Melissa R Kaufman MD PhD Sam S Chang MD

Vanderbilt University, Department of Urologie Surgery, A-1302 Medical Center North, Nashville, TN 37232, USA Testicular germ-cell carcinoma, although a rare disease accounting for only 1 to 2 of all neoplasms in men, is distinguished by being the most common malignancy afflicting young men under 45 years of age 1,2 . The worldwide incidence of testicular cancer has shown an alarming increase during the past 40 years 3,4 , with more than 8000 cases predicted in the United States in 2005 5 ....

Which regimen should be considered standard of care for goodrisk metastatic germ cell tumor

The clinician treating the patient who has good-risk metastatic GCT has an initial decision to make should the patient be treated with BEP for three cycles or EP for four cycles At the 2003 meeting of the American Society of Clinical Oncology (ASCO), Culine and colleagues 16 presented a randomized trial comparing three cycles of BEP to four cycles of EP in patients who had good-risk metastatic GCT. The primary endpoint of the trial was a ''favorable response rate'' (FRR), defined as...

Timely Diagnosis of Testicular Cancer

Division of Urologic Surgery, Duke Prostate Center, Duke University Medical Center, Screening for testicular cancer, like any true disease-screening effort, involves evaluation of an asymptomatic population for the disease in question. The goal of any cancer screening effort is to diagnose the disease at an early, more easily treatable stage with the ultimate goal of improving the disease-specific survival and minimizing treatment morbidity. Screening efforts can also be directed toward...

ITGCN of the Testis Contralateral Testicular Biopsy and Bilateral Testicular Cancer

Karellas, MDa, Ivan Damjanov, MD, PhDb, Jeffery M. Holzbeierlein, MDc* aDepartment of Surgery, Division of Urology, Memorial Sloan Kettering Cancer Center, 353 E. 68th Street, New York, NY 10021, USA bDepartment of Pathology, University of Kansas School of Medicine, 2017 Wahl Hall West, Mailstop 3045, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA cDepartment of Urology, University of Kansas School of Medicine, 5017 Sudler Hall, Mailstop 3016, 3901 Rainbow Boulevard, Kansas City,...

Management of Clinical Stage I Nonseminomatous Germ Cell Testicular Cancer

Stephenson, MDb, Timothy Gilligan, MDa, Eric A. Klein, MDb* aDepartment of Solid Tumor Oncology, Taussig Cancer Center, Cleveland Clinic Foundation, 9500 Euclid Avenue, R35, Cleveland, OH 44195-0001, USA hSection of Urologic Oncology, Glickman Urological Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Desk A100, Cleveland, OH 44195-0001, USA Approximately one third of patients who have nonseminomatous germ cell testicular cancer (NSGCT) have clinical...

Late effects of cisplatinbased chemotherapy

For many patients who have GCT, cisplatin-based chemotherapy is required for cure. Because patients who have GCT are usually young and are likely to become long-term survivors, issues related to long-term complications of this treatment are important. Cisplatin-based chemotherapy for patients who have GCT may be associated with long-term consequences that may affect several organ systems (Box 3). A review concerning the medical management of the long-term GCT survivor has recently been...

Chemotherapy programs in advanced disease

Germ cell tumors (GCT) are considered a model for curable cancer based on the successful treatment of metastatic disease with cisplatin-containing chemotherapy (More than 90 of newly diagnosed GCT patients are cured.) 1 . Accumulated data from phase II and III trials show that treatment with cisplatin, vinblastine, and bleomycin (VAB series, PVB) achieves a durable response in 70 to 80 of patients who have metastatic GCT 2-5 . Treatment-related toxicity was substantial in these regimens,...

Early trials of adjuvant chemotherapy

Before the advent of cisplatin-based chemotherapy, patients who had completely resected node-positive disease (pN1 and pN2) were offered either no adjuvant chemotherapy, minimally effective chemotherapy, or postoperative radiotherapy 15,16 . The relapse rate in this patient population was 20 to 70 , with most studies showing a relapse rate of 50 to 60 17 . As cisplatin-based chemotherapeutic regimens were found to be effective in stage III GCT, these regimens were studied in the adjuvant...

