Predictors of recurrent clinical stage I nonseminomatous testicular cancer A prospective clinicopathologic study

A prospective clinicopathologic study of 60 patients with clinical Stage I nonseminomatous testicular cancer (NSTC) has been reported. Of 60 patients with clinical Stage I NSTC who underwent retroperitoneal lymphadenectomy (RPLA), 6 proved to be Stage II, a staging error of 10 per cent. In 4 patients of the remaining 54, metastases developed in the lungs. In 1 patient metastases developed both in the lung and in retroperitoneal lymph nodes. There was no death in these groups of patients. These 10 patients with staging error and/or recurrence after RPLA have been analyzed for the causes of treatment failure utilizing a set of prognostic criteria (tumor cell type, vascular or lymphatic invasion in the primary tumor, extension to the spermatic cord, and size of the primary tumors). It has been concluded that embryonal carcinoma (P less than 0.001), vascular invasion (P less than 0.001), and extension of the tumor to the spermatic cord (P less than 0.001) are significant predictors of metastases and/or recurrence after RPLA in Stage I NSTC. A plan of management is suggested based on these criteria.     

SURVIVAL AND PROGNOSTIC FACTORS ASSOCIATED WITH METASTATIC NONSEMINOMATOUS TESTICULAR AND EXTRAGONADAL GERM CELL TUMORS

To assess prognostic factors in patients with metastatic nonseminomatous germ cell tumors, 50 patients with testicular germ cell tumors (TGCT) and 10'patients with extragonadal germ cell tumors (EGGCT) were studied. The clinical staging system for testicular tumors proposed by The Japanese Urological Association and The Japanese Pathological Society was applied. All patients with EGGCT had primary sites in the retroperitoneum. The 3-year survival rates of TGCT and EGGCT were 71.9% and 60.0%, respectively, and there were no differences in patient characteristics. Patients had significantly worse survival rates if the following applied: choriocarcinoma in the primary tumors, serum lactate dehydrogenase level greater than twice the upper limit of normal, liver, brain, or mediastinal metastases, or retroperitoneal tumors greater than 10 cm. It was concluded that the poor-risk group could be defined as those patients having lymph nodal disease only (stage II or III A) with retroperitoneal tumors greater than 10 cm, having pulmonary disease (stage III B) with retroperitoneal tumors greater than 5 cm, or liver, bone or brain metastases (stage III C), and these criteria will predict the prognosis for patients with advanced disease because the good-risk patients (53% of all patients) and poor-risk patients (47%) in this study had 3-year survival rates of 88.7% and 49.7% (p less than 0.0001), and complete response rates of 96.9% and 60.7% (p less than 0.005), respectively.     

alpha-Catenin expression pattern and DNA image-analysis cytometry have no additional value over primary histology in clinical stage I nonseminomatous testicular cancer

OBJECTIVE: To determine whether the alpha-catenin expression pattern and DNA content have additional value over primary tumour histology, including information on vascular invasion and tunica albuginea invasion, in detecting occult metastasis in patients with clinical stage I nonseminomatous germ cell tumours of the testis (NSGCT). PATIENTS AND METHODS: Fifty consecutive patients with clinical stage I NSGCT underwent retroperitoneal lymphadenectomy (RPLND) between 1986 and 1992. The orchidectomy specimens were histopathologically reviewed and immunohistochemically stained with mouse monoclonal anti-alpha-catenin antibody. The presence of an aberrant or negative staining in >10% of the malignant cells was defined as abnormal; in all other cases tumours were classified as normal. Furthermore, intact nuclei were isolated from 50 microm thick paraffin sections of the primary tumour, Feulgen stained, and analysed with an image-analysis system. RESULTS: Of the 50 patients, 14 had positive retroperitoneal nodes (stage IIa, 28%), one pathologically staged I patient developed a lung metastasis (stage IV) within 3 months of RPLND. Univariate analysis showed that the presence of embryonal cell carcinoma, vascular invasion and tunica albuginea invasion were predictive for occult metastases. In multivariate logistic regression analysis only vascular and tunica albuginea invasion were significant. All 11 patients with no embryonal cell carcinoma in the primary tumour were classified as having pathological stage I disease. Also, the tumours which were DNA-diploid (three) or DNA-polyploid (two) were pathologically stage I. In screening for occult metastases the DNA content and the alpha-catenin expression pattern had no additional value. CONCLUSION: Vascular and tunica albuginea invasion have prognostic value in identifying patients with clinical stage I NSGCT at high risk for occult retroperitoneal disease. In contrast, the absence of embryonal cell carcinoma could predict all patients at low risk for metastasis. The DNA-ploidy also identified patients at low risk. Other DNA-analyses and the alpha-catenin expression pattern provided no additional information. Further studies are recommended to identify patients who are at low or high risk for metastasis.     

