Tackling the progression of benign prostatic hyperplasia/benign prostatic obstruction progression: Deobstructing within the “window of curability” (a hypothesis-generating review)

Abstract

Benign prostatic hyperplasia (BPH) and benign prostatic obstruction (BPO) remain significant contributors to male lower urinary tract symptoms, often leading to bladder damage and dysfunction. The traditional approach focuses on the management of bothersome symptoms through the use of BPH medications and may delay essential interventions, leading to disease progression and a negative impact on quality of life. This review proposes a paradigm shift to focus on bladder health preservation, as the bladder is an end organ that cannot be transplanted. Therefore, earlier diagnosis and timely surgical treatment within the “window of curability” are required. We introduce the Man vs Prostate “Five Stages of Bladder Health” to provide the needed framework to build the next iterations of BPH/BPO care. This patient-facing decision-making aid categorizes BPH/BPO progression. It integrates clinical observations with underlying pathophysiology and patient experience. This categorization highlights how untreated BPH/BPO can progress to more serious and pressing stages, the possible consequences of not taking action, and the goal to prevent late-stage disease: stage I, BPO; stage II, detrusor overactivity; stage III, urgency incontinence; stage IV, acute retention; and stage V, detrusor underactivity. On an individual patient basis, transitions are not distinct, stages can coexist, and stages can be skipped. Although promising, this proposed staging system requires further validation through prospective randomized clinical trials to confirm its clinical value and prognostic accuracy.

The concept of the “window of curability” emphasizes the need for therapeutic intervention at the optimal time. By identifying patients in earlier stages and initiating appropriate treatment, disease progression can be potentially stabilized or even reversed while aiming to optimally preserve detrusor function. Along with the Man vs Prostate staging system, this framework provides a structure for future research, shared decision making, and personalized treatment strategies. This paradigm shift necessitates a collaborative effort among urologists to reevaluate current practices, focus on earlier intervention within the “window of curability,” and prioritize bladder health preservation.

1. Introduction

In the landscape of male lower urinary tract symptoms (mLUTSs), the bladder plays a central role, with benign prostatic hyperplasia (BPH)/benign prostatic obstruction (BPO) being a major contributor to secondary bladder damage and dysfunction. As a result, urologists are on a mission to better define the proper timing for diagnostic testing and deobstructive surgeries.^[1,2] The fact that the bladder cannot be transplanted, just like the brain, has motivated urologists to rethink and reengineer a more bladder-centric BPH care pathway.^[3,4] The bladder is an end organ whose complex neural innervation, blood supply, functional physiology, mucosal interface, and supratentorial regulation continuously inspire research endeavors and the generation of hypotheses.^[5–10] The cause of compromised bladder health is multifactorial, including contributory etiologies such as aging and metabolic syndrome (Fig. 1).^[11,12]

Figure 1.

Man vs Prostate mLUTS: the central role of bladder dysfunction and damage. BPH = benign prostatic hyperplasia; BPO = benign prostatic obstruction; CPPS = chronic pelvic pain syndrome; DOA = detrusor overactivity; DUA = detrusor underactivity; FB = foreign body; mLUTS = male lower urinary tract symptoms; OSA = obstructive sleep apnea; PBNO = primary bladder neck obstruction; UTI = urinary tract infection.

With an aging global male population, BPH/BPO progression and its impact on the health of this precious end-organ (the bladder) have become a topic of interest for urologists over the last quarter century. A PubMed search with the terms “progression” and “prostatic hyperplasia” as MeSH terms yielded 24,866 results. A secondary search in combination with “progression” in the title and/or abstract yielded 1290 results (“prostatic hyperplasia” [mesh] and “progression” [tiab] on September 20, 2024). In the last decade alone, an average of 56 papers per year have been published using these search terms, underscoring the exponentially growing awareness of BPH progression.

2. A linguistic need for a BPH/BPO staging system

The latest technology better characterizes BPH progression as the golden era of BPH diagnostics continues to advance. A unique combination of artificial intelligence, smartphones, miniaturized electronics, and sophisticated ultrasonography is responsible for the better understanding of BPH. We are fast approaching a time where more accurate and precise personalized data can be acquired efficiently at home and in the clinic. This will bring significant value to shared decision-making processes.^[13–17] To keep pace with these technological breakthroughs, the language surrounding BPH progression is equally evolving.

