High-dose sequential chemotherapy (HDS) versus PEB chemotherapy as first-line treatment of patients with poor prognosis germ-cell tumors: mature results of an Italian randomized phase II study.

BACKGROUND: In the late 1990s, the use of high-dose chemotherapy (HDCT) and stem-cell rescue held promise for patients with advanced and poor prognosis germ-cell tumors (GCT). We started a randomized phase II trial to assess the efficacy of sequential HDCT compared with cisplatin, etoposide, and bleomycin (PEB). PATIENTS AND METHODS: Patients were randomly assigned to receive four cycles of PEB every 3 weeks or two cycles of PEB followed by a high-dose sequence (HDS) comprising HD-cyclophosphamide (7.0 g/m(2)), 2 courses of cisplatin and HD-etoposide (2.4 g/m(2)) with stem-cell support, and a single course of HD-carboplatin [area under the curve (AUC) 27 mg/ml × min] with autologous stem-cell transplant. Postchemotherapy surgery was planned on responding residual disease in both arms. The primary end point was progression-free survival (PFS). The study was designed to detect a 30% improvement of 5-year PFS (from 40% to 70%), with 80% power and two-sided α at 5%. RESULTS: From December 1996 to March 2007, 85 patients were randomized: 43 in PEB and 42 in HDS arm. Median follow-up was 114.2 months [interquartile range (IQR): 87.7-165.8]. Complete or partial response with normal markers (PRm-) were obtained in 28 (65.1%) and 29 (69.1%) patients, respectively. Five-year PFS was 55.8% [95% confidence interval (CI) 42.8-72.8] and 54.8% (95% CI 41.6%-72.1%) in PEB and HDS arm, respectively (log-rank test P = 0.726). Five-year overall survival was 62.8% (95% CI 49.9-79.0) and 59.3% (95% CI 46.1-76.3). One toxic death (PEB arm) was recorded. CONCLUSIONS: The study failed to meet the primary end point. Furthermore, survival estimates of conventional-dose chemotherapy higher than expected should be accounted for and will likely limit further improvements in the first-line setting. CLINICALTRIALS.GOV: NCT02161692.

Modified cisplatin, etoposide, and ifosfamide (PEI) salvage therapy for male germ cell tumors: long-term efficacy and safety outcomes.

BACKGROUND: Since 1985, we introduced a modified combination of etoposide, ifosfamide, and cisplatin (PEI) as second-line therapy of adult male germ cell tumors with the aim to reduce toxic effect while maintaining efficacy over the original regimen. PATIENTS AND METHODS: Patients received four cycles of ifosfamide at 2.5 g/m(2) on days 1-2, etoposide, and cisplatin at 100 and 33 mg/m(2), respectively, on days 3-5 every 21 days, followed by surgery. Results were stratified according to the International Germ Cell Consensus Classification Group-2 (IGCCCG-2). RESULTS: From February 1985 to January 2012, 189 patients were treated. 72.6% were IGCCCG-2 intermediate-to-very high risk. Thirty-five patients (18.5%) had a complete response, 67 (35.4%) a marker normalization (PRm-). Median follow-up was 122.1 months (inter-quartile range [IQR]: 71.4-232.0). Two-year progression-free and 5-year overall survival were 34.3% [95% confidence interval (CI) 28.1% to 41.9%] and 42.1% (95% CI 35.3% to 50.2%), respectively. Survival estimates compared favorably with those obtained by conventional dose chemotherapy (CDCT) regimens in each prognostic category. 70.4% of grade 3-4 neutropenia (25.5% febrile neutropenia), 48.1% thrombocytopenia, 21.2% anemia, 3.2% neurotoxic effect, and no severe renal toxic effect were recorded. CONCLUSION: Dose-modified Italian PEI should be considered as an appropriate benchmark for CDCT in the first salvage setting.

[Long-term results of laparoscopic retroperitoneal lymph node dissection (RPLND) in low-stage nonseminomatous germ-cell testicular tumors (NSGCTT) performed by a senior surgeon: 1999-2003]. / Risultati a lungo termine della linfadenectomia retroperitoneale laparoscopica nei tumori germinali non seminomatosi del testicolo; esperienza di un chirurgo anziano: 1999-2003.