Primary chemotherapy followed by a selective retroperitoneal lymphadenectomy in the management of clinical stage II testicular carcinoma: a preliminary report

In 28 patients with primary clinical stage II testicular carcinoma (retroperitoneal mass of less than 10 cm. in diameter) or persistently elevated levels of serum biomarkers after orchiectomy primary chemotherapy was administered followed by selective lymphadenectomy for patients with a persistent retroperitoneal mass. Of the patients 21 were treated with cyclophosphamide, doxorubicin, cisplatin/vinblastine and bleomycin, and 7 who were not candidates for this regimen received less aggressive chemotherapy. All 28 patients were free of disease after a mean followup of 93.6 weeks and a median of 89 weeks (range 28 to 199.5 weeks). No patient who achieved complete remission has had relapse. Of the 28 patients 1 had a seminoma and an elevated alpha-fetoprotein level, 15 had embryonal carcinoma (Dixon-Moore category II) and 12 had teratocarcinomas (Dixon-Moore category IV). Only 1 of the 15 patients with embryonal carcinoma required surgical exploration for a persistent radiographic abnormality, whereas 6 of the 12 patients with Dixon-Moore category IV tumors required surgical exploration (p less than 0.0147). This delayed approach did not increase surgical complications. Our experience with primary chemotherapy followed by selective lymphadenectomy for stage II testicular carcinoma resulted in universal survival. Only 8 of the 28 patients (29 per cent) required lymphadenectomy.     

Histopathological and biological prognostic risk factors in low stage testicular nonseminomatous germ cell tumors

Purpose of our study was to develop a reliable model to define clinical stage I nonseminomatous germ cell tumors (NSGCT) being at low risk and at high risk for occult retroperitoneal metastases based on pathohistological and immunohistochemical parameters in order to stratify the therapeutic approach. 3-5 paraffin-embedded formalin fixed tissue blocks of 149 clinical stage I NSGCT were available from all patients and were analyzed for histopathological features associated with pathological stage: presence/absence of vascular invasion, presence/absence of tunical invasion, percentage of each histological cell type present in the primary tumor. Immunohistochemical expression of MIB-1, p53, bcl-2, cathepsin D and e-cadherin was evaluated using a semiquantitative scoring ystem. Statistical analysis was performed by univariate and multivariate logistic regression models. Percentage of embryonal carcinoma [%EC (p < 0.001)] and presence of vascular invasion [VI (p < 0.0001)] were the most significant independent risk factors associated with pathological stage II disease. Combination of %EC and VI allowed correct prediction of final pathological stage in 88% of patients. Cut-off values including both variables identified correct pathological stage in 131/149 patients (88%). Less than 45% EC and absence of VI correctly identified pathological stage I disease in 91.5%; more than 80% EC and presence of VI correctly predicted pathological stage II in 88% of the patients. %EC and presence/absence of VI appear to be reliable prognosticators to identify both patients at high risk and at low risk for occult retroperitoneal disease. P53, bcl-2, MIB-1, cathepsin D and e-cadherin did not appear to be of prognostic value in clinical stage I NSGCT.     

Histopathological and biological prognostic risk factors in low stage testicular nonseminomatous germ cell tumors Implikationen für eine risikoadaptierte Therapie

