No impact of blood transfusion on oncological outcome after radical prostatectomy in patients with prostate cancer.

PURPOSE: To assess the association between blood loss, blood transfusion (BT) and biochemical recurrence (BCR)-free, metastasis-free and overall survival after radical prostatectomy (RP) in a large single-center cohort of patients. Perioperative BT at oncologic surgery has been reported to be a potential risk factor for cancer recurrence and survival in several cancer entities. Current studies addressing the relationship between BT, blood loss and BCR-free survival in prostate cancer patients are controversial and include only series with fairly small patient cohorts. MATERIALS AND METHODS: The data of 11,723 patients who underwent RP between 01/1992 and 08/2011 were analyzed. Cox regression analysis, including preoperative PSA level, pT stage, lymph node status, Gleason score, margin status, blood loss, transfusion rate (allogeneic or autologous), tested the relationship between blood loss, transfusion and BCR-free, metastasis-free and overall survival. Additionally, propensity score-matching analysis was performed to adjust differences in tumor characteristics. RESULTS: There was no statistically significant relationship between blood loss or BT and BCR-free, metastasis-free or overall survival. In multivariate analysis PSA level, pT stage, Gleason score, margin status and lymph node status were independent factors for a BCR (p < 0.0001). These results were identical after propensity score matching analysis, comparing patients with and without BT. CONCLUSIONS: This large-scale analysis revealed no correlation between blood loss, blood transfusion and oncological outcome in prostate cancer patients treated with RP. Therefore, the association between higher blood loss or transfusion rate and cancer recurrence as described in other surgical treated tumor entities seems to be irrelevant in prostate cancer patients.

Standard of Care Versus Metastases-directed Therapy for PET-detected Nodal Oligorecurrent Prostate Cancer Following Multimodality Treatment: A Multi-institutional Case-control Study.

BACKGROUND: Most prostate cancer (PCa) patients with a biochemical failure following primary multimodality treatment (surgery and postoperative radiotherapy) relapse in the nodes. OBJECTIVE: To perform a matched-case analysis in men with lymph node recurrent PCa comparing standard of care (SOC) with metastasis-directed therapy (MDT). DESIGN, SETTING, AND PARTICIPANTS: PCa patients with a prostate-specific antigen (PSA) progression following multimodality treatment were included in this retrospective multi-institutional analysis. INTERVENTION: The SOC cohort (n=1816) received immediate or delayed androgen deprivation therapy administered at PSA progression. The MDT cohort (n=263) received either salvage lymph node dissection (n=166) or stereotactic body radiotherapy (n=97) at PSA progression to a positron emission tomography-detected nodal recurrence. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint, cancer-specific survival (CSS), was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses. RESULTS AND LIMITATIONS: At a median follow-up of 70 (interquartile range: 48-98) mo, MDT was associated with an improved CSS on univariate (p=0.029) and multivariate analysis (hazard ratio: 0.33, 95% confidence interval [CI]: 0.17-0.64) adjusted for the year of radical prostatectomy (RP), age at RP, PSA at RP, time from RP to PSA progression, Gleason score, surgical margin status, pT- and pN-stage. In total, 659 men were matched (3:1 ratio). The 5-yr CSS was 98.6% (95% CI: 94.3-99.6) and 95.7% (95% CI: 93.2-97.3) for MDT and SOC, respectively (p=0.005, log-rank). The main limitations of our study are its retrospective design and lack of standardization of systemic treatment in the SOC cohort. CONCLUSIONS: MDT for nodal oligorecurrent PCa improves CSS as compared with SOC. These retrospective data from a multi-institutional pooled analysis should be considered as hypothesis-generating and inform future randomized trials in this setting. PATIENT SUMMARY: Prostate cancer patients experiencing a lymph node recurrence might benefit from local treatments directed at these lymph nodes.

[Active surveillance for prostate cancer]. / Aktive Uberwachung des Prostatakarzinoms.

