20-Year-Old Male with Recurrent Right Flank Pain

CASE SCENARIO 20-Year-Old Male with Recurrent Right Flank Pain Ojas Shah, MD, Brian R. Matlaga, MD, MPH, Dean G. Assimos, MD Department of Urology, Wake Forest University School of Medicine, Winston-Salem, NC [Rev Urol. 2003;5(2):126–129] © 2003 MedReviews, LLC CASE REPORT welve months prior to referral, a 20-year-old man had intermittent right flank pain associated with nausea and emesis. A right ureteropelvic junction (UPJ) obstruction was diagnosed. The patient was treated with a cutting balloon incision of the UPJ and did well for 6 months, at which time his symptoms recurred. While symptomatic, he was evaluated with diuretic nuclear renography, which demonstrated functional obstruction of the right kidney but otherwise symmetric function. CT angiography showed moderate right hydronephrosis and an accessory crossing artery at the right UPJ. The ureter distal to this point appeared normal on postcontrast abdominal radiography. Serum creatinine, electrolytes, and urinalysis results were normal. T After being informed of his treatment options, the patient elected to undergo open surgical pyeloplasty. An 11th rib flank incision was made, and the renal pelvis and proximal ureter were exposed. Approximately 5–6 cm of the proximal ureter, starting just below the renal pelvis, was densely adherent to the inferior vena cava. The renal pelvis was moderately dilated and mostly intrarenal. The accessory renal artery was identified, isolated, and preserved. The ureter was transected and suture ligated just below the UPJ with 3-0 absorbable suture. The ureter distal to this point was dissected free from the inferior vena cava, and a 2-cm segment of poorly vascularized ureter was resected. The remaining ureter could not be brought up to the level of the renal pelvis for tension-free dismembered pyeloplasty, despite renal mobilization. MANAGEMENT OPTIONS Select one: ❑ 1. Renal autotransplantation ❑ 2. Flap pyeloplasty ❑ 3. Partial lower-pole nephrectomy with ureterocalicostomy ❑ 4. Ileal ureter substitution ❑ 5. Nephrectomy Vote online at www.medreviews.com; or fax your response to MedReviews: (212) 971-4047; or send an e-mail message with your selection to dgern@medreviews.com. Selections will be tabulated and presented in the next issue of Reviews in Urology. VOL. 5 NO. 2 2003 REVIEWS IN UROLOGY ✁ 126 Case Scenario Discussion of Last Issue’s Case Scenario IN THE LAST ISSUE, DRS. PARTIN AND 54-year-old healthy male is referred for prostate cancer evaluation after presenting with an elevated prostate-specific antigen level (PSA) of 4.5 ng/dL on a routine screening examination. He denies any urologic complaints, is without medical problems, denies any family history of cancer, does not smoke, and leads a A GRETZER PRESENTED THIS CASE REPORT: healthy and active lifestyle. Physical examination is unremarkable, and digital rectal examination is benign. Prostate biopsies are performed secondary to the elevated PSA. Pathological review of the biopsies reveals high-grade prostatic intraepithelial neoplasia (HGPIN) with a predominant pattern of flat/tufting in 3/12 biopsy cores. MANAGEMENT ISSUES 1. Does the patient need repeat biopsies? If so, please explain. 2. What if HGPIN is repeated on the next biopsy? How would you proceed? 3. What follow-up is recommended? AUTHOR’S DISCUSSION Increasing evidence within the literature suggests that HGPIN represents a pre-malignant lesion to the development of prostatic adenocarcinoma.1 As with prostate cancer, HGPIN is often multifocal, exhibits similar histopathology, and may be associated with prostate cancer in as many as 85% of cases.2 With an incidence ranging from 5% to 25%,1 management of this vexing diagnosis continues to repre- sent a “gray zone" for many urologists. Recent publications, however, shed new light and bring into question the established dogma regarding management issues associated with PIN. The reflex to rebiopsy a patient diagnosed with HGPIN is borne out of data from multiple series that identify the frequency of adenocarcinoma on subsequent biopsies VOL. 5 NO. 2 2003 REVIEWS IN UROLOGY 127 Case Scenario continued following HGPIN to range from 30% to 80%.3–9 Given the accepted status as a precursor lesion to prostate cancer, as well as the aforementioned range of cancer rates on repeat biopsy, few urologists would not rebiopsy following such a diagnosis. In a study by Kronz and associates,10 the risk of cancer on subsequent biopsy and the impact of histologic and clinical variables on risk stratification has been evaluated. They concluded that the likelihood of finding cancer on follow-up ranged from 25% to 32%. These findings support previous large studies on this issue that reported risks ranging from 23% to 35%.4,6 Although these studies The study by Kronz also suggested that select histologic characteristics, such as patterns of flat/tufting or papillary/cribiform in the initial biopsy might also provide additional risk stratification. illustrate the risk for cancer following a diagnosis of HGPIN, current false-negative prostate biopsy rates range between 10% and 25%.11 Thus, caution must be exercised when interpreting the risk of cancer following a diagnosis of isolated HGPIN, as this increased risk appears to be marginally elevated over the risk of cancer following a benign biopsy. Whereas attempts to further risk-stratify men with HGPIN using clinical factors such as PSA, digital rectal examination, or transrectal ultrasound findings remain controversial, the number of cores positive for HGPIN has been shown to aid in subsequent cancer diagnosis.10 When one to two, three, or more than three cores contain HGPIN, the risk of cancer on follow-up biopsies has been shown to be 30%, 40%, or 