A randomized trial of intensive versus minimal surveillance of patients with resected Dukes B2-C colorectal carcinoma.

BACKGROUND: Colorectal cancer is the third most common and the third most lethal cancer in both men and women in developed countries. About 75% of cases are first diagnosed when the disease is classified as localized or regional, undergo potentially curative treatment and enter a post-treatment surveillance program. Although such programs drain significant resources from health systems, empirical evidence of their efficacy is scanty. PATIENTS AND METHODS: Dukes B2-C colorectal cancer patients who had no evidence of disease at the end of their front-line treatment (surgery and adjuvant radiochemotherapy, if indicated) were eligible for the trial and randomized to two different surveillance programs. These programs differed greatly in the frequency of diagnostic imaging. They had similar schedules of physical examinations and carcinoembryonic antigen (CEA) assessments. Patients received baseline and yearly health-related quality-of-life (HR-QoL) questionnaires. Primary outcomes were overall survival (OS) and QoL. RESULTS: From 1998 to 2006, 1228 assessable patients were randomized, 933 with colon cancer and 295 with rectal cancer. More than 90% of patients had the expected number of diagnostic procedures. Median follow-up duration was 62 months [interquartile range (IQR) 51-86] in the minimal surveillance group and 62 months (IQR 50-85) in the intensive group. At primary analysis, 250 patients had recurred and 218 had died. Intensive surveillance anticipated recurrence, as shown by a significant difference in mean disease-free survival of 5.9 months. Comparison of OS curves of the whole intention-to-treat population showed no statistically significant differences. HR-QoL of life scores did not differ between regimens. CONCLUSION: Our findings support the conclusions of other randomized clinical trials, which show that early diagnosis of cancer recurrence is not associated with OS benefit. CLINICALTRIALSGOV: NCT02409472.

PD-1 blockade therapy in renal cell carcinoma: current studies and future promises.

RCC is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Evasion of immune surveillance, a process defined immune-editing, leads to malignant progression. The striking improvement of knowledge in immunology has led to the identification of immune checkpoints (such as CTLA-4 and PD-1), whose blockage enhances the antitumor immunity. The interaction between PD-1, an inducible inhibitory receptor expressed on lymphocytes and DCs, and PD-L1 ligand, expressed by tumor cells, results in a down-regulation of the T-cell response. Therefore, the PD-1/PD-L1 axis inhibition by targeted-antibodies, increasing the T-cell proliferation and cytotoxicity, represents a promising mechanism to stimulate the anti-tumor activity of the immune system, improving the outcomes of cancer patients. Several PD-1 and PD-L1 inhibitors have been evaluated in different tumor types, showing promising results. The interesting correlation between lymphocytes PD-1 expression and RCC advanced stage, grade and prognosis, as well as the selective PD-L1 expression by RCC tumor cells and its potential association with worse clinical outcomes, have led to the development of new anti PD-1/PD-L1 agents, alone or in combination with anti-angiogenic drugs or other immunotherapeutic approaches, for the treatment of RCC. In this review we discuss the role of PD-1/PD-L1 in RCC, focusing on the biological rationale, current clinical studies and promising therapeutic perspectives to target the PD-1 pathway.

Angiogenic and signalling proteins correlate with sensitivity to sequential treatment in renal cell cancer.

BACKGROUND: We aimed to study key signalling proteins involved in angiogenesis and proliferation on the response to inhibitors of tyrosine kinases and mammalian target of rapamycin in first- and in second-line treatment of renal cell carcinoma (RCC). METHODS: In a panel of human RCC tumours, in vitro and in nude mice, we evaluated the effect of sunitinib, sorafenib and everolimus, alone and in sequence, on tumour growth and expression of signalling proteins involved in proliferation and resistance to treatment. RESULTS: We demonstrated that, as single agents, sunitinib, sorafenib and everolimus share similar activity in inhibiting cell proliferation, signal transduction and vascular endothelial growth factor (VEGF) secretion in different RCC models, both in vitro and in tumour xenografts. Pre-treatment with sunitinib reduced the response to subsequent sunitinib and sorafenib but not to everolimus. Inability by sunitinib to persistently inhibit HIF-1, VEGF and pMAPK anticipated treatment resistance in xenografted tumours. After first-line sunitinib, second-line treatment with everolimus was more effective than either sorafenib or rechallenge with sunitinib in interfering with signalling proteins, VEGF and interleukin-8, translating into a significant advantage in tumour growth inhibition and mice survival. CONCLUSION: We demonstrated that a panel of angiogenic and signalling proteins can correlate with the onset of resistance to sunitinib and the activity of everolimus in second line.

