncology, San Camillo and Forlanini Hospitals, Circonvallazione Gianicolense 87, I Rome, Italy. References [1] Ruchlin HS, Pellissier JM. An economic overview of prostate carcinoma. Cancer 2001;92: [2] Holmberg L, Bill-Axelson A, Helgesen F, Salo JO, Folmerz P, Haggman M, et al. 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9 P. Dahm et al. / Critical Reviews in Oncology/Hematology 48 (2003) [14] Perrotti M, Rabbani F, Farkas A, Ward WS, Cummings KB. Trends in poorly differentiated prostate cancer 1973 to 1994: observations from the surveillance, epidemiology and end results database. J Urol 1998;160: [15] Gillitzer R, Thuroff J. Relative advantages and disadvantages of radical perineal prostatectomy versus radical retropubic prostatectomy. Crit Rev Oncol Hematol 2002;43:167. [16] Gingrich JR, Paulson DF. The impact of PSA on prostate cancer management. Can we abandon routine staging pelvic lymphadenectomy. Surg Oncol Clin North Am 1995;4: [17] Partin AW, Kattan MW, Subong EN, Walsh PC, Wojno KJ, Oesterling JE, et al. Combination of prostate-specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer. A multi-institutional update [see comments]. J Am Med Assoc 1997;277: [18] Frazier HA, Robertson JE, Paulson DF. 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Factors predicting recovery of erections after radical prostatectomy. J Urol 2000;164: [29] Han M, Partin AW. Nomograms for clinically localized prostate cancer. Part I. Radical prostatectomy. Semin Urol Oncol 2002;20: [30] Penson DF, Albertsen PC, Nelson PS, Barry M, Stanford JL. Determining cause of death in prostate cancer: are death certificates valid. J Natl Cancer Inst 2001;93: [31] Albertsen PC, Walters S, Hanley JA. A comparison of cause of death determination in men previously diagnosed with prostate cancer who died in 1985 or J Urol 2000;163: Biographies Philipp Dahm, received his M.D. degree at the University of Heidelberg, Germany and graduated from the Urology Residency Program at Duke University Medical Center in 2002 where he is currently an Assistant Professor of Urology. His is a scholar of the American Foundation for Urological Disease (AFUD) and recipient of the James Ewing Clinical Science Research Award by the Society of Surgical Oncology (SSO). His research focus lies in the area of urologic oncology with particular emphasis on applied immunotherapy. Ari D. Silverstein, received his M.D. degree at Emory University School of Medicine in Atlanta, Georgia and is member of the Alpha Omega Alpha Medical Honor Society. He is currently a Senior Resident at Duke University Medical Center. His interests include the surgical correction of erectile dysfunction and research in bio film formation on urologic prosthetics. Alon Z. Weizer, received his M.D. degree at Baylor College of Medicine in Houston, Texas and is member of the Alpha Omega Alpha Medical Honor Society. He is currently a Senior Resident at Duke University Medical Center. His interests include urological oncology and minimal invasive approaches to urologic surgery. Alfonso Crisci, received his M.D. degree at the University of Florence, Italy where he graduated with honors from the Urology Residency Program in He is currently a Senior Fellow in Urologic Oncology at Duke University Medical Center. The focus of his current research lies in cancer immunotherapy and minimal invasive approaches to surgical oncology. Johannes W. Vieweg, received his M.D. degree at the University of Munich, Germany Following a Fellowship in the Molecular Therapeutic Program at Memorial Sloan Kettering Cancer Center he graduated from the Urology Residency Program at Duke University Medical Center in He is an Associate Professor of Urology and an Assistant Professor of Immunology. He specializes in urologic oncology with an emphasis on applied cancer vaccines and gene therapy. David F. Paulson, received his M.D. degree at Duke University School of Medicine. Following a Urology Residency at Duke University Medical Center he completed a 3-year fellowship at the National Cancer Institute in Bethesda, Maryland. He is a Professor of Urology and has led the Division of Urology as Chief since His academic focus lies in urologic oncology with a particular focus on the surgical management of bladder and prostate cancer.