PEDIATRIC TESTICULAR TUMORS: THE JOHNS HOPKINS EXPERIENCE MICHAEL R LEONARD, M.D. ROBERT D. JEFFS, M.D. BRIGID LEVENTHAL, M.D. JOHN P. GEARHART, M.D. From the Division of Pediatric Urology, The James Buchanan Brady Urological Institute, and the Department of Pediatrics, Division of Pediatric Oneology, The Johns Hopkins Hospital, Baltimore, Maryland

dar neoplasms constitute 1 percent of all childhood malignancies and rank •,ancer mortality. From 1970 to 1988, 25 testicular tumors in children eighteen e seen. The majority of the patients were white (88 %). Pathologic analysis of ~,hat 68 percent were germinal and 32 percent were nongerminal. Staging was :tients with serum markers, chest x-ray film, and computerized tomography graphy. All patients underwent radical orchiectomy, and further therapy was umor type and stage. The survival among this cohort was excellent, with only g to their disease. Detailed results of treatment, and approaches to avoid excess are reviewed.

s and adnexae constitute iatrie tumors and rank dhood cancer mortality. se at anytime during indoleseenee, and prompt 3riate treatment are neent survival with minimal te incidence of testieular Lmeriean males up to firbeen quoted as 1.04 per ,~sticular tumors are more children than black s and ave an association with ;evious inguinal herniorhave a different pathotheir adult counterparts. eumented that germinal ereent and nongerminal pediatric testieular neo~e with pediatric testieuLution has been reviewed

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Material and Methods This study was based on a retrospective chart review of patients eighteen years and under with a diagnosis of testicular tumor seen at Johns Hopkins Hospital between 1970 and 1988. Histologie confirmation of all tumor specimens was carried out at Johns Hopkins regardless of where the initial orehieetomy was performed. All treatment was coordinated through the Johns Hopkins Pediatric Oneology Division. A total of 25 patients were available for study. They ranged in age from six months to eighteen years (mean age 10.6 yrs). Among the patients, there were 3 blacks (12%) and 22 whites (88 %). All patients were staged by obtaining tumor markers (AFP, bhCG), chest xray examination, lymphangiogram, and/or CT scan of chest/abdomen. Treatment was appropriate to tumor type and stage, and included radical orehieetomy in all. Follow-up ranged from one month to one hundred seventy-three months (average 55 mos).

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TABLEII.

Management of seminoma stage for stage (Stage IIc signifies bulky retroperitoneal

TABLEI. Distribution of tumors according to age of presentation (note bimodal distribution of paratesticular rhabdomyosarcomas) Age (Yrs).-Tumor Type

% Total

Range

Average

Teratocarcinoma Paratesticular rhabdomyosarcoma Yolk sac Embryonal carcinoma Seminoma Gonadal stromal Teratoma

28 28

16-18 3-6 13-17 0.75-5 15-18 13-17 0.75 0.5

16.9 4 15 1.9 16.6 15 0.75 0.5

16 12 8 4 4

Stage

Radical orchiectomy Radiotherapy (2,500 rad over 3 wc ipsilateral inguinoiliac and entire para-aortic/caval nodes to level of diaphragm) o r surveillance Radical orchiectomy II A, B Radiotherapy (as described above) Radical orchiectomy II C Chemotherapy (PVB or VAB 6) x 3-4 III cycles NB. No role for cytoreductive surgery Salvage chemotherapy (VP16 and Relapse KEY: PVB = eisplatin, vinblastine, bleomyein; VA clophosphamide, eisplatin, vinblastine, aetinomyein 1 ein.

I

Classification and age distribution Among the tumors 17/25 (68%) were germinal neoplasms, and 8/25 (32 %) were nongerminal neoplasms. There was no side predilection. Previous inguinal herniorrhaphy was a factor in 2 patients, and cryptorchidism in 1. The following histologic categories comprised the germinal tumors: teratocarcinoma 7/25, yolk sac tumor 4/25, embryonal carcinoma 3/ 25, seminoma 2/25, and teratoma 1/25. The nongerminal tumors consisted of paratesticular rhabdomyosareoma 7/25, and gonadal stromal tumor 1/25. Table I summarizes the age and histologic distribution pattern of the tumors.

