Testicular Cancer Group Research Articles

Primum Non Nocere: Of Course! But How?

TO THE EDITOR: “Primum non nocere” stands for nonmaleficence in the Hippocratic Corpus, meaning “first, do no harm.” Colleagues who favor active surveillance for all patients with stage I testicular cancer consider adjuvant chemotherapy a potentially harmful and unnecessary intervention. However, the “surveillance for all” recommendation may infringe on patient autonomy and prove harmful. Adjuvant chemotherapy is, with few exceptions, well tolerated and without relevant long-term toxicities. Salvage treatment for relapsing patients, on the other hand, causes acute and long-term toxicities in a dose-dependent manner. Therefore, the fear of potential long-term effects of adjuvant chemotherapy seems disproportionate to the real and established toxicities after three to four cycles of bleomycin, etoposide, and cisplatin, including additional postchemotherapy RPLND in 26% of nonseminoma patients. Recently, Vidal et al published their article “Long-Term Outcome of Patients With Clinical Stage I High-Risk Nonseminomatous Germ Cell Tumors 15 Years After One Adjuvant Cycle of Bleomycin, Etoposide and Cisplatin Chemotherapy” in Annals of Oncology, in which essentially no relevant toxicity was reported. The editorial “Primum Non Nocere. Do We Harm Stage I Testicular Cancer Patients Less by Applying Adjuvant Chemotherapy Than by Failing to Present This Option?” hailed this report. Primum non nocere is thereby embraced both by the proponents of a risk-based management as well as by those advocating active surveillance for all patients with stage I testicular cancer. Both sides consider unnecessary treatment as the potential harm, identifying either adjuvant or salvage chemotherapy as the culprit. According the Spanish Germ Cell Group, a patient with a 6-cm testicular seminoma invading the rete testis and vasculature, like the one discussed by Vaughn, has a 40% risk of micrometastases. Typically, such men vote for adjuvant treatment, when counseled by proponents of a risk-based strategy like us. The majority of patients whose outcomes were published by Kollmannsberger et al were managed by the Swedish and Norwegian Testicular Cancer Group with a risk-based approach in which low-risk patients were selected for surveillance. Unfortunately, the Oncology Grand Rounds article appears biased in favor of active surveillance: Stating that “only 13% of 1,344 patients with CS I seminoma relapsed” while failing to mention the selection bias by including predominantly low-risk patients renders these numbers not representative for high-risk patients. Merely pointing to a lack of publications on long-term toxicities 20 to 30 years after carboplatin (while confirming their absence within 9 years) might cause patients to refrain from this “potentially harmful” treatment. This evasive approach appears, in light of the considerable toxicities after salvage treatment, questionable and potentially more harmful.

Sick leave and disability pension among Swedish testicular cancer survivors according to clinical stage and treatment

Purpose. To investigate if testicular cancer survivors (TCSs) have a higher incidence of work loss compared with the population, accounting for stage, treatment and relapse.Material and methods. A cohort of 2146 Swedish TCSs diagnosed 1995–2007 (seminoma n = 926, non-seminoma n = 1220) was identified in the SWENOTECA (Swedish-Norwegian Testicular Cancer Group) register, and matched 1:4 to population comparators. Prospectively recorded work loss data (both before and after diagnosis) were obtained from national registers through September 2013. Adjusted relative risks (RR) and 95% confidence intervals (CI) of sick leave and/or disability pension were calculated annually and overall with Poisson- and Cox regression, censoring at relapse. The mean number of annual work days lost was also estimated.Results. TCSs were at a modestly increased annual risk of work loss up to the third year of follow-up (RR3rd year 1.25, 95% CI 1.08, 1.43), attributed to a more pronounced risk among extensively treated patients (4 chemotherapy courses: RR3rd year 1.60, 95% CI 1.19, 2.15; > 4 courses: RR3rd year 3.70, 95% CI 2.25, 6.11). Patients on surveillance or limited treatment (radiotherapy, 1–3 chemotherapy courses) did not have an increased risk of work loss beyond the first year. TCSs receiving > 4 chemotherapy courses had higher mean number of annual days of work loss up to the 10th year post-diagnosis, and a five-fold risk of disability pension (RR 5.16, 95% CI 2.00, 10.3).Conclusion. Extensively treated TCSs, but not those on surveillance or limited treatment, are at increased risk of work loss long-term, not explained by relapse. These patients may benefit from early rehabilitation initiatives.

