Late relapse of stage I testicular seminoma metastatic to just a para-ureteropelvic region

A follow-up ultrasonography study 43 months after an operation for left stage I testicular seminoma in a 39-year-old man revealed left hydronephrosis. Serum beta-human chorionic gonadotropin (beta-hCG) levels were slightly increased. Computed tomography scans of the abdomen showed a bulky tumor around the ureteropelvic region without para-aortic lymph node enlargement, but did not show a clear distinction between a recurrence of the testicular tumor and an invasive ureteral tumor. After the patient underwent two cycles of chemotherapy with cisplatin and etoposide, the tumor mass decreased by approximately 60% and beta-hCG levels returned to normal. We then performed a resection of the residual tumor involving the upper ureter and left kidney and a retroperitoneal lymph node dissection under a clinical diagnosis of recurrence of the testicular tumor. Histologically, no viable cancer cells remained. The patient has been well with no evidence of recurrence for more than two years.     

Incidence of second malignancies after external beam radiotherapy for clinical stage I testicular seminoma

Study Type – Harm (case series) Level of Evidence 4 What's known on the subject? and What does the study add? We know that radiation therapy is associated with an increased risk of second malignancies in patients with testicular cancer. However, we know that radiation is being used very commonly in patients with clinical stage I seminoma, despite evidence that it is not required. Moreover, we have now identified which specific second malignancies occur in these patients after radiotherapy.

OBJECTIVES

• ? To determine the use of adjuvant external beam radiotherapy (EBRT) for patients with clinical stage I testicular seminoma in the USA.
• ? To quantify the risk of specific second primary malignancies (SPMs) associated with radiation exposure in these patients.

PATIENTS AND METHODS

• ? We used the Surveillance, Epidemiology and End Results database to identify patients diagnosed with clinical stage I testicular seminoma between 1973 and 2000.
• ? We evaluated the use of EBRT in these patients.
• ? We calculated standardized incidence ratios of specific SPMs in these patients.
• ? We stratified the incidence of SPMs based on age at seminoma diagnosis and time to SPM from initial seminoma diagnosis.

RESULTS

• ? Adjuvant EBRT use declined from the first decade of the study period to the last decade of the study period (80.6% vs 70.2%).
• ? Overall, there was a 19% increase in SPMs in patients exposed to EBRT (observed/expected, O/E, 1.51; 95% CI, 1.08–1.31) compared to the general population.
• ? Specifically, significantly increased risks were observed for thyroid cancer (O/E, 2.32; 95% CI, 1.16–4.16), pancreatic cancer (O/E, 2.38; 95% CI, 1.43–3.72), non‐bladder urothelial malignancies (O/E, 4.27; 95% CI, 1.57–9.29), bladder cancer (O/E, 1.47; 95% CI, 1.01–2.28), all haematological malignancies (O/E, 1.44; 95% CI, 1.08–1.89) and non‐Hodgkin's lymphoma (O/E, 1.77; 95% CI, 1.22–2.48).
• ? Patients had a persistently elevated risk of SPMs 15 years from the time of initial clinical stage I testicular seminoma diagnosis (O/E, 1.29; 95% CI, 1.10–1.49).

CONCLUSIONS

• ? We confirmed the increased risk of SPMs after EBRT for seminoma, and we identified the specific types of SPMs that develop.
• ? The risk of EBRT‐associated SPM persists for years after the initial seminoma diagnosis, and patients should be informed about these long‐term risks.

     

Patterns of care in the management of seminoma stage I: results from a European survey

Study Type – Therapy (practise pattern survey) Level of Evidence 3b What's known on the subject? and What does the study add? The uncertainties about differences in relapse and rates of other late events such as second malignancy and cardiovascular events for the three post‐orchidectomy strategies in seminoma stage I patients has led to debates about whether the three strategies are equally effective and safe. The differences in interpretation of the data as well as the debates are likely to result in differences in treatment after orchidectomy in seminoma stage I patient management. Current care patterns after orchidectomy are, however, unknown. We assessed patterns of care for seminoma stage I patients after orchidectomy by distributing a survey among doctors treating such patients across Europe. The 969 respondents showed large differences in care strategies between specialties and countries that indicate the need for research into long‐term relapse rates and long‐term adverse effects to standardize and optimize care for seminoma stage I patients.

OBJECTIVE

• ? To assess precise patterns of care after orchidectomy in Europe for stage I seminoma patients, we aimed to perform a survey among doctors in the various European countries.

PATIENTS AND METHODS

• ? We distributed a survey in 2009 and 2010 among American Society of Clinical Oncology and European Association of Urology members.