Purpose of our study was to develop a reliable model to define clinical stage I nonseminomatous germ cell tumors (NSGCT) being at low risk and at high risk for occult retroperitoneal metastases based on pathohistological and immunohistochemical parameters in order to stratify the therapeutic approach. 3–5 paraffin-embedded formalin fixed tissue blocks of 149 clinical stage I NSGCT were available from all patients and were analyzed for histopathological features associated with pathological stage: presence/absence of vascular invasion, presence/absence of tunical invasion, percentage of each histological cell type present in the primary tumor. Immunohistochemical expression of MIB-1, p53, bcl-2, cathepsin D and e-cadherin was evaluated using a semiquantitative scoring ystem. Statistical analysis was performed by univariate and multivariate logistic regression models. Percentage of embryonal carcinoma [%EC (p < 0.001)] and presence of vascular invasion [VI (p < 0.0001)] were the most significant independent risk factors associated with pathological stage II disease. Combination of %EC and VI allowed correct prediction of final pathological stage in 88 % of patients. Cut-off values including both variables identified correct pathological stage in 131/149 patients (88 %). Less than 45 % EC and absence of VI correctly identified pathological stage I disease in 91.5 %; more than 80 % EC and presence of VI correctly predicted pathological stage II in 88 % of the patients. %EC and presence/absence of VI appear to be reliable prognosticators to identify both patients at high risk and at low risk for occult retroperitoneal disease. P53, bcl-2, MIB-1, cathepsin D and e-cadherin did not appear to be of prognostic value in clinical stage I NSGCT.     

Comparison between clinical and pathological staging in low stage nonseminomatous germ cell testicular tumors.

Between January 1985 and December 1990, 208 consecutive patients with low stage nonseminomatous germ cell testicular tumors underwent retroperitoneal lymphadenectomy. In all of the patients the disease was staged with post-orchiectomy serum alpha-fetoprotein and beta subunit of human chorionic gonadotropin determinations, as well as chest x-rays and computerized tomography or magnetic resonance imaging of the abdomen and pelvis. Bipedal lymphangiography was performed in 139 patients. Of the 208 patients 173 (83%) had clinical stage 1 and 35 (17%) had low clinical stage 2 disease: 21 had tumors on radiographic imaging that were smaller than 2 cm. (clinical stage 2A) and 14 had tumors between 2 and 3 cm. (clinical stage 2B less than 3 cm.). Retroperitoneal metastases were found in 31 of 156 clinical stage 1 cancer patients (19.8%) with negative or normally decreasing serum tumor markers after orchiectomy, 15 of 16 (93.8%) with persistent positive markers, 8 of 14 clinical stage 2A cancer patients (57.1%) with negative or normally decreasing markers, all 7 stage 2A cancer patients with positive markers and all 14 clinical stage 2B cancer patients. Lymphangiography added little to the reliability of clinical staging. We conclude that due to the relatively low accuracy of clinical staging, retroperitoneal lymphadenectomy remains the treatment of choice for clinical stages 1 and 2A nonseminomatous germ cell testicular tumors with normal serum markers after orchiectomy.     

The Role of Retroperitoneal Lymphadenectomy in Mature Teratoma of the Testis

Purpose

Pure testicular teratoma is rare in adulthood with an incidence of 5%. Pure teratoma is considered less aggressive and less likely to metastasize than other nonseminomatous germ cell tumors. Therefore, patients with mature teratoma have been considered candidates for surveillance protocols. We report our experience with 44 cases of primary pure testicular teratoma.

Materials and Methods

We retrospectively identified 44 patients (5.7%) with primary pure teratoma of the testis of the 772 treated for testicular germ cell tumors at our institutions. Archival tumor blocks were available for pathological reevaluation and serial sections were obtained in all cases. A total of 35 patients (79.5%) who presented with clinical low stage disease, including stage I in 26 (59.1%) and stage IIA/B in 9 (20.4%), underwent radical orchiectomy followed by retroperitoneal lymphadenectomy. Nine patients (20.5%) who presented with clinically advanced disease (stages IIC to IV) were treated with primary chemotherapy and secondary retroperitoneal lymphadenectomy of residual masses.

Results

The frequency of lymph node metastases was 19.2% in clinical stage I disease and 66% in stage IIA/B. Histopathological diagnosis of mature teratoma was confirmed in all cases. However, of 20 patients 16 (80%) had scars or calcifications in the adjacent parenchyma, indicating a burned out tumor, and 4 (20%) had microfocal embryonal carcinoma. None of the patients with clinical stage I disease had relapse during followup and the relapse rate in those with stage IIA/B disease was 33%. Median followup was 97 months (range 24 to 250). Overall 43% of patients with pure teratoma presented with metastatic disease.