BACKGROUND: Laparoscopic RPLND for low-stages NSGCTT is controversial: it is performed and recommended by excellent laparoscopic surgeons, but it is not widely used. The aim of this paper is to evaluate the results achieved by a senior surgeon, expert in open RPLND, who was introduced to laparoscopic surgery by excellent laparoscopists (LN, CU, GJ). PATIENTS AND METHODS: of the 48 operated patients, 36 had primary RPLND for clinical stage I disease (22 TIN0, 7 TxN0, 5 T2-3 N0 and 2 TIS1 N0) and 12 had post-chemotherapy surgery for IIA and IIB retroperitoneal nodes with normalized AFP and HCG. L-RPLND was performed with 4 ports and the en bloc removal of unilateral retroperitoneal nodes with the spermatic vessels. No post-operative adjuvant chemotherapy was planned for patients with documented nodal metastases as for open RPLND since 1985. RESULTS: Average operative time was 3.30' for the 36 clinical stage I patients and 4 hours for post-chemotherapy surgery. Blood loss was minimal in all cases, because of early conversion to open surgery in all patients with no immediate hemostasis at L-RPLND. Metastases were found in 6 (17%) out of the 36 clinical stage I patients: none in the 22 pTI, 1 in the 7 Tx, 3 in the 5 pT2-3 and in 2 of the 2 pT1S1 patients. Residual teratoma was found in 6 of the 12 patients who received neo-adjuvant chemotherapy for clinical stage IIA or IIB disease. The other 6 had fibrosis-necrosis. Further metastases developed in 2 of the 30 patients with negative nodes: 1 in the lung in a pT1, and 1 in a pT2 patient with increasing markers. Surprisingly, the first two pT2-3 patients with positive nodes developed liver metastases in a few months after L-RPLND. Consequently, all following patients with active metastases at L-RPLND received 2 courses of adjuvant PEB. All 4 patients who relapsed were cured, are alive and disease-free. CONCLUSIONS: L-RPLND is a very demanding operation, which appears to be more a staging procedure than a curative operation. It is ideal for pT1 clinical stage I and for post-chemotherapy stages IIA& B with residual teratoma and normalized markers, but wait & see in good risk and open RPLND in high risk patients are very competing. Only few reports compared laparoscopic versus open RPLND, but not in a randomized study.

A randomised trial of high-dose chemotherapy in the salvage treatment of patients failing first-line platinum chemotherapy for advanced germ cell tumours.

BACKGROUND: Incomplete remission or relapse from first-line chemotherapy has poor prognosis in male germ cell tumour patients. This phase III randomised trial compares conventional salvage to high-dose-intensification chemotherapy. PATIENTS AND METHODS: Between February 1994 and September 2001, 280 patients from 43 institutions in 11 countries, were randomly assigned to receive either four cycles of cisplatin, ifosfamide and etoposide (or vinblastine) (arm A), or three such cycles followed by high-dose carboplatin, etoposide and cyclophosphamide (CarboPEC) with haematopoietic stem cell support (arm B). RESULTS: Similar complete and partial response rates were observed in both treatment arms (56%; 95% CI 50% to 62%). There were 3% and 7% toxic deaths in arms A and B, respectively. No significant improvements with CarboPEC were observed in either 3-year event-free survival (35% versus 42%, P=0.16) or overall survival (53%; 95% CI 46% to 59%). Complete responders with CarboPEC had a significant improvement in disease-free survival (55% versus 75% at 3 years, P <0.04). CONCLUSIONS: The single cycle of high-dose salvage chemotherapy after three cycles of standard dose chemotherapy had no effect on treatment outcomes. These results suggest that data from uncontrolled studies should not be used to justify routine use of a toxic and expensive treatment without confirmation in a randomised trial.

European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG).

Germ cell tumour is the most frequent malignant tumour type in young men with a 100% rise in the incidence every 20 years. Despite this, the high sensitivity of germ cell tumours to platinum-based chemotherapy, together with radiation and surgical measures, leads to the high cure rate of > or = 99% in early stages and 90%, 75-80% and 50% in advanced disease with 'good', 'intermediate' and 'poor' prognostic criteria (IGCCCG classification), respectively. The high cure rate in patients with limited metastatic disease allows the reduction of overall treatment load, and therefore less acute and long-term toxicity, e.g. organ sparing surgery for specific cases, reduced dose and treatment volume of irradiation or substitution of node dissection by surveillance or adjuvant chemotherapy according to the presence or absence of vascular invasion. Thus, different treatment options according to prognostic factors including histology, stage and patient factors and possibilities of the treating centre as well may be used to define the treatment strategy which is definitively chosen for an individual patient. However, this strategy of reduction of treatment load as well as the treatment itself require very high expertise of the treating physician with careful management and follow-up and thorough cooperation by the patient as well to maintain the high rate for cure. Treatment decisions must be based on the available evidence which has been the basis for this consensus guideline delivering a clear proposal for diagnostic and treatment measures in each stage of gonadal and extragonadal germ cell tumour and individual clinical situations. Since this guideline is based on the highest evidence level available today, a deviation from these proposals should be a rare and justified exception.

