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Purpose: The aim of our study was to identify factors which influence survival in patients with disseminated seminoma in the good prognostic group according to IGCCCG, as well as to evaluate the impact of treatment intensification in patients with negative prognostic factors., Methods: We analyzed the database of the patients with metastatic seminoma who had received treatment at our department from 1986 to 2005. Inclusion criteria were as follows: morphologically verified seminoma; favorable prognosis according to IGCCCG; modern chemotherapy regimen (EP ± bleomycin); AFP level <15 IU/ml; and HCG level <300 mIU/ml. The primary endpoint was overall survival (OS)., Results: With median follow-up 83 months, 5-year OS rate was 91% in 206 patients. Only three negative prognostic factors were associated with OS: retroperitoneal lymph nodes >5 cm (p < 0.01), pulmonary metastases (p < 0.01) and LDH level ≥ 2.25 × ULN (p = 0.01). In view of the obtained data, we have changed our treatment approach since 2005. In case of any negative prognostic factors, we administered an intensified CT regimen--4BEP or 3BEP + 1EP. Prospective phase of the study included 34 patients with unfavorable prognosis. We observed an increase of 5-year OS rate in the intensified CT group in comparison with the standard CT group in patients with unfavorable prognostic from 85 to 100%., Conclusion: Administration of 4 cycles of induction CT (4BEP or 3BEP + 1EP) in patients with metastatic seminoma who have LDH level ≥ 2.25 ULN, and/or retroperitoneal lymph nodes >5 cm and/or pulmonary metastases results in decreased disease progression rate and significant gain in OS.

Objectives: Late relapses (>2 years) after completion of chemotherapy are rare and often platinum-resistant. There are limited data concerning late relapses in chemotherapy-naïve patients with stage I germ cell tumors. This retrospective analysis was performed to compare the outcome between patients with stage I germ cell tumors, who had late (≥2 years) and early (≥3 months and <2 years) relapse after orchiectomy., Methods and Materials: We analyzed data of 1,069 chemotherapy-naïve patients with advanced germ cell tumors of testis treated in our department from 1986 to 2008. All patients had cisplatin- and etoposide-based chemotherapy. We identified 169 (15.8%) patients with prior stage I disease, who had not received adjuvant treatment: 140 and 29 patients had early and late relapse, respectively. Among patients with late relapse, pure seminoma was revealed in 14 patients, and nonseminoma in 15 patients. Median follow-up time for 169 patients was 35 (range, 2-218) months., Results: Patients with late relapse were older, 35 years (23-57) and had more frequent pure seminoma in primary tumor, 14/29 (48.3%), than patients with early relapse, 30 years (16-63) (P = 0.0008) and 46/140 (32,8%, P = 0.08), respectively. At the time of disease progression, both groups were very similar according to well-known prognostic factors including IGCCCG classification. The only difference was larger size of retroperitoneal lymph nodes in late (9 cm) than in early relapse (4 cm, P < 0.0001). The outcome in patients with late relapse was significantly worse than in patients with early relapse: complete response rate after induction chemotherapy was 20.7% (6/29) vs. 42.1% (59/140) (P = 0.01), 3-year progression-free survival 66% vs. 84% (P = 0.02, HR = 2.4, 95% CI 1.2-8.8) and 3-year overall survival, 72% vs. 88% (P = 0.04, HR = 2.4, 95% CI 1.05-10.25), respectively. In patients with pure seminoma, this difference in overall survival was even more significant: 65% vs. 91% (P = 0.04, HR = 3.8, 95% CI 1.06-32.4)., Conclusions: Late relapses following stage I germ cell tumors were associated with seminoma, older age, and worse outcome after induction chemotherapy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The first stage in the treatment of disseminated germinogenic ovarian tumours (HOT) is induction chemotherapy in accordance with the IGCCCG prognosis group. Dynamic observation is indicated in case of incomplete induction in patients with seminoma excepting those with PET-positive residual tumours bigger than 3 cm to whom second-line chemotherapy or retroperitoneal lymphadenectomy is indicated. Ablation of residual tumour of any localization is indicated to patients with disseminated non-seminoma HOT (NHOT), incomplete induction, and negative level of tumour markers. The necessity of adjuvant chemotherapy in case of a viable malignant HOT in the removed tissues remains debatable. Refractory and recurring HOT are usually treated with a combination of fosfamide and vinblastine. Residual tumours need to be removed after salvation chemotherapy. Surgical treatment is the preferred option for the management of late NHOT relapses.

