Lothar Weissbach

Risk Factors for Relapse in Clinical Stage I Nonseminomatous Testicular Germ Cell Tumors: Results of the German Testicular Cancer Study Group Trial

PURPOSE To prospectively assess potential risk factors for relapse in clinical stage I nonseminomatous germ cell tumors of the testis (CS I NSGCT). PATIENTS AND METHODS From September 1996 to May 2002, 200 patients with CS I NSGCT were prospectively assigned to retroperitoneal lymph node dissection (RPLND), and risk factor assessment was performed within a multicenter protocol. One hundred sixty-five patients had an adequate minimum follow-up of 12 months (mean, 34.5 months) or had pathologic stage II. RESULTS Pathologic stage II disease was found in 27.9% of patients. Only 0.6% of patients relapsed in the retroperitoneum after confirmation of pathologic stage I disease. With reference pathology, vascular invasion (VI) was most predictive of stage in multifactorial analysis (accuracy, 65.1%). However, the positive predictive value (PPV) of VI to predict patients who have metastatic disease or relapse during follow-up was only 52.7%. With absent VI, low-risk patients had a negative predictive value (NPV) of 76.9%. With a combination of several risk factors, the PPV increased to 63.6% and the negative predictive value increased to 86.5%. CONCLUSION Even with an optimal combination of prognostic factors and reference pathology, more than one third of patients predicted to have pathologic stage II or relapse during follow-up will not harbor metastatic disease and, therefore, would be overtreated with adjuvant therapy. However, patients at low risk may be predicted at an 86.5% level, and thus, surveillance in highly compliant patients would be a valuable option. For high-risk patients, further reduction of adjuvant treatment is necessary.

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

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

[18F]Fluorodeoxyglucose Positron Emission Tomography in Nonseminomatous Germ Cell Tumors After Chemotherapy: The German Multicenter Positron Emission Tomography Study Group

PURPOSE In patients with metastatic nonseminomatous germ cell cancer (NSGCT), residual masses after chemotherapy (CTX) can consist of vital carcinoma, mature teratoma, or necrosis. This prospective trial has evaluated the accuracy of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) for the prediction of histology compared with computed tomography (CT) and serum tumor markers (STM). PATIENTS AND METHODS A total of 121 patients with stage IIC or III NSGCT scheduled for secondary resection after cisplatin-based CTX were included. FDG-PET was performed after completion of CTX. All results were confirmed by histopathology and correlated to STM and CT. RESULTS Prediction of tumor viability with FDG-PET was correct in 56%, which did not reach the expected clinically relevant level of 70%, and was not better than the accuracy of CT (55%) or STM (56%). Sensitivity and specificity of FDG-PET were 70% and 48%. The positive predictive values were not significantly different (55%, 61%, and 59% for CT, STM, and PET, respectively). Judging only vital carcinoma as a true malignant finding, the negative predictive value increased to 83% for FDG-PET. CONCLUSION The presence of vital carcinoma and mature teratoma is common (55%) in residual masses in patients with NSGCT, and CT and STM cannot reliably predict absence of disease. In contrast to prior studies, this prospective trial, which is the only with histologic confirmation in all patients, demonstrated that FDG-PET is unable to give a clear additional clinical benefit to the standard diagnostic procedures, CT and STM, in the prediction of tumor viability in residual masses.

Organ Preserving Surgery of Malignant Germ Cell Tumors

If a tumor arises in a solitary testis the patient loses fertility and requires lifelong androgen substitution. We describe the technique and results of organ preserving enucleation resection performed in 14 patients. The tumor was excised under (cold) ischemia via a mini-surgical technique using 2-fold magnification and blood vessels were localized intraoperatively by Doppler sonography. The procedure was successful in 10 of 14 patients. In 2 patients the organ required ablation later because of insufficient blood supply. Two patients had subnormal testosterone levels after treatment. There were no local recurrences. Prerequisites for this type of treatment are detailed knowledge of the vascular anatomy of the testis, tumor not too close to the rete testis, largest diameter 20 mm. or less, normal preoperative plasma testosterone level, postoperative local irradiation with 20 Gy., followup biopsies and hormonal status obtained 6 months after enucleation resection, and meticulous followup for early detection of local recurrences or systemic progression.

Bilateral testicular tumor.

Of 396 cases of bilateral testicular tumors reported in the literature through 1979 the tumors were the same histologically in 217 cases (seminoma in 163 and nonseminoma in 54), different in 47 and malignant lymphomas in 68; no histological details were given in 64 cases. In our 18 cases of bilateral testicular tumors the tumors were the same histologically in 5 patients (seminoma in 4 and nonseminoma in 1), different in 6 and malignant lymphomas in 7. The epidemiology, interval between the first and second tumors, histology, diagnosis, therapy and prognosis are discussed. Diagnostic measures are determined by the histology of the first tumor and its treatment. Therapy of the second tumor depends on the interval between the 2 tumors as well as on histologic differentiation of the second tumor. The exceptions in the diagnosis, therapy and prognosis for malignant lymphomas are discussed. We do not believe that the prognosis in cases of bilateral germinal cell tumors is poor.