EAU Guidelines on Penile Cancer.

OBJECTIVES: The European Association of Urology (EAU) consensus group on penile cancer has prepared these guidelines to help urologists assess the scientific evidence for the management of penile cancer and to incorporate recommendations into their clinical practice. METHOD: References used in the text have been assessed according to the level of scientific evidence involved and guideline recommendations have also been evaluated according to the Agency for Health Care Policy and Research [Clinical Practice Guidelines Development: Methodological Perspectives. Washington DC: US Department of Health and Human Services, Public Health Service; 1992, pp. 115-127]. RESULTS: The diagnosis, treatment and follow-up of patients suspected of, or diagnosed with, penile cancer is listed as an easy reference text. CONCLUSION: A guidelines text is presented which aims at aiding medical specialists in determining the most optimal diagnostic and treatment options for this pathology.

Chemotherapy with an every-2-week regimen of gemcitabine and paclitaxel in patients with transitional cell carcinoma who have received prior cisplatin-based therapy.

BACKGROUND: An every-2-week regimen of gemcitabine and paclitaxel was adapted for patients with advanced transitional cell carcinoma (TCC) who had received prior cisplatin-based chemotherapy. METHODS: Forty-one patients with advanced or metastatic TCC who had received prior cisplatin-based systemic chemotherapy were treated with an outpatient regimen of gemcitabine 2500-3000 mg/m(2) and paclitaxel 150 mg/m(2) every 2 weeks. RESULTS: Forty of 41 patients had measurable disease. Response was observed in 24 patients (60%; 95% confidence interval [CI], 45-75%). Eleven (28%) achieved complete response, and 13 (33%) obtained partial response. Twenty of 25 patients (80%; 95% CI, 64-96%) who had been previously treated in the neoadjuvant or adjuvant setting responded versus 4 of 15 (27%; 95% CI, 5-49%) in patients who received prior methotrexate, vinblastine, doxorubicin, cisplatin (M-VAC) for metastatic disease. The median duration of survival for patients given gemcitabine and paclitaxel after failing neoadjuvant or adjuvant M-VAC was 12 months (range, 2-43+), as compared with only 8 months (range, 2-28) for patients who had been treated after failure of prior therapy for metastatic disease. For all patients, the median duration of response was 6.4 months (range, 2-43.3+ months), and the median survival was 14.4 months (range, 2-43+). Thirteen patients (32%) developed World Health Organization Grade 3-4 neutropenia, with febrile neutropenia in 3 (7%) patients. Granulocyte colony-stimulating factor was given to 10 (24%) patients. There was no Grade 3-4 anemia or thrombocytopenia. CONCLUSIONS: The combination of gemcitabine and taxol in previously treated patients with recurrent TCC is highly effective and produces objective durable responses. This every-2-week schedule is a well tolerated outpatient regimen with minimal toxicity.

[Thyroid nodule pathology: proposal of a diagnostic approach based on the experience of a thyroid disease unit]. / Patologia nodulare tiroidea: proposta di un approccio diagnostico sulla base dell'esperienza di una unità tiroidologica.

Thyroid nodules are commonly found in clinical practice, and their detection by either the physician or the patients always gives rise to concern as to the possible existence of a malignancy. Technological developments have had a major impact on the study and treatment of thyroid nodules. The application of fine-needle aspiration biopsies (FNAB) and the availability of high-resolution thyroid ultrasonography have modified thyroid nodule management even if important differences of opinion remain. This article describes the progress as well as contemporary controversies in thyroid nodule diagnosis and considers the effect these advances have had on the treatment of patients with nodular disease. It includes a brief description of the clinical importance of thyroid nodules, of the use and limitations of imaging studies in thyroid nodule diagnosis and of the usefulness, limitations, and impact of FNAB on nodule management.

EAU guidelines on testicular cancer.