Surveillance vs. adjuvant therapy of clinical stage I testicular tumors - a review and the SWENOTECA experience.

Although clinical stage I (CS I) testicular cancer is highly curable, the optimal management is controversial. The aims of the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) studies for CS I non-seminoma (NS) and seminoma (S) have been to reduce treatment intensity while maintaining high survival rates, reduce the number of patients needing salvage treatment and implement patient autonomy with regard to adjuvant treatment. During 1998-2010 NS CSI patients with lymphovascular invasion (LVI) of the primary tumor (high risk) were recommended bleomycin, etoposide, cisplatin (BEP)×1. During 2000-2006 S CS I patients had the option to choose surveillance or adjuvant radiotherapy (AR). In 2004, carboplatin×1 (AUC7) was added as a third treatment option. In 2007 a new risk-adapted treatment protocol for S CS I was initiated. Patients with two risk factors (tumor size>4cm, tumor growth in the rete testis) were recommended carboplatin×1 and patients with 0-1 risk factor were recommended surveillance. All patients were provided with oral and written information of possible management options and could choose the other alternative. The relapse rate for NS CS I with BEP×1 was 3.2% for high risk, and 1.6% for low-risk patients. Five-year cause-specific survival was 100%. For S CS I-patients treated before 2007, 14.3% on surveillance relapsed, 3.9% after carboplatin, and 0.8% after AR. Five-year cause-specific survival was 99.9%. For S CS I-patients treated from 2007, a relapse rate <3% was confirmed for patients without risk factors. SWENOTECA considers BEP×1 standard adjuvant treatment in NS CS I high-risk patients. Low-risk patients should have the opportunity to receive BEP×1 following thorough information regarding pros and cons. For S CS I patients without risk factors, adjuvant treatment is not necessary. For patients with risk factors, patient autonomy should be respected.

Sperm concentration, hyaluronic acid-binding capacity, aneuploidy and persistent histones in testicular cancer.

