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Long-term cancer control of radical prostatectomy in men younger than 50 years of age: update 2003
ADULT UROLOGY
LONG-TERM CANCER CONTROL OF RADICAL PROSTATECTOMY IN MEN YOUNGER THAN 50 YEARS OF AGE: UPDATE 2003 MASOOD A. KHAN, MISOP HAN, ALAN W. PARTIN, JONATHAN I. EPSTEIN, PATRICK C. WALSH
AND
ABSTRACT Objectives. To compare the cancer control in men younger than 50 years with that in older men treated with radical retropubic prostatectomy (RRP) for localized prostate cancer in a contemporary series. In the 1970s and 1980s, men younger than 50 years old represented approximately 1% of newly diagnosed prostate cancer cases. However, with the widespread use of serum prostate-specific antigen (PSA) testing and increased public awareness of prostate cancer, this figure has risen (3.7% to 4%). Previous studies, mostly carried out before the PSA era, reported conflicting data with respect to cancer control for these younger men treated with RRP. Methods. We analyzed the data from 2897 men who underwent RRP between April 1982 and September 2001. Preoperative PSA level, clinical and pathologic stage, and biochemical recurrence were compared between 341 men younger than 50 years old and 2556 men 50 years old or older. Disease-free (PSA less than 0.2 ng/mL) survival rates were compared using Kaplan-Meier analysis. Pathologic staging was compared using logistic regression analysis. Results. Men younger than 50 years old had pathologic variables and 5, 10, and 15-year biochemical disease-free survival rates comparable to men aged 50 to 59 years (88%, 81%, and 69% versus 87%, 78%, and 71%, respectively). However, younger men had a lower incidence of extraprostatic extension (25% versus 31%; P ⬍0.02), seminal vesicle involvement (2% versus 6%; P ⬍0.03), and positive surgical margins (3% versus 9%; P ⬍0.03), a greater organ-confined disease rate (65% versus 49%; P ⬍0.0001), and a trend toward greater 5, 10, and 15-year biochemical disease-free survival rates, which did not reach statistical significance, compared with men aged 60 to 69 years (84%, 74%, and 67%, respectively; P ⬍0.09). Furthermore, younger men not only had a lower rate of extraprostatic extension (25% versus 36%; P ⬍0.001), seminal vesicle involvement (2% versus 10%; P ⬍0.001), and positive surgical margins (3% versus 9%; P ⬍0.001) and a greater organ-confined disease rate (65% versus 36%; P ⬍0.0001), they also demonstrated significantly (P ⬍0.003) greater 5, 10, and 15-year biochemical disease-free survival rates compared with men aged 70 years or older (72%, 58%, and 58%, respectively). Conclusions. Men diagnosed with prostate cancer who are younger than 50 years of age and are candidates for RRP tend to have a greater probability of organ-confined disease than older men. Younger men also demonstrate greater long-term cancer control rates than older men. UROLOGY 62: 86–92, 2003. © 2003 Elsevier Inc.
I
t is well established that prostate cancer predominantly occurs in men with advanced age.1 To this effect, in the 1970s and 1980s, approximately 1% of men diagnosed with prostate cancer were younger than 50 years old. However, data from the
National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program have indicated that the development and subsequent widespread use of prostate-specific antigen (PSA) testing, as well as improved public awareness, has
From the Departments of Urology, James Buchanan Brady Urological Institute and Pathology, Johns Hopkins University School of Medicine, Johns Hopkins Hospital, Baltimore, Maryland Reprint requests: Masood A. Khan, M.D., Department of Urol-
ogy, James Buchanan Brady Urological Institute, Johns Hopkins Hospital, 600 North Wolfe Street, Marburg 1, Baltimore, MD 21287 Submitted: November 1, 2002, accepted (with revisions): February 25, 2003
86
© 2003 ELSEVIER INC. ALL RIGHTS RESERVED
0090-4295/03/$30.00 doi:10.1016/S0090-4295(03)00404-7
led to increased detection of prostate cancer at an earlier stage and age (3.7% to 4% younger than 50 years old), making these men suitable candidates for radical retropubic prostatectomy (RRP).2 Early studies suggested that young men who presented with prostate cancer usually had clinically advanced disease and were not regarded as suitable candidates for RRP.3–5 However, other studies have suggested that younger men present with more favorable disease.6 – 8 The aim of this study was to address the effect of age on cancer control in men who are candidates for RRP. MATERIAL AND METHODS PATIENT POPULATION AND INCLUSION CRITERIA Between April 1982 and September 2001, 2993 men underwent anatomic RRP with pelvic lymph node dissection for clinically localized adenocarcinoma of the prostate (Stage T1T3a) at our institution by a single urologist. The following age groups were examined: younger than 50 years, 50 to 59 years, 60 to 69 years, and 70 years or older. Of the 347 men younger than 50 years old, 341 (98.3%), with a mean age of 46 years (range 33 to 49), were included in the analysis. Six (1.7%) were excluded from the study group: one (0.3%) was lost to follow-up, two (0.6%) underwent immediate adjuvant radiotherapy, and three (0.8%) had received preoperative hormonal therapy. Of the 2646 men aged 50 years or more, 2556 (96.6%), with a mean age of 58 years (range 50 to 76), were included in the analysis. Ninety (3.4%) were excluded from the study group: 16 (0.6%) were either lost to follow-up or had inadequate postoperative PSA data, 30 (1.2%) underwent immediate adjuvant radiotherapy, 17 (0.6%) had received preoperative hormonal therapy, 13 (0.5%) received immediate adjuvant hormonal therapy, 9 (0.3%) were clinical Stage D0-D2; 3 (0.1%) had received preoperative radiotherapy, and 2 men (0.1%) died soon after surgery (within 1 year) but not of prostate cancer. Only 1.7% and 3.4% of men younger than 50 years or aged 50 years or older, respectively, were excluded from the study; thus, the inclusion or exclusion of these men in the study would not have had any impact on the statistics.
