Korean J Urol Oncol 2014;12(2):86-88

Metachronous Triple Genitourinary Tumors in a Single Patient Treated by Partial Nephrectomy, Retropubic Radical Prostatectomy, and Transurethral Resection of Bladder Tumor

Jang Hee Han1, Jong Kyou Kwon1, Joo Yong Lee1, Kang Su Cho2, Won Sik Ham1, Young Deuk Choi1 1Department of Urology, Severance Hospital, Urological Science Institute, Yonsei University College of Medicine, 2Gangnam Severance Hospital, Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea

A 75-year-old man was referred to our department for an incidentally detected right renal mass which was later treated by partial nephrectomy. Seven years later, a serum PSA level of 5.87ng/ml was detected and a digital rectal examination revealed a tiny, palpable in the left lobe of prostate. The results of the prostate biopsy revealed prostate with a Gleason score of 7 (3＋4) in 5 of 12 cores. Retropubic radical prostatectomy was carried out. In follow-up imaging studies, positron emission tomography-computed tomography revealed a 1.3-cm papillary tumor located in the bladder and he underwent transurethral resection. To the best of our knowledge, this the first report of metachronous, triple primary, genitourinary malignant tumors in Korea. (Korean J Urol Oncol 2014;12:86-88) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏 Key Words: Urogenital ; , Second primary

Multiple primary (MPC) in a single patient have be- niques have also attributed to the increase of this diagnosis. come a frequent finding in recent decades. However, MPC of To the best of our knowledge, there is little data reporting three or more sites is extremely rare reporting prevalence of the incidence and clinical features of this rare disease entity,4 0.029 to 1.7%.1-3 The etiologies of MPC appear to be complex and metachronous, triple primary, genitourinary malignant tu- and the main driving cause varies widely. Number of factors mors have not been reported in Korea so far. Herein, we pres- could interact with each other to cause this uncommon disease.4 ent a report of metachronous, triple primary, genitourinary ma- Furthermore, an aging society producing an increasing elderly lignant tumors occurring in the kidney, prostate, and bladder patient population, as well as advances in novel diagnostic tech- that were treated by an open partial nephrectomy (OPN), retro- pubic radical prostatectomy (RRP), and transurethral resection

Received June 23, 2014, Revised August 7, 2014, of the bladder tumor(TURBT). Accepted August 11, 2014 Corresponding Author: Young Deuk Choi, Department of Urology CASE REPORT and Robot and Minimal Invasive Surgery Center, Severance Hospital, and Urological Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul On December 2005, a 75 year-old male patient was referred 120-752, Korea. Tel: 82-2-2228-2317, Fax: 82-2-312-2538, to Severance Hospital, Yonsei University Health System, Seoul, E-mail: [email protected] Korea, department of urology for an incidentally detected renal

86 Jang Hee Han, et al：Triple Genitourinary Metachronous Tumors 87

Fig. 1. (A) Computed tomography revealed an approximately 2-cm, well-enhanced, exophytic, mass enri- ching blood flow located in the anterior aspect of the midportion of the right kidney (arrow head). (B) Upon preoperative magnetic reso- nance image, PCa was suspected in both peripheral zones without defi- nite extraprostatic extention or seminal vesicle .

Fig. 2. (A) A 1.3-cm focal enhan- cing mass lesion was detected at the left ureterovesical junction of the urinary bladder in the PET-CT suggesting a bladder tumor (arrow- head). (B) Multiple bladder tumors up to 2cm were noted in the whole bladder wall during cystoscopy. mass. He had a smoking history of 90 pack-years and had no resonance images, prostate (PCa) was suspected in both other remarkable past medical history. Ultrasonography and peripheral zones without a definite extraprostatic extention or computed tomography (CT) revealed an approximately 2cm, seminal vesicle invasion (Fig. 1B). Considering his age, per- well-enhanced, exophytic mass enriching blood flow located in formance status (ECOG 0), and Charlson Comorbidity Index the right kidney (Fig. 1A). He had undergone partial neph- (CCI), the patient underwent RRP for PCa. In the CCI, the his- rectomy with preservation of the ipsilateral adrenal gland. tory of RCC was excluded because RCC had been diagnosed Pathological evaluation revealed a 2.5x2.2cm mass consistent 5 years ago and his score was 0. The pathological diagnosis with renal cell (RCC), conventional type, Fuhrman revealed prostate adenocarcinoma, with a Gleason score of 7 grade 1, without involvement of the resection margin or peri- (3＋4) and extracapsular extention without focal surgical mar- nephric fat (pT1aN0M0). There was no reported evidence of gin involvement or pelvic lymph node invasion (pT3aN0Mx). post-operative complications or recurrence during the routine Three months after surgery the PSA decreased to 0.1ng/ml follow-up periods. without adjuvant androgen deprivation therapy. On March 2012, he visited again presenting with lower uri- On May 2013, positron emission tomography-CT (PET-CT) nary tract symptoms (LUTS). As part of the routine evaluation was performed to evaluate recurrence or progression of the for LUTS, prostate-specific antigen (PSA) and transrectal ultra- which revealed 1.3-cm focal enhancing mass le- sonography (TRUS) were performed. Serum PSA level was sion at the left ureterovesical junction of the urinary bladder. 5.87ng/ml and prostate volume was 16ml. During the digital (Fig. 2A). Multiple bladder tumors up to 2cm were noted in rectal examination, a tiny nodule was palpable on the left lobe the whole bladder wall during cystoscopy (Fig. 2B), and metic- of the prostate gland. Finally, a TRUS-guided biopsy of the ulous TURBT was carried out. The pathological results re- prostate was performed for confirmative diagnosis. The patho- vealed urothelial carcinoma, low grade, pTaN0M0. After 6 cy- logical report indicated prostate adenocarcinoma with a Gleason cles of intravesical BCG instillation, routine postoperative fol- score of 7 (3＋4) in 5 of 12 cores. From preoperative magnetic low-up studies have shown no complications or recurrence for 88 대한비뇨기종양학술지：제12권 제2호 2014