Review of renal carcinoid tumor with focus on clinical and pathobiological aspects.

Renal carcinoid tumor is a rare neoplasm. In this article, we review this neoplasm with a focus on clinical and pathobiological aspects. The majority of patients present in the fourth to seventh decades, but there is no gender predilection. Clinically, patients with renal carcinoid tumor frequently present with abdominal, back or flank pain. This tumor is occassionally associated with horseshoe kidney and/or mature cystic teratoma located in the kidney. Macroscopically, these tumors are well demarcated with a lobulated appearance and yellow or tan-brown color cut surface. Microscopically, these tumors are composed of monomorphic round to polygonal cells with granular amphophilic to eosinophilic cytoplasm. Tumor cells are arranged in trabecular, ribbon-like, gyriform, insular, glandular and solid patterns. The nuclei are round to oval and with evenly distributed nuclear chromatin, frequently with a "salt and pepper"-pattern. Immunohistochemically, tumor cells demonstrate immuno-labeling for chromogranin A and synaptophysin. Ultrastructurally, the neoplastic cells contain abundant dense core neurosecretory granules. In previous genetic studies, abnormalities of chromosomes 3 or 13 have been reported. The clinical behavior of renal carcinoid tumors is variable, but is more indolent than most renal cell carcinomas. Further investigations are warranted in order to elucidate the critical genetic abnormalities responsible for the pathogenesis of this rare entity in renal neoplastic pathology.

Oncocytic papillary renal cell carcinoma: potential pitfall in small enucleation.

OBJECTIVE: We describe an emerging entity, recently recognized as a pitfall in the diagnostic practice among eosinophilic renal cell tumours. METHODS: A 60-year-old male underwent enucleation of a 1.2 cm nodule. Immunohistochemistry and FISH analysis were performed. RESULTS: Histology revealed a neoplasm composed of large cells with eosinophilic cytoplasm, Fuhrman grade 3, arranged in papillae. At the immunohistochemical level, cells showed positivity for AMACR and CD10. Fluorescence in situ hybridization (FISH) demonstrated gains of chromosomes 7 and 17 and loss of Y. A diagnosis of oncocytic papillary renal cell carcinoma was made. CONCLUSIONS: The distinction between renal oncocytoma and oncocytic papillary renal cell carcinoma is of substantial importance because of their different behaviour and prognosis, since the latter has malignant potential. Although the available evidence supporting tumour enucleation as the surgical treatment for renal cortical tumours < or = 4 cm, due to aforementioned clinicopathological features such tumours need to be evaluated using appropriate immunophenotypical and cytogenetic analyses.

Typical signs of oncocytic papillary renal cell carcinoma in everyday clinical praxis.

PURPOSE: Types 1 and 2 by Delahunt of papillary renal cell carcinoma (PRCC) are traditionally differentiated. An oncocytic variant of PRCC (O-PRCC) has recently been described. We compare clinical data of O-PRCC with other subtypes of PRCC such as the main tumour size, necrotic changes, presence of pseudocapsula and real extrarenal growth in retrospective study. METHODS: From 1/1992 to 10/2009, 1,398 patients with 1,436 renal tumours were surgically treated in our institution. PRCCs were described in 109 (7.6%). Among PRCC, O-PRCCs were in 12 (11%), PRCC type 1 in 86 (78.9%), PRCC type 2 in 8 (7.3%) and others in 3 (2.8%) cases. RESULTS: The patient's mean age with O-PRCC (M:F ratio = 2:1) was 67.5 +/- 10.9 versus 63.5 +/- 14.1 in type 1 and 57.9 +/- 5.7 in type 2, the mean tumour size was 35 +/- 12 mm versus 47 +/- 22 and 37 +/- 17, respectively. The follow-up of O-PRCC is 35.3 +/- 12.3 months and all cases are without recurrence. We did not find any pseudocapsula in O-PRCC but it was a major sign of PRCC type 1 (32.6%). Huge microscopic necrotic changes were described in 33.3% of O-PRCC, in 33.7% of PRCC type 1 and 62.5% of PRCC type 2. Extrarenal growth was found only in 16.7% O-PRCC versus 40.7% in PRCC type I. CONCLUSIONS: None of the O-PRCC had pseudocapsula and none had massive necroses in comparison of O-PRCC with PRCC types I and II. Extrarenal growth in O-PRCC is relatively rare. The malignant potential of O-PRCC is low.

