Predictors of residual mass histologyafter chemotherapy for advanced testis cancer

The records of 15 patients with Stage B3 or B2/C germ cell testis tumors who underwent full surgical debulking of a residual mass after completion of chemotherapy were reviewed retrospectively to look for predictors of residual mass histology. The density, character, and change in volume of the retroperitoneal mass on computerized tomography before and after chemotherapy were compared with the histology in the primary tumor and in the residual mass. One of 6 patients without teratoma in the primary tumor had a 97 percent reduction in the mass which contained residual teratoma. Two patients with residual seminoma had a 50 percent decrease in tumor volume, and both patients died of tumor progression despite salvage chemotherapy. Two patients with pure seminomas had only residual fibrosis in masses that decreased in volume by 77 and 75 percent, respectively. One of these masses was discrete and the other was diffuse. Seven of 9 patients (78%) with teratoma in the primary tumor had either teratoma (4 of 9, 44%) or carcinoma (3 of 9, 33%) in the residual mass, and the change in mass volume ranged from a 93 percent decrease to a 540 percent increase in size. All 7 patients with residual teratoma and/or carcinoma remain free of disease after observation or further chemotherapy. For the entire series, the mass density and character did not correlate consistently with the primary tumor or residual mass histology. Residual fibrosis alone or teratoma and/or carcinoma were seen with least (0 to 50%) and greatest (more than 90%) decreases in mass volume.     

Status epilepticus in MVEC chemotherapy of urothelial cancer

We present a patient with an urethral urethelial carcinoma (T3N2M0) treated by chemotherapy with methotrexate, vinblastine, epirubicin and cisplatin, which induced a non-convulsive status epilepticus. In this report the possible mechanism for this phenomenon and its management are discussed.     

The contemporary role of chemotherapy for advanced testis cancer: a systematic review of the literature

Context

Germ cell tumours (GCTs) of the testis are the most common cancer in young men; they are also one of the most curable cancers. Standard treatment of metastatic GCTs has evolved on the basis of randomised trials and prognostic factors.

Objective

This review summarises the evolving role of chemotherapy in the treatment of previously treated and untreated patients with metastatic GCTs and outlines the current standard treatment.

Evidence acquisition

Randomised and nonrandomised trials of first-line, salvage, and palliative therapy were reviewed.

Evidence synthesis

Three cycles of standard bleomycin, etoposide, and platinum (BEP) can be considered the gold-standard treatment in good-risk patients, and four cycles of the same combination can result in cure in approximately 80% of intermediate-risk and 50% of poor-risk patients. The routine use of high-dose chemotherapy in patients with intermediate- or poor-prognosis GCT has not improved treatment outcome, but the role of tumour marker decline during the first cycles may provide useful prognostic information. Prognostic variables in patients who experience treatment failure after cisplatin-based chemotherapy can be used to guide salvage strategies, and many new drugs or combinations have shown activity in this setting. Patients and physicians should be aware of the risk of short- and long-term toxicity of treatments, and guidelines for screening and prevention of this risk should be established.

Conclusions

A risk-based strategy offers the best chance of cure, even in patients with refractory GCT.     

Quality of care for testis cancer

This article explores the delivery of high quality care in patients with testicular cancer. Critical issues relate to an individualized, risk-stratified, and multidisciplinary approach to patient care at centers of excellence and subsequent close patient follow-up. The necessary integration of multiple therapeutic modalities makes testis cancer outcomes highly susceptible to variations in quality of care, which deserves further investigation in well designed population-based studies.     

Distribution of nodal metastases after chemotherapy in nonseminomatous testis cancer: a possible indication for limited dissection

OBJECTIVE: To assess the clinical and pathological findings of patients treated by bilateral retroperitoneal lymph node dissection (RPLND) after chemotherapy, to identify a subset for whom modified template nodal resection might be contemplated, as bilateral RPLND is the treatment of choice in patients with residual retroperitoneal disease after chemotherapy for nonseminomatous germ-cell tumour (GCT). PATIENTS AND METHODS: The medical records were reviewed of 50 consecutive patients who had RPLND after chemotherapy between 1996 and 2005. Bilateral template RPLND was performed uniformly. Extracted lymph nodes were surgically stratified into three distinct anatomical zones by two sagittal planes running in front of the aorta and the inferior vena cava. The pathological findings were correlated with the side of the primary lesion and the extent of metastatic disease before chemotherapy. RESULTS: Pathological assessment of the resected lymph nodes revealed teratoma in 28 patients (56%), viable carcinoma in three (6%), and necrosis or fibrosis in 19 (38%). All clinical stage Is, IIA and IIB left-sided primary tumours followed a predictable pattern of spread constricted to a modified left-sided template. Patients with clinical stage IIC and III, or right-sided primary tumour, had a less predictable metastatic pattern, having crossover metastases to the contralateral template. CONCLUSION: Bilateral RPLND should be considered as the reference standard in patients with metastatic GCT and residual retroperitoneal mass after completing chemotherapy. However, the present data suggest that a modified template dissection might be considered even after chemotherapy in patients with left-sided primary tumours and limited nodal involvement at presentation.     