Are the quantitative and qualitative characteristics of semen samples of patients with testicular cancer (TC), prior to anticancer therapy, different from infertile oligozoospermic (IO) and normozoospermic (NZ) age-matched men? Sperm concentration in TC patients was significantly decreased with no difference in estimated numerical chromosome aberrations and nuclear decondensation compared with NZ men, while the infertile, oligozoospermic men had significantly poorer sperm qualitative characteristics versus the TC group overall and oligozoospermic patients with TC. Spermatogenesis is altered in TC patients at the time of diagnosis. However, the mechanism responsible for the decreased semen quantity in patients with TC is not well understood. Anticancer treatment may have gonadotoxic side effects and post-treatment fertility cannot be predicted. Before commencing anticancer treatment, cryopreservation may be suggested to preserve fertility but there are no data regarding the risk of genetic aberrations in these sperms. This is a cross-sectional study examining semen from 28 patients with TC, 20 IO and 20 NZ age-matched men attending the Andrology Center and the Sperm Cryopreservation Laboratory of the Medical and Health Science Center, University of Debrecen. Semen samples from patients with TC were collected after orchidectomy, but prior to anticancer treatment. Semen samples from TC patients recruited over a period of 4 years were studied. Based on their sperm concentration, TC patients were subgrouped into an oligozoospermic TC (TCO) and a normozoospermic TC group. For statistical analysis, the normal group (NZ + IO) comprised non-tumorous NZ and IO men. The ejaculates were assessed as per World Health Organization guidelines. Hyaluronic acid (HA)-binding capacity was the functional test. To determine the numerical chromosome aberrations, we used multi-color fluorescence in situ hybridization. Aniline blue (AB) staining was performed as a nuclear decondensation marker test. The results did not reveal any significant difference in disomy of sex chromosomes and chromosome 17, diploidy and estimated numerical chromosome aberrations and AB staining results upon comparing the NZ and TC groups, although the sperm concentration (P < 0.001) and HA-binding capacity (P < 0.001) were lower in the TC group. Estimated numerical chromosome aberrations (P < 0.001), AB staining (P < 0.001) and HA-binding capacity (P = 0.019) were lower in the infertile, oligozoospermic group when compared with the patients with TC. The TCO group had significantly better results in every examined parameter than the infertile, oligozoospermic group. In the non-tumorous control group (NZ + IO), a significant (P < 0.001) correlation (Spearman's rho = r) was found between sperm concentration and aneuploidy rate (r = -0.642), AB staining (r = -0.876) and HA binding (r = 0.842); the HA-binding capacity was related to the aneuploidy rate (r = -0.678) and the AB staining (r = -0.811); and there was significant correlation between aneuploidy and AB staining (r = 0.559). In the TC group, apart from the negative correlation between sperm concentration and estimated chromosomal aberrations (r = -0.642), no other correlations were observed. Data on confounders influencing sperm characteristics, such as smoking, occupational or environmental hazards, alcoholism, co-morbidities and other andrological conditions, were not collected. This is the first study to demonstrate that sperm qualitative characteristics in anticancer therapy naïve oligozoospermic TC patients differ significantly from those in IO men and do not differ from those in NZ men. Our results need to be validated in similar groups of men and in other patient groups with cancer where cryopreservation is advisable. This research was supported by the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of TÁMOP-4.2.4.A/2-11/1-2012-0001 'National Excellence Program'. The authors have no conflict of interest to declare.

Raw and test-thaw semen parameters after cryopreservation among men with newly diagnosed cancer

To characterize sperm parameters from thawed semen samples of men with different cancers who cryopreserved semen before oncologic therapy. Retrospective cohort study. Tertiary academic medical center. 1,010 semen samples collected between 1994 to 2010. None. Mean total motile count (TMC), change in percentage motility and percentage survival (100 * [postthaw % motility/raw % motility]) for each cancer compared with data from samples of men without cancer (the "procreative management" group), and proportion of postthaw samples with TMC >5 × 10(6). The procreative management group had the best raw and postthaw semen quality. The best raw and postthaw semen quality for cancer patients occurred in those with prostate cancer (TMC of 155.1 and 53.2 × 10(6), respectively) and the worst in those with leukemias. Lymphoid leukemias demonstrated the worst raw TMC (26.8 × 10(6)), but myeloid leukemias displayed the worst postthaw TMC (6.9 × 10(6)). The testicular cancer group was the only group with a statistically significantly lower chance of having TMC >5 × 10(6). Men with testicular cancer were most commonly referred for sperm cryopreservation and were the only group that was statistically significantly less likely to have TMC >5 × 10(6) on postthaw semen analysis. The most severe reduction in TMC was seen in the myeloid leukemia group, suggesting that these patients along with men with testis cancer and those with lymphoid leukemia should be counseled to provide increased numbers of specimens for fertility preservation.

Five years into the national second-opinion project of the German Testicular Cancer Group (GCTSG): Impact on guideline implementation and the quality of care for testicular cancer patients.