TABLEIII. Treatment of yolk sac tu~ stage by stage (most centers have op~ for surveillance in Stage I) Stage

Management

I

Diagnosis and staging The majority of the testis tumors in this series presented as a painless testicular mass. This mass was usually noted by the mother in infants, and by the patient in older children and teens. The time to presentation with a testicular mass is significantly less in infants than among adolescents. 4 Two tumors were brought to medical attention due to minor trauma, one tumor presented as a hydrocele, while another was originally treated with antibiotics for a presumed diagnosis of epididymitis. Three patients with metastatic tumors presented with back pain and testicular enlargement; another patient presented with an enlarged Virchow node, and testicular mass was noted subsequently. All patients were staged with tumor markers (AFP, bhCG), chest x-ray films, lymphangiography, and/or CT scan of chest/abdomen. Surgical staging via retroperitoneal lymph node dissection (RPLND) was available in 9 patients. The stage distribution among our patients was: Stage I, 10/25; Stage II, 8/25; and Stage III/IV, 7/25. Stage I represents disease localized to the testicle and adnexae, Stage II represents retroperitoneal nodal disease, and Stage III represents nonregional nodal disease and/or distant 254

Management

Radical orchieetomy Follow up monthly: CXR, AFP levels; if relapse, PVB; if pulmonary metastases; radiotherapy II Radical orchiectomy RPLND Chemotherapy (PVB) x 1 year; r a d i o t h e ~ to bulk disease; if relapse, salvage ~ ehemotherapy; if pulmonary metastase ~ radiotherapy; NB follow-up serial CXB~i~ AFP levels III Radical orehiectomy Chemotherapy (PVB x 1 year) Radiotherapy to bulk disease; if relapse, salvage ehemotherapy; if p u l m o n a r y metastases, radiotherapy; NB follow-u~;~ serial CXR, AFP levels ~ KEY: CXR = chest x-ray film; AFP = alpha_fetopr~N~~ri~ll = retroperitoneal node dissection. PVB = e i s D l ~ ~ bleomyein.

organ metastases (liver, lung, brain). For testieular rhabdomyosareoma, the s t a g i n G ~ lowed the guidelines of IRS III. Treatment and outcome Seminoma. The two patients seminoma presented with Stage I d i s e a s e i ~ were managed according to the guideline lined in Table II. They are both alive w evidence of disease (NED) an average 0 months post-treatment. A surveillance pr for Stage I seminomas has not been unde at Hopkins. ~ 4 ~ i ,,., Yolk sac tumor. Two patients p r e ~ with Stage I, 1 with Stage II, and 1 wit~:~

UROLOGY / MARCH 1991 / VOLUMEXXXVII,

TaBL~IV. Treatment for embryonal carcinoma or teratocarcinoma stage by stage Stage

Treatment of paratesticular rhabdomyosarcoma stage by stage

TABLE V. Stage

Management Radical orchieetomy RPLND or surveillance Radical orehiectomy RPLND Close follow-up (CXR, markers) or adjuvant chemotherapy (PVB, VAB6) x 2 cycles; close follow-up Radical orchiectomy Chemotherapy (PVB, VAB6) x 4 cycles Salvage cytoreduetive surgery (if markers negative), or salvage chemotherapy (eisplatin, VP-16, ifosfamide) Salvage chemotherapy (cisplatin, VP-16, ifosfamide)