RCC, PC, or bladder tumors thus far. tween RCC, PCa, and bladder tumors in metachronous MPC. Recently, genetic factors have been associated with urological DISCUSSION malignancies. SNORD43 is a reference gene suitable for ana- lyzing circulating micro-ribonucleic acids in patients with po- MPCs are a relatively well-known phenomenon. The etiology tential urological malignancies including PCa, urothelial carci- of multiple primary malignant tumors is rather complex and in- noma, and RCC.10 cludes environmental factors like tobacco, occupation, pollu- We firstly reported extremely rare case of metachronous tri- tion, ultraviolet light, genetic predisposition, previous medical ple genitourinary gumors in a single patient and suggested that treatment like or , gender-specif- the primary tumors are not as advanced initially when com- ic factors, hormonal factors, and finally interactions between pared to the synchronous type, the secondary tumor may be these factors.5 A few cases of genitourinary MPCs have been more advanced and more aggressive treatment should be con- reported throughout the world; however, none of them were sidered for such patients. metachronous MPCs which were detected more than 5 years later since the first cancer had developed. There also have been REFERENCES no reported case of metachronous, triple genitourinary MPC in 1. Hajdu SI, Hajdu EO. Multiple primary malignant tumors. Korea. Journal of the American Geriatrics Society 1968;16:16-26 In terms of the chronicity, we defined synchronous and meta- 2. Nemeth Z, Czigner J, Ivan L, Ujpal M, Barabas J, Szabo G. chronous cancer based on Moertel's definition.6 Synchronous Quadruple cancer, including triple cancers in the head and cancers are defined as those occurring within 6 months of the neck region. Neoplasma 2002;49:412-4 first primary cancer, while metachronous cancers were defined 3. Kim JH, Rha SY, Kim C, Kim GM, Yoon SH, Kim KH, et al. Clinicopathologic features of metachronous or synchronous more than 6 months later. It has been reported that the synchro- gastric cancer patients with three or more primary sites. Cancer nous MPC group had a greater number of advanced stage, ini- research and treatment : official journal of Korean Cancer tial primary malignancies and fewer advanced stage, subsequent Association 2010;42:217-24 primary malignancies, and that genitourinary MPCs were more 4. Arikan-Sengul C, Pehlivan Y, Sevinc A, Karakok M, Kalender frequent in the metachronous MPC group.7 The prostate was ME, Camci C. A case of metachronous triple primary urogen- ital cancer: urinary bladder, prostate, and renal cancer. the most frequent site of initial primary malignancy in the Onkologie 2009;32:122-4 metachronous MPC group, whereas the lung, bladder, and ure- 5. Beisland C, Talleraas O, Bakke A, Norstein J. Multiple pri- ter were the most common initial sites in the synchronous MPC mary malignancies in patients with : a na- group. The most common malignancy pairing was PCa with ur- tional population-based cohort study. BJU Int 2006;97:698-702 othelial carcinoma involving the bladder and ureter (12%).7 6. Moertel CG. Multiple primary malignant neoplasms: historical perspectives. Cancer 1977;40:1786-92 Regarding risk factors for each cancer, is the 7. Powell S, Tarchand G, Rector T, Klein M. Synchronous and fourth most common malignancy in men and the tenth in metachronous malignancies: analysis of the Minneapolis women. Cigarette smoking is believed to contribute to ur- Veterans Affairs (VA) tumor registry. Cancer causes & con- othelial cancer, up to 50% in men and up to 40% in women. trol: CCC 2013;24:1565-73 Other implicated agents include aniline dyes, drugs, and ex- 8. Scher HI MR. Bladder and renal cell ; in Hauser K, Longo B, Jameson F (eds): Harrison’s Principles of Internal ternal-beam radiation. RCCs account for 90-95% of malignant Medicine New York, McGraw-Hill, 2005:539-43 kidney neoplasms. Presenting signs and symptoms include hem- 9. Gong Z, Agalliu I, Lin DW, Stanford JL, Kristal AR. Cigarette aturia, abdominal pain, and a flank or abdominal mass. It also smoking and prostate cancer-specific mortality following diag- shows the strongest association with cigarette smoking and nosis in middle-aged men. Cancer causes & control : CCC obesity.8 Smoking at the time of diagnosis, independently of 2008;19:25-31 key clinical prognostic factors, is associated with an increased 10. Sanders I, Holdenrieder S, Walgenbach-Brunagel G, von Ruecker A, Kristiansen G, Müller SC, et al. Evaluation of ref- risk of prostate cancer death.9 In our case the patient only had erence genes for the analysis of serum miRNA in patients with the risk factor of old age and smoking history; however, there prostate cancer, bladder cancer and renal cell carcinoma. Int was no sufficient evidence to suggest a close relationship be- J Urol 2012;19:1017-25