“Linguistic determinism” inspires us to hold words in high regard because they can shape our thoughts, which shape our actions and habits.^[18] Moreover, “we can only see what we have words for.”^[19] The precedent was established by Dr Paul Abrams and Dr Alan Wein in the 1990s. In 1994, “prostatism” gave way to “LUTS,” and in 1997, an “unstable bladder” evolved into an “overactive bladder.”^[20,21] In 1999, Dr Abrams implored urologists to use the proper terminology “BPO” to accurately reflect “bladder outlet obstruction (BOO) due to benign prostatic enlargement.” His request was in response to the inaccurate and formulaic use of “BPH” because urologists do not treat histologic findings on a microscopic level. Proper diagnostic confirmation can provide a more detailed definition of mechanical obstructions that require mechanical solutions.^[22] Although it is technically feasible to stop the wrong use of BPH, we agree that BPH is a universally entrenched term in the vernacular of both patients and urologists. With the communal familiarity of BPH as its strength, a greater impact can be realized when BPH is integrated with the accuracy of BPO. Therefore, in this review, the compound term “BPH/BPO” will be used where appropriate.

Following these issues, the European Urological Association guidelines have adapted their updated version to highlight the evolution of BPH over the past 20 years. It now reflects changes to our understanding of the etiology, pathophysiology, assessment, and treatment of mLUTS. Based on the long-held belief that lower urinary tract symptom (LUTS) in men is caused (directly or indirectly) by benign prostatic enlargement (BPE) and BOO related to histological BPH, the causal link between BPE and the pathogenesis of mLUTS has been criticized with increasing evidence that only 50% of men complaining of LUTS have true obstruction with multichannel advanced urodynamics. It was then concluded that the cause of LUTS might be multifactorial (including urological and/or nonurological conditions).^[23]

A linguistic framework is needed to give structure to the dialogue surrounding “the progression of BPH/BPO.” In medicine, the term “progression” defines the course of a disease, such as cancer, as it worsens or spreads throughout the body. Disease progression implies the existence of a temporal time frame (the so-called “window of curability”) during which timely intervention can halt, slow, or even reverse the escalation of illness (progression). Urology continues to lead by example, using the term “window of curability” for other pathologies such as prostate cancer, bladder cancer, and erectile dysfunction.^[24–26] Interestingly, a search of the PubMed database with the term “window of curability” yielded only 25 publications, of which 76% were focused on the aforementioned urologic diseases.

A staging system is a common medical construct that incorporates 2 concepts: “disease progression” and “window of curability.” Parkinson's disease, heart failure, chronic kidney disease, Peyronie's disease, and breast cancer have staging systems that have been proposed or actively implemented to outline how these diseases can escalate and “progress” to more serious and pressing levels.^[27–31] Staging systems also indicate a worsening prognosis as higher stages are reached.^{[27,29,30,32,33]} Over the last 30 years, urologists have refined highly effective staging systems for both prostate and bladder cancers that affect 1 in 8 and 1 in 28 men, respectively.^[34] Comparatively, with moderate-to-severe LUTS affecting 39% (more than 1 in 3) of men 60 years and older, the absence of a globally accepted staging system for BPH/BPO is alarming but understandable.^[35] Over the last half century, resources have been dedicated to the prevention, management, and treatment of prostate diseases. Having gained a deep evidence-based understanding of prostate health, “preservation of bladder health” is a new focus for the next iterations of the BPH/BPO care pathway, including earlier deobstruction and better patient education.^[36–38]

3. The Man vs Prostate “Five Stages of Bladder Health”

In 2021, Man vs Prostate (MVP) published the eBook “Five Stages of Bladder Health” that was introduced to academia as a 2024 editorial titled, “When you say ‘Prostate,’ don't forget to say ‘Bladder’!”^[36,37] It reflects the convergence of patient-centered medicine and evidence-based medicine.^[39–41] It is an amalgamation of the following 3 divergent urological constructs: (1) the 5 clinical scenarios that patients with BPH/BPO may experience, (2) the 3 stages of bladder remodeling underlying the pathogenesis of BPH/BPO, and (3) the pathophysiologic comprehension of bladder health (Fig. 2).

Figure 2.

Man vs Prostate “Five Stages of Bladder Health”: hypothesis-generating framework for BPH/BPO progression. AUR = acute urinary retention; BPH = benign prostatic hyperplasia; BPO = benign prostatic obstruction; DOA = detrusor overactivity; DUA = detrusor underactivity; UUI = urgency urinary incontinence.