Active surveillance is a valuable treatment option in patients with newly diagnosed low-risk prostate cancer. Studies considering a watchful waiting approach showed favourable cancer-specific survival rates in such patients and it is assumed that patients benefit from a definitive therapy if life expectancy exceeds 10-15 years. Therefore active surveillance is especially valuable in older men and in patients with an elevated comorbidity profile. Precise identification of histologically and clinically insignificant prostate cancers is still not possible today. Active surveillance includes regular PSA measurements combined with follow-up biopsies; however, no standardized protocol exists so far. Histological progression in the follow-up biopsy and PSA elevation are the most important criteria for initiating definitive therapy. Today only a minority of low-risk patients join an active surveillance protocol and a substantial proportion of these men leave such a protocol early without evidence of progression. The psychological burden of living with an untreated cancer seems to be responsible for this. Active surveillance has the potential to lead to undertreatment as there is some evidence that prolonged treatment delay might adversely affect outcome of definitive therapy.

Interleukin-2 inhalation therapy temporarily induces asthma-like airway inflammation.

BACKGROUND: Inhaled interleukin-2 (IL-2) is an effective and safe treatment in metastasing renal cell carcinoma (mRCC) but known to potentially elicit respiratory symptoms. OBJECTIVES: The present study analyses the effects of IL-2 using a panel of measures including markers of airway inflammation. METHODS: Ten patients with mRCC (7m/3f; mean age, 63 yrs) were measured at baseline, 6-10 days after start of therapy (n = 5, inhaled IL-2 only; n = 5, inhaled IL-2 plus 1/11th of daily dose subcutaneously), and 16-29 days later under continuous combined (inhaled plus subcutaneous) therapy, including additional subcutaneous IFN-alpha in 8 patients. RESULTS: After start of therapy median FEV1 declined from 108 to 85 to 90 % predicted and the provocative concentration of methacholine eliciting a 20 % fall in FEV1 (PC20 FEV1) from 16 to 8 to 3 mg/mL, while the level of exhaled nitric oxide (FENO) rose from 27 to 79 to 60 ppb and the percentage of sputum eosinophils from 2 to 18 to 37 % (p<0.01, each), accompanied by cough and dyspnoea (p<0.05). One patient who stopped therapy, was back to baseline values when measured 2 months later. Cytokine production by blood or sputum T lymphocytes was not markedly altered by IL-2 inhalation. CONCLUSIONS: IL-2 inhalation therapy in patients with metastasing renal cell carcinoma is capable of temporarily inducing symptomatic, functional and inflammatory alterations similar to those of bronchial asthma.

[Technical aspects of nerve sparing during retropubic prostatectomy]. / Aspects techniques de la préservation nerveuse au cours de la prostatectomie rétropubienne.

Retropubic radical prostatectomy is the most commonly used therapeutic option for the treatment of clinically localized prostate cancer. An ongoing stage migration towards organ-confined cancers allows performing a nerve-sparing procedure in a growing number of patients. Key elements for achieving convincing functional results are a sphincter preserving Ligation of the distal part of Santorini's plexus and the subtle preparation of the neurovascular bundle. This article gives a detailed description of the operative technique. Furthermore, a strategy for patient selection and tumour selection for the indication of nerve-sparing radical prostatectomy (NSRP) is suggested.

[Success rates of two-layer, microsurgical vasovasostomy. Results from a patient questionnaire and comparison with one-layer technique]. / Erfolgsraten der zweischichtigen mikrochirurgischen Vasovasostomie. Ergebnisse einer Patientenbefragung und Vergleich mit der einschichtigen Technik.

UNLABELLED: Vasovasostomy is the most commonly performed procedures in the therapy for occlusive azoospermia after vasectomy. In our clinic the two-layer microsurgical technique (DL VVST) is considered to be the gold standard. We have examined the results of DL VVST by means of a questionnaire and compared them with those of the monolayer technique (ML VVST). MATERIALS AND METHOD: In the period from 1996 to 2001, a microsurgical DL VVST with 10 x 0 Prolene sutures under the operation microscope was performed in 141 patient. Aspects of the operation, social aspects and postoperative results (results of spermiogram, birth rates) were assessed by means of a questionnaire. The results were compared with those of a historical patient collective who had undergone a modified monolayer VVST with 7 x 0 Prolene (n = 64). RESULTS: The questionnaire could be sent to 90/141 patients, the response rate was 63/90 (70 %). The time interval between vasectomy and VVST was on average 9.5 years. The patency rate was 86 %, the birth rate 24 %. Severe or moderately sever complications did not occur. In the historical patient collective, the average occlusion interval was 6.9 years. The patency rate in these patients in whom the VVST was performed merely under the loupe and in a monolayer technique was 87 %, the pregnancy rate 48 %. CONCLUSION: The highly positive results of VVST with pregnancy rates > 80 % from earlier publications could not be reproduced. According to our results, the two-layer VVST does not afford better results than the monolayer technique.