RESULTS

• ? In total, 969 questionnaires were included in the analysis. More than half of the 969 physicians (58%) currently offer only one post‐surgical treatment: 18% only surveillance, 19% only radiotherapy and 21% only chemotherapy. Thirteen percent of the 969 physicians currently offer all three strategies, 25% offer surveillance and adjuvant radiotherapy or chemotherapy, and 5% offer either adjuvant radiotherapy or chemotherapy without surveillance.
• ? We found large differences in care patterns between specialties and countries. Even within countries, care after orchidectomy was not standardized.
• ? Before 2005, 73% of the physicians offered only one treatment and of those 51% gave adjuvant radiotherapy.

CONCLUSIONS

• ? Large differences in pattern of care after orchidectomy for stage I seminoma patients exist between specialties and countries within Europe.
• ? More information on long‐term relapse rates and long‐term adverse effects of the three strategies is needed to standardize and optimize care after orchidectomy.

     

Upper gastrointestinal hemorrhage as a rare extragonadal presentation of seminoma of testis

A rare case of a gastric presentation of a seminoma with burned out primary testicular tumor is described. The patient initially presented with upper gastrointestinal hemorrhage. Endoscopic biopsies were suggestive of seminoma, and testicular ultrasound revealed a focal lesion and testicular microcalcification. Treatment consisted of bilateral orchidectomy, followed by four cycles of etoposide and bleomycin, where a complete response was achieved. Testicular histology was consistent with the "burned out" phenomenon and no tumor cells were found. There are only two previously reported cases of extragonadal seminoma in the stomach.     

Current treatment options for clinical stage I seminoma

Adjuvant radiotherapy, surveillance, and single-agent carboplatin chemotherapy are all accepted treatment options for clinical stage (CS) I seminoma with cure rates approaching 100%. Low-dose (25–35 Gy) adjuvant radiotherapy to the retroperitoneum and ipsilateral pelvis has been the mainstay of treatment for decades and is associated with excellent long-term survival and acceptable short-term toxicity. The use of lower radiation doses (20 Gy) and the omission of pelvic radiation have been investigated to reduce toxicity. However, the risk of late toxicity (specifically cardiovascular disease and secondary malignant neoplasms) resulting from radiation exposure have diminished the appeal of this approach, particularly given the fact that 80–85% of patients are cured by orchiectomy. The appeal of surveillance is the avoidance of treatment-related morbidity in 80–85% of patients and the successful salvage of relapses with 30–35 Gy radiotherapy in most cases. However, given the prolonged time course to relapse in CS I seminoma on surveillance, long-term follow-up with frequent abdominal–pelvic imaging is required. Single-agent carboplatin is associated with comparable short-term relapse rates to adjuvant radiotherapy with the potential for decreased long-term toxicity. However, concerns about the risk of inadequate therapy and late toxicity limit the acceptance of this approach until long-term results are available. With potential of avoiding treatment-related toxicity without compromising curability and given the overall low risk of occult metastasis in clinical stage I seminoma, surveillance is the recommended treatment option. Adjuvant dog-leg radiotherapy is the preferred approach for non-compliant patients or those unwilling to go on surveillance.     

Clinical stage I seminoma: the case for surveillance

We believe that active surveillance is the optimal choice for compliant men who are able to handle the mental burden of not receiving adjuvant treatment. This takes into consideration the fact that a small number of men with clinical stage I (CSI) seminoma on surveillance will recur but are salvageable with equivalent outcome compared to those having adjuvant treatment which exposes eight in ten men to unnecessary short- and long-term risks with still the possibility of recurrence requiring salvation. This review will focus on CSI seminoma and the controversies surrounding its treatment and based upon current available evidence will outline the case for surveillance.     

Case of mediastinal seminoma with testicular microlithiasis

Testicular microlithiasis is a rare condition in which calcified concretions fill the lumina of the seminiferous tubules. We report the case of a 19-year-old Japanese man with mediastinal seminoma, normal testicular physical findings and bilateral testicular microlithiasis seen on ultrasonography. Testicular needle biopsy demonstrated multiple laminated calcifications within the seminiferous tubules without any signals of a viable germ cell tumor. To our knowledge, this is only the sixth reported case of extragonadal germ cell tumor with testicular microlithiasis.     

Late relapse (>2 years) on surveillance in stage I non‐seminomatous germ cell tumours; predominant seminoma only histology

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVES

Surveillance is a standard management approach following orchidectomy for stage I non‐seminomatous and mixed germ cell tumours. Patients who relapse following this approach are treated with cisplatin‐based chemotherapy, with retroperitoneal lymph node dissection considered for patients with post‐chemotherapy residual masses.

PATIENTS AND METHODS

We reviewed the clinicopathological data for all patients who relapse greater than 24 months after commencing our surveillance programme.