The medical lexicon for bladder health is a synthesis of 5 quantitative and qualitative observations derived from the International Continence Society terminology for adult mLUTS: BPO, detrusor overactivity (DOA), urgency urinary incontinence (UUI), acute urinary retention (AUR), and detrusor underactivity (DUA).^[42] The response of the detrusor to the chronic cyclical challenge of BPO has been divided into 3 bladder remodeling stages: (1) hypertrophy, (2) compensation, and (3) decompensation.^[43–45] Patients have reported 5 clinical scenarios that mirror the progression of BPH/BPO: (1) the annoyance of slowing flow caused by BPO; (2) the anxiety and exhaustion from the urgency, frequency, and nocturia; (3) the embarrassment from the smell and stains of leaking urine; (4) the terror of the sudden inability to void; and (5) the deep anguish of having a “dead” bladder.^[36] On first pass, these constructs are seemingly divergent. However, on closer inspection, they can be unified and integrated into the putative MVP “Five Stages of Bladder Health.” Prospective studies are needed to assess its alignment with patient-reported experiences and outcomes.

The MVP “Five Stages of Bladder Health” include the following: stage I, BPO with a decreasing maximum flow rate manifests in patients as “things slow down”; stage II, the storage symptoms of DOA are referred to as an “overactive bladder”; stage III, the uninhibited bladder contractions during the filling phase result in leakage (UUI) with similarities to a “rebellious child” acting out when their needs are not met; stage IV, the emergent suddenness of not being able to urinate (AUR) evokes similar emotions to the abrupt onset of chest pain from a possible “heart attack”; and stage V, the dread of DUA or a “dead bladder” is akin to “heart failure” and exacerbated by a singular difference between the 2 organs. Worst-case scenario, the heart still has the option of being transplanted, unlike the bladder, where a patient with a nonfunctioning bladder is condemned to a life of catheters. The proposed staging system is a simplified patient-facing tool for communication that takes place against the backdrop of the intricate and complex nature of mLUTS. It does not reflect the multifactorial contributions to the pathophysiological steps of progressive bladder dysfunction (Fig. 1). Users of the staging system must recognize its limitations and consider them to avoid misdiagnosis and treatment shortcomings. Of note, no clear quantitative threshold criteria exist to trigger stage escalation or de-escalation as this is only a communication tool.

Every staging system primarily serves as a patient-facing tool in a shared decision-making process. It affects management and treatment choices, as it reflects an increase in gravity and urgency seen at each successive stage. Various diseases have unique pathophysiologies that must be reflected in their specific staging systems. For example, the merits of a system for the regional and metastatic spread of a malignancy will not apply to the staging of declining cardiac output from a weakened heart.^[46,47] More importantly, each staging system is its own “living” construct that evolves over time to constantly improve as demonstrated by Grade Groups based on Gleason scores for prostate cancer.^[48,49]

Specifically, the MVP “Five Stages of Bladder Health” aims to facilitate the discussion and spread awareness about bladder health to help the “misinformed masses of men” who need urological advice. It invites the use of advanced communication skills during office consultations, offering free educational videos and reference materials. Owing to recent technological advances, patients can be better assisted to manage obstruction, temporize symptoms, and preserve bladder health by timely diagnosis to avoid prolonged medical therapies. In this field, a good communication tool and an easy staging system are extraordinary resources that can encourage and facilitate the paradigm shift from a “prostate-centric” to a “bladder-centric” one.^[37]

We recognize the unique attributes of the MVP staging system for BPH/BPO. First, its simplicity does not fully reflect the complex multifactorial nature of mLUTS. Although BPH/BPO is a significant contributor, it is only one of the many causative factors where aging is a significant etiology. Second, the transitions between stages are not distinct and do not have definitive quantitative criteria to trigger escalation to a higher stage. Third, not all patients will experience each stage sequentially. Stages can be skipped, as seen in patients with stage II DOA who progress to stage IV AUR without ever reporting stage III UUI. Fourth, multiple stages can coexist concurrently. This is most commonly observed in patients who present with both storage and voiding symptoms in both stage I BPO and stage II DOA. Fifth, the absence of clinical internal and external validations limits the generalizability of this model, making the reliability of the staging system uncertain. The 5 stages represent a framework to work with for designing future studies to validate its value and identify important subgroups. Currently, this staging system does not reflect a data-driven diagnosis and is only a plainspoken communication tool to help patients deeply engage with their diagnostic and therapeutic care. It does not dictate personalized treatment plans.