Subjective and objective prospective, long-term analysis of quality of life during inhaled interleukin-2 immunotherapy.

PURPOSE: We conducted both a subjective and objective, prospective quality-of-life analysis during high-dose (36 x 10(6) immunizing units/d) inhalational interleukin (IL)-2 treatment (mean treatment time, 13.4 months) of 15 patients with metastatic renal cell carcinoma (mRCC). Additionally, quality of life for 10 patients with mRCC receiving low-dose (9 x 10(6) IU/m(2)/d for 5 days) intravenous IL-2 treatment also was evaluated. PATIENTS AND METHODS: Patients responded to the European Organization for Research and Treatment of Cancer quality-of-life questionnaire QLQ-C30 before and during inhalational IL-2 treatment at 1, 3, 6, 9, and 12 months and before and once during intravenous IL-2 treatment. A clinician assessed patient well-being using the Quality of Well-Being scale to calculate once weekly quality-adjusted life-years (QALYs) during inhalational IL-2 treatment. RESULTS: Patients completed 103 questionnaires and clinicians performed 892 QALY calculations. For patients treated with inhalational IL-2, the mean quality-of-life score deteriorated modestly but significantly 1 month after treatment initiation (15.1%, P =.01) but did not differ significantly from pretreatment scores after 3, 6, 9, and 12 months of treatment. Inhalational IL-2 therapy stabilized patient quality of life for a mean of 13.4 months. The resulting QALY calculation for patients on inhalation IL-2 was 70.1% of 13.4 months, representing 9.4 months of QALY. In comparison, patients who received intravenous IL-2 showed a more marked, statistically significant deterioration in mean quality-of-life score during treatment (27%, P =.006); moreover, three of these 10 patients experienced treatment-related toxicity that prevented questionnaire completion. CONCLUSION: Quality-of-life analysis during immunotherapy provides valuable information regarding cancer treatment outcomes.

[Fast-track surgery in radical retropubic prostatectomy. First experiences with a comprehensive program to enhance postoperative convalescence]. / Radikale retropubische "Fast-track-Prostatektomie". Erste Erfahrungen mit einem interdisziplinären, multimodalen Behandlungskonzept zur Beschleunigung der postoperativen Rehabilitation.

Fast-track surgery is a comprehensive program for the optimization of perioperative care in elective surgery reducing potential postoperative complications and speeding up convalescence. Recent data from randomized colon resection trials emphasize that fast-track surgery is possible in most major operations. Our initial results in radical retropubic prostatectomy fast-track surgery have been encouraging. Fast-track surgery in major urological operations needs validation using randomized trials.

[DaVinci robot-assisted laparoscopic prostatectomy: benefit for obese men? - A matched-pair analysis]. / Roboterassistierte radikale Prostatektomie : Vorteil bei adipösen Männern? - Eine Matched-pair-Analyse.

BACKGROUND: Open radical retropubic prostatectomy (RRP) in obese patients (BMI ≥30) is associated with increased perioperative morbidity. The aim of the study was to evaluate the possible benefit of DaVinci robotic-assisted laparoscopic prostatectomy (RARP) compared to RRP in obese patients. PATIENTS AND METHODS: We identified 255 patients with a localized prostate cancer (PCa) and BMI ≥30 treated with radical prostatectomy from January 2009 to December 2011. To adjust for risk factors of increased perioperative morbidity (nerve-sparing, pelvic lymph node dissection, prostate volume), a propensity score-based matching was performed between RRP and RARP (n=115 each group). Both groups were compared by taking into consideration histopathological outcomes as well as peri- and postoperative (30 days) morbidity. RESULTS: There were no differences in histopathological characteristics (pT/pN-stage, Gleason score, R-stage; all p>0.05) in both groups. Mean blood loss (276 ml vs. 937 ml), transfusion rate (0.9% vs. 8.7%) and 30-day complications according to the Clavien classification system (Clavien ≥ 2; 9.5% vs. 22.6%) were decreased in RARP (all p<0.05). In a multivariate logistic regression model, RARP vs. RRP was associated with a significantly reduced risk of a Clavien ≥ 2 complication during follow-up (OR 0.3; p= 0.0047). Recovery of continence was significantly better for RARP patients after 3 months (p= 0.02). There was no difference in erectile function 12 months postoperatively. CONCLUSION: Our findings of decreased transfusion and complication rates and a trend of better early recovery of continence in RARP should be considered in obese patients (BMI >30) scheduled for radical prostatectomy.