Rationale for surgery after chemotherapy

The rationale for post-chemotherapy RPLND is based on (1) the established diagnostic role, (2) the therapeutic efficacy of the procedure, (3) the natural history of residual masses, and (4) the decreasing morbidity of these surgical procedures. With regard to the diagnostic role of RPLND, surgical resection after chemotherapy yields one of the following histologic findings (1) pure necrosis or fibrosis, (2) teratoma with or without necrosis fibrosis, (3) viable germ cell carcinoma to any...

Classification of postchemotherapy retroperitoneal lymph node dissection

RPLND constitutes most surgical resection after systemic chemotherapy for advanced testic-ular carcinoma. The Indiana classification of RPLND categorizes different types of RPLND to facilitate assessment of the outcome in this setting 25 . Standard RPLND refers to patients after induction chemotherapy who have disseminated testicular cancer and present with residual radiographic disease in the retroperitoneum and normalized STM. Salvage RPLND refers to cases that are status post second-line...

Patient selection and indications for postchemotherapy retroperitoneal lymph node dissection

The current indications for surgery after initial systemic chemotherapy depend on several factors, including (1) histology of primary tumor, (2) the presence and size of residual radiographic masses, and (3) the known distributions and natural history of the various post-chemotherapy mass histologies. Others have used predictive models to calculate the likelihood of viable GCT, using these models to guide therapeutic decision-making 26-29 . The approach to residual masses after chemotherapy in...

Extent of surgery after chemotherapy

Historically, RPLND encompassed a full bilateral suprahilar dissection from ureter to ureter, from the crus of the diaphragm to the bifurcation of the common iliac arteries 63 . In the early 1980s it was shown that right testicular tumors were more likely to have metastatic tumor deposits in the interaortocaval zone, just below the left renal vein. Left-sided primary testicular tumors were more likely to have tumor spread in the preaortic and left para-aortic areas. The right and left...

Role of adjuvant chemotherapy

Postoperative chemotherapy appears to improve disease-free recurrence in patients with germ-cell cancer after first-line chemotherapy but not when given after second-line chemotherapy 2 . This lack of benefit in the salvage setting is thought to be secondary to the development of tumor che-moresistance. Persistently elevated serum tumor markers after systemic therapy implies a degree of chemoresistance and in the current series adjuvant chemotherapy did not improve patient survival. In the...

Indications for postchemotherapy surgery

Generally accepted indications for postchemo-therapy resection include patients who have residual radiographic disease and normalized serum tumor markers (a-fetoprotein and human chorionic gonadotropin). The added benefit of resection must be weighed against the morbidity of additional surgery. Removal of residual viable cancer offers therapeutic benefit and can be curative in a subset of patients. The excision of residual teratoma is also beneficial because teratoma possesses the potential to...

Case finding and testicular selfexamination

Case finding is similar to screening but involves detecting disease in a symptomatic patient or one who presents to the physician with concerns that he might have the disease in question. As can be surmised from the prior discussion regarding delay in diagnosis, case finding for testicular cancer is critically important for the man who presents with scrotal symptoms, such as a mass, pain, or swelling, or after trauma. As previously noted, testicular cancer should not be overlooked when initial...

Clinical implications of incomplete surgical resection

Several investigators have clearly and consistently shown the prognostic significance of complete resection of retroperitoneal disease 3,7 . Stenning and colleagues 35 reported that the risk of disease progression for patients without complete resection of all residual masses was approximately four times the risk for those with complete resection 35,36 . Data from Indiana University and more recently, MSKCC, clearly show that patients requiring reoperative retroperitoneal surgery are...

Primary chemotherapy

In distinction to adjuvant chemotherapy given to men who have PS II disease after RPLND, primary chemotherapy refers to treatment administered to men who have CS I NSGCT after orchiectomy. The goal of primary chemotherapy is to minimize the risk for relapse and to allow men to avoid RPLND and the longer course of chemotherapy administered for patients who relapse on surveillance. The rationale underlying this approach derives from the 30 relapse rate seen during surveillance and the 20 to 25...

Stage I seminoma surveillance versus treatment

The prognosis for stage I seminoma is excellent, with long-term cure rates approaching 100 30-33 . Stage I is that most commonly assigned to new presentations of seminoma, making up 70 of all incident cases 34 . Seminoma is highly radiosensitive and chemosensitive. Traditionally stage I disease has been most commonly managed with orchidectomy and adjuvant radiotherapy. Of clinical stage I disease, a percentage of patients have occult micrometastases undetectable by imaging. This observation is...