4530 Background: The diagnosis and therapy of testicular germ cell tumors are subject to constant change. Numerous national and international guidelines have been published since the 1990s in order to meet this challenge. It is questionable, however, whether mere publication of guidelines will lead to their implementation. The aim of the present project of the GTCSG was to establish a national second-opinion network in order to improve the implementation of guidelines and the quality of care. Methods: Before determining the primary therapy, participating urologists could communicate with one of 30 second-opinion centers (SOC) via an internet-based platform. The data set comprised the primary clinical, radiological and pathohistological findings, the therapy planned by the advice seeker (first opinion), the therapy recommended by the SOC (second opinion), and the applied therapy as well as the 2-year follow-up data. Primary end points of the study were congruence between the first and second opinion, treatment changes based on the second opinion, and relapse-free 2-year survival. Results: A total of 1722 SOC requests have been submitted since November 2006. At the time of our data analysis 927 cases were evaluated. The response rate was 75.8% for treatment data and 74.4% for 2-year follow-up data. Advice seekers and SOC had discrepant treatment concepts in 43.3% of the cases; this discrepancy was independent of tumor histology and increased in advanced tumor stages (clinical stage ≥IIa: 52.3% vs. &lt;IIa: 34%; p&lt;0.001, Pearson Χ2 test). The SOC request led to reduction of the applied therapy in 11.4% and intensification in 9.5% of the cases. Progression-free 2-year survival was 92% (112/122) for stage I, 90% (17/19) for stage IIa-IIb, and 65% (17/26) for stage ≥IIc. Conclusions: Guidelines for the treatment of germ cell tumors are inadequately implemented, particularly in advanced tumor stages. Every fifth second opinion resulted in a relevant change in the scope of therapy. Patients whose treatment was congruent with the second opinion had a relapse rate comparable to that of study results in the literature.

Salvage Chemotherapy for Patients With Germ Cell Tumors: Is There a Best Regimen?

patients with poor-prognosis metastatic germ cell tumors. J Clin Oncol 25:247-256, 2007 6. de Wit R, Skoneczna I, Daugaard G, et al: Randomized phase III study comparing paclitaxel–bleomycin, etoposide, and cisplatin (BEP) to standard BEP in intermediate-prognosis germ-cell cancer: Intergroup Study EORTC 30983. J Clin Oncol 30:792-799, 2012 7. Kollmannsberger C, Daneshmand S, So A, et al: Management of disseminated nonseminomatous germ cell tumors with risk-based chemotherapy followed by response-guided postchemotherapy surgery. J Clin Oncol 28:537-542, 2010 8. Olofsson SE, Tandstad T, Jerkeman M, et al: Population-based study of treatment guided by tumor marker decline in patients with metastatic nonseminomatous germ cell tumor: A report from the Swedish-Norwegian Testicular Cancer Group. J Clin Oncol 29:2032-2039, 2011 9. Kris MG, Meropol NJ, Winer EP (eds): Accelerating progress against cancer: ASCO’s blueprint for transforming clinical and translational cancer research. http://www.asco.org/ASCOv2/Department%20Content/Cancer% 20Policy%20and%20Clinical%20Affairs/Downloads/Blueprint.pdf 10. Abernethy AP, Etheredge LM, Ganz PA, et al: Rapid-learning system for cancer care. J Clin Oncol 28:4268-4274, 2010 11. Frankovich J, Longhurst CA, Sutherland SM: Evidence-based medicine in the EMR era. N Engl J Med 365:1758-1759, 2011

High-dose chemotherapy with autologous stem cell support in patients with metastatic non-seminomatous testicular cancer – a report from the Swedish Norwegian Testicular Cancer Group (SWENOTECA)