Adherence of the indication to European Association of Urology guideline recommended pelvic lymph node dissection at a high-volume center: Differences between open and robot-assisted radical prostatectomy.

PURPOSE: Contemporary adherence of the indication to European Association of Urology (EAU) guideline recommendation for pelvic lymph node dissection (PLND) at either open (ORP) or robot-assisted radical prostatectomy (RARP) at a high-volume center is unknown. To assess guideline recommended and observed PLND rates in a high-volume center cohort. METHODS: We relied on the Martini-Clinic database and focused on patients treated with either ORP or RARP, between 2010 and 2013. Actual performed PLND was compared to European Association of Urology (EAU) guideline recommendation defined by nomogram predicted risk of lymph node invasion >5%. Categorical and multivariable logistic regression analyses targeted two endpoints: 1) probability of guideline recommended PLND and 2) probability of no PLND, when not recommended by EAU guideline. RESULTS: Within 7868 PCa patients, adherence to EAU PLND guideline recommendation was 97.1% at ORP and 96.8% at RARP (p = 0.7). When PLND was not recommended, it was more frequently performed at RARP (71.6%) than at ORP (66.2%) (p = 0.002). Gleason score, PSA and number of positive biopsy cores were independent predictors for both either PLND when recommended, or no PLND when not recommended (all p < 0.05). Clinical tumor stage, age and surgical approach were also independent predictors for no PLND when not recommended (all p < 0.05). CONCLUSIONS: Adherence of the indication to EAU guideline recommended PLND is high at this high-volume center. Neither ORP nor RARP represent a barrier for PLND, when recommended. However, a high number of patients underwent PLND despite absence of guideline recommendation. Possible staging advantages and PLND related complications needs to be individually considered, especially, when LNI risk is low.

Biomodulatory Treatment of Patients with Castration-Resistant Prostate Cancer: A Phase II Study of Imatinib with Pioglitazone, Etoricoxib, Dexamethasone and Low-Dose Treosulfan.

Therapeutic options for patients with castration-resistant prostate cancer (CRPC) remain limited. In a multicenter, Phase II study, 65 patients with histologically confirmed CRPC received a biomodulatory regimen during the six-month core study. Treatment comprised daily doses of imatinib mesylate, pioglitazone, etoricoxib, treosulfan and dexamethasone. The primary endpoint was prostate-specific antigen (PSA) response. Responders could enter an extension phase until disease progression or intolerable toxicity occurred. Mean PSA was 45.3 ng/mL at baseline, and 77 % of patients had a PSA doubling time <3 months. Of the 61 evaluable patients, 37 patients (60.6 %) responded or had stable disease and 23 of them (37.7 % of 61 patients) were PSA responders. Among the 23 responders mean PSA decreased from 278.9 ± 784.1 ng/mL at baseline to 8.8 ± 11.6 ng/mL at the final visit (week 24). The progression-free survival (PFS) was 467 days in the ITT population. Of the 947 adverse events, 57.6 % were suspected to be drug-related, 13.8 % led to dose adjustment or permanent discontinuation and 40.2 % required concomitant medication. This novel combination approach led to an impressive PSA response rate of 37.7 % in CRPC patients. The good PSA response and PFS rate combined with the manageable toxicity profile suggest an alternative treatment option.

Inhaled interleukin-2 in combination with low-dose systemic interleukin-2 and interferon alpha in patients with pulmonary metastatic renal-cell carcinoma: effectiveness and toxicity of mainly local treatment.