Postchemotherapy retroperitoneal lymph node dissection (RLND) was performed in 70 testicular non-seminoma patients with elevated serum tumor markers (age median 27.0 +/- 8.1 years) from 1983 to 2008. N1, N2, N3, Nx were diagnosed in 4 (5.7%), 10 (14.3%), 35 (50.0%), 21 (30.0%) patients. Distant metastases were present in 23 (32.9%) cases. The level of the initial tumor markers was elevated in all the patients: S1 - 169 (46.0%), S2 - 108 (29.4%), S3 - 51 (13.9%), Sx - 39 (10.6%). According to the IGCCCG prognostic model, 11 (15.7%) patients were classified as good, 19 (27.1%)--as moderate, 16 (22.9%)--as poor prognostic groups. The prognostic group was not identified in 24 (34.3%) cases which started treatment in other hospitals. All the patients received induction cisplatin-based chemotherapy following orchidectomy (first-line--24 (34.3%), second-line--46 (65.7%) which resulted in tumor shrinkage < 50% in 7 (10.0%), 51-90% in 23 (32.9%), > 90%--in 2 (2.9%) cases. The response was not properly assessed in 38 (54.3%) cases. CT scan revealed residual retroperitoneal masses after chemotherapy in all the patients: < 2 cm--5 (7.1%), 2-5 cm--25 (35.7%), > 5 cm--40 (57.1%). The level of the tumor markers remained positive in all the patients. Further chemotherapy was not perspective in all 70 patients who further underwent retroperitoneal lymph node dissection (RLND). Radical RLND was performed in 59 (84.3%) patients. Postoperative chemotherapy was given to 27 (38.6%) cases. Median follow-up was 20.8 (3-137) months. Complications developed in 12.9% (9/70) patients. Mortality was 1.4% (1/70). Histology revealed necrosis in 20 (28.6%), teratoma--in 26 (37.1%), cancer--in 24 (34.3%) specimens. Prognostic factors for cancer in retroperitoneal pathology were the following: S > S1 (p = 0.013), intermediate or poor prognosis group IGCCCG (p = 0.014), absence of embryonal carcinoma (p = 0.003), the presence of choriocarcinoma in the testicular tumor (p = 0.028), second-line chemotherapy (p = 0.001), residual mass > 2 cm (p = 0.006). Five-year overall, specific and progression-free survival of 70 patients was 41.0%, 42.4% and 31.8%, respectively. Univariate analysis revealed an adverse impact on progressive-free survival of category S > S1 (p = 0.015), intermediate or poor prognostic group IGCCCG (p = 0.01), the presence of embryonal carcinoma (p = 0.020) and the absence of choriocarcinoma in the testicular tumor (p = 0.029), tumor shrinkage < 50% (p < 0.0001), incomplete RLND (p = 0.012), an incomplete effect of the combined treatment (p < 0.0001), cancer in the residual mass (p < 0.0001). The multivariate analysis proved predictive value of an incomplete effect of the combined treatment (p < 0.0001). Thus, selected testicular non-seminoma patients with elevated serum tumor markers are curable with surgery. The best candidates for RLND in this group are patients without a tumor markers level increase during chemotherapy, with S1 category, good IGCCCG prognosis, tumor shrinkage > 50% and potentially respectable residual disease.

Cystectomy in the treatment of invasive cancer of the urinary bladder is not the only therapeutic modality in this pathology. In selected patients an alternative exists--transurethral resection of the urinary bladder followed by adjuvant concurrent chemotherapy and radiotherapy. The preserving therapy can be recommended to patients over 60 years of age in the presence of a low-grade solitary tumor of a mobile wall of the urinary bladder respectable with preservation of the organ capacity.