J

,ND = retroperitoneal node dissection; CXR = chest xPVB = cisplatin, vinblastine, bleomycin; VAB6 = cyaamide, cisplatin, vinblastine, actinomyein D, bleomy-

disease. All patients were managed accord~6the treatment recommendations in Table ,~except for the patient with Stage II disease, }~id not undergo RPLND. Radiotherapy ifiot utilized. All patients have NED an ra~e of forty-two months post-treatment tocarcmoma. The 7 patients in this )resented in the following manner: Stage iage II, 4; and Stage III, 2. All patients tanaged according to the outline in Table Stage I patient has undergone surveilnly. The Stage II patients did not receive nt chemotherapy. The results of eytore,~surgery in the 2 patients with metaiisease revealed residual tumor in 1 and c tumor in the other. The patient with il disease required salvage chemotherapy. patients have NED an average of 88.9 ! post-treatment (6-173 mos). iryonal carcinoma. The 3 patients in )up all had low-volume Stage II disease, derwent therapy as outlined in Table IV, ng the use of adjuvant chemotherapy. re NED an average of 50.6 months from ent (14-85 mos). toma. The sole patient in this group ied with Stage I disease, and underwent orchiectomy. This patient has been folup only for one month postoperatively. itesticular rhabdomyosarcoma. There patients in this group; 3 presented with l: disease, and 4 presented with diffuse ases. All patients were treated according recommendations in Table V.6 The Stage ents underwent RPLND. The chemo-

I

If

III IV

Management Radical orchiectomy RPLND (may not be necessary 1I) Chemotherapy (VAC) x 1 year or VADRC or best from IttS III Radical orchieetomy RPLND Chemotherapy (VAC) x 1 year Radiotherapy (5,000 rad over 5 weeks) to retroperitoneum Radical orchiectomy Chemotherapy (VAC) Cytoreductive surgery and/or radiotherapy

KEY:RPLND = retroperitoneai node dissection; VAC = vincriskine, actinomyein D, eyclophosphamide; VADRC = vincristine, Adriamyein, eyelophosphamide; IRS I I I = International Rhabdomyosareoma Study III.

therapy regimen utilized was VAC (vincristine, aetinomycin D, and cyclophosphamide). All patients with metastatic disease had radiotherapy and eytoreductive surgery in addition to chemotherapy. Three patients, all with diffuse metastases at presentation, died an average of sixty-two months (47-79 mos) after treatment; the remaining 4 have NED after an average 38.8 months (2-81 mos). Gonadal stromal tumor. This patient presented with a Stage I lesion and underwent radical orehieetomy. He has NED fifty-nine months post-treatment. Comment An analysis was made of 25 pediatric testieular tumors seen over an eighteen-year period at Johns Hopkins. Germinal tumors comprised 68 percent of this group and nongerminal tumors 39. percent. Yolk sac tumors were the most common tumor seen in infancy. Radical orehieetomy is adequate for Stage I disease, although some groups would advocate adjuvant chemotherapy for children older than two years of age at presentation. ~ Higher stage lesions are treated with BPLND and chemotherapy. Embryonal carcinoma and teratoeareinoma were seen in the late teens. Stage I tumors were managed according to a surveillance protocol, where appropriate, to minimize the morbidity associated with RPLND in young men entering their reproductive years. Other patients required RPLND and, if necessary, chemotherapy. We have used adjuvant chemotherapy in some patients with low-volume Stage II disease, but this remains controversial. 7