We describe here a mainly topical interleukin-2 (IL-2) application in pulmonary metastatic renal-cell carcinoma: a high-dose long-term inhalation of IL-2 (90% of IL-2 dose) and low-dose systemic subcutaneous IL-2 (10% of IL-2 dose) and systemic subcutaneous interferon alpha (IFN alpha). The effectiveness of this treatment is remarkable. No pulmonary metastases progressed during treatment. One complete response, 8 partial responses, and 6 cases of stable disease were achieved in the lungs of the 15 patients. In addition, 3 of 7 patients had partial responses and 1 of 7 had stabilization of non-pulmonary metastases. Overall response according to WHO criteria was 1 complete response, 6 partial responses, 2 mixed responses, 5 stable diseases and 1 progressive disease. Toxicity was low. Only WHO grade I toxicity occurred, except for a single grade II event (bronchospasm). This allowed long-term ambulatory treatment (1-23 months) inclusion of high-risk patients, and inclusion of patients with advanced disease. The expected mean survival of patients was 9.9 months, the actual mean survival is now 19.1 months, and 11 of 15 patients are still alive. Quality of life during treatment was good. Inhalation of IL-2 serves as a clinical model for high effectiveness and low toxicity of long-term local IL-2 application. We conclude that mainly local treatment might be the key to successful nontoxic use of IL-2 in cancer patients.

Toxicity of local, continuous and cyclic, high-dose bladder perfusion with recombinant and natural interleukin-2 in advanced cancer of the urinary bladder.

We evaluated the toxicity of high-dose local interleukin-2 (IL-2) in 18 patients not eligible for standard treatment of advanced transitional cell bladder carcinoma. Seven received continuous high-dose local natural IL-2 via pump system in the bladder for up to 420 days. 11 received cyclic high-dose local natural IL-2 or recombinant IL-2 for up to 420 days. Treatment was well tolerated and, considering the low rate of toxicity, could be offered in an outpatient setting. Except for local contrast-media hypersensitivity, no serious side-effects were observed. This study provides a basis for the non-toxic use of local IL-2 in future studies to evaluate effectiveness of the treatment or prophylaxis of patients with superficial bladder cancer in order to prevent recurrences.

Treatment of pulmonary metastatic renal-cell carcinoma in 116 patients using inhaled interleukin-2 (IL-2).

BACKGROUND: We report 6 years of experience in 116 patients who used inhaled interleukin-2 (IL-2) and were treated in different protocols with natural, recombinant glycosylated and recombinant nonglycosylated IL-2. MATERIALS AND METHODS: All protocols had in common high-dose inhalation of IL-2, either exclusively (11%), with low-dose systemic IL-2 (33%), or with low-dose systemic IL-2 and interferon-alpha (56%). Maximal toxicity per total treatment time (median treatment time, 7.2 months) was mild and at a low incidence (16%) of WHO grade 3 toxicity. Treatment was allowed in patients for whom systemic IL-2 was not suitable. RESULTS: Progressive pulmonary metastases responded in 15% of patients for a median of 15.5 months (range 4.1-33) and were stabilized in 55% for a median of 6.6 months (range, 3-51.7). Overall response rate was 16%, 49%, and 35%, respectively. Median overall response duration was 9.6 mo. Median achieved survival was 11.8 months (range 1.7-68.8). CONCLUSIONS: Inhaled IL-2 prevents progress of pulmonary metastases effectively in 70% of patients. Local use of IL-2 allows the use of the full potential of cytokines with little or no toxicity.

Immunotherapy of pulmonary metastatic renal cell carcinoma: success dependant on risk factors?