OBJECTIVES: To establish guidelines for the diagnosis, staging, treatment and follow-up of germ cell testicular cancer. METHODS: A search of published work was conducted using Medline. Highly evidence-based articles were selected and their findings analysed by the members of the Oncological Urology Working Group of the EAU. Testis cancer is rare and affects young men in their 3rd and 4th decades of life. The majority of these tumours are derived from germ cells (seminomatous and non-seminoma germ cell testicular cancer), and more than 50% of patients are diagnosed with stage I disease. Epidemiological, pathological and clinical risk factors are well established. The tumour, node, metastasis (TNM) staging system is endorsed, and for metastatic disease a recently devised prognostic-factor-based staging system has proven to be useful. Staging assessment includes pre- and post-orchiectomy marker levels, pathology of the testis, and nodal and visceral status. Following orchiectomy, treatment depends on the tumour type, pathological risk factors for stage I disease and clinical prognostic factors for advanced disease. The cure rate is excellent for disease stages I and II, irrespective of the treatment adopted. However, the pattern of relapse (rate, timing and site) is highly influenced by therapeutic policy. For metastatic disease, survival depends on clinical prognostic factors and treatment. Follow-up schedules are tailored according to stage, tumour type and post-orchiectomy treatment schedules. CONCLUSIONS: Excellent cure rates are achieved for early-stage germ cell testis tumours following accurate staging at diagnosis. Satisfactory survival rate can be achieved in advanced metastatic disease using a multidisciplinary therapeutic approach. Follow-up schedules vary, depending on the pathology and stage of the primary tumour and on the treatment policy adopted following orchiectomy.

Viable malignant cells after primary chemotherapy for disseminated nonseminomatous germ cell tumors: prognostic factors and role of postsurgery chemotherapy--results from an international study group.

PURPOSE: To assess the value of postsurgery chemotherapy in patients with disseminated nonseminomatous germ-cell tumors (NSGCTs) and viable residual disease after first-line cisplatin-based chemotherapy. PATIENTS AND METHODS: The outcome of 238 patients was reviewed. Tumor markers had normalized in all patients before resection. A multivariate analysis of survival was performed on 146 patients. RESULTS: The 5-year progression-free survival (PFS) rate was 64% and the 5-year overall survival (OS) rate was 73%. Three factors were independently associated with both PFS and OS: complete resection (P <.001), < 10% of viable malignant cells (P =.001), and a good International Germ Cell Consensus Classification (IGCCC) group (P =.01). Patients were assigned to one of three risk groups: those with no risk factors (favorable group), those with one risk factor (intermediate group), and those with two or three risk factors (poor-risk group). The 5-year OS rate was 100%, 83%, and 51%, respectively (P <.001). The 5-year PFS rate was 69% (95% confidence interval [CI], 62% to 76%) and 52% (95% CI, 40% to 64%) in postoperative chemotherapy recipients and nonrecipients, respectively (P <.001). No significant difference was detected in 5-year OS rates. After adjustment on the three prognostic factors, postoperative chemotherapy was associated with a significantly better PFS (P <.001) but not with better OS. Patients in the favorable risk group had a 100% 5-year OS, with or without postoperative chemotherapy. Postoperative chemotherapy appeared beneficial in both PFS (P <.001) and OS (P =.02) in the intermediate-risk group but was not statistically beneficial in the poor-risk group. CONCLUSION: A complete resection may be more critical than recourse to postoperative chemotherapy in the setting of postchemotherapy viable malignant NSGCT. Immediate postoperative chemotherapy or surveillance alone with chemotherapy at relapse may be reasonable options depending on the completeness of resection, IGCCC group, and percent of viable cells. Validation is necessary.

Interferon adjuvant to radical nephrectomy in Robson stages II and III renal cell carcinoma: a multicentric randomized study.