PREOPERATIVE AND POSTOPERATIVE EVALUATION AND PATHOLOGIC CHARACTERISTICS Prostate cancer was staged according to the 1992 American Joint Committee on Cancer staging guidelines,9 including digital rectal examination by a single surgeon and routine serum PSA studies (Hybritech and Tandem-R and EC Beckman Coulter, San Diego, Calif and TOSOH, Tosoh Medics, San Francisco, Calif). A serum enzymatic acid phosphatase level was measured (thymolphthalein monophosphate assay), and a nuclear bone scan was performed on all patients until recently. For the past 7 years, bone scans were mandated only for men with PSA levels greater than 10 ng/mL. The pathologic diagnosis of prostate cancer was based on an examination of prostatic tissue obtained from digitally or transrectal ultrasound-guided prostate biopsy, or transurethral resection of the prostate. The clinical stage, preoperative PSA level, and preoperative Gleason score for younger and older men undergoing RRP are presented in Table I. Postoperative follow-up data were obtained through routine serum PSA assays and digital rectal examinations performed every 3 months for the first year, semiannually the second year, and annually thereafter. Tumor progression was defined as a postoperative elevation of serum PSA (greater than 0.2 ng/mL). No patients included in this analysis received UROLOGY 62 (1), 2003
TABLE I. Clinical stage, serum PSA, and preoperative Gleason score* Variable TNM stage T1a T1b T1c T2a T2b T2c T3a Total Serum PSA (ng/mL) 0–4 4.1–10 10.1–20 ⬎20 Total Gleason score 2–4 5 6 7 8–10 Total
Age <50 yr (n)
Age >50 yr (n)
3 3 151 98 62 15 9 341
(1) (1) (44) (29) (18) (4) (3) (100)
56 114 1066 818 359 102 41 2556
(2) (4) (42) (32) (14) (4) (2) (100)
NS ⬍0.05 NS NS NS NS NS
125 152 28 10 315
(40) (48) (9) (3) (100)
570 1221 399 99 2289
(25) (53) (18) (4) (100)
⬍0.05 NS ⬍0.05 NS
10 33 213 71 14 341
(3) (10) (62) (21) (4) (100)
49 344 1203 793 167 2556
(2) (13) (47) (31) (7) (100)
NS NS ⬍0.05 ⬍0.05 NS
P Value
KEY: PSA ⫽ prostate-specific antigen; NS ⫽ not significant. * Numbers in parentheses are percentages.
neoadjuvant therapy (chemotherapy or hormonal therapy) or immediate adjuvant hormonal therapy or radiotherapy on the basis of the pathologic features. Hence, adjuvant therapy had no impact on the time to biochemical progression in this analysis. The minimal follow-up was 1 year, and the mean length of follow-up for men younger than 50 years was significantly shorter than that for older men (Table II). Biochemical disease-free survival rates for each group were estimated with the Kaplan-Meier product limit method. The log-rank test was used to evaluate biochemical disease-free survival rates between the different age groups. Logistic regression analysis was used to determine whether the pathologic staging variables and surgical margin rates were significantly different between the different age groups.
RESULTS PATHOLOGIC STAGE AND SURGICAL MARGIN STATUS IN RELATION TO PROGRESSION Men aged 50 to 59 years had similar pathologic staging variables but greater surgical margin rates compared with men younger than 50 years (Table III). However, men aged 60 to 69 years and 70 years or older had significantly greater pathologic staging variables and greater positive surgical margin rates compared with men younger than 50 years (Table III). Table IV shows that the actuarial progression-free probability was reduced as the pathologic stage and positive surgical margin rates increased for all age groups. Figure 1 further illustrates that the actuarial progression-free probability was significantly (P ⬍0.0001) reduced as the 87
TABLE II. Follow-up available for all 2897 men after anatomic radical retropubic prostatectomy* Follow-up (yr)
<50 yr (n)
50–59 yr (n)
60–69 yr (n)
>70 yr (n)
5 6–10 11–15 ⬎15 Total Mean (range)
199 85 50 7 341 5.7
650 367 222 49 1288 6.4†
507 385 280 49 1221 7.2‡
10 15 17 5 47 9.5‡
(58) (25) (14) (3) (100) (1–18)
(50) (29) (17) (4) (100) (1–20)
(42) (31) (23) (4) (100) (1–19)
(21) (32) (36) (11) (100) (1–17)
* Numbers in parentheses are percentages, except for mean (range). † P ⬍0.01 for mean years of follow-up for men ⬍50 years vs. men aged 50 –59 years. ‡ P ⬍0.0001 for mean years of follow-up for men ⬍50 years vs. men aged 60 – 69 years and men ⬍50 years vs. men aged ⱖ70 years.
TABLE III. Pathologic stage and surgical margins: correlation with age Age <50 yr Pathologic Finding Organ confined EPE⫹ (SM⫺, SV⫺, LN⫺) EPE⫹ (SM⫹, SV⫺, LN⫺) SV⫹ (LN⫺) LN⫹ Total
Age 50–59 yr
Age 60–69 yr
Age >70 yr
n
%
n
%
P Value
n
%
P Value
n
%
P Value
221 86 10 6 18 341
65 25 3 2 5 100
769 348 79 46 52 1288
59 27 6 4 4 100
NS NS ⬍0.02 NS NS
596 379 112 66 71 1221
49 31 9 5 6 100
⬍0.0001 ⬍0.02 ⬍0.03 ⬍0.03 NS
17 17 4 5 4 47
36 36 9 10 9 100
⬍0.0001 ⬍0.001 ⬍0.001 ⬍0.001 NS
KEY: EPE ⫽ extraprostatic extension; SM ⫽ surgical margin; (⫹) ⫽ positive; (⫺) ⫽ negative; SV⫹ (LN⫺) ⫽ involvement of seminal vesicles, negative nodes; LN⫹ ⫽ micrometastases to pelvic lymph nodes. P values compared with men ⬍50 years.
TABLE IV. Actuarial 5, 10, and 15-year biochemical recurrence-free rates after anatomic radical retropubic prostatectomy in relation to pathologic stage and surgical margin status Variable
Age ⬍50 yr 5 yr 10 yr 15 yr Age 50–59 yr 5 yr 10 yr 15 yr Age 60–69 yr 5 yr 10 yr 15 yr Age ⱖ70 yr 5 yr 10 yr 15 yr
Organ Confined
EPEⴙ (SMⴚ, SVⴚ, LNⴚ)
EPEⴙ (SMⴙ, SVⴚ, LNⴚ)
SVⴙ (LNⴚ)
LNⴙ
98 (94–99) 96 (88–99) 87 (67–95)
88 (77–94) 78 (63–87) 73 (55–84)
74 (29–93) 37 (05–71) NA
27 (01–69) 27 (01–69) NA
23 (06–46) NA NA
96 (93–97) 94 (91–96) 92 (87–95)
88 (83–91) 77 (71–82) 67 (55–77)
74 (61–83) 51 (35–64) 39 (23–54)
55 (39–69) 31 (17–46) NA
25 (13–38) 8 (02–20) NA
97 (95–99) 92 (88–95) 87 (78–93)
88 (84–91) 78 (73–83) 72 (60–82)
69 (60–77) 57 (47–67) 46 (35–57)
49 (35–62) 34 (20–49) 26 (10–45)
27 (17–38) 13 (06–24) 9 (03–21)
100 81 (44–95) 81 (44–95)
70 (42–86) 60 (30–81) 60 (30–81)
37 (03–77) 25 (01–67) NA
40 (05–75) 40 (05–75) NA
25 (01–67) NA NA
KEY: NA ⫽ not available; other abbreviations as in Table III. Numbers in parentheses are the range.