Predicting histology in nonretroperitoneal residual masses

The ability to predict the histology of post-chemotherapy residual masses, both within and outside the retroperitoneum, is important because the prognosis and management differ for tumors composed of viable GCT, teratoma, and necrosis. For masses within the retroperitoneum, logistic regression analysis has attempted to identify parameters that are predictive of necrosis. This identification is critical because additional surgery, although therapeutic for teratoma and viable GCT, is not...

References

Testicular germ-cell cancer. N Engl J Med 1997 337(4) 242-53. 2 Motzer RJ, Geller NL, Tan CC, et al. Salvage chemotherapy for patients with germ cell tumors. The Memorial Sloan-Kettering Cancer Center experience (1979-1989). Cancer 1991 67(5) 1305-10. 3 Germa-Lluch JR, Begent RH, Bagshawe KD. Tumour-marker levels and prognosis in malignant teratoma of the testis. Br J Cancer 1980 42(6) 850-5. 4 Bosl GJ, Geller NL, Cirrincione C, et al. Multivari-ate analysis of prognostic...

Etoposide and cisplatin adjuvant chemotherapy

In patients who have high-volume metastases, the use of well-tolerated adjuvant chemotherapy should be strongly considered. Substitution of etoposide for vinblastine in two randomized studies of standard therapy for good- and poor-risk patients who had disseminated NSGCT showed less toxicity and equivalent or superior efficacy 7,29,30 . Based on the efficacy and tolerability of four cycles of EP in patients who had disseminated GCT, a prospective trial of two cycles of EP was conducted in the...

Morbidity of retroperitoneal lymph node dissection after chemotherapy

RPLND after induction chemotherapy is a challenging operation because of the complexity of the procedure and the severe desmoplastic reaction from prior exposure to chemotherapeutic agents. The morbidity of post-chemotherapy RPLND ranges from 18 to 29 in the standard group 23,79,80 and up to 39 in the complicated RPLND group 81,82 . Perioperative complications may be subdivided into pulmonary, infectious, lymphatic, vascular, neurologic, and gastrointestinal complications. Pulmonary-related...

Risk factors for ITGCN development

There are several conditions that are believed to predispose an individual to the development of TGCTs. For example, in a patient with a testicular tumor, the contralateral testicle has a 25-fold increased relative risk (RR) of developing another tumor. The finding of contralateral testicular microlithiasis on ultrasound in a patient who has had a TGCT has been reported to increase the risk of having ITGCN by approximately 30 times 23 . The clinical importance of testicular microlithiasis...

Importance of early detection

The common sense importance of early detection and diagnosis of testicular cancer has been known for many years. Before the advent of curative therapy, this was one of the few ways (if not the only way) to prevent deaths in the usually young and otherwise healthy men who are affected. In the current era of effective chemotherapy, most (but not all) patients can be salvaged despite delays in diagnosis and, consequently, more advanced disease 2 . This salvage, however, generally requires much...

Relationship between infertility and testicular cancer

Theoretically, any cause that adversely affects testicular function can result in infertility and testicular tumorigenesis. Many studies evaluating testicular cancer have documented an increased risk for abnormal semen analysis parameters in patients who have testicular tumors. Of 15 patients presenting with germ cell tumors, 10 (66 ) had evidence of abnormal spermatogenesis, including poor motility, low sperm concentration, or low semen volume 5 . Conversely, studies have been published...

Prognostic factors

Determination of treatment based on pretreat-ment clinical characteristics was proposed early in the development of effective chemotherapy 3 . In the 1980s, several major groups identified factors * Department of Medical Oncology, Peter MacCallum Cancer Centre, 7 St Andrews Place, East Melbourne, VIC 3002, Australia. E-mail address guy.toner petermac.org predictive of a poor outcome, including tumor marker elevation, extent or bulk of metastatic disease, visceral organ involvement,...