PURPOSE: Because interferon gave promising results in the management of metastatic renal cell carcinoma in the 1980s, a multicentric randomized controlled trial was planned to compare adjuvant recombinant interferon alfa-2b (rIFNalpha2b) with observation after radical nephrectomy in patients with Robson stages II and III renal cell carcinoma. Overall and event-free survival were to be evaluated together with prognostic factors. PATIENTS AND METHODS: Overall and event-free survival curves for 247 patients (124 controls and 123 treated) were estimated by the Kaplan-Meier method and compared using the log-rank test. Cox's multiple regression models were adopted to perform a joint analysis of treatment and prognostic factors. RESULTS: The 5-year overall and event-free survival probabilities were 0.665 and 0.671, respectively, for controls and 0.660 and 0.567, respectively, for the treated group; the differences were not statistically significant (2P = .861 for overall and 2P = .107 for event-free survival with the log-rank test). Regarding prognostic factors, only grade, pT, and pN demonstrated a significant prognostic role. First-order interactions of treatment with pT and pN category were investigated; a significant interaction was found between pN and treatment. A harmful effect of rIFNalpha2b in the 97 treated pN0 patients and a protective effect in the 13 treated pN2/pN3 patients were statistically significant. CONCLUSION: Adjuvant rIFNalpha2b is not indicated after radical nephrectomy for renal cell carcinoma. The protective effect in the small group of pN2/pN3 patients requires further investigation.

A double-blind, randomised, parallel study comparing intravenous dolasetron plus dexamethasone and intravenous dolasetron alone for the management of fractionated cisplatin-related nausea and vomiting.

Fractionated cisplatin-containing regimens are routinely used for chemotherapy in certain types of cancer. Dolasetron has been shown to be effective in preventing acute emesis related to high-dose cisplatin chemotherapy over 24 h; its effectiveness has not been evaluated in fractionated cisplatin-containing chemotherapy. This trial was designed to assess the efficacy of dolasetron alone or dolasetron plus dexamethasone in preventing nausea and vomiting related to fractionated cisplatin chemotherapy. The patients were 210 cancer in-patients, who were randomised to receive 100 mg dolasetron i.v. or 100 mg dolasetron i.v. plus 20 mg dexamethasone before chemotherapy primarily with cisplatin (15-50 mg/m2) infused over < or =4 h for at least 2 but not more than 5 consecutive days. Dolasetron was administered to all patients 30 min before cisplatin. Dexamethasone was administered in double-blind fashion 5 min before cisplatin. Efficacy was measured at hour 24 of each study day using complete response (no vomiting and no rescue medication) and maximum severity of nausea, self-assessed by patients using a 100mm visual analogue scale. Most (198) of the patients completed the study and were evaluable. Overall complete response rates were significantly higher in the dolasetron plus dexamethasone group than in the dolasetron only group (72.9% vs. 40.8%, respectively; P<0.0001). Complete response rates on each study day were also significantly higher with dolasetron plus dexamethasone than with dolasetron alone (P<0.029), with an attenuated efficacy in the delayed phase in both groups. Chi-square test and logistic regression applied to daily response rates indicated a significant influence of treatment (day 1: P = 0.0002, day 2: P<0.0001, day 3: P = 0.0007, day 4: P = 0.0007, day 5: P = 0.029). Treatment and duration of chemotherapy exerted the only statistically significant subgroup effects on complete response (P<0.0001). Both treatments were administered safely. As seen with other 5-HT3 receptor antagonist antiemetics, the addition of dexamethasone to dolasetron significantly increases effectiveness in preventing nausea and vomiting related to fractionated cisplatin chemotherapy. Both dolasetron and dolasetron plus dexamethasone were well tolerated.

Subcutaneous administration of interleukin-2 and interferon-alpha 2b in advanced renal cell carcinoma: long-term results.

Clinical data have supported the combination of subcutaneous r-interleukin-2 (rIL-2) and r-interferon-alpha (rIFN-alpha) as a promising combination for advanced renal cell carcinoma (RCC), with a reduced toxicity. We evaluated the activity and safety of this outpatient immunotherapy and report on the clinical results and the long-term survival analysis. Objective responses was observed in 9 of 50 (18%) patients, 6 of whom (12%) achieved a complete response. Overall median survival is 12 months, six patients were surviving at a median follow-up of 24 months, and three (6%) are still progression-free.

Intravesical electromotive administration of drugs for treatment of superficial bladder cancer: a comparative Phase II study.