Background. The SWENOTECA IV protocol from 1995 is a prospective population-based study in metastatic non-seminomatous germ cell testicular cancer (NSGCT), designed for early identification of patients with poor response to standard cisplatin-based chemotherapy. A slow tumor marker decline (HCG T½ > 3 days, AFP T½ > 7 days) after BEP or BEP plus ifosfamide was regarded as poor response. The aim of this study was to present survival and toxicity data for patients treated with high-dose chemotherapy (HDCT) within the SWENOTECA IV cancer care program. Material and methods. In total 882 adult men diagnosed with metastatic NSGCT between July 1995 and June 2007 in Sweden and Norway (except one center) were included in SWENOTECA IV and treated accordingly. Among these, 55 men (6.2%) were treated with HDCT according to three different indications in the protocol: A) poor response to standard-dose intensified chemotherapy (BEP plus ifosfamide); B) vital cancer at surgery after intensified chemotherapy; and C) selected relapses after previous chemotherapy. In situation A and C two HDCT cycles and in situation B one HDCT cycle was recommended. Situation A was the reason for HDCT in 36 patients, B in seven and C in 12 patients. The first HDCT cycle consisted of carboplatin 28 × (GFR + 25) mg, cyclofosfamide 6000 mg/m2 and etoposide 1750 mg/m2, administered over four days. In cycle two, etoposide was replaced by tiotepa 480 mg/m2. Results. After a median follow-up of 7.5 years, overall survival was 72%, 100% and 58%, while failure-free survival was 64%, 71% and 42% in situation A, B and C, respectively. Three patients (5.5%) died during HDCT (renal failure or intracerebral hemorrhage). Nephrotoxicity was the most common non-hematological grade 4 toxicity (n = 5, 9%). Conclusion. The population-based SWENOTECA strategy, selecting patients who do not respond adequately to primary standard-dose chemotherapy for immediate treatment intensification with HDCT, is feasible and might be advantageous.

Population-Based Study of Treatment Guided by Tumor Marker Decline in Patients With Metastatic Nonseminomatous Germ Cell Tumor: A Report From the Swedish-Norwegian Testicular Cancer Group

From 1995 to 2003, 603 adult patients from Sweden and Norway with metastatic testicular nonseminomatous germ cell tumor (NSGCT) were included prospectively in a population-based protocol with strict guidelines for staging, treatment, and follow-up. Patients with extragonadal primary tumor or previous treatment for contralateral testicular tumor were excluded. The basic strategy was to individualize treatment according to initial tumor marker response. Initial treatment for all patients was two courses of standard bleomycin, etoposide, and cisplatin (BEP), with tumor markers analyzed weekly. Good response was defined as a half-life (t(1/2)) for α-fetoprotein (AFP) of ≤ 7 days and/or for β-human chorionic gonadotropin (β-HCG) of ≤ 3 days. Patients with prolonged marker t(1/2) (ie, poor response) received intensification with addition of ifosfamide (BEP-if/PEI) in step 1. If poor response continued, the treatment was intensified with high-dose chemotherapy with stem-cell rescue as step 2. Overall, 99% of all patients with metastatic testicular NSGCT in the population were included in the protocol. Median follow-up was 8.2 years. Seventy-seven percent of the patients were treated with BEP alone; 18% received intensification step 1%, and 5% received intensification step 2. Grouped according to International Germ Cell Consensus Classification, 10-year overall survival was 94.7% in good-prognosis patients, 90.0% in intermediate-prognosis patients, and 67.4% in poor-prognosis patients. With detailed treatment protocols and a dedicated collaborative group of specialists, treatment results comparable to those reported from large single institutions can be achieved at national level. With the treatment principles used in Swedish-Norwegian Testicular Cancer Group study SWENOTECA IV, the survival of intermediate-prognosis patients is remarkable and close to that of good-prognosis patients.

Feelings of loss and uneasiness or shame after removal of a testicle by orchidectomy: a population-based long-term follow-up of testicular cancer survivors

Few data illustrate the man's reaction to orchidectomy. We investigated long-lasting feelings of loss and uneasiness or shame about the body after removal of a testicle by orchidectomy. We identified 1173 eligible men diagnosed with non-seminomatous testicular cancer treated according to the national cancer-care programmes Swedish-Norwegian Testicular Cancer Group I-IV between 1981 and 2004. We asked the survivors about feelings of loss and uneasiness or shame after having had a testicle removed by orchidectomy. We obtained information from 960 (82%) testicular cancer survivors. We found that 32% of these men miss or previously missed their removed testicle(s) and that 26% have or previously had feelings of uneasiness or shame about their body because of the removed testicle(s). Men who had never been offered a prosthesis reported feelings of loss [relative risk (RR): 2.0; 95% confidence interval (CI): 1.3-3.0] and uneasiness or shame (RR: 2.0; 95% CI: 1.3-3.2) to a higher extent than those who had been offered, but rejected a prosthesis. An orchidectomy may result in long-lasting feelings of loss and uneasiness or shame in some men; offering a testicular prosthesis may hinder this experience.