Surgical complications

The gold standard for treatment of all primary tumors is unilateral radical inguinal orchiectomy * Corresponding author. E-mail address sam.chang vanderbilt.edu (S.S. Chang). with high ligation of the spermatic cord 10 . Inguinal orchiectomy provides not only histopatho-logic and staging information but also local control of the neoplasm and, potentially, a complete cure for patients with testis-confined disease. Although morbidity is limited, the most frequent complication from inguinal...

Acknowlegements

The authors thank Carol Pearce for her editing assistance. 1 DeVita VT, Hellman S, Rosenberg SA, editors. Cancer principles and practice of oncology. 7th edition. Philadelphia Williams and Wilkins 2005. 2 Cheng E, Cvitkovic E, Wittes RE, et al. Germ cell tumors (II) VAB II in metastatic testicular cancer. Cancer 1978 42 2162-8. 3 Einhorn LH, Donohue J. Cis-diamminedichloropla-tinum, vinblastine, and bleomycin combination chemotherapy in disseminated testicular cancer. Ann Intern Med 1977 87...

Sarah M Lambert MD Harry Fisch MD

Male Reproductive Center, Department of Urology, Columbia University, College of Physicians and Surgeons, New York Presbyterian Hospital, 944 Park Avenue, New York, NY 10028, USA Testicular cancer is one of the few malignancies that affect men in their reproductive years. Testicular cancer represents the most common solid organ tumor in young men between 20 and 35 years of age. The National Cancer Society predicted that 8250 new cases of testicular cancer would be diagnosed in the United States...

Pathology of teratoma

Neonatal Kidney

Teratoma is a neoplasm of germ-cell origin that is composed of several types of tissue * Corresponding author. Department of Urology, Sidney Kimmel Center for Prostate and Urologie Cancers, 353 East 68th Street, New York, NY 10021. E-mail address sheinfej mskcc.org (J. Sheinfeld). representing different germinal layers (endoderm, mesoderm, ectoderm), forming somatic-type tissue in various stages of maturation and differentiation. Based on findings of genetic studies, it is now recommended to...

Joel Sheinfeld MDab Pramod Sogani Md Facsab

ADepartment of Urology, Sidney Kimmel Center for Prostate and Urologie Cancers, Memorial Sloan-Kettering Cancer Center, 353 East 68th Street, New York, NY 10021, USA bDepartment of Urology, Weill College of Medicine, 525 East 68th Street, New York, NY 10021, USA The management of patients with testicular cancer has evolved significantly over the past 25 years, largely as a result of the ability of cisplatin-based chemotherapy to cure advanced disease 1 . The appropriate integration of systemic...

Complications of chemotherapy

Before the era of effective chemotherapy, disseminated testicular cancer was uniformly fatal 51 . Fortunately, new therapeutics emerged that have changed the face of testicular cancer 52,53 . The current regimen for chemotherapeutic intervention provides exceptional survival, greater than 80 , even in highly advanced stages of tes-ticular neoplasms 54 . The standard of treatment for patients with disseminated germ-cell tumors is currently a regimen of bleomycin, an antibiotic with...

Issues concerning contralateral testicular biopsy

Contralateral testicular biopsy in patients with unilateral testis cancer at the time of orchiectomy for the primary tumor is a highly controversial subject. Biopsy patterns differ among countries as well as between high- and low-volume care centers. Contralateral testis biopsy at the time of orchiectomy for unilateral tumor is routinely performed in most large centers in Denmark, Germany, and Austria 32 . Among German urologists at high-volume centers (> 20 cases year), 95 of patients...

Preservation and restoration of fertility

Currently, men who have testicular cancer have many options available to preserve fertility and potential paternity. The availability of sperm cryopreservation, advances in assisted reproductive techniques (ART), and testicular sperm extraction (TESE) provide the potential for fatherhood for men unable to conceive as a result of testicular cancer treatments. It should be noted that men who have testicular cancer status post chemotherapy have decreased fertilization rates per in vitro...

Retroperitoneal lymph node dissection

In the united States and parts of Europe, the conventional approach to patients who have CS I NSGCT has been bilateral infrahilar RPLND. The main factors in favor of RPLND are that the retroperitoneum is the initial site of metastatic spread in 70 to 80 of patients who have occult metastasis, retroperitoneal lymph nodes often harbor chemotherapy-resistant teratomas, and there is a low rate of relapse following RPLND 12 . The argument for RPLND is thus that the therapeutic focus for CS I...