pathologic stage increased in the younger cohort (younger than 50 years). OVERALL PROGRESSION Kaplan-Meier analysis showed that the 5, 10, and 15-year biochemical disease-free progression rate 88
was 88%, 81%, and 69% for men younger than 50 years, respectively. Men aged 50 to 59 years had similar (P ⫽ 0.7) 5, 10, and 15-year biochemical disease-free progression rates (87%, 78%, and 71%, respectively; Fig. 2A). Although men aged 60 to 69 years demonstrated a trend toward lower 5, UROLOGY 62 (1), 2003
FIGURE 1. Kaplan-Meier actuarial likelihood of PSA recurrence by pathologic stage and surgical margin status in 341 men younger than 50 years. OC ⫽ organ confined; EPE ⫽ extraprostatic extension; LN ⫽ micrometastases to lymph nodes; (⫺) ⫽ negative; (⫹) ⫽ positive; SV⫹ ⫽ positive seminal vesicles with negative lymph nodes; SM ⫽ positive surgical margins, negative lymph nodes, and negative seminal vesicles. P ⬍0.0001 for OC versus EPE⫹ (SM⫺, SV⫺, LN⫺), EPE⫹ (SM⫺, SV⫺, LN⫺) versus EPE⫹ (SM⫹, SV⫺, LN⫺), EPE⫹ (SM⫹, SV⫺, LN⫺) versus SV⫹ (LN⫺), and SV⫹ (LN⫺) versus LN⫹.
10, and 15-year biochemical disease-free progression rates (84%, 74%, and 67%, respectively) compared with men younger than 50 years, this did not reach statistical significance (P ⫽ 0.08; Fig. 2B). However, men aged 70 years or older experienced significantly lower (P ⬍0.003) 5, 10, and 15-year biochemical disease-free progression rates (72%, 58%, and 58%, respectively) compared with men younger than 50 years old (Fig. 2C). COMMENT The technological innovation and eventual commercial availability in 1987 of a serum PSA test to screen patients for prostate cancer combined with the availability of improved treatments during the same period have led to alterations in the patient demographics of men presenting with this disease in the 1990s. The use of age-specific total PSA, first proposed by Oesterling et al.,10 led to additional improvement in the sensitivity for the detection of prostate cancer in younger men. Partin et al.11 later applied the concept to men younger than 60 years of age in a study of 4600 men with clinically localized prostate cancer and detected 74 additional cancer cases. Eighty percent of the additional tumors detected in that study were organ confined. Reissigl et al.,12 studying an Austrian population of 21,000 men aged 45 to 75 years, detected an additional 8% positive biopsies (66 of 778), all clinically significant, by applying age-specific total PSA UROLOGY 62 (1), 2003
FIGURE 2. Kaplan-Meier actuarial likelihood of PSA recurrence in men younger than 50 years compared with (A) men aged 50 to 59 years, (B) 60 to 69 years, and (C) 70 years or older.
ranges in men younger than 59 years of age with normal digital rectal examination findings. Hence, during the past two decades, the incidence of prostate cancer detection in younger men has risen significantly. To this end, Tjaden et al.3 reported, in 1965, that only 1.1% of men diagnosed with adenocarcinoma of the prostate were younger than 50 years old. Hubner et al.,13 in their review of men diagnosed before 1975, found a similar low incidence of 0.8%. However, recent data from the SEER program indicate that between 1995 and 1999, 3.7% to 4% of newly diagnosed prostate cancer cases in the United States were in men younger than 50 years old.2 89
The issue of RRP for young men with prostate cancer has only been briefly addressed in published studies.3–5,14 –17 In earlier studies, only a few men with clinically confined cancer were regarded as appropriate candidates for radical surgery.3–5,14 –17 Most of the older studies were limited in size to fewer than 17 young men who underwent RRP.3–5,16 A series compiled from the long-term survey on prostate cancer by the Commission on Cancer of the American College of Surgeons recorded 29 men younger than 50 years who were treated by RRP.13 This study, however, did not specifically comment on the outcome of those young men treated by radical surgery. Recently, Smith et al.18 reviewed the multicenter prostate cancer research database from the Department of Defense Center for Prostate Disease Research to investigate the outcome of 79 men aged 50 years old or younger treated by RRP for localized prostate cancer compared with 398 men aged 51 to 69 years undergoing RRP. The preoperative PSA level, clinical and pathologic stage, surgical margin status, presence of seminal vesicle involvement, and recurrence rate between men in the two age groups were reviewed. These investigators found that the younger men had a significantly lower prebiopsy PSA level, a greater rate of organ confinement, and a lower disease recurrence rate with a significantly better long-term disease-free outcome. However, the study by Smith et al.18 was limited by the relatively short postoperative follow-up period of the younger age group (mean 2.8 years, with only 9 of the 79 men having a follow-up longer than 6 years). We have previously shown in a smaller study, with a shorter follow-up period, consisting of 85 men younger than 50 years, who had undergone anatomic RRP for clinically localized prostate cancer, that these men have a lower rate of positive surgical margins and similar pathologic variables compared with men aged 50 years old or older.6 Furthermore, less progression developed among the younger men, especially during the first 5 years after RRP. In another study investigating the impact of age on pathologic stage, we reported on 444 consecutive patients who underwent RRP and pelvic lymphadenectomy for localized prostate cancer (T2a-b) and found that men aged 60 years or older had a significantly greater pathologic stage.7 In the present study, we report the long-term follow-up (5.7 ⫾ 4.4 years) results for a large cohort of men younger than 50 years who underwent anatomic RRP for localized prostate cancer. A gradual change in the patient population with early detection of prostate cancer is well demonstrated. The proportion of men with T1c disease increased from 17% in our earlier analysis19 to 44% in the current series of men younger than 50 years. The results of 90
our study illustrate that men younger than 50 years old and men aged 50 to 59 years have similar pathologic variables and, not surprisingly, also very similar biochemical disease-free progression rates. However, men aged 60 to 69 years had significantly greater pathologic variables compared with men younger than 50 years and showed a trend toward lower biochemical disease-free progression rates that did not reach statistical significance. This lack of statistical significance may have been related to the length of follow-up. Hence, it will be interesting to determine the biochemical disease-free progression rates between these two groups during the next few years, especially because men aged 70 years or older, with the longest follow-up period of all the age groups, not only exhibited a significantly greater pathologic stage and an increase in positive margins but also experienced lower biochemical disease-free progression rates than men aged younger than 50 years. Our study included men from four different age groups who underwent RRP both before and after the widespread availability of serum PSA testing. As such, although lead-time bias may have been a factor in those detected with prostate cancer on the basis of an elevated PSA level alone, this would have had an effect in all the age groups. To this end, it is unlikely that lead-time bias had a significant impact in our study. The results of our study demonstrate that men younger than 50 years old, who are candidates for RRP, have greater curative disease and exhibit better long-term progression-free survival than older men. This is particularly important, because the recent routine use of serum PSA and greater availability and acceptance of screening have led to a rise in the detection of early prostate cancer in increasingly younger men that is amenable to curative intervention. This study also provides encouraging evidence for the value of prostate cancer screening in younger men and also supports previous studies that have indicated that young age is an important positive prognostic factor.8,20 CONCLUSIONS In a large series of 341 men younger than 50 years with a mean follow-up of 5.7 ⫾ 4.4 years (range 1 to 18) after anatomic RRP for clinically localized prostate cancer, the actuarial 5, 10, and 15-year biochemical recurrence-free survival rate was 88%, 81%, and 69%, respectively. RRP was curative more often in men younger than 50 years old than in men aged 60 years or older. Furthermore, these younger men also exhibited higher biochemical disease-free progression rates than men aged 70 years or older. This may also be the case when compared with men aged 60 UROLOGY 62 (1), 2003
to 69 years; however, longer term follow-up is required before this can be confirmed. Anatomic RRP, with excellent long-term results for early-stage disease, is an effective way to manage clinically localized prostate cancer in men younger than 50 years old. RRP as the definitive curative monotherapy is likely to play an increasing role in this age group, because the proportion of men with early-stage prostate cancer will continue to increase with the widespread use of serum PSA testing and prostate cancer screening.