75%, respectively. Thus, even though some men will be considered low-risk, depending on the extent of HGPIN, repeat biopsy is warranted when isolated HGPIN is discovered on biopsy. Using our case scenario as an example, this patient with three cores of HGPIN carries a 40% risk of cancer on repeat biopsy. Although the number of cores with PIN was shown to be the only overall histologic variable useful in stratifying risk, the study by Kronz10 also suggested that select histologic characteristics, such as patterns of flat/tufting or papillary/cribiform in the initial biopsy might also provide additional risk stratification. When a pattern of flat/tufting is noted in any number of cores, the risk of cancer is lower (21%–23%), and when the pattern includes papillary/cribiform, the risk of cancer is higher and may range from 40% to 70%, depending on whether one or more cores are involved. Returning to the scenario above, although repeat biopsy is warranted, the patient’s risk is sufficiently low 128 VOL. 5 NO. 2 2003 REVIEWS IN UROLOGY that a less aggressive follow-up regimen may be warranted. Due to the controversy and lack of knowledge regarding the natural history of HGPIN, this diagnosis on biopsy has committed many patients to a vicious cycle of unrelenting repeat biopsies. However, given the above findings, if cancer is not found on repeat biopsy, the risk of subsequent cancer may be as low as 10%. Furthermore, if this patient’s initial biopsy exhibited a more favorable histologic pattern (flat/tufting) and is limited to a few cores, he may return to a routine screening regimen (based on PSA and digital rectal examination). However, if the initial biopsy contained many cores of HGPIN with unfavorable features, such as papillary/cribiform or any features described as atypical, substantial enough risk exists to maintain a higher index of suspicion and obtain further biopsy material. What about when HGPIN is diagnosed on repeat biopsy? The risk of cancer for these men is 26%; however, once again this is within the range of false negatives.10 To aid in their risk assessment, one should refer to the initial biopsy and review the extent and pattern of HGPIN. If a favorable pattern and limited cores are noted, a less aggressive follow-up may be considered. However, if less favorable patterns are noted, and certainly if any atypical patterns are described in the repeat HGPIN biopsy, then the risk of cancer may be as high as 60%, and continued biopsy surveillance is warranted.10 Currently, there is no definitive guideline for the appropriate interval and follow-up regimen for men diagnosed with HGPIN.2,12–14 Some practitioners currently recommend that men found to have HGPIN undergo repeat biopsy at 3–6-month intervals for 2 years, and annually thereafter. However, as noted, not all men have similar risk, and some may not need to have their remaining prostate removed core by core via biopsies over the remainder of their lives. For men with a negative repeat biopsy, a return to PSA monitoring is sufficient. Men found to have HGPIN on repeat biopsy present more of a challenge. Reviewing the extent and type of HGPIN on initial biopsy appears to aid in risk stratification of these men. Although there is no defined consensus, these men should have their prostates re-biopsied in 3–6 months, and if cancer is not found after two follow-up biopsies, it is unlikely to be discovered.10 References 1. 2. 3. 4. Epstein JI. Pathology of prostatic neoplasia. In: Walsh PC, ed. Campbell’s Urology. 8th ed. Philadelphia: W.B. Saunders; 2002:3025–3026. Qian J, Wollen P, Bostwick DG: The extent and multicentricity of high-grade prostatic intraepithelial neoplasia in clinically localized prostatic adenocarcinoma. Hum Pathol. 1997;28:143–148. Aboseif S, Shinohara K, Weidner N, et al. The significance of prostatic intraepithelial neoplasia. Br J Urol. 1995;76:355–359. Davidson D, Bostwick D, Qian J, et al. Prostatic intraepithelial neoplasia is a risk factor for adenocarcinoma: predictive accuracy in needle biopsies. J Urol. 1993;154:1295–1299. Case Scenario 5. 6. 7. 8. 9. Langer JE, Rover ES, Coleman BG, et al. Strategy for repeat biopsy of patients with prostatic intraepithelial neoplasia detected by prostate needle biopsy. J Urol. 1996;155:228–231. O’Dowd GJ, Miller MC, Orozco R, et al. Analysis of results within 1 year after a noncancer diagnosis. Urology. 2000;55:553–559. Raviv G, Janssen T, Zlotta AR, et al. Prostatic intraepithelial neoplasia: influence on clinical and pathological data on the detection of prostate cancer. J Urol. 1996;156:1050–1055. Shepherd D, Keetch DW, Humphrey PA, et al. Repeat biopsy strategy in men with isolated prostatic intraepithelial neoplasia on prostate needle biopsy. J Urol. 1996;156:460–463. Weinstein MH, Epstein JI. Significance of high-grade prostatic intraepithelial neoplasia (PIN) on needle biopsy. Hum Pathol. 1993;24:624–629. 10. 11. 12. 13. 14. Kronz JD, Carol AH, Shaikah AA, Epstein JI. Predicting cancer following a diagnosis of high-grade intraepithelial neoplasia on needle biopsy: data on men with more than one follow-up biopsy. Am J Surg Pathol. 2001;25:1079–1085. Gretzer MB, Partin AW. PSA levels and the probability of prostate cancer on biopsy. Eur Urol Supplements. 2002;1:21-27. Zlotta AR, Schulman CC. Clinical evolution of prostatic intraepithelial neoplasia. Eur Urol. 1999;35:498–503. Lefkowitz GK, Taneja SS, Brown J, et al. Follow-up interval prostate biopsy 3 years after diagnosis of HGPIN is associated with high likelihood of prostate cancer, independent of change in PSA levels. J Urol. 2002;268:1415–1418. Bostwick DG. Prostatic intraepithelial neoplasia is a risk factor for cancer. Semin Urol Oncol. 1999;17:187–198. VOL. 5 NO. 2 2003 REVIEWS IN UROLOGY 129