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Abbreviations
RP

radical prostatectomy.

INTRODUCTION

  1. Top of page
  2. INTRODUCTION
  3. DIFFERENCES IN CLINICAL PRESENTATION
  4. IS PROSTATE CANCER MORE AGGRESSIVE IN THE YOUNG?
  5. HOW SHOULD YOUNG MEN WITH POTENTIALLY CURABLE DISEASE BE TREATED?
  6. TREATMENT-ASSOCIATED MORBIDITY IN YOUNG MEN
  7. CONCLUSION
  8. REFERENCES

Prostate cancer is currently the most common cancer in men in the UK, accounting for 20% of newly diagnosed cancers [1]. The peak incidence is in men aged 70–79 years, whilst 4% of new cases are aged <50 years, an increase from a reported 0.8% of cases in the early 1970s [1]. As PSA testing becomes more widespread, this number will continue to rise. The natural history of prostate cancer is still poorly understood. Furthermore, few studies have assessed the disease characteristics in young men. They are an important group, given the expected rise in new cases and their long life-expectancy. Does prostate cancer behave differently in young men, and if so, what are the implications for their treatment?

DIFFERENCES IN CLINICAL PRESENTATION

  1. Top of page
  2. INTRODUCTION
  3. DIFFERENCES IN CLINICAL PRESENTATION
  4. IS PROSTATE CANCER MORE AGGRESSIVE IN THE YOUNG?
  5. HOW SHOULD YOUNG MEN WITH POTENTIALLY CURABLE DISEASE BE TREATED?
  6. TREATMENT-ASSOCIATED MORBIDITY IN YOUNG MEN
  7. CONCLUSION
  8. REFERENCES

Many studies have investigated how men with prostate cancer present to the clinician, but few have concentrated on age-related differences. However, Ruska et al.[2] reviewed 87 men aged < 40 years who had prostate biopsies for suspected cancer. The two commonest reasons for biopsy were an abnormal DRE (61 men) and an elevated PSA level (14 men); 25% of men with an abnormal DRE and half of those with an elevated PSA level were then diagnosed with cancer. Other presentations included 12 with inflammatory symptoms, seven with ejaculatory problems, and three with a positive family history. Overall, 23 of the 87 men were diagnosed with prostate cancer.

IS PROSTATE CANCER MORE AGGRESSIVE IN THE YOUNG?

  1. Top of page
  2. INTRODUCTION
  3. DIFFERENCES IN CLINICAL PRESENTATION
  4. IS PROSTATE CANCER MORE AGGRESSIVE IN THE YOUNG?
  5. HOW SHOULD YOUNG MEN WITH POTENTIALLY CURABLE DISEASE BE TREATED?
  6. TREATMENT-ASSOCIATED MORBIDITY IN YOUNG MEN
  7. CONCLUSION
  8. REFERENCES

One problem in ascertaining whether younger men with prostate cancer have more aggressive disease is that there are few cases available, most of which are published as case reports or retrospective analysis, making direct comparisons difficult. Furthermore, the endpoints used to assess outcome are varied. With the advent of PSA screening in some areas, there is also now a possibility of ‘age-specific lead-time bias’, i.e. cancers detected in older men at the commencement of screening might be seen as more aggressive, as they were not detected at an earlier age.

Early clinical studies tended to report that men aged <50 years who develop prostate cancer had worse outcomes than older men, suggesting that they tend to develop more biologically aggressive tumours [3]. More recently, Riopel et al. [4] reviewed the data of 543 men who had a radical prostatectomy (RP); those aged <50 years (85 men), although having similar tumour grade, stage and capsular penetration, had significantly more cases of lymph node metastases than those aged >50 years. However, this did not play a role in disease progression, and the younger men had a better prognosis at 5 years. There was also a greater incidence of metastatic disease in men aged <50 years in a long-term survey of 20 156 patients, reported by the Commission on Cancer of the American College of Surgeons [5]. However, again, survival in all stages of disease was better for men aged <50 years.

RACIAL DIFFERENCES

African-American men were reported to be a ‘high-risk’ subgroup for the development of and poor survival from prostate cancer. One retrospective study found that African-American men aged 50–59 years had significantly higher PSA levels and Gleason scores at diagnosis, and higher recurrence rates after RP, than White men in the same age group [6]. It is suggested that socio-economic factors might influence the medical-seeking behaviour of African-American men and the subsequent conservative approach from some clinicians, leading to a delay in diagnosis and worsened prognosis.

