Risk Factors for Clinical Progression

1.5.1 Prostate volume

Several longitudinal studies have confirmed age-related increases in prostate volume, although pros-tate volume has been noted to decrease with aging in a small proportion of men (99–103). Serum PSA, a valid surrogate marker of prostate volume in the absence of prostate cancer diagnosis (104,105), predicts future prostate growth (106). Prostate volume is likely to increase when the transition zone is either visible with a clear border (103,107) (Figure 2) or enlarged on trans-rectal ultrasound at baseline (108).

FIGURE 2 Change in prostate volume over 15 years in Japanese men. Prostates on TRUS with the borders not clearly delineated;

Group 3: TZ clearly visible on TRUS (A). Adapted based survey in Japan. J Urol. 1997;157(5):1718-1722

The growth rate of the prostate during follow-up is greater in men with BPH than in men in the general population (109,110). The Medical Therapy of Prostatic Symptoms (MTOPS) study, which observed patients on placebo or doxazosin for 4.5 years, reported that prostate growth could be predicted by baseline prostate volume and serum PSA levels (111). This suggests that prostate growth may not occur linearly with age and that prostate growth is more prominent in men with anatomical or clinical BPH.

1.5.2 Urinary flow rate

One longitudinal analysis demonstrated that younger men showed a smaller decrease per year of peak urinary flow rate than older men. Men in their 40s at baseline had a 1.3% per year decrease, whereas men in their 70s had a 6.5% per year decrease (Figure 3) (112). Detrusor underactivity due to long-lasting BOO and/or aging may be involved in enhanced decrease in urinary flow rate in the older population. On the other hand, a 15-year longitudinal community-based study in Japan

showed a significant decrease in peak urinary flow rate only in men in their 50s at baseline (113).

However, this study may have underestimated the decrease of peak urinary flow rate, since men who received LUTS treatment during the long-term follow-up period were excluded from the analysis.

FIGURE 3

Change in peak urinary flow rate over 6 years in different age cohorts.

Younger men showed a lower percentage decrease per year of peak urinary flow rate than older men. Men in their 40s, 50s, 60s, and in peak urinary flow rates in a community based cohort.

1.5.3 Cystometry and pressure-flow study

To our knowledge, no longitudinal data on cystometry and pressure-flow studies are available in the general population. Thomas et al. reported serial urodynamic parameters in 170 male patients with BOO who initially opted for a conservative approach (114). Although 141 patients remained untreated for an average of 13.9 years, pressure-flow studies showed no significant increase in BOO with time. However, a small but significant reduction in detrusor contractility was observed, and the prevalence of detrusor overactivity increased with follow-up. These changes in bladder function would explain the exaggerated voiding and storage symptoms in elderly men.

1.5.4 Health-care seeking

Health-care seeking behaviour depends on country, culture, medical environment, income, and education. A population-based study in Olmsted County revealed that health-care seeking behav-iour was influenced by the severity of symptoms, particularly if they were bothersome and interfered with an individual’s daily activities (115). There is a marginal overlap in the distribution of HRQOL

scores of the general population and patients with BPH in a Japanese study (116). Thus, regardless of country and race, it is likely that men with deteriorated HRQOL that is LUTS-related bother to seek medical care.

1.5.5 Acute urinary retention

Acute urinary retention (AUR) is an indicator of disease progression. The incidence of AUR in the general US population is 6.8 per 1000 person-years (117). Older age, a higher IPSS, peak urinary flow rate <12 mL/s, and prostate volume >30 mL are all risk factors for AUR in community-dwelling American men. Older age and greater prostate size (as indicated by prostate length on urethral pres-sure profile at baseline) were the only significant factors that predicted future failure, defined as either AUR or significant symptomatic deterioration leading to surgery in untreated men with BOO (114). The placebo arm in the MTOPS study demonstrated that baseline prostate volume >31 mL and serum PSA level ≥1.6 ng/mL are predictors of AUR, symptomatic progression, need for surgery, and clinical progression (118).

1.5.6 Need for surgical treatment

The Baltimore Longitudinal Study of Aging prospectively followed 1,057 healthy male volunteers for up to 30 years, and demonstrated that weak stream, incomplete emptying, and prostate enlargement on digital rectal examination are risk factors for subsequent prostatectomy (119). This risk increased with increasing number of factors (3.0%, 8.9%, 15.7%, and 36.6% in men with 0, 1, 2, and 3 risk factors, respectively). Probability of prostatectomy was double in men with prostate enlargement and voiding symptoms compared with those without these two symptoms (probability also increased with increasing age) (120). In the Olmsted County longitudinal community-based study, the prob-ability of trans-urethral resection of the prostate (TURP) was related to age, symptoms, low urinary flow rate, prostate enlargement, and increased serum PSA levels (121). Men in their 70s at baseline were 51.7 times at risk for TURP compared with those in their 40s. Similarly, men with prostate volumes >30 mL and serum PSA >1.4 ng/mL had 9.2 and 9.3 times the risk for TURP compared with those with ≤30 mL and ≤1.4 ng/mL, respectively. In the Japanese longitudinal study, 0%, 4%, and 21% of men having mild (IPSS ≤7), moderate (IPSS 8–19), and severe symptoms (20–35), respectively, received TURP within 3 years (122). Prostate volume at baseline was higher in men who received TURP (53.9 mL) than those who did not (19.8 mL).

1.5.7 Failure of watchful and waiting

Studies have shown that male LUTS generally worsen progressively in men with BPH, although symptoms do improve or stabilize in some patients. Symptomatic deterioration, development of AUR, and conversion to BPH-related surgery tend to occur in patients with severe LUTS, large pros-tate volume, and high PSA levels at baseline (104,118,123). Wasson et al. reported that patients with affected HRQOL at baseline had a higher failure rate of watchful and waiting than those who were less affected (124). Thus, the option of watchful and waiting would not be recommended for patients with severe LUTS-with-bother, large prostate volume, or high PSA levels at baseline.

1.5.8 Other complications

A recent study has found that BPH-related deaths or comorbidities, such as hydronephrosis, renal failure, urinary tract infection (UTI), and bladder stones, are rare (111,124). In a study of 737 patients treated with placebo, only one patient developed recurrent UTI and none developed renal insuf-ficiency during 4.5 years of follow-up (111).

1.6 Epidemiology of Benign