18. Smith CV, Bauer JJ, Connelly RR, et al: Prostate cancer in men age 50 years or younger: a review of the department of defense center for prostate disease research multicenter prostate cancer database. J Urol 164: 1964 –1967, 2000. 19. Partin AW, Pound CR, Clemens JQ, et al: Serum PSA after anatomic radical prostatectomy: the Johns Hopkins experience after 10 years. Urol Clin North Am 20: 713–725, 1993. 20. Ruska KM, Partin AW, Epstein JI, et al: Adenocarcinoma of the prostate in men younger than 40 years of age: diagnosis and treatment with emphasis on radical prostatectomy findings. Urology 53: 1179 –1183, 1999.
REFERENCES 1. Greenlee RT, Murray T, Bolden S, et al: Cancer statistics, 2000. CA Cancer J Clin 50: 7–33, 2000. 2. Data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program web site. http://seer.cancer.gov/faststats/html/inc_prost.html;2003. 3. Tjaden HB, Culp DA, and Flocks RHF: Clinical adenocarcinoma of the prostate in men under 50 years of age. J Urol 93: 618 –621, 1965. 4. Silber I, and McGabran MH: Adenocarcinoma of the prostate in men less than 56 years old: a study of 65 cases. J Urol 105: 283–285, 1971. 5. Johnson DE, Lanieri JP, and Ayala AG: Prostate adenocarcinoma occurring in men under 50 years of age. J Surg Oncol 4: 207–216, 1972. 6. Riopel MA, Polascik TJ, Partin AW, et al: Radical prostatectomy in men less than 50 years old. Urol Oncol 1: 80 –83, 1995. 7. Alexander RB, Maguire MC, Epstein JI, et al: Pathological stage is higher in older men with clinical stage B1 adenocarcinoma of the prostate. J Urol 141: 880 –882, 1989. 8. Carter HB, Epstein JI, and Partin AW: Influence of age and prostate-specific antigen on the chance of curable prostate cancer among men with nonpalpable disease. Urology 53: 126 –130, 1999. 9. Beahrs OH, Henson DE, Hutter RVP, et al: American Joint Committee on Cancer Staging Manual. Philadelphia, JB Lippincott, 1992. 10. Oesterling JE, Jacobsen SJ, Chutte CG, et al: Serum prostate-specific antigen in a community-based population of healthy men: establishment of age-specific reference ranges. JAMA 270: 860 –864, 1993. 11. Partin AW, Criley SR, Subong ENP, et al: Standard versus age-specific antigen reference ranges among men with clinically localized prostate cancer: a pathological analysis. J Urol 155: 1336 –1339, 1996. 12. Reissigl A, Pointner J, Horninger W, et al: Comparison of different prostate-specific antigen cutpoint for the early detection of prostate cancer: results of a large screening study. Urology 46: 662–665, 1995. 13. Huben R, Natarajan N, Pontes E, et al: Carcinoma of the prostate in men less than 50 years old. Data from American College of Surgeons’ National Survey. Urology 20: 585–588, 1982. 14. Harrison GSM: The prognosis of prostate cancer in the younger man. Br J Urol 55: 315–320, 1983. 15. Steinberg GS, Carter BS, Beaty TH, et al: Family history and the risk of prostate cancer. Prostate 17: 337–347, 1990. 16. Byar DP, and Mostofi FK: Cancer of the prostate in men less than 50 years old: an analysis of 51 cases. J Urol 102: 726 –733, 1969. 17. Aprikian AG, Zhang ZF, and Fair WR: Prostate adenocarcinoma in men younger than 50 years. Cancer 74: 1768 – 1777, 1994.
EDITORIAL COMMENT This article gives insight into the issue of prostate cancer in men younger than 50 years old. It compares the surgical pathologic findings and long-term PSA fate of men younger than 50 years undergoing RRP at Johns Hopkins Hospital with older cohorts and is an extension of this group’s earlier reports on the subject. Specifically, this group analyzed the fate of 2897 consecutive men who underwent RRP between 1982 and 2001; 341 younger than 50 years and 2556 in age groups 50 to 59, 60 to 69, and 70 years or older (average follow-up 5.7, 6.4, 7.2, and 9.5 years, respectively, with about 25% to 30% with more than 5 years in each group). Using the pathologic parameters of organ-confined disease, extracapsular extension, seminal vesicle invasion, and positive pelvic lymph nodes, they found that the parameters of local pathologic adversity in the younger than 50-year old group were the same as in the age group of 50 to 59 years but were statistically greater in the 60 to 69 and 70 years or older age groups. As would be expected from these results, they also found that the biochemical freedom from disease rates in the younger than 50-year-old group was the same as in the 50 to 60-year-old group, but greater than in the older age groups. Although the authors argue that patient exclusion and lead-time bias were not big factors in their findings, this retrospective uncontrolled analysis could suffer from other unforeseen selection biases. Nonetheless, these results do reinforce the general impression that in the PSA era, prostate cancer discovered in younger men is not inherently worse than that discovered in older men. I believe we can glean additional insights from this excellent article. For example, that men younger than 50 years old seem to have curable cancer more often (ie, better pathologic features and biochemical freedom from disease rates) than older men (ie, older than 60 years) is consistent with the disease model that many prostate cancers grow slowly and logically progress to a larger size and eventually extend beyond the gland and then presumably distantly as metastasis. Such a model favors an attitude for early detection and aggressive treatment of local disease. However, this study also revealed that the percentage of men with positive pelvic lymph nodes in each age group seemed the same (5%, 6%, 7%, and 9%). If these numbers can be believed, it would suggest another disease model favored by those antagonistic to prostate cancer screening. In the latter model, the so-called turtles1 of prostate cancer grow slowly and extend beyond the gland and metastasize late if at all before intercurrent death, and the so-called birds of prostate cancer grow faster, and the size at which they metastasize is such that they are rarely captured by current PSA screening strategies. In this regard, it would be interesting to know the grade and cancer-specific survival rates in each cohort in this series. Does this mean that we should begin recommending that men who are not African American or who do not have a family history of prostate cancer begin screening before age 50? I think not. In this series, no difference was found in pathologic features or biochemical freedom from disease rates