Individualized intensification of treatment based on tumor marker decline in metastatic nonseminomatous germ cell testicular cancer (NSGCT): A report from the Swedish Norwegian Testicular Cancer Group, SWENOTECA

5015 Background: From July 1995 to December 2003, 602 adult patients from Sweden and Norway with metastatic testicular NSGCT were included in a population-based multicenter SWENOTECA protocol with strict guidelines for staging, treatment and follow-up. Methods: The basic strategy of this protocol was to individualize treatment according to AFP and β-HCG decline (t1/2). Satisfactory response to treatment was defined as a t½ for AFP ≤ 7 days and/or β-HCG ≤ 3 days. Initial treatment for all patients was 2 courses of standard BEP. Tumor markers were analyzed once a week during treatment. Patients with satisfactory response went on with BEP while patients with unsatisfactory t1/2 received intensified treatment in two steps with addition of ifosfamide (BEP-if/PEI) in step 1. If still unsatisfactory response the treatment was intensified according to step 2 involving high-dose chemotherapy with stem cell rescue. Postchemotherapy surgery was performed according to protocol guidelines. Results: 99,7% (602 of 604) of all patients with metastatic testicular NSGCT in the population were included in the protocol. Median FU was 72 months. 75% of the patients were treated with BEP, median 4 courses, without intensification, 19% according to intensification step 1 and 6% according to intensification step 2. Five year progression free survival (PFS), cancer specific survival (CSS) and overall survival (OS) grouped according to IGCCCG prognostic score are given in the Table below. There was no significant difference in PFS between the good and intermediate risk group. Death due to all causes was 10,1% (n=61) and treatment related deaths were 1,3 % (n=8). Conclusions: Our results, in a population based patient material, with individualized treatment based on tumor marker decline, are highly encouraging in all risk groups, but most notably in the intermediate risk group. [Table: see text] No significant financial relationships to disclose.

Sperm nuclear apoptotic DNA fragmentation in men with testicular cancer

To verify whether sperm from patients with a seminoma and patients with a non-seminoma present with an increased rate of apoptotic DNA fragmentation, when compared with men without testicular cancer and who had fathered a child in the 2 years preceding the study. Controlled prospective study. Patients referred to a sperm bank in an academic research environment. Men with a diagnosed seminoma, men with a diagnosed non-seminoma, both after orchiectomy and before adjuvant therapy, and men with proven paternity in the 2 previous years. Rate of nuclear apoptotic sperm DNA fragmentation as assessed by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) assay, classified as positive (with DNA fragmentation) or negative (without DNA fragmentation). Of the 48 men with testicular cancer included in the study, 29 (60.4%) presented a non-seminoma and 19 (39.6%) a seminoma. Patients with non-seminoma presented with lower progressive sperm motility than the control group (57.4% and 66.3%, respectively), but both were still within normal ranges. Sperm concentration was lower in seminoma (31.2 x 10(6)/mL) and in non-seminoma (20.6 x 10(6)/mL) when compared with the control group (78.1 x 10(6)/mL), but values did not differ between the two testicular cancer groups. Sperm morphology was lower in patients with non-seminoma than in the control group (10% and 13.1%, respectively). Results for sperm nuclear apoptotic DNA fragmentation (mean; standard deviation) were 12.6%; 4.5% for the control group, 12.2%; 5.5% for the non-seminoma group, and 12.5%; 6.4% for the seminoma group. No differences were found between the three groups. Our results demonstrate that the presence of a seminoma or a non-seminoma is not associated with an increase in sperm apoptotic DNA fragmentation.