BACKGROUND/AIMS: Risk factors may influence not only prognosis in metastic renal cell carcinoma but also probability of response to immunotherapy. Response of patients treated with inhalation of interleukin-2 (IL-2), which can be offered to those not suitable for systemic therapy, was compared to risk factors. We report on 116 patients who used inhaled IL-2 and were treated in different protocols with natural, recombinant glycosylated and recombinant non-glycosylated. METHODOLOGY: All protocols had in common a high-dose inhalation of IL-2, either exclusively (11%), with low-dose systemic IL-2 (33%), or with low-dose systemic IL-2 and interferon-alpha (56%). Maximal toxicity per total treatment time (median treatment time: 7.2 months) was mild and there was a low incidence (16%) of WHO grade 3 toxicity. Treatment response was analyzed in a subgroup of patients having at least one given risk factor and treated with recombinant IL-2 (n=86). In all patients having risk factors the following distribution was found: more than 1 metastic location (86%), diagnosis to treatment interval (DTI) <12 months (62%), weight loss prior to therapy (41%), and ECOG performance status > or =2 (13%). In comparison, a group of patients having no risk factors at all was analyzed accordingly. RESULTS: Response to immunotherapy is dependant on risk factors, the most prominent one being the ECOG. Patients with an ECOG > or =2 achieved no overall response compared to patients with no risk factors who responded to immunotherapy (33%). Progressive pulmonary metastases responded in 15% of patients for a median of 15.5 months (range: 4.133) and were stabilized in 55% for a median of 6.6 months (range: 3-51.7). Overall response rate was 16%, 49%, and 35%, respectively. Median overall response duration was 9.6 months. Median achieved survival was 11.8 months (range: 1.7-68.8). CONCLUSIONS: We conclude that risk factors have to be considered in the interpretation of response to immunotherapy. Exclusion of patients because of risk factors alone does not seem to be justified according to our data. Responses, including long-term stabilization, can be achieved in 27-57% of such patients. IL-2 immunotherapy can also be considered as useful antitumor therapy in patients with risk factors, especially if given without major toxicity.

A comparison of systemic versus inhaled recombinant IL-2 administration for the treatment of metastatic renal cell carcinoma.

The aim of the current study was to compare the objective response and survival rates of patients with mRCC treated with IL-2 administered either systemically (SYST, subcutaneously) or via inhalation (INH), using relatively large sample sizes to afford a more meaningful comparison. We used univariate and multivariate analyses to retrospectively evaluate the data from two different databases generated from 277 patients treated with IL-2 during the 1993-1997 period, one developed at the University Hospital Hamburg-Eppendorf, and the other at Chiron-Amsterdam. Patients treated with INH IL-2 tended to have a poorer ECOG performance status than patients receiving SYST IL-2. Of 75 patients receiving INH IL-2, eight (10.7%) achieved an objective response; of 202 patients administered SYST IL-2, 45 (22.2%) achieved an objective response. The median survival time was 13.8 months for patients receiving INH IL-2 and 13.1 months for patients treated with SYST IL-2. One- and two-year survival rates were also comparable for the two treatment modalities (one-year: INH, 55%; SYST, 56%; two-year: INH, 28%; SYST, 26%). There was no significant difference in the likelihood of survival for patients receiving INH IL-2 versus SYST IL-2 (risk ratio = 0.82, P = 0.27). Patients administered INH IL-2 experienced considerably less toxicity and complications than patients administered SYST IL-2. We conclude that INH IL-2 treatment is at least as effective as SYST IL-2 treatment in promoting the survival of patients with mRCC. Given that INH IL-2 treatment of patients with a poorer ECOG performance status elicited a survival rate comparable to that seen with SYST IL-2 treatment of patients with a superior performance status, the potential exists for INH IL-2 treatment to be even more effective for patients having a better performance status. Additionally, INH IL-2 treatment is considerably less toxic and associated with fewer complications than SYST IL-2 treatment, thus providing a therapeutic option for otherwise untreatable patients, offering patients a relatively good quality of life, and requiring fewer co-medications. Nonetheless, selection of an IL-2 treatment modality should be based on several patient-related considerations. Moreover, these two IL-2 treatment modalities need not be mutually exclusive.

Efficacy and safety of inhaled recombinant interleukin-2 in high-risk renal cell cancer patients compared with systemic interleukin-2: an outcome study.