UROLOGY 62 (1), 2003
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LONG-TERM CANCER CONTROL OF RADICAL PROSTATECTOMY IN MEN YOUNGER THAN 50 YEARS OF AGE: UPDATE 2003 MASOOD A. KHAN, MISOP HAN, ALAN W. PARTIN, JONATHAN I. EPSTEIN, PATRICK C. WALSH
AND
ABSTRACT Objectives. To compare the cancer control in men younger than 50 years with that in older men treated with radical retropubic prostatectomy (RRP) for localized prostate cancer in a contemporary series. In the 1970s and 1980s, men younger than 50 years old represented approximately 1% of newly diagnosed prostate cancer cases. However, with the widespread use of serum prostate-specific antigen (PSA) testing and increased public awareness of prostate cancer, this figure has risen (3.7% to 4%). Previous studies, mostly carried out before the PSA era, reported conflicting data with respect to cancer control for these younger men treated with RRP. Methods. We analyzed the data from 2897 men who underwent RRP between April 1982 and September 2001. Preoperative PSA level, clinical and pathologic stage, and biochemical recurrence were compared between 341 men younger than 50 years old and 2556 men 50 years old or older. Disease-free (PSA less than 0.2 ng/mL) survival rates were compared using Kaplan-Meier analysis. Pathologic staging was compared using logistic regression analysis. Results. Men younger than 50 years old had pathologic variables and 5, 10, and 15-year biochemical disease-free survival rates comparable to men aged 50 to 59 years (88%, 81%, and 69% versus 87%, 78%, and 71%, respectively). However, younger men had a lower incidence of extraprostatic extension (25% versus 31%; P ⬍0.02), seminal vesicle involvement (2% versus 6%; P ⬍0.03), and positive surgical margins (3% versus 9%; P ⬍0.03), a greater organ-confined disease rate (65% versus 49%; P ⬍0.0001), and a trend toward greater 5, 10, and 15-year biochemical disease-free survival rates, which did not reach statistical significance, compared with men aged 60 to 69 years (84%, 74%, and 67%, respectively; P ⬍0.09). Furthermore, younger men not only had a lower rate of extraprostatic extension (25% versus 36%; P ⬍0.001), seminal vesicle involvement (2% versus 10%; P ⬍0.001), and positive surgical margins (3% versus 9%; P ⬍0.001) and a greater organ-confined disease rate (65% versus 36%; P ⬍0.0001), they also demonstrated significantly (P ⬍0.003) greater 5, 10, and 15-year biochemical disease-free survival rates compared with men aged 70 years or older (72%, 58%, and 58%, respectively). Conclusions. Men diagnosed with prostate cancer who are younger than 50 years of age and are candidates for RRP tend to have a greater probability of organ-confined disease than older men. Younger men also demonstrate greater long-term cancer control rates than older men. UROLOGY 62: 86–92, 2003. © 2003 Elsevier Inc.
I
t is well established that prostate cancer predominantly occurs in men with advanced age.1 To this effect, in the 1970s and 1980s, approximately 1% of men diagnosed with prostate cancer were younger than 50 years old. However, data from the
National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program have indicated that the development and subsequent widespread use of prostate-specific antigen (PSA) testing, as well as improved public awareness, has
From the Departments of Urology, James Buchanan Brady Urological Institute and Pathology, Johns Hopkins University School of Medicine, Johns Hopkins Hospital, Baltimore, Maryland Reprint requests: Masood A. Khan, M.D., Department of Urol-
ogy, James Buchanan Brady Urological Institute, Johns Hopkins Hospital, 600 North Wolfe Street, Marburg 1, Baltimore, MD 21287 Submitted: November 1, 2002, accepted (with revisions): February 25, 2003
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© 2003 ELSEVIER INC. ALL RIGHTS RESERVED
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led to increased detection of prostate cancer at an earlier stage and age (3.7% to 4% younger than 50 years old), making these men suitable candidates for radical retropubic prostatectomy (RRP).2 Early studies suggested that young men who presented with prostate cancer usually had clinically advanced disease and were not regarded as suitable candidates for RRP.3–5 However, other studies have suggested that younger men present with more favorable disease.6 – 8 The aim of this study was to address the effect of age on cancer control in men who are candidates for RRP. MATERIAL AND METHODS PATIENT POPULATION AND INCLUSION CRITERIA Between April 1982 and September 2001, 2993 men underwent anatomic RRP with pelvic lymph node dissection for clinically localized adenocarcinoma of the prostate (Stage T1T3a) at our institution by a single urologist. The following age groups were examined: younger than 50 years, 50 to 59 years, 60 to 69 years, and 70 years or older. Of the 347 men younger than 50 years old, 341 (98.3%), with a mean age of 46 years (range 33 to 49), were included in the analysis. Six (1.7%) were excluded from the study group: one (0.3%) was lost to follow-up, two (0.6%) underwent immediate adjuvant radiotherapy, and three (0.8%) had received preoperative hormonal therapy. Of the 2646 men aged 50 years or more, 2556 (96.6%), with a mean age of 58 years (range 50 to 76), were included in the analysis. Ninety (3.4%) were excluded from the study group: 16 (0.6%) were either lost to follow-up or had inadequate postoperative PSA data, 30 (1.2%) underwent immediate adjuvant radiotherapy, 17 (0.6%) had received preoperative hormonal therapy, 13 (0.5%) received immediate adjuvant hormonal therapy, 9 (0.3%) were clinical Stage D0-D2; 3 (0.1%) had received preoperative radiotherapy, and 2 men (0.1%) died soon after surgery (within 1 year) but not of prostate cancer. Only 1.7% and 3.4% of men younger than 50 years or aged 50 years or older, respectively, were excluded from the study; thus, the inclusion or exclusion of these men in the study would not have had any impact on the statistics.