Conclusions

Our data demonstrate the malignant potential of pure testicular mature teratoma. Based on our results metastases in testicular mature teratoma seem to result from metastasizing nongerm cell components undergoing early regression, as demonstrated by the high frequency of burned out tumors. We recommend that serial sections be taken of the orchiectomy specimen in all cases of pure mature teratoma to determine adequate management: retroperitoneal lymphadenectomy in cases of associated scars, calcifications or microfocal malignant germ cell components and surveillance in cases of pure mature teratoma.     

Nonseminomatous germ cell tumor of the testicle: does extensive staging of the primary tumor predict the likelihood of metastatic disease?

To assess the hypothesis that local extent of the primary lesion in patients with nonseminomatous germ cell tumors of the testicle can predict disseminated disease, clinicopathological correlations of the primary tumor and metastases were determined in a retrospective review of 120 patients treated at our institution from 1970 to 1982. Pathological staging was available for all 93 patients with subdiaphragmatic disease and the primary tumor was examined by routine histological techniques in all cases. Increased primary tumor stage, as evidenced by invasion into the tunica vasculosa or extension into the rete testis, epididymis and/or lower or upper spermatic cord, was associated with metastatic disease in 91, 96, 97 and 97 per cent of the patients, respectively. Only 9 per cent of the patients with pathological stage A disease had vascular invasion compared to 45 and 67 per cent of those with stages B and C disease, respectively (p less than 0.01). Furthermore, metastases and/or eventual dissemination occurred in 84 per cent of the patients with clinical stage A disease and vascular invasion, and in only 23 per cent of those without vascular invasion (p less than 0.01). Size of the primary tumor was not of predictive value. Local extension of the primary lesion was common with embryonal carcinoma but it was not demonstrated when the predominant histological type was teratoma or teratocarcinoma, although metastases were present in 37 and 46 per cent of the latter cases, respectively. The implications of these findings, especially with regard to expectant management for clinical stage A nonseminomatous germ cell testis tumors, are discussed.     

Evolution of the management of stage I nonseminomatous germ-cell tumors of the testis.

The sequence of treatment modalities for stage I nonseminomatous germ-cell cancer presented herein represents the evolution of treatment over the past three decades: from retroperitoneal lymphadenectomy or radiation therapy to surveillance to modified retroperitoneal lymphadenectomy or nerve-sparing retroperitoneal lymphadenectomy. Each new concept has prompted investigators to critically assess patient eligibility criteria and predictors of response and relapse. Primary predictors of treatment success have been local tumor stage (T status), the presence of vascular or lymphatic invasion, and primary tumor histology. These studies have also allowed critical review of the accuracy of radiologic staging, which, although markedly improved over the past decade, remains imperfect. With the advent of effective chemotherapy and improved patient salvage at relapse, these studies have allowed quality of life issues to become incorporated into management decisions. If there can be one conclusion concerning the management of stage I nonseminomatous germ-cell cancer, it must be that there is no one best treatment for all patients. Each treatment is associated with advantages and disadvantages. The treatment therefore should be individualized for each patient. As patients are evaluated, emphasis must be placed on the identification of relapse risk factors through meticulous pathologic review and accurate radiologic staging. Thus, the patients with clinical stage I disease and unfavorable prognostic factors (such as the presence of vascular invasion in the primary tumor, embryonal carcinoma, T2-T4 tumor) should be advised to undergo retroperitoneal lymphadenectomy; if the nodes are negative on frozen section, then modified retroperitoneal lymphadenectomy or nerve-sparing retroperitoneal lymphadenectomy should be performed; otherwise, bilateral retroperitoneal lymphadenectomy would provide the best chance of cure. Patients with stage I disease and favorable prognostic factors (such as T1 tumor, teratocarcinoma, absence of vascular invasion in the primary tumor) are suitable for either surveillance or modified or nerve-sparing retroperitoneal lymphadenectomy; these options should be thoroughly explained to the patient before any decision is made. Future efforts in this field may take a number of directions. As fertility remains a paramount issue to most patients, long-term studies will be necessary to investigate changes in semen characteristics and eventual paternity in patients followed on surveillance protocols or after either nerve-sparing or modified retroperitoneal lymphadenectomy. With continuing improvements in chemotherapy--improved efficacy with reduced toxicity--pathologic, radiographic, or serologic predictors of the site of eventual relapse will become of increasing importance. Indeed, if patients can be identified who are at a significant risk of distant relapse, an initial chemotherapy protocol may be warranted.(ABSTRACT TRUNCATED AT 400 WORDS)     

