Surveillance following orchiectomy for stage I testicular seminoma: Long-term outcome

Objectives:   To report the long-term outcome of surveillance for stage I seminoma at a single institution in Japan.
Methods:   A retrospective review of medical records of 64 patients who underwent orchiectomy between January 1982 and December 2005 was carried out. All of them were managed by surveillance for stage I seminoma.
Results:   Median follow-up time was 123.8 months. Of the 64 patients, seven developed relapse. Four relapses occurred within the first year after orchiectomy, but three occurred over 4 years after orchiectomy. The actuarial relapse-free rates at 5, 10, and 15 years were 92.1%, 90.0%, and 86.0%, respectively. All patients received salvage chemotherapy at relapse. Four of these seven patients were alive without evidence of disease. One patient died of seminoma and one was alive with this disease. The remaining one patient died of leukemia without secondary relapse of seminoma. T classification was a statistically significant ( P  = 0.028) risk factor for relapse on univariate analysis. In T1 patients, relapse-free rates at 5, 10, and 15 years were all 97.1%, whereas in T2/T3 patients the corresponding relapse-free rates were 86.4%, 82.1%, and 71.8%, respectively.
Conclusions:   The relapse-free rate in the present study was similar to previous reports. Late relapse should be considered during surveillance.     

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.

     

Primary seminoma of the prostate

A 54‐year‐old gentleman was suspected of having sarcoma of the prostate because of his low serum prostate‐specific antigen level (1.9 ng/mL) and an enlarged heterogeneous mass on computed tomography and magnetic resonance imaging scans. Pathological examination of the prostate needle biopsy indicated seminoma, which was confirmed with immunohistochemical staining. There was no evidence of disease in other areas on physical examination or on radiographic tests. Therefore, we diagnosed the case as a primary seminoma of the prostate, which was consequently treated with a total of three courses of bleomycin, etoposide and cisplatin chemotherapy. Complete response was obtained on computed tomography, magnetic resonance imaging and prostate needle re‐biopsy. To our knowledge, there have only been five cases of primary seminoma of the prostate reported.     

Outcome of different post‐orchiectomy management for stage I seminoma: Japanese multi‐institutional study including 425 patients

Objectives: To clarify the contemporary clinical outcome of stage I seminoma and to provide information on treatment options to patients. Methods: A retrospective analysis of 425 patients who underwent orchiectomy for stage I seminoma between 1985 and 2006 at 25 hospitals in Japan. Relapse‐free survival rates were calculated using the Kaplan–Meier method and clinicopathological factors associated with relapse were examined by univariate and multivariate analyses using the Cox proportional hazards model. Results: A total of 30 out of 425 patients had relapsed. Relapse‐free survival rates at 10 years were 79, 94 and 94% in the surveillance, chemotherapy and radiotherapy groups, respectively. Post‐orchiectomy management and rete testis invasion were identified as independent predictive factors associated with relapse. Rete testis invasion remained to be an independent predictive factor, even if the cases with relapses in the contralateral testis were censored. Only one patient, who relapsed after adjuvant radiotherapy, died of the disease. Overall survival at 10 years was 100, 100 and 99% in the surveillance, chemotherapy and radiotherapy groups, respectively. More than half of the patients were lost to follow up within 5 years. Conclusions: The outcome of Japanese patients with stage I seminoma is similar to previously published Western reports. Surveillance policy is becoming a popular option in Japan, although the relapse rate in patients opting for surveillance policy is higher than those opting for adjuvant chemotherapy or radiotherapy. Rete testis invasion is an independent predictive factor associated with relapse regardless of the post‐orchiectomy management. Long‐term follow up is mandatory for detection of late relapse.     

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.     

Retrospective analysis of 74 cases of seminoma treated with radiotherapy

BACKGROUND: Standard post-orchiectomy radiotherapy (RT) is accepted as a standard management option for stage I seminoma. METHODS: Retrospective evaluation of 74 patients with stage I seminoma was performed according to the Royal Marsden staging system. All of the patients underwent RT in the Radiation Oncology Department of Gülhane Military Medical Academy between 1974 and 1995. The median age of patients was 27 years (range, 20-56). Radiotherapy was applied to all of the patients after orchiectomy for adjuvant purposes. Sixty-nine patients underwent RT while five patients who had recurrence received chemotherapy following radiotherapy. RESULTS: After a mean follow-up period of 54 months, the 5-year overall survival rate was 98.61%, which complied with the literature. The disease-free survival rate was 90.54%. According to the World Health Organization toxicity scale, acute enteritis was 9.4% for grade I and 5.4% for grade II, while nausea/vomiting was 36.4% for grade I and 5.4% for grade II. CONCLUSION: To avoid acute toxicity related to RT, prognostic risk factors should be well-known and patients with low risk factors should be monitored carefully after orchiectomy. RT should be directed to the para-aortic +/- ipsilateral pelvic lymph nodes in high risk patients. Although post-orchiectomy RT is a traditional management option for clinical stage I seminoma, the results of RT should be well-known to compare it with other treatment options (e.g. RPLND, adjuvant chemotherapy and surveillance).     

Guideline of guidelines: follow-up after orchidectomy for clinical stage 1 testicular cancer

Several medical organisations have developed evidence-based guidelines for the diagnosis, management, and follow-up of testicular cancer. This article aimed to review, compare, and summarise the most updated international guidelines and surveillance protocols for clinical stage 1 (CS1) testicular cancer. We reviewed a total of 46 articles on proposed follow-up strategies for testicular cancer, and six clinical practice guidelines including four guidelines published by urological scientific associations and two guidelines published by medical oncology associations. Most of these guidelines have been developed by panels of experts with different backgrounds in clinical training, and geographic practise patterns, which explains the considerable variability between published schedules, and recommended follow-up intensity. We present you with a comprehensive review of the most important clinical practice guidelines and propose unifying recommendations based on the most up to date evidence to help standardise follow-up schedules based on patterns and risk of disease relapse.     

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.     

Pelvic recurrence in stage I seminoma: A new phenomenon that questions modern protocols for radiotherapy and follow-up

OBJECTIVE: To highlight the increased risk for pelvic relapse in patients with stage 1 seminoma treated with adjuvant radiotherapy limited to para-aortic template alone. PATIENTS AND METHODS: Over a four-year period, three patients presented with early pelvic recurrence after radical orchidectomy and adjuvant irradiation for stage 1 seminoma. In each case, radiotherapy had been limited to the para-aortic region with omission of the ipsilateral hemi pelvis. RESULTS: Pelvic recurrences occurred on the ipsilateral tumor side. Durable complete remission was achieved in each case; however, treatment was complex and there was associated morbidity. CONCLUSION: This significant incidence of pelvic recurrence questions the validity of modern radiotherapy protocol which excludes the ipsilateral pelvis from the radiation field.     

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.