PREOPERATIVE AND POSTOPERATIVE EVALUATION AND PATHOLOGIC CHARACTERISTICS Prostate cancer was staged according to the 1992 American Joint Committee on Cancer staging guidelines,9 including digital rectal examination by a single surgeon and routine serum PSA studies (Hybritech and Tandem-R and EC Beckman Coulter, San Diego, Calif and TOSOH, Tosoh Medics, San Francisco, Calif). A serum enzymatic acid phosphatase level was measured (thymolphthalein monophosphate assay), and a nuclear bone scan was performed on all patients until recently. For the past 7 years, bone scans were mandated only for men with PSA levels greater than 10 ng/mL. The pathologic diagnosis of prostate cancer was based on an examination of prostatic tissue obtained from digitally or transrectal ultrasound-guided prostate biopsy, or transurethral resection of the prostate. The clinical stage, preoperative PSA level, and preoperative Gleason score for younger and older men undergoing RRP are presented in Table I. Postoperative follow-up data were obtained through routine serum PSA assays and digital rectal examinations performed every 3 months for the first year, semiannually the second year, and annually thereafter. Tumor progression was defined as a postoperative elevation of serum PSA (greater than 0.2 ng/mL). No patients included in this analysis received UROLOGY 62 (1), 2003
TABLE I. Clinical stage, serum PSA, and preoperative Gleason score* Variable TNM stage T1a T1b T1c T2a T2b T2c T3a Total Serum PSA (ng/mL) 0–4 4.1–10 10.1–20 ⬎20 Total Gleason score 2–4 5 6 7 8–10 Total
Age <50 yr (n)
Age >50 yr (n)
3 3 151 98 62 15 9 341
(1) (1) (44) (29) (18) (4) (3) (100)
56 114 1066 818 359 102 41 2556
(2) (4) (42) (32) (14) (4) (2) (100)
NS ⬍0.05 NS NS NS NS NS
125 152 28 10 315
(40) (48) (9) (3) (100)
570 1221 399 99 2289
(25) (53) (18) (4) (100)
⬍0.05 NS ⬍0.05 NS
10 33 213 71 14 341
(3) (10) (62) (21) (4) (100)
49 344 1203 793 167 2556
(2) (13) (47) (31) (7) (100)
NS NS ⬍0.05 ⬍0.05 NS
P Value
KEY: PSA ⫽ prostate-specific antigen; NS ⫽ not significant. * Numbers in parentheses are percentages.
neoadjuvant therapy (chemotherapy or hormonal therapy) or immediate adjuvant hormonal therapy or radiotherapy on the basis of the pathologic features. Hence, adjuvant therapy had no impact on the time to biochemical progression in this analysis. The minimal follow-up was 1 year, and the mean length of follow-up for men younger than 50 years was significantly shorter than that for older men (Table II). Biochemical disease-free survival rates for each group were estimated with the Kaplan-Meier product limit method. The log-rank test was used to evaluate biochemical disease-free survival rates between the different age groups. Logistic regression analysis was used to determine whether the pathologic staging variables and surgical margin rates were significantly different between the different age groups.
RESULTS PATHOLOGIC STAGE AND SURGICAL MARGIN STATUS IN RELATION TO PROGRESSION Men aged 50 to 59 years had similar pathologic staging variables but greater surgical margin rates compared with men younger than 50 years (Table III). However, men aged 60 to 69 years and 70 years or older had significantly greater pathologic staging variables and greater positive surgical margin rates compared with men younger than 50 years (Table III). Table IV shows that the actuarial progression-free probability was reduced as the pathologic stage and positive surgical margin rates increased for all age groups. Figure 1 further illustrates that the actuarial progression-free probability was significantly (P ⬍0.0001) reduced as the 87
TABLE II. Follow-up available for all 2897 men after anatomic radical retropubic prostatectomy* Follow-up (yr)
<50 yr (n)
50–59 yr (n)
60–69 yr (n)
>70 yr (n)
5 6–10 11–15 ⬎15 Total Mean (range)
199 85 50 7 341 5.7
650 367 222 49 1288 6.4†
507 385 280 49 1221 7.2‡
10 15 17 5 47 9.5‡
(58) (25) (14) (3) (100) (1–18)
(50) (29) (17) (4) (100) (1–20)
(42) (31) (23) (4) (100) (1–19)
(21) (32) (36) (11) (100) (1–17)
* Numbers in parentheses are percentages, except for mean (range). † P ⬍0.01 for mean years of follow-up for men ⬍50 years vs. men aged 50 –59 years. ‡ P ⬍0.0001 for mean years of follow-up for men ⬍50 years vs. men aged 60 – 69 years and men ⬍50 years vs. men aged ⱖ70 years.
TABLE III. Pathologic stage and surgical margins: correlation with age Age <50 yr Pathologic Finding Organ confined EPE⫹ (SM⫺, SV⫺, LN⫺) EPE⫹ (SM⫹, SV⫺, LN⫺) SV⫹ (LN⫺) LN⫹ Total
Age 50–59 yr
Age 60–69 yr
Age >70 yr
n
%
n
%
P Value
n
%
P Value
n
%
P Value
221 86 10 6 18 341
65 25 3 2 5 100
769 348 79 46 52 1288
59 27 6 4 4 100
NS NS ⬍0.02 NS NS
596 379 112 66 71 1221
49 31 9 5 6 100
⬍0.0001 ⬍0.02 ⬍0.03 ⬍0.03 NS
17 17 4 5 4 47
36 36 9 10 9 100
⬍0.0001 ⬍0.001 ⬍0.001 ⬍0.001 NS
KEY: EPE ⫽ extraprostatic extension; SM ⫽ surgical margin; (⫹) ⫽ positive; (⫺) ⫽ negative; SV⫹ (LN⫺) ⫽ involvement of seminal vesicles, negative nodes; LN⫹ ⫽ micrometastases to pelvic lymph nodes. P values compared with men ⬍50 years.
TABLE IV. Actuarial 5, 10, and 15-year biochemical recurrence-free rates after anatomic radical retropubic prostatectomy in relation to pathologic stage and surgical margin status Variable
Age ⬍50 yr 5 yr 10 yr 15 yr Age 50–59 yr 5 yr 10 yr 15 yr Age 60–69 yr 5 yr 10 yr 15 yr Age ⱖ70 yr 5 yr 10 yr 15 yr
Organ Confined
EPEⴙ (SMⴚ, SVⴚ, LNⴚ)
EPEⴙ (SMⴙ, SVⴚ, LNⴚ)
SVⴙ (LNⴚ)
LNⴙ
98 (94–99) 96 (88–99) 87 (67–95)
88 (77–94) 78 (63–87) 73 (55–84)
74 (29–93) 37 (05–71) NA
27 (01–69) 27 (01–69) NA
23 (06–46) NA NA
96 (93–97) 94 (91–96) 92 (87–95)
88 (83–91) 77 (71–82) 67 (55–77)
74 (61–83) 51 (35–64) 39 (23–54)
55 (39–69) 31 (17–46) NA
25 (13–38) 8 (02–20) NA
97 (95–99) 92 (88–95) 87 (78–93)
88 (84–91) 78 (73–83) 72 (60–82)
69 (60–77) 57 (47–67) 46 (35–57)
49 (35–62) 34 (20–49) 26 (10–45)
27 (17–38) 13 (06–24) 9 (03–21)
100 81 (44–95) 81 (44–95)
70 (42–86) 60 (30–81) 60 (30–81)
37 (03–77) 25 (01–67) NA
40 (05–75) 40 (05–75) NA
25 (01–67) NA NA
KEY: NA ⫽ not available; other abbreviations as in Table III. Numbers in parentheses are the range.