4. BPH/BPO progression: Window of curability

Although the MVP staging system provides a structure for the concept of disease progression in BPH/BPO, it also provides an infrastructure to outline a “window of curability.” A timeframe exists during which timely deobstruction can stop or slow progression through the disease stages, or even partially or fully reverse the disease. The benefits and outcomes of surgery for mLUTS in patients with BPH/BPO with evidence of DUA and DOA have been debated for many years because the presence of these dysfunctions may account for poor surgical outcomes or surgical failures despite deobstruction. Systematic reviews and meta-analyses have concluded that, even when urodynamic-proven DOA or DUA exists, these patients should undergo deobstruction, as good results have been reported.^[50,51]

As with other diseases, the best time for intervention is within the early stages when the disease is mild. At the front end of the window, interventions are more effective and yield better patient outcomes for the following reasons: first, the regenerative and reparative cellular mechanisms are more likely to still be intact; second, the disease itself is limited to its more basic clinical manifestations, which are more manageable.

The quantitative results of enhanced urodynamic pressure-flow studies from 50,000 patients with mLUTS shed light on the natural history and expected progression of BPH/BPO (Fig. 3).^[52] With advancements in age, a decrease in the maximum flow rate is observed and attributed to the tightening prostatic fossa caused by BPE. As suspected, a compensatory increase in bladder pressure is observed in the second stage of bladder remodeling. On average, at around the age of 62 years, the detrusor enters the decompensatory third stage.^[45] By speculative reasoning, a conceptual “window of curability” can be unveiled when the minimally invasive surgical therapy age indication of 45 years and abnormal maximum flow rate cutoff of 10 mL/s are applied to these data (Fig. 3). Figure 3 is a reminder of how similar images like this one also play a role in sculpting thoughts, actions, and habits. “We can only describe what we have perceived” is the inverse corollary to “We can only see what we have words for.” Both visual and linguistic determinisms are useful tools for advancing the BPH/BPO care pathway.

Figure 3.

Window of curability: limited capacity of the detrusor to compensate for BPH/BPO (adapted from Ref. ⁵²). BPH = benign prostatic hyperplasia; BPO = benign prostatic obstruction; Pcuff = pressure at which urinary flow is interrupted with penile cuff testing; Qmax = maximum urinary flow rate.

Self-reporting bias is an unavoidable confounder for the majority of LUTS BPH/BPO studies that use the International Prostate Symptom Score (IPSS) with supplementary history taking to document a patient's storage and/or voiding symptoms. Although this helps to place patients in stages I, II, III, and V, the use of such questionnaires or interviews has the limitation of self-reporting bias, specifically social desirability bias, and recall bias.^[53] A deep dive into each stage is beyond the scope of this review; however, reports of stage IV AUR events are uniquely binary and provide greater clarity of results without the aforementioned biases. Centering this review on stage IV also allows the concepts of window of curability and disease progression to be more fully illustrated (Table 1).

Table 1.

Hypothesis-generating clinical insights into BPH/BPO progression and its window of curability.