A simple model for predicting nodal metastasis in patients with clinical stage I nonseminomatous germ cell testicular tumors undergoing retroperitoneal lymph node dissection only

PURPOSE: In patients with clinical stage I nonseminomatous germ cell testicular tumor the identification of risk categories for nodal metastases and/or distant metastases could permit selective management. We built 2 models for distinguishing these risk categories. MATERIALS AND METHODS: Data on 322 consecutive patients with clinical stage I nonseminomatous germ cell testicular tumor patients treated with retroperitoneal lymphadenectomy (RPLND) alone between 1985 and 1995 were analyzed. The interval between orchiectomy and RPLND, vascular invasion (VI), pT stage, percent embryonal carcinoma (ECa) and teratoma in the primary tumor were considered clinically relevant for their association with nodal or distant metastases. Two logistic models were constructed. Model 1 was meant to discriminate 2 patient categories, namely those with and without nodal metastases at RPLND. Model 2 was meant to discriminate 3 patient categories, namely those without any metastases, with nodal metastases only and with distant metastases independent of retroperitoneal metastases. The models were based on these above variables, which were inserted as categorical and then processed through a backward selection procedure. RESULTS: At RPLND nodal metastases were found in 60 patients (18.6%). During followup distant metastases were observed in 43 patients (13.4%) and retroperitoneal recurrences were noted in 6 (1.9%). Of all recurrences 93.8% were within 2 years since RPLND. RPLND had a high curative rate since 73% of all pN+ cases were cured by surgery alone. The final logistic model 1, including percent ECa and VI, was reassessed in 202 patients with available data. Absent VI and ECa 90% or greater identified a category of 110 patients at low risk for nodal metastasis (14%), while VI and/or ECa greater than 90% identified a category of 92 at higher risk (35%). The identified categories were also related to distant metastases, which occurred in 9.3% of low risk and in 23.1% of high risk cases. Model 2 was not clinically suitable because it did not allow us to distinguish patients at risk for nodal metastases only from those at risk for distant metastases. CONCLUSIONS: Simplicity is the main advantage of model 1 since only 2 well-known prognostic parameters are involved. Although the model must be validated in an independent case series, the identification of a low risk category with few expected nodal metastases could permit us to replace traditional RPLND with a less invasive staging procedure.     

Retroperitoneal lymph node dissection in patients with low stage testicular cancer with embryonal carcinoma predominance and/or lymphovascular invasion

PURPOSE: The outcome after primary retroperitoneal lymph node dissection (RPLND) was analyzed in patients with clinical stage I-IIA nonseminomatous germ cell testicular cancer with embryonal carcinoma predominance (ECP) or lymphovascular invasion (LVI). MATERIALS AND METHODS: Between 1989 and 2002, 267 patients with clinical stage I-IIA nonseminomatous germ cell testicular cancer, and ECP and/or LVI underwent RPLND. Patient information was obtained from a prospective database. Median followup was 53 months. RESULTS: Overall 42% of patients had pathological stage (PS) II disease, of whom 54% had low volume (PN1) disease and 16% had retroperitoneal teratoma. The 5-year progression-free probability was 90% overall, 90% for PS I and 86% for PN1. All patients with relapse were continuously free of disease following standard chemotherapy with or without resection of residual masses and the 10-year actuarial overall survival was 100%. When adjuvant chemotherapy was restricted to patients with PN2 disease, the estimated 5-year relapse rate was 9% and an estimated 72% of patients avoided chemotherapy. CONCLUSIONS: The low risk of systemic relapse in patients with PS I and PN1 after RPLND alone combined with the 16% incidence of retroperitoneal teratoma and the favorable morbidity profile supports RPLND over primary chemotherapy for the treatment of patients with low stage disease with ECP and/or LVI who are not candidates for surveillance. An estimated 72% of patients are spared the potential toxicity of chemotherapy if adjuvant therapy is restricted to patients with PN2. After primary RPLND and selective adjuvant chemotherapy late recurrence is distinctly uncommon and long-term cancer control is anticipated in essentially all patients.     