Stages of the Cycle of the Seminiferous Epithelium in the Dog

Stadieneinteilung der normalen Spermatogenese beim Hund

Chemotherapy Is of Limited Efficacy in the Control of Contralateral Testicular Intraepithelial Neoplasia in Patients with Testicular Germ Cell Cancer

Introduction: Testicular intraepithelial neoplasia (TIN, also called carcinoma in situ of the testis), the precursor of testicular germ cell tumors, will progress to invasive cancer unless appropriate treatment is instituted. Orchiectomy and local radiotherapy have been shown to eradicate TIN safely. The efficacy of chemotherapy is equivocal to date. Patients and Methods: Eleven patients with unilateral testicular cancer (5 pure seminoma, 6 nonseminoma) and biopsy-proven contralateral TIN underwent chemotherapy. Four patients received 2 courses of carboplatin single agent, 4 had 2 courses of platin, etoposide, bleomycin (PEB) treatment and 3 had a full 3-cycle treatment with PEB. Rebiopsy to look for persistent TIN was performed after a mean interval of 8.8 months (range 2–31). The patients were then followed clinically. Results: Five patients had persistent TIN upon rebiopsy. Each of the patients failing to chemotherapy had undergone 2 or 3 cycles of the PEB regimen, while 3 had received carboplatin treatment. Two of the patients with no TIN upon rebiopsy developed invasive testis cancer subsequently. In summary, 7 of 11 patients thus failed to chemotherapy (64%; exact 95% confidence interval 30.8–89.1%). Three of the patients had complete absence of spermatogenesis upon rebiopsy histologically, while the remaining cases showed various forms of spermatogenetic arrest. Three of the failing patients were rescued by local radiotherapy, 4 patients underwent partial orchidectomy followed by local radiotherapy. No relapse occurred thereafter. Conclusions: Chemotherapy was shown to be of only littleeffect in eradicating TIN. The failure rate of 64% is much higher than reported previously. As the majority of failing cases had received carboplatin single-agent therapy or adjuvant PEB therapy with 2 cycles, it may be speculated that the efficacy of chemotherapy regarding TIN clearance is dose dependent. Multidrug regimens appear to be more efficacious than single-agent therapy. As spermatogenesis is only incompletely eliminated by chemotherapy, it is postulated that chemotherapy does no more than temporarily suppress TIN, while only selected cases are cleared of the lesion. Practically, rebiopsy to look for retained TIN about 2 years after completion of chemotherapy is valuable.

German second-opinion network for testicular cancer: Sealing the leaky pipe between evidence and clinical practice

In 2006, the German Testicular Cancer Study Group initiated an extensive evidence-based national second-opinion network to improve the care of testicular cancer patients. The primary aims were to reflect the current state of testicular cancer treatment in Germany and to analyze the project’s effect on the quality of care delivered to testicular cancer patients. A freely available internet-based platform was developed for the exchange of data between the urologists seeking advice and the 31 second-opinion givers. After providing all data relevant to the primary treatment decision, urologists received a second opinion on their therapy plan within <48 h. Endpoints were congruence between the first and second opinion, conformity of applied therapy with the corresponding recommendation and progression-free survival rate of the introduced patients. Significance was determined by two-sided Pearson’s χ2 test. A total of 1,284 second-opinion requests were submitted from November 2006 to October 2011, and 926 of these cases were eligible for further analysis. A discrepancy was found between first and second opinion in 39.5% of the cases. Discrepant second opinions led to less extensive treatment in 28.1% and to more extensive treatment in 15.6%. Patients treated within the framework of the second-opinion project had an overall 2-year progression-free survival rate of 90.4%. Approximately every 6th second opinion led to a relevant change in therapy. Despite the lack of financial incentives, data from every 8th testicular cancer patient in Germany were submitted to second-opinion centers. Second-opinion centers can help to improve the implementation of evidence into clinical practice.

Patient–physician communication and health-related quality of life of patients with localised prostate cancer undergoing radical prostatectomy – a longitudinal multilevel analysis

To examine whether patient–physician communication is associated with health‐related quality of life (HRQoL) in a sample of patients with localised prostate cancer undergoing radical prostatectomy (RP).

Clinical and Endocrinological Characterization of Two Subjects with Reifenstein Syndrome Associated with Qualitative Abnormalities of the Androgen Receptor

The androgen receptor in fibroblasts cultured from a biopsy of scrotal skin from 1 subject with Reifenstein syndrome has been found to be normal in amount and to bind dihydrotestosterone with normal affinity but to be qualitatively abnormal as evident by thermolability and instability upon ultracentrifugation. The family study of this subject and endocrine studies document androgen resistance in the index patient and his affected uncle. These findings provide evidence for X-linkage of this disorder, and suggest that the mutations that give rise to this phenotype are probably allelic to the mutations of the androgen receptor that cause testicular feminization.