Recurrent testis cancer: seeding from retroperitoneal nodes after complete remissions by chemotherapy

Routine retroperitoneal lymph node dissection is generally not required after a complete remission is achieved by chemotherapy in initially disseminated nonseminomatous testis cancer. However, in patients with multiple relapses retroperitoneal lymph node dissection should be considered even if the retroperitoneum is unremarkable by radiographic staging. We report on a patient with initial stage III disease in whom a complete clinical response to chemotherapy was achieved multiple times but there was repeatedly re-seeding of the lungs from an undetected focus of nodal cancer later proved by retroperitoneal lymph node dissection. Controversies in management as well as potential mechanisms of drug resistance are discussed.     

Cis-platin combination chemotherapy for non-seminomatous germ-cell tumours of the testis

Eighteen patients with metastatic non-seminomatous germ-cell tumours (NSGCTs) of the testis were treated with cis-platin combination chemotherapy between 1979 and 1985. Three of the patients received chemotherapy after a staging lymphadenectomy (stage 2 disease) and were free of disease at follow-up. Fifteen patients with stage II disease and adverse prognostic factors or stage III disease received initial chemotherapy followed in 11 cases by surgical exploration. Eleven of these patients were free of disease at a median follow-up of 52 months, 1 was alive at 35 months with a mature teratoma, which is non-progressive, 2 died of their cancer, and 1 died of acute respiratory distress syndrome after surgery. The patients who failed to respond to therapy had associated bulky disease. The overall 5-year survival rate is 81%. Before the introduction of cis-platin there were no survivors among 9 patients with metastatic NSGCTs treated initially with chemotherapy. These findings indicate that the good results reported with cis-platin combination chemotherapy for NSGCTs are reproducible in other populations and centres.     

Role for retroperitoneal lymphadenectomy for testis cancer

There continue to be several controversies surrounding the role for retroperitoneal lymphadenectomy (RPL) in the management of patients with germ cell cancer of the testis. The initial treatment options for those with clinical stage I disease are surveillance (orchiectomy only), RPL or chemotherapy. Survival rates are similar with RPL and surveillance. Surgical morbidity has been reduced as techniques for RPL continue to improve. The likelihood of early or late (> 2 years) recurrence in the retroperitoneum is almost eliminated by RPL. Fewer follow-up computerized tomography scans of the abdomen are required and there are opportunities to reduce the duration and methods of follow-up, compared with surveillance. For patients with stage II disease, chemotherapy and RPL are equally effective initial treatment options but many patients require a combined approach. Initial RPL should be reserved for patients with smaller volume disease and possibly with lower preoperative marker levels. With RPL, patients are accurately staged and cured most of the time without double treatment. Approximately 30% of those with larger masses will have residual disease after initial chemotherapy and will require RPL as a second treatment. The third indication for RPL is to excise residual retroperitoneal masses following primary chemotherapy. Models to predict the presence of residual viable tumor, rather than necrosis only, at the time of surgery have been developed. If the orchiectomy specimen contained no teratoma, the tumor markers normalize after three or four courses of chemotherapy, and if the residual mass on computerized tomography scan is less than 2 cm in diameter, the rate of viable tumor may be low enough to omit RPL. In this way, the greater morbidity often associated with post-chemotherapy RPL may be avoided.     

Correlation of clonogenic growth with histologic diagnosis after resection of residual tissue following chemotherapy for nonseminomatous testis cancer

Patients who undergo chemotherapy for metastatic nonseminomatous germ cell cancer of the testis often undergo subsequent resection of residual tissue. We performed a retrospective review of 11 consecutive patients who had their resected residual tissue cultured in a soft agar clonogenic assay to determine if there were any biological data that could be obtained in this setting. Twelve assays were performed on the 11 patients. Some colony formation occurred in 10 of the 12 assays, including 4 of 5 assays in which cancer was found and 6 of 7 in which no cancer was found. The rate of colony formation, however, was significantly less for the noncancerous tissues than for the ones with cancer noted (p = 0.019). Three of the patients with cancer are dead, while all of those with benign tissue remain free of disease, with follow-up ranging from three to six years. Our data suggest that clonogenic growth from resected tissue after chemotherapy has the potential to supplement histologic findings, possibly as a predictor of the future biologic behavior of a patient's disease process.     