Risk of systemic metastases in clinical stage I nonseminoma germ cell testis tumor managed by retroperitoneal lymph node dissection

PURPOSE: We assess the risk of systemic recurrence after retroperitoneal lymph node dissection for clinical stage I nonseminoma germ cell testis tumor based on predominance of embryonal carcinoma and/or vascular invasion in the orchiectomy specimen. MATERIALS AND METHODS: A total of 292 cases of clinical stage I nonseminoma germ cell testis tumor treated with retroperitoneal lymph node dissection from 1990 to 1995 were identified from the Indiana University database. A minimum of 2 years of followup was required for study entry. Review of the written pathological reports classified tumors as embryonal carcinoma predominant, when it was present at a level greater than any other histology, nonpredominant, when it was present but not as the main histological subtype, and absent. Vascular invasion was categorized as present or absent. RESULTS: Of the 292 cases 226 (77. 4%) were pathological stage I and relapse rate after retroperitoneal lymph node dissection was 10.2%. Vascular invasion and embryonal carcinoma predominance in the orchiectomy specimen were predictors of relapse in this group. None of the 35 pathological stage II cases treated with adjuvant chemotherapy had relapse, whereas relapse occurred in 7 of 31 pathological stage II cases (22.6%) not treated with adjuvant chemotherapy. CONCLUSIONS: Pathological stage I cases with predominant embryonal carcinoma and/or vascular invasion in the orchiectomy specimen have a higher probability of systemic recurrence after retroperitoneal lymph node dissection. Dissection alone still has a major therapeutic impact (77%) in patients with clinical stage I, pathological stage II nonseminoma germ cell testis tumor.     

Unilateral lymphadenectomy in intraoperative stage I nonseminomatous germinal testis cancer

Bilateral retroperitoneal lymphadenectomy is mainly a staging procedure in patients with stage I nonseminomatous testis cancer, and it causes permanent loss of antegrade ejaculation in approximately two-thirds of the cases. Between May 1978 and August 1981, 61 consecutive patients with no intraoperative evidence of lymph node involvement underwent unilateral retroperitoneal lymph-adenectomy for nonseminomatous germinal testis tumors. Microscopic metastases were found in 1 to 4 retroperitoneal nodes in 6 cases (9.8 per cent). Antegrade ejaculation was absent postoperatively in 11 patients (18 per cent), with no significant difference between patients who underwent lymph node dissection on the left or right side. Ejaculation returned spontaneously in 3 patients, 1 of whom fathered a child. The disease recurred in 10 patients 3 to 35 months after lymphadenectomy (median 6 months). Disease recurred in 8 of 55 patients (14.5 per cent) with negative nodes and 2 of 6 (33.3 per cent) with positive histological findings. No patient suffered retroperitoneal recurrence. The more than 3-year survival rates free of disease were 96.4 and 83.3 per cent in patients with pathological stages I and II disease, respectively. Unilateral retroperitoneal lymphadenectomy in patients with intraoperative stage I nonseminomatous germinal testis cancer preserves antegrade ejaculation in more than 80 per cent of the cases without apparently compromising the long-term survival.     

Neural Network Analysis of Quantitative Histological Factors to Predict Pathological Stage in Clinical Stage I Nonseminomatous Testicular Cancer

A great deal of controversy exists in staging clinical stage I (CSI) nonseminomatous testicular germ cell tumors (NSGCT) because of the difficulty of distinguishing true stage I patients from those with occult retroperitoneal or distant metastases. The goal of this study was to quantitate primary tumor histologic factors and to apply these in a neural network computer analysis to determine if more accurate staging could be achieved. All available primary tumor histological slides from 93 CSI NSGCT patients were analyzed for vascular invasion (VI), lymphatic invasion (LI), tunical invasion (TI) and quantitative determination of percentage of the primary tumor composed of embryonal carcinoma (percent EMB), yolk sac carcinoma (percent YS), teratoma (percent TER) and seminoma (percent SEM). These patients had undergone retroperitoneal lymphadenectomy or follow-up such that final stage included 55 pathologic stage I and 38 stage II or higher lesions. Two investigators were provided identical datasets for neural network analysis; one experienced researcher used custom Kohonen and back propagation programs and one less experienced researcher used a commercially available program. For each experiment, a subset of data was used for training, and subsets were blindly used to test the accuracy of the networks. In the custom back propagation network, 86 of 93 patients were correctly staged for an overall accuracy of 92 percent (sensitivity 88 percent, specificity 96 percent). Using Neural Ware commercial software 74 of 93 (79.6 percent) were accurately staged when all 7 input variables were used; however, accuracy improved from 84.9 to 87.1 percent when 2, 4 and 5 of the variables were used. Quantitative histologic assessment of the primary tumor and neural network processing of data may provide clinically useful information in the CSI NSGCT population; however, the expertise of the network researcher appears to be important, and commercial software in general use may not be superior to standard regression analysis. Prospective testing of expert methodology should be instituted to confirm its utility.     