Initial versus recent outcomes with a non–risk adapted surveillance policy in stage I non-seminomatous germ cell tumors (NSGCT)

5021 Background: Since 1981 the Princess Margaret Hospital testicular cancer group has used surveillance as the preferred management option for all patients (pts) with clinical stage I NSGCT. In a report of the first 105 pts [Sturgeon et al. J Clin Oncol, 1992] the relapse rate was 35% and the disease specific 5-year survival 99%. Improvements in imaging technique over time could cause stage migration with an overall lower relapse rate in this patient population. We compare our experience with surveillance over different time points. Methods: Three-hundred and five pts with stage I NS-GCT were placed on an active surveillance protocol between 1981–2004. They were not stratified by risk and only received treatment on the event of a relapse. Recurrence rates, time to relapse, risk factors predictive for recurrence, disease specific and overall survival were determined. For the analysis by time period, pts were divided in two groups based on diagnosis date. (Initial=1981–1992 [N=141] and Recent=1993–2004 [N=164]). Results: With a median follow-up of 6.3 years, 77/305 pts (25%) relapsed; 46/141 pts (32.6%) in the initial group and 31/164 (18.9%) in the recent. All but 3 (4%) relapses occurred within 2 years after orchiectomy with a median time to relapse of 7 months. A multivariate analysis established lympho-vascular invasion (p&lt;0.01) and pure embryonal carcinoma (p= 0.03) as independent predictors of recurrence. Overall 104/305 (34.1%) pts were designated as ‘high- risk’ based on the presence of at least one of these factors. In the initial group 60/141 (42.6%) pts were high risk and 32/60 (53%) relapsed versus 14/81 (17.3%) low-risk (p=0.047). In the recent group 44/164 (26.8%) pts were high-risk and 17/44 (38.6%) recurred, versus 14/120 (11.7%) low-risk (p&lt;0.001). There were 2 (0.7%) deaths due to testis cancer. The estimated 5-year disease specific survival was 98.9% in the initial group and 100% in the recent one. Conclusions: Surveillance is an effective strategy for the management of all stage I NSGCT. A risk-adapted policy would result in more than 50% of the patients being unnecessarily treated. The relapse rate has reduced over time, likely due to improvements in imaging causing stage migration. No significant financial relationships to disclose.

Testicular cancer and Hodgkin's disease: evaluation of semen quality.

The aim of our study was to establish whether there is a difference in semen quality between patients with testicular cancer (TC) and Hodgkin's disease (HD). We evaluated 342 patients affected by TC (n = 232) or HD (n = 110) who cryobanked sperm before initiating chemo- or radiotherapy. All TC patients were evaluated approximately 1 month after orchidectomy. A total of 14 patients were azoospermic or cryptozoospermic. In the TC group (n = 222) the mean of the semen parameters was normal according to the World Health Organization (1992). However, dividing the cases into total sperm count > or =40x10(6)/ejaculate and <40x10(6)/ejaculate, 35.5% of the patients showed an impaired semen quality. The quality of sperm parameters was higher in seminoma patients than for the other histological groups. A significant difference for all semen variables was observed between patients with serum betahCG levels classified as pathological (>5 mIU/ml) and those with normal serum betahCG. Comparison of semen parameters between TC stages I and II showed no significant differences. In the HD group (n = 106), we found that by and large they showed normal spermatogenesis, with only 24.5% having a total sperm count <40x10(6)/ejaculate. There was a significant decrease in semen quality in stages III and IV of HD. Better semen quality was observed in patients with HD than in those with TC. The semen quality observed in our TC and HD groups seems better than previous results reported in the literature.