RESULTS

Between 1989 and 2008, 453 patients with a median age of 30 years were entered into our surveillance program for stage I non‐seminomatous germ cell tumours (NSGCTs) after orchidectomy alone. All primary tumour specimens contained NSGCT, with seminomatous elements identified in 168 cases (37%). One‐hundred patients (22%) relapsed and the majority of relapses occurred within the first 2 years (76 ≤ 12 months, 15 ≥ 12 months ≤ 2 years). Nine patients relapsed after more than 2 years of surveillance. We found a high incidence of pure seminoma (56%) at sites of metastatic disease in this group. All late‐relapsing patients were alive and disease free at a median follow up of 45 months from relapse.

CONCLUSIONS

We recommend that late‐relapsing patients with normal serum alpha fetoprotein levels undergo biopsy to define histologically the nature of recurrent disease. In those with pure seminoma retroperitoneal lymph node dissection for post chemotherapy residual masses can be avoided.     

Retroperitoneal lymph node dissection for high-risk stage I and stage IIA seminoma

Introduction: The clinical results of radiotherapy in low-stage seminoma are excellent with negligible early morbidity. However, in a long-term follow-up various complications may occur. On the other hand, experience in nonseminomas shows that surgical morbidity has decreased markedly after invention of a nerve-sparing technique. These issues served as a rationale for us to perform the primary retroperitoneal lymph node dissection (RPLND) in seminoma patients. Materials and methods: Fourteen pure seminoma patients (10 high-risk stage I and four with clinical stage IIA) underwent nerve-sparing RPLND from September, 1997 to December, 2002. Results: Pathological evaluation revealed lymph node involvement in three out of 10 clinical stage I and in all four stage IIA cases. The patients’ acceptance of the surgery was good. Minor intra- and early postoperative complications were observed in two cases. Antegrade ejaculation was preserved in all patients. No retroperitoneal or distant recurrences have been observed. All patients were free of disease with the mean follow-up period of 56 months. Conclusion: The excellent results and minimum morbidity of nerve-sparing RPLND together with the increased concerns on late complications of radiotherapy may turn the preference of surgery in low-stage seminoma into the subject of future discussion.     

Treating stage I nonseminomatous germ cell tumours with a single cycle of chemotherapy

OBJECTIVE: To estimate the rate of relapse in men with stage I nonseminomatous germ cell tumours (NSGCT) of the testis treated with one cycle of chemotherapy instead of the usual two cycles. PATIENTS AND METHODS: Between 1992 and 1996, 22 men with stage I NSGCT who had normalized tumour markers after orchidectomy and negative findings on computed tomography, and who were at moderate risk of relapse, were treated with one cycle of platinum-containing chemotherapy (bleomycin and etoposide with either cisplatin or carboplatin). RESULTS: At a median follow-up of 10.2 years, none of the patients have relapsed with malignant GCTs. CONCLUSION: The results after one cycle of chemotherapy are no worse than after two cycles. The present study needs to be replicated in a larger cohort of patients to define the relapse risk more accurately. This approach is soon to be tested in a large multicentre trial randomizing patients between one and two cycles.     

Population based incidence and age distribution of spermatocytic seminoma

PURPOSE: Spermatocytic seminoma is a rare subtype of testicular germ cell tumor which has been reported to occur in elderly men. We report the first population based estimate of incidence, temporal trends and age distribution of this tumor. MATERIALS AND METHODS: All cases of primary testicular cancer identified by cancer registries in Australia between 1982 and 2002 were available for analysis. The International Classification of Diseases for Oncology code M-9063/3 was used to identify spermatocytic seminomas. Incidence trends were modeled using Poisson regression. RESULTS: There were 58 cases of spermatocytic seminoma out of 9,658 cases of primary malignant testicular neoplasms identified by the cancer registries. This tumor comprised 1.1% of all seminoma and the age standardized incidence rate was 0.4 per million (95% CI 0.3-0.6). A temporal increase in incidence was found but not one reaching statistically significance. Age at diagnosis ranged from 19 to 92 years with a mean of 53.5 (SD 16.7) and a median of 54 years. CONCLUSIONS: Spermatocytic seminoma should be considered in the differential diagnosis for testicular germ cell tumors presenting in young adults because this tumor occurs as often in men younger than 55 years as it does in older men. Although rare, the occurrence of this tumor is not as singular as the current literature suggests.     