Cathepsin-K immunoreactivity distinguishes MiTF/TFE family renal translocation carcinomas from other renal carcinomas.

The microphthalmia transcription factor/transcription factor E (TFE)-family translocation renal cell carcinomas bear specific translocations that result in overexpression of TFE3 or TFEB. TFE3 fusion gene product overexpression occurs as consequence of different translocations involving chromosome Xp11.2, whereas TFEB overexpression is the result of the specific translocation t(6;11)(p21;q12), which fuses the Alpha gene to TFEB. Both TFE3 and TFEB are closely related members of the microphthalmia transcription factor/TFE-family, which also includes TFEC and microphthalmia transcription factor. These transcription factors have overlapping transcriptional targets. Overexpression of microphthalmia transcription factor has been shown to mediate the expression of cathepsin-K in osteoclasts. We hypothesize that the overexpression of the related TFE3 fusion proteins and TFEB in translocation renal cell carcinomas may have the same effect. We studied cathepsin-K in 17 cytogenetically confirmed microphthalmia transcription factor/TFE-family translocation renal cell carcinomas. Seven cases showed a t(6;11)(p21;q12), ten cases showed translocations involving Xp11.2; five cases t(X;1)(p11;q21) resulting in a PRCC-TFE3 gene fusion; three cases t(X;1)(p11;p34) resulting in a PSF-TFE3 gene fusion, one t(X;17)(p11;q25) resulting in an ASPL-TFE3 gene fusion, and one t(X;3)(p11;q23) with an unknown TFE3 gene fusion. As control we analyzed cathepsin-K in 210 clear cell, 40 papillary, 25 chromophobe renal cell carcinomas and 30 oncocytomas. All seven TFEB translocation renal cell carcinomas were labeled for cathepsin-K. Among the cytogenetically confirmed TFE3 translocation renal cell carcinomas, 6 out of 10 were positive. None of the other renal neoplasms expressed cathepsin-K. We conclude the following: (1) cathepsin-K is consistently and strongly expressed in TFEB translocation renal cell carcinomas and in 6 of 10 TFE3 translocation renal cell carcinomas. (2) Cathepsin-K immunolabeling in both TFE3 and TFEB translocation renal cell carcinomas distinguishes these neoplasms from the more common adult renal cell carcinomas, and may be a specific marker of these neoplasms. (3) These results further support the concept that the overexpression of TFE3 or TFEB in these neoplasms activates the expression of genes normally regulated by microphthalmia transcription factor in other cell types.

Fluorescent cytogenetics of renal cell neoplasms.

Renal cell neoplasms are a heterogeneous group of tumours in terms of pathological features and prognostic behaviour. The genetics of these tumours may aid in correct diagnosis and accurate assessment of prognosis. In ambiguous cases it may be necessary to utilise new markers that are capable of further discerning renal cell neoplasms. Fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin-embedded tissue is an increasingly useful technique in the detection of many diagnostic chromosomal abnormalities, among which chromosomes 1, 2, 3p, 6, 7, 10, 17 and Y are the most common. The addition of FISH to histological evaluation improves the diagnostic accuracy of core biopsies from renal masses, which may have an important impact in clinical management of many cases due to newer therapeutic approaches, including cryo- or radiofrequency ablation, nephron-sparing surgeries and target therapies.

High curative resection rate with weekly cisplatin, 5-fluorouracil, epidoxorubicin, 6S-leucovorin, glutathione, and filgastrim in patients with locally advanced, unresectable gastric cancer: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD).

The aim of the present study was to evaluate the role of a weekly preoperative chemotherapy in locally advanced, unresectable gastric cancer. In all, 82 patients with an Eastern Oncology Cooperative Group PS

Prognostic value of renal cell carcinoma nuclear grading: multivariate analysis of 333 cases.