Expression of peroxisome proliferator-activated receptors in human testicular cancer and growth inhibition by its agonists

Objectives. To investigate the expression of peroxisome proliferator activator-receptor (PPAR)-alpha, beta, and gamma in human testicular cancer (TC) and normal testicular (NT) tissues, as well as the effects of the PPAR-gamma ligand. Recent studies have demonstrated that PPAR-gamma is expressed in various cancer tissues and its ligand induces growth arrest of these cancer cells through apoptosis. However, the expression of PPARs and the effects of PPAR-gamma ligand in testis have not been examined. Methods. Tumor specimens were obtained from 72 patients with TC. Specimens were obtained from 20 patients with NT tissue. The expressions were investigated using reverse transcriptase-polymerase chain reaction and immunohistochemical methods. We also investigated the inhibitory effect of the PPAR-gamma ligand on the TC-derived cell line. Results. Immunoreactive PPAR-alpha and beta were significantly apparent in TC tissues. Marked expression of PPAR-alpha and beta was also detected in the NT group. However, very weak or no expression of immunoreactive PPAR-gamma was found in the NT cases. In contrast, we found significant expression of immunoreactive PPAR-gamma in the cancer cells in the TC group. The synthetic PPAR-gamma agonists thiazolidinedione compounds and the endogenous PPAR-gamma ligand, 15-deoxy-Δ 12,14-prostaglandin J 2, inhibited the growth of the TC cells. Conclusions. PPAR-gamma is induced in TC, and the results suggest that PPAR-gamma ligands may mediate potent antiproliferative effects against TC cells through differentiation. Thus, PPAR-gamma may become a new target in the treatment of TC.

Is chemotherapy associated with development of Barrett's esophagus?

Columnar-lined or Barrett's esophagus is a premalignant condition. It is almost unvariably due to chronic gastroesophageal reflux. Since there are some reports that Barrett's esophagus can be induced by chemotherapy, we investigated 20 male patients, treated with chemotherapy for testicular cancer, and 18 female patients, treated with high-dose chemotherapy for breast cancer. Only one patient in the testicular cancer group had Barrett's esophagus of the circumferential type, in addition to typical reflux esophagitis and a hiatal hernia four years after chemotherapy. In the breast cancer group one patient had an indeterminate junction. Our results do not support the hypothesis that chemotherapy poses a substantially increased risk for the development of Barrett's esophagus.

Prognostic factors in clinical stage I nonseminomatous germ cell tumors of the testis: multivariate analysis of a prospective multicenter study. Swedish-Norwegian Testicular Cancer Group.

Between 1981 and 1986, 279 consecutive patients with clinical stage I (CS1) nonseminomatous germ cell tumors (NSGCT) of the testis underwent pathological staging (PS) with retroperitoneal lymphadenectomy (RPLND). Patients with retroperitoneal metastases (PS2) received adjuvant chemotherapy. The median follow-up time after RPLND was 50 months (range, 30 to 90). Clinical and histopathologic features were registered prospectively and analyzed for association with risk of having PS2, relapse despite pathological stage 1 (PS1) or the combined risk of either event, metastatic disease (MET). Seventy-five (26.9%) of the patients had PS2 disease, and 30 (14.7%) of the 204 PS1 patients relapsed, indicating that at least 105 (37.6%) of this CS1 population had subclinical MET at the time of orchiectomy. Four (1.4%) of the 279 CS1 patients died of testicular cancer. Multivariate analyses showed several variables to be significantly associated with outcome for the CS1 patients; vascular invasion in primary tumor and normal preorchiectomy serum alpha-fetoprotein (Pre-AFP) level indicated PS2 disease. If Pre-AFP was excluded from the model, the absence of teratoma or yolk sac elements in the primary tumor became significant predictors of PS2. Vascular invasion, absence of teratoma, and a short interval between orchiectomy and RPLND indicated increased risk of relapse in PS1 patients. Vascular invasion, normal Pre-AFP, absence of teratoma elements, and a short orchiectomy to RPLND interval were predictive of MET. Our results indicate that prognostic factors useful for stratification of CS1 patients with NSGCT to different treatment options may be established.