Long-term Results of Adjuvant Irradiation or Surveillance in Stage I Testicular Seminoma

Background : Excellent treatment results are obtained for stage I testicular seminoma treated with orchiectomy and prophylactic radiotherapy. In patients with stage I nonseminomatous testicular tumors, surveillance alone is successful, however, this treatment option for stage I testicular seminomas is controversial. There have been few reports of long-term follow-up of surveillance alone for patients with stage I testicular seminoma.
Methods : To assess the appropriateness of this treatment option, a retrospective survey of stage I testicular seminoma was undertaken. Twenty-seven patients who underwent prophylactic radiation therapy (RT group) and 41 patients followed only by surveillance (S group) after high orchiectomy were evaluated. Their follow-up consisted of frequent clinical examinations, abdominal CT scans, chest x-rays and serum tumor markers.
Results : In the RT group, with a median follow-up period of 15 years, 1 patient (3.6%) had a recurrence in the lung at 4 months after orchiectomy and died, but the remaining 26 are alive with no evidence of disease (NED). In the S group, with a median follow-up period of 7.3 years, 5 (12.2%) relapsed in the retroperitoneal lymph nodes, but all are alive with NED following chemotherapy. The remaining 36 are all alive without recurrence (follow-up period, 38 to 132 months). Although the relapse rate in the S group was relatively higher than in the RT group, there was no significant difference between the 2 groups.
Conclusion : If a frequent follow-up protocol is administered and followed by the patient, surveillance alone may be a recommended management for stage I testicular seminoma.     

The significance of resections for residual masses after chemotherapy in metastatic testicular tumors

BACKGROUND: After chemotherapy for metastatic testicular tumors, masses may remain, often in the metastatic sites. This study analyses the role of resections for the residual masses. METHODS: Seventy-seven patients with advanced (stage II, III) testicular tumors were treated. Of these, 38 patients, including eight with seminoma and 30 patients with non-seminomatous germ cell tumors, underwent resection of residual masses after chemotherapy and have been followed for a median of 41.5 months (range 2-138) after the resection. RESULTS: Residual masses were necrosis/fibrosis in 19 patients, mature teratoma in 11 and cancer in eight. The ratio of cancer in stage III (41.2%) was significantly higher than that in stage II (4.8%). Ten of 38 (26.3%) patients experienced recurrences in sites other than the resected sites, and five of 10 patients have died of cancer. Most recurrences (80%) occurred within two years. Recurrences after resection were detected in 4.8% of stage II patients, 52.9% of stage III, 16.7% of necrosis/fibrosis and mature teratoma, and 62.5% of cancer. The survival rate of patients with cancer was significantly lower in spite of adjuvant chemotherapy after surgery. CONCLUSIONS: Resection for residual masses after chemotherapy in metastatic testicular tumors was useful in confirming the tissue and in controlling the metastatic sites. Recurrences were often found in patients with cancer in the residual mass and the prognosis of patients with cancer was poor, therefore the development of more effective therapy for patients with cancer is required to improve the prognosis.     

Limitations to the use of surveillance as an option in the management of stage I seminoma

Improved definition of seminoma using step sections and tumour markers makes such patients a more selected group than when radiotherapy was first introduced. This and the improvements in radiological staging and the exquisite sensitivity of metastatic seminoma to chemotherapy justifies reappraisal of the role of prophylactic radiotherapy. To investigate this, twenty-six patients have been entered onto a programme of prospective biochemical and radiological surveillance. Though only four (15%) have relapsed, and all easily salvaged by chemotherapy, the relative difficulty and lateness of establishing the diagnosis makes this approach unsuitable for service use. Whether given the chemosensitivity of seminomas, radiotherapy would remain the treatment of choice compared to short courses of adjuvant carboplatin requires testing in a randomized trial.     

Stage I seminoma of the testis: a bi-institutional retrospective analysis of patients treated with radiation therapy only

OBJECTIVE: To analyse relapse patterns, toxicity and second malignancy in patients with stage I pure germ cell testicular tumours, treated in 1970-1999. PATIENTS AND METHODS: In all, 487 patients received irradiation after surgery to the infra- (407, 83.5%) or infra- and supra-diaphragmatic volumes (80, 16.5%). Treatment-related toxicity was classified according to previous criteria and fertility investigated in 246 men. Second malignancies were identified by retrospective analysis of clinical records or telephone interviews in men who no longer needed a long-term follow-up. RESULTS: The 10-year overall survival was 97% (98% and 96%, respectively, for the aortic nodes only, or aortic and iliac nodes, i.e. the 'dog leg' field) and disease-free survival was 94%. Twenty-one patients relapsed (five with a true 'in-field' recurrence, nine progressed to the mediastinum, and seven had disseminated disease). Acute toxicity was mainly gastrointestinal, with 7.6% classified as grade II. In all, 73 men achieved paternity after irradiation; nine did not but had normal sperm. Second malignancies were diagnosed in 16 (3.3%) men. CONCLUSION: Para-aortic irradiation may be used safely in patients with stage I seminoma and undisturbed testicular drainage, with equivalent results to the 'dog-leg' group; these unrandomized data confirm the lower toxicity and equivalent survival rates of this treatment.