pathologic stage increased in the younger cohort (younger than 50 years). OVERALL PROGRESSION Kaplan-Meier analysis showed that the 5, 10, and 15-year biochemical disease-free progression rate 88
was 88%, 81%, and 69% for men younger than 50 years, respectively. Men aged 50 to 59 years had similar (P ⫽ 0.7) 5, 10, and 15-year biochemical disease-free progression rates (87%, 78%, and 71%, respectively; Fig. 2A). Although men aged 60 to 69 years demonstrated a trend toward lower 5, UROLOGY 62 (1), 2003
FIGURE 1. Kaplan-Meier actuarial likelihood of PSA recurrence by pathologic stage and surgical margin status in 341 men younger than 50 years. OC ⫽ organ confined; EPE ⫽ extraprostatic extension; LN ⫽ micrometastases to lymph nodes; (⫺) ⫽ negative; (⫹) ⫽ positive; SV⫹ ⫽ positive seminal vesicles with negative lymph nodes; SM ⫽ positive surgical margins, negative lymph nodes, and negative seminal vesicles. P ⬍0.0001 for OC versus EPE⫹ (SM⫺, SV⫺, LN⫺), EPE⫹ (SM⫺, SV⫺, LN⫺) versus EPE⫹ (SM⫹, SV⫺, LN⫺), EPE⫹ (SM⫹, SV⫺, LN⫺) versus SV⫹ (LN⫺), and SV⫹ (LN⫺) versus LN⫹.
10, and 15-year biochemical disease-free progression rates (84%, 74%, and 67%, respectively) compared with men younger than 50 years, this did not reach statistical significance (P ⫽ 0.08; Fig. 2B). However, men aged 70 years or older experienced significantly lower (P ⬍0.003) 5, 10, and 15-year biochemical disease-free progression rates (72%, 58%, and 58%, respectively) compared with men younger than 50 years old (Fig. 2C). COMMENT The technological innovation and eventual commercial availability in 1987 of a serum PSA test to screen patients for prostate cancer combined with the availability of improved treatments during the same period have led to alterations in the patient demographics of men presenting with this disease in the 1990s. The use of age-specific total PSA, first proposed by Oesterling et al.,10 led to additional improvement in the sensitivity for the detection of prostate cancer in younger men. Partin et al.11 later applied the concept to men younger than 60 years of age in a study of 4600 men with clinically localized prostate cancer and detected 74 additional cancer cases. Eighty percent of the additional tumors detected in that study were organ confined. Reissigl et al.,12 studying an Austrian population of 21,000 men aged 45 to 75 years, detected an additional 8% positive biopsies (66 of 778), all clinically significant, by applying age-specific total PSA UROLOGY 62 (1), 2003
FIGURE 2. Kaplan-Meier actuarial likelihood of PSA recurrence in men younger than 50 years compared with (A) men aged 50 to 59 years, (B) 60 to 69 years, and (C) 70 years or older.
ranges in men younger than 59 years of age with normal digital rectal examination findings. Hence, during the past two decades, the incidence of prostate cancer detection in younger men has risen significantly. To this end, Tjaden et al.3 reported, in 1965, that only 1.1% of men diagnosed with adenocarcinoma of the prostate were younger than 50 years old. Hubner et al.,13 in their review of men diagnosed before 1975, found a similar low incidence of 0.8%. However, recent data from the SEER program indicate that between 1995 and 1999, 3.7% to 4% of newly diagnosed prostate cancer cases in the United States were in men younger than 50 years old.2 89
The issue of RRP for young men with prostate cancer has only been briefly addressed in published studies.3–5,14 –17 In earlier studies, only a few men with clinically confined cancer were regarded as appropriate candidates for radical surgery.3–5,14 –17 Most of the older studies were limited in size to fewer than 17 young men who underwent RRP.3–5,16 A series compiled from the long-term survey on prostate cancer by the Commission on Cancer of the American College of Surgeons recorded 29 men younger than 50 years who were treated by RRP.13 This study, however, did not specifically comment on the outcome of those young men treated by radical surgery. Recently, Smith et al.18 reviewed the multicenter prostate cancer research database from the Department of Defense Center for Prostate Disease Research to investigate the outcome of 79 men aged 50 years old or younger treated by RRP for localized prostate cancer compared with 398 men aged 51 to 69 years undergoing RRP. The preoperative PSA level, clinical and pathologic stage, surgical margin status, presence of seminal vesicle involvement, and recurrence rate between men in the two age groups were reviewed. These investigators found that the younger men had a significantly lower prebiopsy PSA level, a greater rate of organ confinement, and a lower disease recurrence rate with a significantly better long-term disease-free outcome. However, the study by Smith et al.18 was limited by the relatively short postoperative follow-up period of the younger age group (mean 2.8 years, with only 9 of the 79 men having a follow-up longer than 6 years). We have previously shown in a smaller study, with a shorter follow-up period, consisting of 85 men younger than 50 years, who had undergone anatomic RRP for clinically localized prostate cancer, that these men have a lower rate of positive surgical margins and similar pathologic variables compared with men aged 50 years old or older.6 Furthermore, less progression developed among the younger men, especially during the first 5 years after RRP. In another study investigating the impact of age on pathologic stage, we reported on 444 consecutive patients who underwent RRP and pelvic lymphadenectomy for localized prostate cancer (T2a-b) and found that men aged 60 years or older had a significantly greater pathologic stage.7 In the present study, we report the long-term follow-up (5.7 ⫾ 4.4 years) results for a large cohort of men younger than 50 years who underwent anatomic RRP for localized prostate cancer. A gradual change in the patient population with early detection of prostate cancer is well demonstrated. The proportion of men with T1c disease increased from 17% in our earlier analysis19 to 44% in the current series of men younger than 50 years. The results of 90
our study illustrate that men younger than 50 years old and men aged 50 to 59 years have similar pathologic variables and, not surprisingly, also very similar biochemical disease-free progression rates. However, men aged 60 to 69 years had significantly greater pathologic variables compared with men younger than 50 years and showed a trend toward lower biochemical disease-free progression rates that did not reach statistical significance. This lack of statistical significance may have been related to the length of follow-up. Hence, it will be interesting to determine the biochemical disease-free progression rates between these two groups during the next few years, especially because men aged 70 years or older, with the longest follow-up period of all the age groups, not only exhibited a significantly greater pathologic stage and an increase in positive margins but also experienced lower biochemical disease-free progression rates than men aged younger than 50 years. Our study included men from four different age groups who underwent RRP both before and after the widespread availability of serum PSA testing. As such, although lead-time bias may have been a factor in those detected with prostate cancer on the basis of an elevated PSA level alone, this would have had an effect in all the age groups. To this end, it is unlikely that lead-time bias had a significant impact in our study. The results of our study demonstrate that men younger than 50 years old, who are candidates for RRP, have greater curative disease and exhibit better long-term progression-free survival than older men. This is particularly important, because the recent routine use of serum PSA and greater availability and acceptance of screening have led to a rise in the detection of early prostate cancer in increasingly younger men that is amenable to curative intervention. This study also provides encouraging evidence for the value of prostate cancer screening in younger men and also supports previous studies that have indicated that young age is an important positive prognostic factor.8,20 CONCLUSIONS In a large series of 341 men younger than 50 years with a mean follow-up of 5.7 ⫾ 4.4 years (range 1 to 18) after anatomic RRP for clinically localized prostate cancer, the actuarial 5, 10, and 15-year biochemical recurrence-free survival rate was 88%, 81%, and 69%, respectively. RRP was curative more often in men younger than 50 years old than in men aged 60 years or older. Furthermore, these younger men also exhibited higher biochemical disease-free progression rates than men aged 70 years or older. This may also be the case when compared with men aged 60 UROLOGY 62 (1), 2003
to 69 years; however, longer term follow-up is required before this can be confirmed. Anatomic RRP, with excellent long-term results for early-stage disease, is an effective way to manage clinically localized prostate cancer in men younger than 50 years old. RRP as the definitive curative monotherapy is likely to play an increasing role in this age group, because the proportion of men with early-stage prostate cancer will continue to increase with the widespread use of serum PSA testing and prostate cancer screening.