OBJECTIVE: To evaluate the independent predictive value of the nuclear grading system according to Fuhrman in relation to the disease-specific survival of patients with renal clear cell carcinoma. MATERIAL AND METHODS: 333 patients who underwent radical nephrectomy for renal clear cell carcinoma between 1983 and 1999 were evaluated. In all patients we retrospectively studied nuclear grading, average tumor size, multifocality, pathologic stage of primary tumor, vein invasion, lymph node involvement and distant metastases. The Kaplan-Meier method was applied to evaluate disease-specific survival rates. The log rank test was used to compare survival curves and for univariate analysis. The Cox proportional hazards model was used for the multivariate analysis. RESULTS: Histologic grade was G1 in 83 cases (25%), G2 in 117 cases (35%), G3 in 110 cases (33%) and G4 in 23 cases (7%). Our data showed that nuclear grading according to Fuhrman is related to medium tumor size (p < 0.0001), pathologic stage of cancer (p < 0.001), venous system invasion (p < 0.001), lymph node involvement (p < 0.001) and distant metastases (p < 0.001). The disease-specific survival after 5 and 10 years was 94 and 88%, respectively, in patients with G1, 86 and 75% in patients with G2, 59 and 40% in patients with G3 and 31% in patients with G4 (log rank p value < 0.0001). Multivariate analysis showed that nuclear grading by Fuhrman has a prognostic independent predictive value (hazard ratio = 1.8461, p = 0.002). CONCLUSIONS: Nuclear grading is an important independent predictive factor of disease-specific survival in patients with renal cell carcinoma.

Parvalbumin is constantly expressed in chromophobe renal carcinoma.

Chromophobe renal carcinoma is composed of neoplastic cell showing several features similar to those found in the intercalated cells of the collecting ducts. Because the distal nephron expresses calcium-binding proteins playing a role in calcium homeostasis, we reasoned that these proteins could be expressed by chromophobe carcinoma and therefore represent a diagnostic marker. We studied the immunohistochemical expression of different calcium-binding proteins (parvalbumin, calbindin-D28K, and calretinin) in 140 renal tumors, including 75 conventional (clear cell) carcinomas, 32 chromophobe carcinomas, 17 papillary renal cell carcinomas, and 16 oncocytomas. Parvalbumin was strongly positive in all primary chromophobe carcinomas and in one pancreatic metastasis; it was positive in 11 of 16 oncocytomas and absent in conventional (clear cell) and papillary renal cell carcinomas, either primary or metastatic. Calbindin-D28K and calretinin were negative in all tumors, with the exception of two chromophobe carcinomas, four oncocytomas, and two papillary renal cell carcinomas showing inconspicuous calretinin expression. Our data demonstrate that parvalbumin may be a suitable marker for distinguishing primary and metastatic chromophobe carcinoma from conventional (clear cell) and papillary renal cell carcinoma. Moreover, they suggest a relationship between chromophobe renal carcinoma and renal oncocytoma and indicate that chromophobe carcinoma exhibits differentiation toward the collecting-duct phenotype.

[Lymphoepithelioma-like carcinoma of the esophagus: description of a case]. / Carcinoma simil linfoepitelioma (LELC) dell'esofago: descrizione di un caso.

The authors describe a case of lymphoepithelioma-like carcinoma (LELC) of the esophagus occurring in a 77-year-old man. To date, 13 cases have been described in the literature, all in natives of Japan. Histological features, immunohistochemical findings and differential diagnosis are discussed. In our case epithelial neoplastic cells were completely negative for the EBV genome.

Molecular analysis of CDKN1C and TP53 in sporadic adrenal tumors.

OBJECTIVE: To evaluate the roles of the CDKN1C (P57KIP2) gene, which encodes for the cyclin-dependent kinase inhibitor CDNC, and the TP53 tumor suppressor gene in adrenal tumorigenesis, as a means of investigating the molecular basis of sporadic adrenal tumors, which is unknown. DESIGN: Screening for the presence CDKN1C and TP53 mutations and analyzing the expression pattern of CDNC, P53 and its downstream effector CDN1 (P21WAF1/CIP1) in a series of 79 sporadic adrenal tumors. METHODS: Single-strand conformation polymorphism and sequencing were used for mutation analysis of CDKN1C and TP53 in blood and adrenal tissue samples. In a subgroup of 48 tissues, CDKN1C expression was evaluated by RT-PCR and immunohistochemistry. Immunohistochemical analysis of P53 and CDN1 was performed. RESULTS: No somatic mutations of CDKN1C were found in the tumors analyzed, in spite of low/absent CDNC expression in adrenocortical adenomas and carcinomas. Mutations in the TP53 gene were present in 70% of adrenocortical carcinomas, associated with abnormal P53 and CDN1 expression, but not in benign neoplasms. In the normal adrenal cortex, CDNC expression was strictly nuclear and confined to the cortical zone (i.e. zona glomerulosa and reticularis), with no staining in the medulla. CONCLUSIONS: Mutations in the TP53 gene are frequent in adrenocortical carcinomas and might be used as a marker of malignancy. In the normal adrenal cortex, the zone-specific pattern of expression of CDNC suggests a role in adrenal differentiation.