Impalpable testis cancer

OBJECTIVE: To assess the significance of ultrasonographically detected hypoechoic lesions of the testis when the clinical examination is normal, and to highlight the management difficulties thereafter. PATIENTS AND METHODS: Over a 2-year period four patients underwent radical orchidectomy where the sole indication for surgery was a hypoechoic lesion detected on ultrasonography (US). The indications for US were persistent scrotal discomfort in two men, contralateral orchitis, and the follow-up of testicular microlithiasis. The lesions were 4-11 mm in size and one man had several. None of the lesions were palpable; the tumour markers were normal in all patients. RESULTS: Three of the testes contained seminoma; in one there were two foci of seminoma and in all intratubular germ cell neoplasia was also identified. The remaining case was a Leydig-cell tumour. All tumours were staged as pT1 after radical inguinal orchidectomy. CONCLUSION: Impalpable lesions of the testis are likely to be malignant if they are hypoechoic on US and should be considered as seminoma until proved otherwise. The management thereafter is not straightforward, but must ensure an adequate histological diagnosis if the US appearances do not resolve.     

Adjuvant chemotherapy in non-seminomatous testis cancer: "mini-VAB" regimen: long-term followup

Since 40 to 50 per cent (range 20 to 80 per cent) of patients with stage II non-seminomatous germ cell tumors of the testis suffer relapse after orchiectomy and retroperitoneal lymph node dissection, relatively non-toxic adjuvant chemotherapy (consisting of vinblastine, actinomycin D, bleomycin and chlorambucil) was given to 62 patients after lymphadenectomy. Of these patients 82 per cent remained free of disease with a 4-year median followup and 18 per cent had relapse. Retrospective analysis reveals that no patient (0 of 33) with stage IIA and 38 per cent (11 of 29) with stage IIB disease had relapse. Patients with histologic evidence of extranodal extension of disease (N3 category) had the highest relapse rate (62 per cent). Based on our experience we recommend that patients with resected stage IIB disease, particularly those with extranodal extension of tumor, receive aggressive adjuvant chemotherapy.     

Refractory germ cell cancer of testis treated by salvage high-dose chemotherapy: report of three cases

We reported three cases (42, 20 and 18-year-old men) of advanced nonseminomatous testicular germ cell cancer treated by salvage high-dose chemotherapy (HDC) supported by peripheral blood stem cell autotransplantation. Two cases which had been refractory to (B) EP (bleomycin, etoposide, cisplatin) and VIP (etoposide, ifosfmide, cisplatin) chemotherapies received one course of high-dose CEI (carboplatin 1,250 mg/m2, etoposide 1,500 mg/m2 and ifosfamide 7.5 g/m2), and the other case had been refractory to PVB (cisplatin, vinblastine, bleomycin) and VIP chemotherapies received one course of high-dose CEI and high-dose CCT (carboplatin 800 mg/m2, cyclophosphamide 6 g/m2 and thiotepa 720 mg/m2). Only one case achieved an incomplete remission by HDC, which was verified as a pathological complete response at the following salvage surgery, and has been alive with no evidence of disease for 68 months. The others achieved no change of disease following HDC and died from cancer progression. Hepatotoxicity, neurotoxicity and severe depression occurred, but not fatal in 2 cases.     

Polyembrioma of the testis: case report following chemotherapy for non-Hodgkin's lymphoma

Testicular tumours represent 2% of all male malignancies, mostly concerning young men (20-40 years old). The polyembryoma is one of the uncommonest lesions and just recently it has been identified as autonomous nosographic entity. The reported case is peculiar because the patient was older than the most ones described in the literature and the tumour arose after polychemotherapy for non Hodgkins' disease. The Authors analyse some aspects concerning etiology, pathology and clinical approach to such rare neoplasm.     

Infertility and testis cancer

Testicular cancer is the most common solid organ tumor in young men and affects men during their reproductive years. Current therapeutic regimens have significantly improved survival but often adversely impact fertility. Understanding the effects of testicular cancer, the systemic effects of neoplasia, and the effects of treatment protocols, such as radiotherapy, chemotherapy, and retroperitoneal lymph node dissection, is essential to restoring and maintaining fertility in men who have germ cell neoplasms.