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agents are the most extensively studied with r ~ Seminomas are rare in pediatric patients, s spect to male fertility. Impairment of testicul~! Surveillance for Stage I lesions has been advofunction is observed following the use o f e ~ cated by some, 9 but we have had no experience clophosphamide before or during puberty, a ~ with such at our institution. a safe dosage regimen has not bee There was only one teratoma in our series. for the immature or mature male These tumors have eomprised up to 14 percent PVB regimen is known to cause s of other series.I° This is essentially a benign tusterility in adults for several mont mor of childhood. Weissbach, Altwein, and years after treatment.iv The effect Stiens2 reviewed a series of 63 children with this motherapy on prepubertal and put diagnosis followed up to three years postorless well documented. ehieetomy; all free of disease. With increasing physician and l; Paratesticular rhabdomyosareomas were the ness of the need to bring serotal 1 most common nongerminal neoplasm seen. early attention of a urologist, and the approp~ I Stage I patients were managed with radical orate investigation and treatment of such p a t i e ~ chiectomy, RPLND, and chemotherapy. There in concert with oncologists, testieular t u m o r ~ is, however, some debate over the necessity for children should be curable with a m i n i m u m ~ RPLND in these low-stage patients. Olive, et morbidity. This will allow affected ehildre~i~ al. ~ have documented two-year survival in grow and experience a full and productive 1 ~ Stage I patients treated by orehiectomy and chemotherapy, which is equivalent to the surBaltimore, Maryland 2 ~ vival seen in patients whose treatment has also (DR. LE ONAR~}~ included RPLND. Gonadal stromal tumors were uncommon in References our series. These tumors are usually benign and 1. Wockel W, and Unger R: Zum Pro loealized. 12 Radical orehiectomy is usually Gesehwulste des Saugling--und Kindesall curative. If nodal metastases are detected at inichenschr 94:1080 (1969). tial staging, it would be appropriate to proceed 2. Weissbach L, Altwein JE, and Stiens 1 tumors in childhood, report of observations with RPLND and/or chemotherapy. These neoEur Urol 10:73 (1984). plasms may present with feminizing/maseu3. Mostofi FK: Testieular tumors: Epi, linizing syndromes due to hormone production and pathologic features, Cancer 32:1186 ( 4. Exelby PR: Testicular cancer in child by the tumor. (1980). Since the survival among children with pedi5. Griffin GC, et ah Yolk sac carcin atric testicular tumors is excellent, an attempt children, J Urol 137:954 (1987). 6. Cromie WJ, Raney RB Jr, and Duck must be made to reduce the morbidity of our rhabdomyosarcoma in children, J Urol 12~ current therapies. The avoidance of RPLND by 7. Vugrin D, et ah Adjuvant chemoth careful surveillance, where appropriate, is a matous cancer: "mini-VAB" regimen, long-t Overview p 20, Oct. 1984. step in the right direction. When RPLND is re8. Perry C~and Servadio C: Seminom~ quired, every attempt should be made to limit 124:932 (1980). the dissection to the ipsilateral side if microno9. Oliver RTD: Surveillance for Stage I agent cisplatinum for metastatic seminom~ dal disease is absent on frozen section. If a more Soc Clin Oncol 3:162 (1984). extensive dissection is required, a nerve-sparing 10. Hopkins TB, et ah The management procedure, as described by Jewett e t al. ~3 children, J Urol 120:96 (1978). 11. Olive D, et ah Para-aortic lymphad should be contemplated. sary in treatment of localized paratesticula Radiotherapy is a modality which may cause Cancer 54:1283 (1984). temporary impairment to spermatogenesis at 12. Brosman SA: Testicular tumors in Urology 13:581 (1979). testieular doses of 30-50 tad and may cause per13. Jewett MAS, et ah Retroperitoneal manent impairment of spermatogenesis and ditestis tumor with nerve-sparing for ejacula minished Leydig cell function at testicular doses (1988). 14. Ash P: The influence of radiation ol of 200-300 r a d ) 4 Thus, the use of radiotherapy Radiol 53:271 (1980). should not be taken lightly, and the adjunct of 15. Pedrick TJ, and Hoppe RT: Recovc testieular shielding for the remaining gonad following pelvic irradiation for Hodgkin'~ Oncol Biol Phys 12:117 (1986). should be strongly considered, t5 16. Shalet SM: Effects of cancer chen Chemotherapy also carries with it many toxfunction of patients, Cancer Treat Rev 7: ieities, and the concern about its eventual effect 17. Drasga RE, Einhorn LH, and Willi~ chemotherapy for testicular cancer, J Clin on s p e r m a t o g e n e s i s is real. The alkylating

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