Primary lymphoma of the epididymis: case report and review of the literature.

OBJECTIVE: To report an extremely rare clinical pathological observation of a case of primary lymphoma of the epididymis, without testicular or systemic involvement, and to update the relevant literature. MATERIALS AND METHODS: A 25-year-old white male patient complaining of right scrotal pain was referred to our department. Clinical examination detected a hard painful mass at the right epididymal head. Epididymitis was diagnosed and conservative therapy with antibiotics and anti-inflammatory drugs was given. After 2 months of therapy the patient was admitted to our department because a tumor was suspected. Tumor markers were normal. Right scrotal exploration was performed through a standard inguinal incision. The epididymal head was completely replaced by a hard white mass. Fresh frozen sections indicated a malignant tumor. Right radical orchiectomy was performed. RESULTS: High-grade primary epididymal non-Hodgkin's lymphoma with diffuse large cells (group G according to the Working Formulation) was diagnosed. Clinical pathological staging detected stage IE (extranodal) primary epididymal lymphoma. The patient was referred to the Hematologic Unit for combined chemotherapy, according to the VACOP-B protocol. After an 18-month follow-up the patient is well and disease free. CONCLUSIONS: When an epididymal mass does not benefit from medical treatment, scrotal exploration and fresh frozen sections of the lesion should be done. The possible bilateral involvement by primary epididymal lymphoma has to be kept in mind. Radical orchiectomy is the treatment of choice for primary lymphoma of the epididymis. Adjuvant chemotherapy is indicated in high-grade malignant lymphoma. Prognostic parameters of the disease may be the grade of malignancy and the size of the tumor.

Abdominopelvic sarcoma of perivascular epithelioid cells. Report of four cases in young women, one with tuberous sclerosis.

The perivascular epithelioid cell has been proposed to be the unifying proliferating cell type in a number of lesions such as angiomyolipoma, lymphangiomyomatosis, clear cell "sugar" tumor and renal capsuloma. With the exception of rare examples of angiomyolipoma, they are non-metastasizing. We report four examples of a new member of this family of perivascular epithelioid cell neoplasms that occur in abdominopelvic location and show metastatic properties. The patients, all women, were aged 19 to 41 years (mean, 32), and presented with a tumor mass involving the serosa of the ileum, uterus or pelvic cavity. Morphologically, the tumors were composed of sheets of large polygonal cells with glycogen-rich clear or eosinophilic cytoplasm and moderately pleomorphic nuclei, traversed by a delicate vasculature, mimicking clear cell carcinoma. There were areas of coagulative necrosis and occasional mitotic figures. Intracytoplasmic brown pigment was present in two cases. Spindly cells, smooth muscle and fat were absent. Lymphovascular invasion was present in all, lymph node metastasis was documented in two and metastasis to the ovary was present in one case. Two patients developed widespread metastatic disease after 10 and 28 months from diagnosis. One patient showed the clinical signs of tuberous sclerosis. In spite of the epithelial-like appearance, the tumor cells were negative for epithelial markers but were strongly positive with the melanogenesis-related marker HMB45. Another melanogenesis marker (MART-1) was positive in two cases. Other markers including S-100 protein, vimentin, muscle-specific actin, desmin and chromogranin A were negative. Thus, these tumors are not readily classifiable in the existing schema of known entities, and show overlapping morpho-phenotypic features of clear cell "sugar" tumor of the lung and epithelioid angiomyolipoma. We consider them as sarcomas composed of a pure population of uncommitted perivascular epithelioid cell, that lack modulation toward smooth muscle or adipose cells.

Long-term results of aggressive surgical treatment of primary and recurrent retroperitoneal liposarcomas.

The aim of this study was to establish the role of surgery in the treatment of retroperitoneal liposarcomas. Data concerning 28 patients submitted to surgery for retroperitoneal liposarcoma in our department over the period from 1972 to 1999 were reviewed retrospectively and analysed. Seventy-four operations were performed; in 54% of the operations it was necessary to resect contiguous organs (kidney 60%, colon 50%, adrenal gland 35%). In 89%, grossly curative resection was achieved at the first operation; 20 patients had at least one local recurrence after first operation (median time interval: 22 months). The mean follow-up was 80 months; median survival time was 51 months and 5-year actuarial survival time 51%. Patients with low-grade liposarcoma showed a statistically significant improvement (P < 0.001) in median survival (153 months) versus those with medium- (37 months) and high-grade sarcomas (8 months). At present surgery is still the treatment of choice in the treatment of primary and recurrent liposarcoma; in the case of low-grade liposarcomas especially, an aggressive surgical approach can result in long-term survival.