18. Smith CV, Bauer JJ, Connelly RR, et al: Prostate cancer in men age 50 years or younger: a review of the department of defense center for prostate disease research multicenter prostate cancer database. J Urol 164: 1964 –1967, 2000. 19. Partin AW, Pound CR, Clemens JQ, et al: Serum PSA after anatomic radical prostatectomy: the Johns Hopkins experience after 10 years. Urol Clin North Am 20: 713–725, 1993. 20. Ruska KM, Partin AW, Epstein JI, et al: Adenocarcinoma of the prostate in men younger than 40 years of age: diagnosis and treatment with emphasis on radical prostatectomy findings. Urology 53: 1179 –1183, 1999.
REFERENCES 1. Greenlee RT, Murray T, Bolden S, et al: Cancer statistics, 2000. CA Cancer J Clin 50: 7–33, 2000. 2. Data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program web site. http://seer.cancer.gov/faststats/html/inc_prost.html;2003. 3. Tjaden HB, Culp DA, and Flocks RHF: Clinical adenocarcinoma of the prostate in men under 50 years of age. J Urol 93: 618 –621, 1965. 4. Silber I, and McGabran MH: Adenocarcinoma of the prostate in men less than 56 years old: a study of 65 cases. J Urol 105: 283–285, 1971. 5. Johnson DE, Lanieri JP, and Ayala AG: Prostate adenocarcinoma occurring in men under 50 years of age. J Surg Oncol 4: 207–216, 1972. 6. Riopel MA, Polascik TJ, Partin AW, et al: Radical prostatectomy in men less than 50 years old. Urol Oncol 1: 80 –83, 1995. 7. Alexander RB, Maguire MC, Epstein JI, et al: Pathological stage is higher in older men with clinical stage B1 adenocarcinoma of the prostate. J Urol 141: 880 –882, 1989. 8. Carter HB, Epstein JI, and Partin AW: Influence of age and prostate-specific antigen on the chance of curable prostate cancer among men with nonpalpable disease. Urology 53: 126 –130, 1999. 9. Beahrs OH, Henson DE, Hutter RVP, et al: American Joint Committee on Cancer Staging Manual. Philadelphia, JB Lippincott, 1992. 10. Oesterling JE, Jacobsen SJ, Chutte CG, et al: Serum prostate-specific antigen in a community-based population of healthy men: establishment of age-specific reference ranges. JAMA 270: 860 –864, 1993. 11. Partin AW, Criley SR, Subong ENP, et al: Standard versus age-specific antigen reference ranges among men with clinically localized prostate cancer: a pathological analysis. J Urol 155: 1336 –1339, 1996. 12. Reissigl A, Pointner J, Horninger W, et al: Comparison of different prostate-specific antigen cutpoint for the early detection of prostate cancer: results of a large screening study. Urology 46: 662–665, 1995. 13. Huben R, Natarajan N, Pontes E, et al: Carcinoma of the prostate in men less than 50 years old. Data from American College of Surgeons’ National Survey. Urology 20: 585–588, 1982. 14. Harrison GSM: The prognosis of prostate cancer in the younger man. Br J Urol 55: 315–320, 1983. 15. Steinberg GS, Carter BS, Beaty TH, et al: Family history and the risk of prostate cancer. Prostate 17: 337–347, 1990. 16. Byar DP, and Mostofi FK: Cancer of the prostate in men less than 50 years old: an analysis of 51 cases. J Urol 102: 726 –733, 1969. 17. Aprikian AG, Zhang ZF, and Fair WR: Prostate adenocarcinoma in men younger than 50 years. Cancer 74: 1768 – 1777, 1994.
EDITORIAL COMMENT This article gives insight into the issue of prostate cancer in men younger than 50 years old. It compares the surgical pathologic findings and long-term PSA fate of men younger than 50 years undergoing RRP at Johns Hopkins Hospital with older cohorts and is an extension of this group’s earlier reports on the subject. Specifically, this group analyzed the fate of 2897 consecutive men who underwent RRP between 1982 and 2001; 341 younger than 50 years and 2556 in age groups 50 to 59, 60 to 69, and 70 years or older (average follow-up 5.7, 6.4, 7.2, and 9.5 years, respectively, with about 25% to 30% with more than 5 years in each group). Using the pathologic parameters of organ-confined disease, extracapsular extension, seminal vesicle invasion, and positive pelvic lymph nodes, they found that the parameters of local pathologic adversity in the younger than 50-year old group were the same as in the age group of 50 to 59 years but were statistically greater in the 60 to 69 and 70 years or older age groups. As would be expected from these results, they also found that the biochemical freedom from disease rates in the younger than 50-year-old group was the same as in the 50 to 60-year-old group, but greater than in the older age groups. Although the authors argue that patient exclusion and lead-time bias were not big factors in their findings, this retrospective uncontrolled analysis could suffer from other unforeseen selection biases. Nonetheless, these results do reinforce the general impression that in the PSA era, prostate cancer discovered in younger men is not inherently worse than that discovered in older men. I believe we can glean additional insights from this excellent article. For example, that men younger than 50 years old seem to have curable cancer more often (ie, better pathologic features and biochemical freedom from disease rates) than older men (ie, older than 60 years) is consistent with the disease model that many prostate cancers grow slowly and logically progress to a larger size and eventually extend beyond the gland and then presumably distantly as metastasis. Such a model favors an attitude for early detection and aggressive treatment of local disease. However, this study also revealed that the percentage of men with positive pelvic lymph nodes in each age group seemed the same (5%, 6%, 7%, and 9%). If these numbers can be believed, it would suggest another disease model favored by those antagonistic to prostate cancer screening. In the latter model, the so-called turtles1 of prostate cancer grow slowly and extend beyond the gland and metastasize late if at all before intercurrent death, and the so-called birds of prostate cancer grow faster, and the size at which they metastasize is such that they are rarely captured by current PSA screening strategies. In this regard, it would be interesting to know the grade and cancer-specific survival rates in each cohort in this series. Does this mean that we should begin recommending that men who are not African American or who do not have a family history of prostate cancer begin screening before age 50? I think not. In this series, no difference was found in pathologic features or biochemical freedom from disease rates
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