Clinical principle	Study* (year)	Description	Intervention	Sample size	Clinical group	Inclusion criteria	Exclusion criteria	Outcome definitions	Clinical observation/limitations†
Stages of bladder remodeling	Fusco et al.,[45] 2018	Literature review	N/A	36 Studies	N/A	Before 2018	N/A		Three stages: hypertrophy, compensation, and decompensation
Progression of BPH/BPO	Kaplan et al.,[52] 2020	Retrospective cross-sectional	N/A	50,680 men Multicenter USA	LUTS BPH patients	Penile cuff test VV ≥50 mL Cuff inflation ≥1× Age >20 yr	N/A		Compensatory and decompensatory phases; detrusor function decreases with age starting at 62 yr (VV <150 mL; not multichannel)
	Jacobsen et al.,[54] 1997	Retrospective cohort	N/A	8344 person-years USA	General male population	Age 40–79 yr	Prostate cancer Prostatectomy Non-BPH LUTS		7.8-fold increase in relative risk for AUR (precipitated and spontaneous) from age 40–49 yr to 70–79 yr (47% precipitated)
	Meigs et al.,[55] 1999	Retrospective cohort	N/A	15,851 person-years USA	Health professionals	Age 45–83 yr	Prostate cancer Prostatectomy Previous AUR		13.3-fold increase in relative risk for stage IV spontaneous AUR from age 45–49 yr to 70–79 yr
	Verhamme et al.,[56] 2005	Retrospective cohort	N/A	157,620 person-years Netherlands	LUTS BPH patients	Age ≥45 yr	Cystectomy Previous AUR		21.5-fold increase in relative risk for AUR (precipitated and spontaneous) from age 45–49 yr to 70–74 yr (40% precipitated)
	Cathcart et al.,[57] 2006	Retrospective cohort	N/A	648,834 person-years UK	LUTS BPH patients	Diagnosis AUR Previous TURP	Prostate cancer Multiple sclerosis Parkinson's		10.2-fold increase in relative risk for stage IV spontaneous AUR from age 45–54 yr to 65–74 yr
Impact of delayed deobstruction	Wasson et al.,[58] 1995	Randomized control	Deobstruction (TURP) Control (WW)	n = 276 WW n = 280 TURP	LUTS BPH patients	Age ≥55 yr	Prostate cancer* Bladder cancer Nonambulatory PVR >350 mL Nonoperative Abnormal Cr|UTI	Treatment failure: death, retention, postvoid residual volume >350 mL, bladder stones, severe IPSS, de novo incontinence with pads, doubling of Cr	48.2% reduction in risk of treatment failure with TURP vs. WW 8-fold reduction in stage IV AUR (2.8 yr follow-up) *Exclusion includes surgery and/or radiation
	Flanigan et al.,[59] 1998	Same as Wasson et al. (1995)	Same as Wasson et al. (1995)	Third cohort: crossover “delayed” TURP	Same as Wasson et al. (1995)	Same as Wasson et al. (1995)	Same as Wasson et al. (1995)	Same as Wasson et al. (1995)	Extended follow-up from Wasson et al. (1995) to 5 yr WW still with 2-fold increase in failure rate. TURP with8-fold decrease in stage IV AUR. Crossover “delayed” TURP with less favorable outcomes vs “immediate” TURP
	Frendl et al.,[60] 2023	Retrospective cohort	Deobstruction (TURP or PVP)	n = 15,702 (no AUR) n = 1772 (AUR preop)	AUR preop vs. no preop AUR	Age ≥40 yr Hx TURP Hx PVP	Prostate cancer BPH surgery	Surgical failure: time to operation or recatheterization	Predicted surgical failure rates at 10 yr are reduced by 31% if deobstruction is before any episode of stage IV AUR
Drugs and stage IV AUR	Izard and Nickel,[61] 2011	Retrospective cross-sectional	Deobstruction (TURP)	1988 (n = 157) 1998 (n = 64) 2008 (n = 84)	LUTS BPH patients	Hx TURP	Prostate cancer Chronic prostatitis Non-BPH pathology	N/A	Over 2 decades, TURPs decreased by 46%, whereas patients on BPH drugs increased from 0% to 87%. The incidence of stage IV AUR rose by 87%.
	Young et al.,[62] 2018	Retrospective cross-sectional	Deobstruction (TURP)	1990 (n = 100) 2000 (n = 100) 2010 (n = 113)	LUTS BPH patients	Hx TURP	N/A	N/A	Over 2 decades, TURPs decreased by 65%, whereas patients on BPH drugs increased from 2% to 43%. The indication of stage IV AUR more than doubled from 33% to 68%.

AUR = acute urinary retention; BPH = benign prostatic hyperplasia; BPO = benign prostatic obstruction; Cr = creatinine; Hx = history; LUTS = lower urinary tract symptoms; N/A = not applicable; PVR = post-void residual; TURP = transurethral resection of the prostate; UTI = urinary tract Infection; VV = voided volume; WW = watchful waiting.