FAMILIAL DIFFERENCES

Men with a family history of prostate cancer tend to develop the disease earlier in life [7,8], but they do not carry a poorer prognosis than men with no family history. Indeed, Bratt et al.[7] found that men diagnosed with prostate cancer before 51 years old had a better (but not significantly better) prognosis if they had a positive family history.

HOW SHOULD YOUNG MEN WITH POTENTIALLY CURABLE DISEASE BE TREATED?

  1. Top of page
  2. INTRODUCTION
  3. DIFFERENCES IN CLINICAL PRESENTATION
  4. IS PROSTATE CANCER MORE AGGRESSIVE IN THE YOUNG?
  5. HOW SHOULD YOUNG MEN WITH POTENTIALLY CURABLE DISEASE BE TREATED?
  6. TREATMENT-ASSOCIATED MORBIDITY IN YOUNG MEN
  7. CONCLUSION
  8. REFERENCES

Younger men obviously have a greater life-expectancy. This makes watchful waiting less attractive, but it is still an option; 10-year survival rates of 70–90% in localized disease have been reported [8] and there are no side-effects apart from perhaps prolonged anxiety. However, the recent study by Bill-Axelson et al.[9] suggested that watchful waiting is inferior to surgery, particularly in men aged <65 years. After randomizing 695 men with localized prostate cancer, 14.4% of men managed by watchful waiting died from prostate cancer-related causes, compared to 8.9% of the surgical group at 10 years [9]. Although most of the conservatively treated patients were also given hormonal therapy, their local recurrence and distant metastasis rates were significantly worse [9]. The concept of ‘active surveillance’, with very close PSA level and clinical monitoring combined with regular prostate biopsies, is more appropriate for this age group, but is likely simply to postpone radical treatment rather than supplant it.

For localized disease, there are three main curative options, i.e. RP, radical radiotherapy and brachytherapy. According to Donovan et al.[10], most UK urologists would advise RP for patients aged <70 years, and radical radiotherapy for those aged >70 years. The reasons for this approach are unclear, particularly as the success rates are similar (10-year survival rate of 80–90% for RP, vs 65–90% for radical radiotherapy), and the complications associated with radical surgery might be more significant and prolonged [10].

Some studies showed that younger men have better outcomes after RP. This might suggest that the disease is less aggressive in younger men. However, these results were not controlled for the year of surgery, which is an important predictor of PSA outcome. Freedland et al.[11] took this into account when studying the data of 1753 men who had radical surgery; recently treated men included a higher proportion of younger men, and men aged <50 years had significantly lower recurrence rates. More recently, a study of 790 men undergoing RP (by the same surgeon) found no age-related differences in pathological or clinical outcome [12]. Men aged <50 years had similar preoperative and pathological predictors of organ-confined disease, as well as postoperative complication rates and biochemical recurrence rates, to those aged >50 years.

There are no studies currently available comparing clinical or biochemical outcomes of radiotherapy with surgery in prostate cancer, for any age group. However, Rosser et al.[13] retrospectively assessed the biochemical outcomes of 964 men who all had radical radiotherapy alone for localized or locally advanced prostate cancer; 46% of those aged <60 years had biochemical failure, compared to 30% of older men.

TREATMENT-ASSOCIATED MORBIDITY IN YOUNG MEN

  1. Top of page
  2. INTRODUCTION
  3. DIFFERENCES IN CLINICAL PRESENTATION
  4. IS PROSTATE CANCER MORE AGGRESSIVE IN THE YOUNG?
  5. HOW SHOULD YOUNG MEN WITH POTENTIALLY CURABLE DISEASE BE TREATED?
  6. TREATMENT-ASSOCIATED MORBIDITY IN YOUNG MEN
  7. CONCLUSION
  8. REFERENCES

In this specific cohort of men, any treatment-induced morbidity confers increased significance, as they tend to be more physically active, socially aware, and potentially burdened with side-effects for a prolonged period. Radical surgery confers a 3% risk of total incontinence, and a varied (20–80%) risk of erectile dysfunction, depending on the level of expertise of the surgeon, and the use of nerve-sparing techniques [10]. However, potency rates appear more favourable in younger men. In a retrospective study of 366 men who had uni- or bilateral nerve-sparing RP, men aged <60 years had more reported erections sufficient for penetration than older men (19% vs 13% for unilateral surgery; 45% vs 38% for bilateral surgery) [14]. Unfortunately, no age-specific incontinence and potency rates after radiotherapy have been compared.

