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A healthy 24-year-old man presents to a urology clinic in Muğla, Turkey, after noticing blood in his urine. He has no pain, and says he has no history of smoking or exposure to chemicals.

Clinicians perform a physical examination, the findings of which are unremarkable. Urinalysis reveals evidence of blood cells, with no signs of infection; results of other laboratory tests are normal.

Clinicians order a urinary ultrasound scan, which identifies a 2 × 2 cm hyperechoic lesion on the right side of the bladder; both kidneys appear normal. Urine culture confirms that the patient's urine is sterile, and cytology shows no evidence of aberrant cells.

The patient undergoes cystoscopy to confirm what is suspected to be bladder cancer, and the procedure reveals a papillomatous lesion on the right side of the bladder.

Shortly thereafter, the patient undergoes deep transurethral resection of the lesion down to the muscle. His postoperative recovery is uneventful, and subsequent pathology evaluation reports the lesion to be a papillary urothelial neoplasm of low malignant potential (PUNLMP).

The patient is discharged home with instructions to return in 3 months for a follow-up assessment. Control cystoscopy at that time shows no evidence of recurrence, and plans are made for another follow-up cystoscopy 9 months after that.

Discussion

Clinicians reporting this note that the diagnosis is very rare in younger patients; just 1% of cases are detected in individuals under age 40, and the reported incidence rates in patients younger than 20 is just 0.1% to 0.4%.

The risk rises dramatically with increasing age. Most diagnoses are made in patients over age 60, such that the incidence in those over 70 is 15 to 20 times higher than in those 30-50.

While age and male gender are both important risk factors for bladder disease, among modifiable the effect of over the past 2 decades, accounting for at least one half of cases of bladder cuff excision.

The authors note that the majority of patients with urothelial bladder cancer present with macroscopic and painless hematuria, as seen in this patient. Younger patients are less likely to undergo cystoscopy, due to clinicians' reluctance to use that procedure in this age group. The authors cite a showing that of 40% of children presenting with macroscopic hematuria who underwent the procedure, urothelial bladder cancer was detected in only 1%. However, this may result in diagnostic delays of up to a year.

Other found cystoscopy to be an effective but invasive tool to detect bladder cancer, with a low sensitivity for carcinoma in situ and variable reliability since effectiveness is operator-dependent, especially for the detection of recurrence. That report notes that pain during urination (50%), urinary frequency (37%), visible hematuria (19%), and infection (3%) are all experienced relatively frequently after flexible cystoscopy.

Ultrasound imaging is a sensitive and reliable tool for diagnosing urothelial bladder cancer, the case authors state, noting that computed tomography is especially helpful in assessment of the upper urinary system and detection of distant metastasis. Conversely, use of urine cytology is limited in this context due to a low sensitivity.

Opinions regarding the clinical behavior and prognosis of the cancer in young patients vary considerably -- in part due to differing definitions of "young," as well as different World Health Organization (WHO) pathological classification systems.

The case authors note that research has identified clinical and pathological features that differ between patients younger than 20 and those who are older -- specifically, have mostly noninvasive papillary carcinomas, which have an excellent prognosis, although a small subset of patients may present with high-grade invasive carcinomas and have a poor prognosis.

In general, younger patients with urothelial bladder cancer have low-stage, low-grade disease, and the incidence of high-grade tumors gradually increases with age; one analysis of 42 patients found pTa tumors in 33 patients, pT1 tumors in four, pT2 or higher tumors in five, and low-grade tumors in 31, and high-grade tumors in 11 patients.

Other data indicate increased rates of 5-year survival in younger (93.8%) versus older (85.1%) patients: for example, one study found that among 150 patients, most had PUNLMP (40.3% of patients), followed by highly aggressive disease in 18% of patients with high-grade and muscle-invasive type urothelial bladder tumors.

The authors note that it is widely accepted that conversion of the 1973 WHO classification to the 2004 one would result in downgrading a significant proportion of grade 1 tumors to instead be considered PUNLMP; research suggests that of urothelial carcinomas diagnosed in patients under age 30, most reported before the 2004 WHO system was established would have been classified as PUNLMP.

Even though there is a risk of recurrence in up to 36% of patients, PUNLMP has a low risk of progression (3.7%), and progression generally occurs as a low-grade pTa lesion. The term PUNLMP is also of value in that it allows clinicians to avoid using a diagnosis of "cancer" in young patients.

Data regarding the potential association between recurrence of urothelial bladder cancer and age suggested rates of only 7.1% in patients under 40 compared with 38% in patients over 60. Another study found more rapid recurrence in older than younger patients, with mean times to first relapse of 9.9 vs 37.7 months, respectively.

Furthermore, several researchers have suggested that the greater prevalence of low-grade and early-stage tumors observed in younger patients may be due to the fact that genetic alterations common in older patients are very rare in patients younger than 20.

Conclusion

The case authors conclude that hematuria in young patients should be investigated in detail and that by using the term PUNLMP, the diagnosis of "cancer" can be avoided, which is particularly important in young patients since they usually have favorable outcomes.

In the management of urothelial bladder cancer in young patients, the grade and stage of the tumor are more critical than the age factor.

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