Systemic IL-2 is an effective treatment for low to intermediate risk mRCC patients, its efficacy is marginal in high-risk cases. Therefore, other treatment approaches are required for this population. Ninety-four high-risk patients with RCC and pulmonary metastases were treated with inhaled plus concomitant low-dose subcutaneous rhIL-2. Clinical response, survival and safety were compared with those from IL-2 given systemically at the registered dose and schedule in 103 comparable historical controls. In the rhIL-2 INH group, treatment consisted of 6.5 MIU rhIL-2 nebulized 5x/day and 3.3 MIU rhIL-2 SC once daily. The rhIL-2 SYS group received treatment which consisted of intravenous infusion of 18.0 MIU/m2/day rhIL-2 or SC injection of 3.6-18.0 MIU rhIL-2. Some patients in both groups also received IFNalpha. Mean treatment durations were 43 weeks rhIL-2 INH and 15 weeks rhIL-2 SYS. Significantly longer overall survival and progression-free survival durations were observed in the rhIL-2 INH group. The probability of survival at 5 years was 21% for the rhIL-2 INH group. No patients survived 5 years in the rhIL-2 SYS group. A multivariate analysis of overall survival adjusting for differences in baseline characteristics between the two treatment groups resulted in a risk ratio of 0.43 (95% CI 0.30-0.63; P < 0.0001). The data suggested an association between the response (SD or better) and survival, especially in the rhIL-2 INH group. The inhalation regimen was well tolerated. This outcome study suggests that administration of rhIL-2 by inhalation is efficacious and safe in high-risk mRCC patients with pulmonary metastases, who have no other treatment option available.

[Treatment of metastatic renal cell carcinoma. Value of immunotherapy compared with surgery of metastases]. / Behandlung des metastasierten Nierenzellkarzinoms. Stellenwert der Immuntherapie gegenüber der Metastasenchirurgie.

The prognosis for patients in whom metastatic renal cell carcinoma (RCC) is not treated is unfavorable, with a reported 5-year survival of 0-18%. Before the era of immunotherapy and in the absence of effective nonsurgical therapy, resection of metastases was the accepted way to prolong survival, giving a 5-year survival of 7-69%. Retrospective studies have shown that several clinical factors are associated with a relatively good prognosis. Some patients will benefit from resection of metastases, but most patients with metastatic RCC are not candidates for such aggressive surgery. The use of interleukin-2 has demonstrated that immunotherapy can produce durable remissions. Without randomized trials, it is difficult to know whether survival is longer than that in untreated patients, but there is clear evidence that immunotherapy improves survival and yields long-lasting remissions in selected patients. Many questions remain concerning quality of life and the benefit-to-risk ratio of immunotherapy, but it is the most effective treatment for metastatic RCC.

[Immunotherapy of renal cell carcinoma. With special emphasis on therapy of the elderly patient]. / Immuntherapie des Nierenzellkarzinoms. Unter spezieller Berücksichtigung der Therapie des alten Patienten.

Interleukin-2 (IL-2) and/or interferon-alpha (IFN-alpha) induce remissions and prolong life in patients with metastatic renal cell carcinoma when carefully selected for a possibly toxic treatment. However, better-tolerated and more effective therapies are needed, especially in the elderly and patients with comorbidities. Recent achievements in the treatment of advanced renal cell carcinoma highlight potentially significant improvements. Immune cells within the tumor correlate with response and survival indicating the importance of local immune modulation. Such modulation has allowed introducing well-tolerated treatments such as inhalation of IL-2 to control lung metastases, which results in a significant survival benefit for high-risk patients as suggested by a recent cohort study in 200 patients. Antibody-based tumor targeting against cG250, specifically expressed on RCC, seems to stabilize progressive metastatic disease and does not induce toxicity. Vaccination strategies are also well tolerated, but have not shown convincing results in advanced disease so far. Other approaches have not fulfilled expectations. Stem cell transplantation still has significant toxicity and cannot be recommended for the elderly.

[Regional immunotherapy of metastatic renal cell carcinoma]. / Regionale Immuntherapie beim metastasierten Nierenzellkarzinom.

We summarized the current literature concerning regional immunotherapy of pulmonary metastases in metastatic renal cell carcinoma and other malignancies using inhaled interleukin-2 (IL-2). Inhaled IL-2 therapy is associated with minimal toxicity and is effective in preventing progression in metastatic renal cell carcinoma, melanoma, and possibly other diseases such as breast cancer. Local (physiologic) use and systemic (pharmacologic) use of IL-2 are not mutually exclusive; a combination may be very appropriate in metastatic cancer. Local physiologic therapy intensifies treatment without intensifying toxicity.