In 1997, Jacobsen et al.^[54] measured the incidence of stage IV AUR in the renowned Olmsted County study based on 8344 person-years of follow-up. As expected, for a consistently advancing disease process, the cumulative incidence was positively correlated with age, with an increase from 1.6% (men in their 40s) to 10.0% (men in their 70s). Between these 2 age groups, an almost 8-fold increase in relative risk was observed. Notably, men in their 70s with moderate-to-severe LUTS fared even worse, with an incidence of 13.8%.^[54]

In 1999, another US-based study with 15,851 person-years of follow-up confirmed a correlation with advancing age, similar to the study by Jacobsen et al. The incidence of stage IV increased more than 13-fold (0.7 vs. 9.3 events/1000 person-years for men aged 45 to 49 years and 70 to 79 years, respectively).^[55] Later in 2005, Verhamme et al.^[56] found that the situation in the Netherlands was even more dramatic. Compared with a baseline stage IV incidence of 0.2 per 1000 person-years for men aged 45 to 49 years, the incidence rose to 4.3 and 6.3 for men aged 70 to 74 years and 75 to 79 years, respectively.^[56] Finally in 2006, Cathcart et al.^[57] made the reinforcing observation that the incidence of stage IV increased exponentially with age, approximately doubling with every 10-year increase.

Dialogues exploring the concept of timely deobstruction within the window of curability continue to grow.^[1,63–66] In 1995, Wasson et al.^[58] performed a randomized multicenter clinical trial on patients with moderate symptoms of BPH during the 1980s who underwent watchful waiting (WW; n = 276) or transurethral resection of the prostate (TURP) within 2 weeks after randomization (n = 280) with an average of 2.8 years of follow-up. This study defined treatment failure as death, repeated/intractable retention, postvoid residual >350 mL, bladder stones, de novo pad-requiring incontinence, a severe IPSS, or a doubling of serum creatinine level. Deobstruction with TURP resulted in 52.8% reduction in treatment failure as compared with WW from 17.0% to 8.2% (relative risk, 0.48; confidence interval, 0.30–0.77). Notably, the intention-to-treat statistical analysis appropriately included all 280 patients assigned to the surgery group. A subanalysis suggested that timely deobstruction lowers the risk of patients entering retention by 8-fold as compared with WW (from 2.9% to 0.36% [relative risk, 0.12; confidence interval, 0.02–0.98]).^[58]

In 1998, Flanigan et al.^[59] provided a secondary update from this same Department of Veterans Affairs Cooperative Study for the 2 groups: WW (n = 276) or “immediate” TURP (n = 280). This study had the benefit of a longer follow-up (5 years) with a more detailed comparison to patients who underwent WW followed by TURP (crossover group). The risk reduction for treatment failure and stage IV AUR of 2-fold and 8-fold was still evident with this long follow-up. To underscore the unfavorable risk of waiting longer for deobstruction, this study included crossover patients who underwent “delayed” TURP (n = 76). Comparatively, the “immediate” TURP group had greater reductions in IPSS, larger increases in maximum flow rates, and a more marked decrease in postvoid residual volume, suggesting earlier deobstruction conveys more favorable outcomes for the bladder and patient as a whole.^[59] This highlights how earlier deobstruction within the window of curability may confer more favorable clinical outcomes and prevent more patients from entering late stage IV.

More recently, in 2023, a retrospective cohort study by Frendl et al.^[60] illustrated the negative impact of stage IV AUR on surgical outcomes after TURP or photoselective vaporization of the prostate. They compared 15,702 patients who had no history of preoperative catheterization with 1772 men who had received a catheter for stage IV AUR before surgery. Both retention history and the number of retention episodes were positively correlated with treatment failure, as defined as any BPH-related reoperation or catheterization for AUR one month or more after the primary surgery. Using Fine-Gray competing-risk models, surgical failure rates at 10 years were predicted to be reduced by 31% if deobstruction occurred before any episode of stage IV AUR requiring catheterization (from 29% to 20%; p < 0.001).^[60]

Landmark papers published in 1991 and 1998 recognized the impact of BOO on detrusor function.^[67,68] In 1997, Nitti et al.^[69] showed that post-TURP stage II DOA could persist in as high as 54% of patients, underscoring negative consequences when deobstruction is delayed for too long. Thomas et al.^[70] in 2005 followed patients with BOO using an advanced multichannel urodynamics over a minimum 10-year period and highlighted the consequences when a decision not to intervene was made. Bladder dysfunction with stage II DOA and stage III UUI increased by 100% and 50% of patients, respectively, as the maximum flow rate and bladder contractility index decreased.^[70] In 2014, Mitchell et al.^[71] highlighted that 1 in 5 men with multichannel urodynamics-proven stage V atonic bladders could not be salvaged, even with maximal deobstruction via enucleation. In 2021, a secondary analysis of the UPSTREAM trial (Urodynamics for Prostate Surgery Trial: Randomised Evaluation of Assessment Methods) provided evidence supporting that the most suitable surgical candidates are in stage I BPO with normal contractile strength and without DOA.^[72] Ideal deobstruction often occurs too late, putting patients at risk of permanent bladder damage and dysfunction, prompting questions such as “Are we waiting too long to deobstruct?” and “When is the optimal time to intervene?”.^[73]