CLINICAL STAGE I TESTIS CANCER: LONG-TERM OUTCOME OF PATIENTS ON SURVEILLANCE

Purpose

The long-term outcome results of a prospective surveillance trial for clinical stage I nonseminomatous germ cell tumors of the testis (NSGCT) are reported in an effort to define the natural history of clinical stage I testis cancer treated with orchiectomy alone, and to determine if a subset of patients exists that may be suitable for surveillance.

Materials and Methods

Between September 1979 and December 1987, 105 patients were entered into the study. Patients with persistent elevation of serum tumor markers (AFP, BHCG, and LDH) following orchiectomy, stage T2-T4 primary tumors, any evidence of metastases and pure choriocarcinoma or pure seminoma on histology were excluded from study. Enrolled patients underwent periodic physical examination, serological testing and radiological imaging according to an established protocol.

Results

Median followup was 11.3 years. Of the patients 78 (74.3%) have remained disease-free and 27 (25.7%) have experienced relapse. Of the patients with relapse 24 are currently disease-free after treatment for relapse for a median duration of 10.8 years and 3 (2.8%) died of disease. All relapses occurred within 24 months of orchiectomy (median 5 months). Significant predictors of relapse during surveillance were a predominant embryonal carcinoma histology (p = 0.016) and vascular invasion (p = 0.0005). In patients with neither embryonal carcinoma nor vascular invasion the relapse rate was 12%, and no patients died of disease.

Conclusions

With extended followup 74% of men with clinical stage I (T1) nonseminomatous germ cell tumor of the testis were cured by orchiectomy alone, and cure rates approached 90% when patients with predominant embryonal carcinoma histology or vascular invasion were excluded from surveillance. These findings support management by surveillance alone in a highly select cohort of men who have clinical stage I (T1) nonseminomatous germ cell tumor of the testis, normal serum markers following orchiectomy and neither predominant embryonal carcinoma or vascular invasion on histology.     

Selection of testicular tumor patients for omission of retroperitoneal lymph node dissection

Excluding patients with bulky stages II or III disease, 73 patients with nonseminomatous germ cell testicular tumors were evaluated between September 1979 and April 1983 for a protocol omitting retroperitoneal lymph node dissection. Patient eligibility required clinical stage I (T1 category) disease based upon normal post-orchiectomy serum tumor markers (alpha-fetoprotein, human chorionic gonadotropin and lactic dehydrogenase), chest x-ray, ipsilateral lymphangiography, and a computerized tomography scan of the abdomen and pelvis. Of the 73 patients 10 (14 per cent) were entered and followed for more than 2 years (3 had relapse within 7 months but were salvaged with retroperitoneal lymph node dissection and chemotherapy). Analysis of failures showed embryonal carcinoma in all 3 patients, with vascular invasion in the primary tumor in 1 and undetected spermatic cord involvement in 1, while 1 had a slower than expected decrease to normal of an elevated human chorionic gonadotropin level after orchiectomy. There were 63 patients (86 per cent) excluded from the protocol for various reasons: 2 (3 per cent) refused treatment, 16 (25 per cent) had suspicious or positive lymphangiography, 22 (40 per cent) had a positive CT scan, 6 (9 per cent) had elevated tumor markers, 3 (5 per cent) were less than 15 or more than 15 or more than 40 years old, 8 (13 per cent) had had a prior orchiopexy or scrotal violation, 4 (6 per cent) had extension to the spermatic cord and 2 (3 per cent) were unavailable for monthly followup. These 63 patients underwent retroperitoneal lymph node dissection, and 36 (57 per cent) had negative and 27 (43 per cent) had positive nodes (8 had stage N1, 10 stage N2A, 6 stage N2B and 3 stage N3 disease). Average interval from orchiectomy to final staging was 6 weeks. The results suggest that assessment of local tumor extent and potential sites of metastases via all available means are necessary in an effort to reduce the risk of tumor recurrence in patients who are followed expectantly.     