OBJECTIVES: To evaluate the efficacy of electromotive administration (EMDA) of intravesical mitomycin-C (MMC) in patients with superficial bladder tumors and to evaluate the toxicity of the treatment. METHODS: Thirteen patients with multifocal Stages Ta-T1 and G1-G2 transitional cell carcinoma (TCC) of the bladder, primary or recurrent (group A), received MMC 40 mg (retained in the bladder for 2 hours) once a week for 8 weeks. Fifteen patients with the same characteristics (group B) were treated with EMDA/MMC at a current of 15 mA for 20 minutes once a week for 8 weeks. All lesions in the bladder except one (marker) were resected in each patient. RESULTS: In group A, 5 of 12 patients (41.6%) demonstrated complete macroscopic and histologic disappearance of the marker lesion (complete response [CR]). In group B, 6 of 15 patients (40%) had a similar CR. Recurrence rate in responders was 60% in group A versus 33% in group B after 7.6 and 6 months, respectively. Disease-free interval was 14.5 months in the EMDA/MMC group compared to 10.5 months in the MMC group. Side effects were few. CONCLUSIONS: In intermediate risk patients with TCC of the bladder, EMDA/MMC was not superior to MMC alone with a CR rate of 41% versus 41.6%. In responders, a lower recurrence rate and a longer disease-free interval were observed in the EMDA/MMC group.

Up-to-date management of carcinoma of the penis.

Squamous cell carcinoma is the most common tumour of the penis. It is a rare disease in Western countries, and it is often associated with phimosis, poor hygiene or human papilloma virus infection. It could be prevented or diagnosed early in most cases, but, due to cultural and educational reasons, it is often diagnosed late. Nodal metastases are relatively common, but distant dissemination is very rare. Radical surgery gives the best control of the primary tumour, but it is mutilating. Laser surgery for limited superficial lesions and sophisticated radiotherapy for relatively small infiltrating tumours have been successfully employed, alone or in combination with chemotherapy. The use of radical surgery can therefore be restricted to cases which are unsuitable for conservative treatment or to relapses. Survival mainly depends on nodal metastases, but management of regional lymph nodes is controversial. Radical inguinal or ileoinguinal lymphadenectomy can cure approximately 40-50% of patients with positive nodes, but nearly half of the patients with clinically enlarged nodes actually have no metastases. Invalidating oedema is a frequent complication of inguinal lymphadenectomy. The point is to restrict the operation to patients with positive nodes. Expectant policy can be dangerous because results of delayed lymphadenectomy are usually poor. Fine needle aspiration biopsy and imaging may be of help in diagnosing nodal metastases. Modified surgical procedures have been advocated in order to obtain a pathological staging of the inguinal nodes avoiding invalidating sequelae, but results are controversial. Depth of invasion, tumour grade and growth pattern are of help in identifying patients at a very high risk of harbouring nodal metastases. Squamous cell carcinoma of the penis is relatively responsive to chemotherapy. Limited experiences suggest that adjuvant chemotherapy can improve the long-term survival of patients with radically resected positive nodes, and primary chemotherapy can make resectable approximately 50% of cases with fixed inguinal metastases. However, chemotherapy alone is not curative for metastatic disease.

Postsurgical policy in stage I testicular seminoma: cost and benefit of prophylactic irradiation in a long-term experience.

The definitive cure rate for clinical stage 1 testicular seminoma is very close to 100%, and prophylactic irradiation of the regional lymph nodes is associated with a low morbidity. Nevertheless, in recent years a "wait-and-see" policy has been proposed by some researchers. We analysed the cost/benefit ratio of radiotherapy (RT) by review of the case histories of 299 patients treated at the Department of Radiotherapy of the Istituto Nazionale per lo Studio e la Cura dei Tumori in Milan from January 1968 to December 1989. The 5-year overall survival was 99% (97.5% at 10 years), while the 10-year disease-free survival was 96%. The recurrence rate was 2.3%, but no patient relapsed in the irradiated areas. Acute toxicity was very moderate with only 4 (1.3%) serious radiation sequelae occurring 6 to 27 years after treatment. However, 9 second malignancies (3%) were observed. Lastly, we have calculated the costs for our National Health Service comparing surveillance policy and prophylactic irradiation.

[Therapeutic alternatives in the treatment of class T1N0 squamous cell carcinoma of the penis: indications and limitations]. / Alternative terapeutiche nel trattamento del carcinoma spinocellulare del pene di categoria T1N0: indicazioni e limiti.

At INT of Milan between 1964 and 1990, 204 consecutive native patients suffering from penile cancer have been treated. 101 (59%) patients out of 171 with invasive cancer (23 affected with Tis were excluded) have been classified T1N0M0. 74 patients have been treated with penis conserving methods, such as circumcision, radiotherapy, laser excision and primary chemotherapy + conserving surgery. Overall local failure and/or nodal relapses occurred in 27% (20/74). Relapses are significantly related with grading but there isn't any relationship with macroscopical aspect or size of the tumor. The conservative treatment had been possible in 80% of patients. In our experience T1N0 clinical stage conservative therapy does not worsen the prognosis.