Another potential concern is that of the radiation-induced formation of a second malignancy, particularly in the context of young men with a longer life-expectancy. Two large retrospective studies compared radiotherapy with surgery for prostate cancer in the USA, and found small but significant results. Upon reviewing >50 000 men with prostate cancer, radiotherapy was associated with a greater risk of sarcoma formation, as well as rectal, bladder and even lung cancers, compared to surgery alone [15]. The relative risk increased dramatically from 15% at 5 years to 35% at 10 years. As 9.3% of the men treated were aged <60 years, these ‘long-term survivors’ will therefore be burdened with a very real lifetime risk.

CONCLUSION

  1. Top of page
  2. INTRODUCTION
  3. DIFFERENCES IN CLINICAL PRESENTATION
  4. IS PROSTATE CANCER MORE AGGRESSIVE IN THE YOUNG?
  5. HOW SHOULD YOUNG MEN WITH POTENTIALLY CURABLE DISEASE BE TREATED?
  6. TREATMENT-ASSOCIATED MORBIDITY IN YOUNG MEN
  7. CONCLUSION
  8. REFERENCES

Clearly little is still known about the characteristics of prostate cancer in young men. However, several important conclusions can be drawn from recent studies. First, young men tend to be asymptomatic at presentation. Studies within the ‘PSA era’ found that men aged <50 years are more likely to have familial cancer, and might have a higher incidence of metastatic disease at presentation. However, this does not lead to poorer clinical outcomes than older men or men with no family history. Although radical surgery confers the risk of significant long-term side-effects, they occur less often in young men, and it remains the most effective choice of treatment for localized disease. Further studies into the characteristics of prostate cancer in this very important subgroup are warranted.

REFERENCES

  1. Top of page
  2. INTRODUCTION
  3. DIFFERENCES IN CLINICAL PRESENTATION
  4. IS PROSTATE CANCER MORE AGGRESSIVE IN THE YOUNG?
  5. HOW SHOULD YOUNG MEN WITH POTENTIALLY CURABLE DISEASE BE TREATED?
  6. TREATMENT-ASSOCIATED MORBIDITY IN YOUNG MEN
  7. CONCLUSION
  8. REFERENCES
  • 1
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  • 2
    Ruska KM, Partin AW, Epstein JI, Kahane H. Adenocarcinoma of the prostate in men younger than 40 years of age: diagnosis and treatment with emphasis on radical prostatectomy findings. Urology 1999; 53: 117983
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    Kotsis SV, Spenser SL, Peyser PA, Montie JE, Cooney KA. Early onset prostate cancer: predictors of clinical grade. J Urol 2002; 167: 165963
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    Riopel MA, Polacik TJ, Partin AW, Sauvageot J, Walsh PC, Epstein JI. Radical prostatectomy in men less than 50 years old. Urol Oncol 1995; 1: 803
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    Huben R, Natarajan N, Pontes E, Mettlin C, Smart CR, Murphy GP. Carcinoma of prostate in men less than fifty years old. Data from American College of Surgeons’ National Survey. Urology 1982; 20: 5858
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    Powell I, Banerjee M, Sakr W et al. Should African-American men be tested for prostate carcinoma at an earlier age than White men? Cancer 1999; 85: 4727
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    Lee KL, Marotte JB, Ferrari MK, McNeal JE, Brooks JD, Presti JC Jr. Positive family history of prostate cancer not associated with worse outcomes after radical prostatectomy. Urology 2005; 65: 3115
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    Bill-Axelson A, Holmberg L, Ruutu M et al.; Scandinavian Prostate Cancer Group Study No. 4. Radical Prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 2005; 352: 197784
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    Donovan JL, Frankel SJ, Faulkner A, Selley S, Gillatt D, Hamdy FC. Dilemmas in treating early prostate cancer: the evidence and a questionnaire survey of consultant urologists in the United Kingdom. BMJ 1999; 18: 299300
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    Noldus J, Michl U, Graefen M, Haese A, Hammerer P, Huland H. Patient-reported sexual function after nerve-sparing radical retropubic prostatectomy. Eur Urol 2002; 42: 11824
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