Surgical treatment of patients with stages I and II nonseminomatous testicular cancer

We analyzed treatment outcomes for 98 consecutive patients who underwent retroperitoneal lymphadenectomy for nonseminomatous germ cell testicular cancer between 1972 and early 1979. There were no surgical deaths. Major and minor complications occurred in 8 and 15 patients, respectively. Of the 57 patients with pathological stage I tumors 9 (16 per cent) had recurrences and were given chemotherapy, and all 57 are well 2 or more years after completion of treatment. Of the 12 patients with stage IIA disease who received no adjuvant treatment 5 had relapse, 2 of whom died. Relapse occurred in 13 of 14 patients with stage IIB disease who received no adjuvant treatment and 2 of 4 who received adjuvant radiation. All 3 patients with stage IIC tumor who received no adjuvant treatment had relapse. In contrast, none of the 7 patients with stage II disease who received adjuvant vinblastine and bleomycin with or without cisplatin had relapse. Our long-term survival rates are 100 per cent for patients with stage I and 88 per cent with stage II disease, and all of the patients who died either were treated before the introduction of cisplatin-based chemotherapy or did not complete the treatment protocol as recommended. In experienced hands retroperitoneal lymphadenectomy with chemotherapy, either as adjuvant or as needed for patients with stage I, IIA and IIB disease, remains the most cost-effective treatment for nonseminomatous testicular cancer and has the least short-term and long-term morbidity.     

18F-fluoro-2-deoxyglucose-positron emission tomography in the evaluation of nonseminomatous germ cell tumours at relapse

OBJECTIVES: To compare the performance of 18F-fluoro-2-deoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) in the follow-up of nonseminomatous germ cell tumours (NSGCT) in the retroperitoneum. PATIENTS AND METHODS: FDG-PET was used 25 times in 15 patients diagnosed with NSGCT. At the time of diagnosis five patients each were in stage I, II and III. Five patients had pure embryonal carcinoma, two had yolk sac tumours, one choriocarcinoma and seven had mixed tumours. RESULTS: Eleven patients either presented with retroperitoneal disease or this did not disappear after chemotherapy. The results of both examinations coincided in 18 cases and were contradictory in the other seven, the difference being statistically significant (P=0.042). CONCLUSION: In these patients FDG-PET detected the retroperitoneal relapse of NSGCT, in advanced stages treated with surgery plus chemotherapy, earlier than did CT; it also detected the presence of mature teratoma in residual retroperitoneal masses more accurately than CT. More extensive trials are needed before making conclusions about FDG-PET imaging as a routine method for NSGCT.     

Localization of solitary and multiple metastases in stage II nonseminomatous testis tumor as basis for a modified staging lymph node dissection in stage I

Because of a continuing need for pathological staging of clinical stage I testicular tumors an investigation was performed to determine the primary sites of metastatic involvement of the retroperitoneal lymph nodes and to define narrowly limited ipsilateral areas of lymph node dissection strictly for the purpose of staging. Surgical/pathological localization of solitary metastases provides the most direct evidence of primary lymphatic spread. There were 214 consecutive patients with stage II disease (excluding bulky disease) evaluated with respect to localization relative to the side of the involved testis and the number of metastases up to 5 cm. Solitary metastases of 5 cm. or less were found in 74 patients, 53 patients had 5 or less lymph nodes of 2 cm. or less and 87 patients had more than 5 lymph nodes of between 2 and 5 cm. Solitary nodes of the right testis tumor were located with decreasing frequency in the upper and lower interaortocaval, lower paracaval and precaval, upper precaval and right common iliac, upper paracaval and upper preaortic zones. Primary deposits of the left testis tumor were seen predominantly in the upper para-aortic zone. Upper preaortic and lower para-aortic zones were involved infrequently, and other areas were affected only in rare cases. These data contradict the assumption of a testicular lymph center located at the openings of the testicular veins into the vena cava and left renal vein, respectively. Multiple metastases were spread over the entire retroperitoneum, except for the external iliac regions. Hilar/suprahilar metastases were seen infrequently. Ipsilateral areas are defined according to primary involvement. A modified retroperitoneal lymph node dissection within ipsilateral areas is proposed as a staging operation for clinical stage I disease and a radical retroperitoneal lymph node dissection is indicated for pathological stage II disease.