[Treatment of lymphatic metastasis of squamous cell carcinoma of the penis: experience at the National Tumor Institute of Milan]. / Trattamento delle metastasi linfonodali da carcinoma spinocellulare del pene: l'esperienza dell'Istituto Nazionale tumori di Milano.

Between 1964 and 1990 inclusive, 204 consecutive naive patients with penile cancer and 14 patients with recurrence in the inguinal nodes have been referred at INT, Milano. Nodal metastases occurred in 100% of category T3, T4 patients, in 82% T2, in 60% G2-3 T1 and only in 16.5% of G1 T1. Out of the 47 patients who had primary ileoinguinal lymphadenectomy, 16 (34%) had negative nodes, versus 100% metastases in the 25 patients operated during the follow-up. The relapse rate was 45% in the 31 patients treated only surgically in the 1964-77 period, versus 16% in the 25 cases submitted to adjuvant chemotherapy between 1978 and 1990. All 4 relapses in the adjuvant treatment group occurred in the 8 patients with bilateral metastases. Twenty-six patients had fixed inguinal nodes: the first 10 were treated with radiotherapy, with or without methotrexate or bleomycin, and the last 16 have been submitted to neoadjuvant chemotherapy. Only one patient of the first group could be operated and all 10 died of cancer within 3 years. On the contrary, 9 (56%) of the 16 patients treated with neoadjuvant chemotherapy could undergo subsequent surgery and 5 (31%) are alive disease free since over 5 years. Prophylactic lymphadenectomy may be indicated in all T2, T3, T4 patients and in indifferentiated T1 tumors. Adjuvant and neoadjuvant chemotherapy can improve the results of radical surgery, significantly.

Subcutaneous administration of interleukin 2 and interferon-alpha-2b in advanced renal cell carcinoma: a confirmatory study.

Recent clinical studies have suggested that the combination of subcutaneous recombinant human interleukin 2 (rIL-2) and interferon alpha (rIFN-alpha) is especially promising in advanced renal cell carcinoma. We assessed the safety, activity and toxicity of home therapy with these two agents in 50 patients. Each treatment cycle consisted of a 2 day pulse phase, with 9 x 10(6) IU m-2 of rIL-2 being given subcutaneously every 12 h, followed by a 6 week maintenance phase during which rIL-2 1.8 x 10(6) IU m-2 was administered subcutaneously every 12 h on days 1-5 and rIFN-alpha 2b 5 x 10(6) IU m-2 once a day on days 1, 3 and 5. Objective responses (CR+PR) occurred in 9/50 (18%) patients, six of whom (12%) achieved a complete response. Disease stabilisation was observed in 17 cases (34%) and 18 patients progressed during therapy. In the other six cases, treatment was interrupted early for toxicity or patient refusal. One patient died of myocardial infarction during the second cycle. The overall median survival was 12 months. Home therapy with subcutaneous rIL-2 + rIFN-alpha 2b proved to be active, feasible and moderately toxic, but serious adverse events can sometimes occur.

A surveillance study of clinical stage I nonseminomatous germ cell tumors of the testis: 10-year followup.

PURPOSE: We evaluate the 10-year results of a surveillance study of clinical stage I nonseminomatous germ cell tumors of the testis. MATERIALS AND METHODS: Between 1981 and 1984 we recruited 85 consecutive evaluable patients with nonseminomatous germ cell tumors of the testis and normal post-orchiectomy physical examination, chest x-rays, bipedal lymphangiography, abdominal scans and serum tumor markers. The patients were followed for at least 10 years after orchiectomy alone, which was performed elsewhere in 90% of the cases. RESULTS: The interval between visits was twice as long as it was scheduled. Relapses occurred in 25 patients (29.4%) after a median disease-free interval of 7 months (range 2 to 68). Five patients had further relapses and 3 (3.5%) died of cancer. Retroperitoneal relapses (19%) occurred later than lung relapses, and they were diagnosed when larger than 5 cm. in 7 patients. The percentage of embryonal carcinoma within the tumor associated with relapse (p = 0.008), T category (p = 0.023), scrotal violation (p = 0.042) and vascular invasion (p = 0.063) had a weak correlation but data on T category and vascular invasion were available for only some patients. CONCLUSIONS: Surveillance is a difficult type of study and missing data may compromise the therapeutic program based on prognostic factors.