Nephrogenic adenoma of the urinary bladder: our experience and review of the literature.

OBJECTIVE: To assess our experience in the treatment and clinical outcome of bladder nephrogenic adenoma (NA) updating and reviewing the literature concerning this issue. PATIENTS AND METHODS: From September 1976 to June 1999, bladder NA was diagnosed in 8 patients: 6 men and 2 women with a 3:1 male ratio, aged 26-80 (mean 58.3) years. Follow-up ranged from 4 to 194 (mean 93.5) months. RESULTS: NA was associated with transitional cell carcinoma in 3 cases. Predisposing factors were assessed in all patients. Previous surgery of the lower urinary tract was detected in 5 cases: ureterocystoneostomy in 2, partial cystectomy in 1, repair of vesicouterine fistula in 1, and multiple urethroplasties in 1. Previous endoscopic treatments were carried out in 2 patients, transurethral resection of the prostate in 1 and repeated transurethral resection of the vesicle in the other. A history of intravesical instillation of bacillus Calmette-Guérin was assessed in 1 case. Patients complained of irritative voiding symptoms in 6 cases and hematuria in 2. Endoscopically, the lesions appeared polypoid and multifocal in 5 patients, and flat and single in 3. The lesions were removed endoscopically, providing relief of symptoms in all cases. Histopathology assessed the diagnosis of nephrogenic adenoma, detecting focal atypic cells in 1 case only. Five patients (63%) relapsed 2-24 months after management. Recurrences were also treated endoscopically. CONCLUSIONS: Clinical and endoscopic features of bladder NA are not specific, simulating urothelial carcinoma or chronic cystitis. Endoscopic management allows accurate histological diagnosis and provides long-lasting relief of symptoms. NA needs careful and long-term follow-up, because of the high risk of recurrences and the potential neoplastic degeneration of the metaplastic urothelium.

[Histopathologic risk factors in patients with non-seminomatous germ tumors of the testis in clinical stage 1. Retrospective study of 75 patients]. / Fattori istopatologici di rischio in pazienti con tumore germinale non seminomatoso del testicolo in stadio clinico 1. Uno studio retrospettivo su 75 pazienti.

OBJECTIVES: This retrospective study was performed to evaluate histopathologic prognostic risk factors in 75 patients on clinical stage 1 nonseminomatous germ cell cancer of the testis (NSGCTT). METHODS: From September 1976 to February 2000 we operated on 75 patients for NSGCTT on clinical stage 1 disease. Average age was 29.5 years (range 16-71). After orchiectomy, therapeutic options included retroperitoneal lymph node dissection (RLND) for 44 patients (58.6%), surveillance for 26 (34.6%) and neoadjuvant chemotherapy for 5 (6.6%). Testis primary tumor samples were assessed for studying prognostic risk factors that included vascular and/or lymphatic invasion (IV/IL+), percentage of embryonal carcinoma (%EC) and absence of yolk sac tumor (YS-). RESULTS: All patients were alive and disease-free. The average age follow-up was 84.5 months (range 1-254). Relapses occurred in 11 (14.6%) patients after an average follow-up of 9.09 months (range 3-24). Prognostic risk factors were detected as follows: IV/IL+ in 17 cases (22.7%), (50-80%) EC in 23 (30.6%), CE% > 80 in 23 (30.6%), YS- in 55 (72%). In 8 (10.6%) patients there was not any prognostic risk factor. Disease relapse related to prognostic risk factors was detected as follows: 18.1% for VI/LI, 90.9% for EC% > 50 (27.2% for 50-80% EC and 63.6% for CE% > 80) and 90.9% for YS-. Relapsing rates between patients with EC% > 80 and 50-80% EC resulted statistically significant (p = 0.02, odds ratio = 12.25). Relapsing rates between patients on surveillance and those who underwent RLND was next to be significant (p = 0.05, odds ratio 3.68). CONCLUSIONS: EC% > 80 is a prognostic risk factor for disease relapse in patients with clinical stage 1 NSGCT who are selected in a high risk group requiring RPLND or neoadjuvant chemotherapy as therapeutical option.