5. Medications do not eliminate the risk of BPH/BPO progression

A secondary level of evidence supports how the MVP “Five Stages of Bladder Health” illustrates how BPH medications needlessly place more patients at risk for stage IV AUR. The heralded CombAT trial (Combination of Avodart (dutasteride) and Tamsulosin) convincingly shows how drugs in combination can improve bothersome symptoms (IPSS) and reduce the risk of episodes of retention.^[74,75] This 4-year trial did not consider that many men are on an individual drug or a combination of drugs for far longer than the study period. Encountering patients who have been on BPH drugs for almost a decade is not unexpected.^[76] Notably, these drugs do not eliminate the risk of stage IV AUR. The authors applied inductive reasoning and extrapolated the data lines to a decade of follow-up using the same incidence slope as that seen over the trial's 4-year follow-up. More than 1 in 3 patients on tamsulosin alone and more than 1 in 10 patients on combination drugs (dutasteride plus tamsulosin) would plausibly undergo BPH surgery or experience stage IV AUR if followed up for 10 years (authors' analysis).

In 2010, Izard and Nickel^[61] evaluated the effect of BPH medication use on the indications of patients who underwent TURP over a 20-year period. The year 1988 represents the era before the use of BPH drugs, 1998 marks the inception of drug use for BPH, and 2008 denotes the time when it was standard management for men to be the default population for drug trials. Over 2 decades, surgical deobstruction via TURP has decreased by 46% (n = 157 in 1988 vs. n = 84 in 2008). Conversely, the proportion of men taking BPH drugs increased from 0% in 1988 to 87% in 2008. Using stage IV disease as a barometer of the negative impact on patients with BPH, the incidence of preoperative AUR increased by 87% (from 23% in 1988 to 43% in 2008).^[61]

To reinforce how BPH drug use contributes to progression into later stages, Young et al.^[62] reported on a similar retrospective cohort of patients who underwent TURP in 1990, 2000, and 2010. They also found the number of TURPs over this 20-year period to have decreased significantly by 65%. Concurrently, the percentage of patients taking BPH drugs increased from 2% to 43%. Similar to the study by Izard and Nickel,^[61] the indications shifted significantly from early stages I to III in 1990 to stage IV in 2010. In 1990, 65% of TURPs were performed for early stage LUTS, whereas, in 2010, 68% of surgeries were performed for late-stage AUR indications. In addition, a 6-fold increase in “long-term failure to void after surgery” was observed. Although multichannel advanced urodynamics are required to confirm the diagnosis of DUA, this finding as a surrogate for late stage V is a cause for concern.^[62]

Medications are pivotal in reshaping the management of mLUTS when surgical deobstructive options are limited. In this golden era of BPH/BPO, drugs can be regarded as extremely useful temporizing measures to manage symptoms as we complete the diagnostic pathway to present a personalized therapeutic plan.

6. Conclusions

A paradigm shift is required in the management of BPH/BPO. Patient outcomes can be significantly improved by focusing on bladder health and earlier interventions. The putative MVP “Five Stages of Bladder Health” provides a valuable framework for understanding disease progression and guiding personalized treatment decisions. This staging system, coupled with the concept of a window of curability, can empower urologists to generate hypotheses for prospective research to identify at-risk patients, initiate timely interventions, and ultimately prevent late-stage disease. By embracing this new approach, we are moving toward a future where BPH/BPO is managed proactively, rather than reactively, leading to better patient experiences and improved quality of life, as bladder health becomes the focus of our attention.

Acknowledgments

We would like to acknowledge Christopher Kuang for design and creation of figures/table; MVP Tribe on LinkedIn for inspirational dialogue; and EAU, AUA, and NICE Guideline Committees for academic wisdom.

Statement of ethics

Not applicable.

Conflict of interest statement

The authors declare no conflicts of interest.

Funding source

This review received no external funding.

Author contributions

WWK: Conceptualization, investigation, writing – original draft preparation.

WWK, LC, TA, BIC: Writing – review and editing.

Data availability

Data discussed in this article are drawn from previously published studies, which are cited within this article.