The study included 30 patients with surface cancer of the urinary bladder stage TA-T1 G1-3. As the first step of the treatment, all the patients were operated with removal of the tumor then the patients were randomized to postoperative intravesicular immunotherapy with ronkoleucine in single doses 500,000 IU (15 patients of group 1) or 1,000,000 IU (15 patients of group 2). It was found that group 2 patients had recurrences much less frequently (26.7 vs 66.7%, respectively). With higher degrees of differentiation of the tumor cells recurrences occurred more frequently in both groups. Group 2 patients developed recurrences significantly less frequently in G1 and G2 (22.2%). In G3 all the patients had recurrences. Intravesicular administration of ronkoleukine raised absolute number of CD3 and CD4 subpopulations during the treatment and after it as well as raised concentration of TNF. The levels of the latter in the urine rose after the end of each immunoprophylaxis course. Intravesicular use of ronkoleukine entailed no specific toxic reactions. Thus, intravesicular prophylactic immunotherapy of recurrent surface cancer of the urinary bladder with ronkoleukine in a single dose 1,000,000 IU is effective prevention in patients with high (G1) and moderate (G2) grade of tumor cell differentiation. The single dose 500,000 IU is uneffective. A rise in subpopulations CD3, CD4 and TNF cytokine in the urine evidences for systemic activation of the immunity.

87 patients with urinary bladder cancer (UBC) stage T2-3aN0M0 have received an organ-saving treatment which combined neoadjuvant chemotherapy (methotrexate, adriamycin, vinblastin, cysplatinum) followed by transurethral or open resection of the bladder. The patients were followed up for 3 to 60 months. Recurrent tumors arose in 49(56.3%) patients, at the primary site in 94%. Recurrence-free 5-year survival made up 32.8 +/- 14.1 and 24.2 +/- 15.2% after transurethral and open resections of the bladder, respectively. In patients with a complete response to the neoadjuvant chemotherapy 5-year overall and recurrence-free survival reached 89.0 +/- 11.1 and 68.5 +/- 18.9%, respectively. It is thought valid to consider planning organ-saving treatment only in relation to patients with a complete regression of the tumor after neoadjuvant chemotherapy.

Three different approaches to treatment of non-seminomal germinogenic testicular tumors (NSGTT) of stage I after orchidofuniculectomy: preventive retroperitoneal lymphadenectomy, preventive chemotherapy, expectant treatment. Recurrences, 5-year recurrence-free and overall survivals reached 17.4, 81.8 and 95.4%; 6.3, 93.8 and 100%; 33.3, 66.4 and 83.5%, respectively. Progression occurred more frequently in patients having invasion of tumor cells in lymphatic and blood vessels in the primary tumor. The authors conclude on preferable use of preventive chemotherapy after removal of the primary tumor.

The role of neoadjuvant chemotherapy for invasive transitional cell carcinoma (TCC) of the bladder is not determined yet. M-VAC and CMV regimens have a complete response rate of 10-47% with an overall response reaching 80%. In 16.7-35% of all the responders and 42.9-92% of the complete responders a functioning bladder can be preserved. The influence of neoadjuvant chemotherapy on long-term survival is questionable. Nevertheless, the authors conclude that neoadjuvant chemotherapy is feasible in patients with invasive TCC as it improves the results of following surgery and in some cases enables an organ sparing operation.

Immunotherapy consisting in intravesical injection of BCG vaccine to a 44-year-old patient with surface relapsing cancer of the bladder resulted in development of sepsis. The vaccine in a dose of 120 mg was injected directly after bougienage of the urethra and catheterization of the bladder. As soon as in 2 h the patient developed chill, fever (38.5 degrees C), and felt bad. The condition progressed, but only in 15 days did the patient applied for medical care. Intensive care including antibiotics and antituberculous drugs in massive doses and repeated sessions of hemoperfusion were of no avail. The patient died with signs of progressive hepatorenal failure. Autopsy confirmed vaccinal mycobacterial sepsis. Intravesical immunotherapy after injury to the urethra was an error, promoting generalization of the infection; another cause of lethal outcome was late application for medical care.

101 patients with cancer of the bladder were operated in the Moscow Cancer Research Center from 1990 to 1995. Cystectomy with varying urinary bypass was made in 49 patients. 52 patients were subjected to bladder resection. The former developed recurrences in 28.9%, the latter in 62% of the patients. Recurrences after the resections were primarily local. 5-year survival of transient-cell bladder carcinoma patients after cystectomy made up 68.2%, after the resection 80.7%. The authors hold that both operations are applicable, but they have specific indications.