Carsten H. Ohlmann

Ibandronate: its pharmacology and clinical efficacy in the management of tumor-induced hypercalcemia and metastatic bone disease.

It is well accepted that tumor cells in the bone, especially from breast cancer, prostate cancer and multiple myeloma, can stimulate osteoclast formation and activity. Bisphosphonates are potent inhibitors of osteoclast-mediated normal and pathologic bone resorption. Besides their apoptotic and antiproliferative activity on osteoclasts, bisphosphonates can also exert similar effects on macrophages and tumor cells. Currently, it is unknown if this effect can be translated into clinical practice with regard to an effective adjuvant therapeutic regimen for high-risk patients with systemic recurrences following primary treatment of a given cancer. There are several new aspects that might extend the clinical use of ibandronate, a bisphosphate, in oncology: prevention of hypogonadal osteoporosis in men, palliative management of painful osseous metastases and adjuvant therapy of high-risk prostate cancer patients. Safety and tolerability are excellent for the oral and intravenous formulations, and ibandronate can even be safely applied in pre-existing renal insufficiency. The purpose of this review is to critically reflect the pharmacology and clinical efficacy of ibandronate in the management of tumor-induced hypercalcemia, osteoporosis and metastatic bone disease.

Radical prostatectomy in T4 prostate cancer after inductive androgen deprivation: results of a single-institution series with long-term follow-up

To determine the outcomes of complete surgical resection of T4 prostate cancer after inductive androgen‐deprivation therapy (ADT), as inductive ADT and subsequent radical prostatectomy (RP) is not recommended by any guideline yet.

Erstlinientherapie beim lokal fortgeschrittenen oder metastasierten Urothelkarzinom

Für die Erstlinientherapie des lokal fortgeschrittenen oder metastasierten Urothelkarzinoms stellt eine Cisplatinbasierte Chemotherapie den leitlinienkonformen Behandlungsstandard dar. Für Cisplatin-ungeeignete Patienten kann eine Kombinationstherapie aus Gemcitabin und Carboplatin angeboten werden. Die mediane Gesamtüberlebenszeit von maximal 15 Monaten ist bei der Cisplatin-basierten Chemotherapie begrenzt. Hier bieten immuntherapeutische Ansätze mit CheckpointInhibitoren neue Möglichkeiten. Erste

Adjuvante Nivolumab-Behandlung versus Placebo

Bei Patienten mit einem muskelinvasiven Blasenkarzinom wird in internationalen Leitlinien die Cisplatin-basierte Chemotherapie vor der radikalen Zystektomie empfohlen, da sie das Fünf- und Zehn-Jahres-Überleben deutlich verbessert. Derzeit fehlt jedoch eine Standardbehandlung für diejenigen Patienten, die eine solche Therapie ablehnen oder für eine solche neoadjuvante Therapie ungeeignet sind. Für diese Patientengruppe soll in der Studie Checkmate-274 ein neuer Therapieansatz geprüft werden.

MP97-16 ROBOTIC SALVAGE-LYMPHADENECTOMY FOR NODAL-ONLY RECURRENCES AFTER RADICAL PROSTATECTOMY: PERIOPERATIVE AND EARLY ONCOLOGICAL OUTCOMES

advantages of LESS-RP, such as lower postoperative pain and its cosmetic excellence, have been pointed out. However, LESS-RP is recognized to be a technically challenging procedure even for experts, especially in suturing and dissection. To overcome these challenges, we introduce transurethral-assisted transumbilical laparoendoscopic single-site radical prostatectomy (TU-LESS-RP) . With the technology, many operational equipments can be used through natural orifice to lower the operation difficulty and shorten the operation time. This study is to evaluate the feasibility and advantages of transurethral-assisted technology in LESS-RP for PCa patients. METHODS: From Jan. 2014 to Dec.2015, 118 patients underwent RP in our center, including 11 patients were performed by LESSRP (a single-port with four channels was inserted into the 2.5 cm periumbilical incision), and 107 were performed by TU-LESS-RP (homemade transurethral port were used, Suction and dissociation devices were inserted into transurethral port to assist the surgical operator). All data referring to patient demographics, pathology, and perioperative outcomes were recorded and analyzed. RESULTS: All the operations were successfully accomplished. No conversion into conventional laparoscopic or open surgery was performed. Compared with LESS-RP, TU-LESS-RP is easier to identify the neck of bladder, avoid the injury of rectum, make anastomosis quickly, expose the anatomic structures clearly, and so on. Consequently, with this technology we make the LESS-RP easy to master and shorten the operation and anastomosis time significantly. Meanwhile, we got satisfied cosmetic and continent results for patients. According to our data, TULESS-RP has more significant advantage than LESS-RP in following aspects: the mean operating time (135 min vs 215 min), the median estimated blood loss (108 ml vs 466 ml), the length of stay (9 d vs 16.5 d), and indwelling catheter time (7.5 d vs 14.5 d). All these patients had satisfied continent and cosmetic effects. For patients experienced lymph nodes dissection, the operating time was 36 min, the average lymph nodes was 10.6, and two patients with positive results (3/9 and 2/12). CONCLUSIONS: LESS-RP is technically challenging although with advantage of less invasive and more cosmetic effects even for experts. To solve these problems, TU-LESS-RP has been developed in our institution, and it has been proved more feasible and safer for localized PCa patients. The technology could minimize the interference between the laparoscopic equipments, shorten the operating time, decrease the risk and complications. TU-LESS-RP for localized PCa patients has just begun, and the number of cases experienced is still small. Being cosmetically highly favorable, this procedure will likely be further developed as a less invasive surgery in the future.

Organ-Preserving Surgical Treatment of a Horseshoe Kidney Occupied by a Large Renal Cell Carcinoma with Extensive Venous Invasion: A Case Report

The horseshoe kidney is one of the most common congenital disorders affecting the urogenital system. Following a fusion of the lower kidney poles, which in turn lead to the formation of an isthmus, this anatomical variation is accompanied by other characteristic properties like an incomplete ascension, ventral rotation of the pelvices as well as atypical vascular supply. Even though renal carcinoids and Wilms tumors are more common in horseshoe kidneys, the incidence of renal cell carcinomas seems to be unaffected. Here we report the case of a locally advanced renal cell carcinoma with extensive venous invasion occurring in a horseshoe kidney and its complex surgical management. The whole primary tumor as well as a majority of venous tumor thrombi could be removed by a combination of 2/3 nephrectomy and cavotomy with thrombectomy. During 1 year of follow-up, the patient neither suffered from a tumor relapse, nor did he require renal replacement therapy. Thus, we conclude that even in cases of RCC where advanced disease is associated with complex anatomical situations, organ-preserving surgical treatment should be pursued to achieve excellent functional and oncological results.

Abstract 5231: Zoledronic acid encapsulated into liposomes and nanoparticles: Enhanced antitumor activity in 3D-prostate carcinoma spheroids

Introduction: Zoledronic acid is currently used for the treatment of bone metastases in hormone-resistant prostate cancer patients. The rapid plasma half-life and the high affinity for Osteoclasts, the primary targets of bisphosphonates, limit the use for extra-skeletal tissues. Moreover, it remains still unclear, whether cancer-associated fibroblasts (CAF) influence the toxicity of ZOL. The use of nanomedicine is one promising strategy to improve the availability of drugs within the tumor tissue. To investigate the benefit of such approach, we used two different nanovectors encapsulating ZOL on 3D-spheroids from prostate carcinoma cells and CAF in combination with standard toxicity assays. Material and Methods: Stealth liposomes (PGNP_ZOL) and a new generation of nanovector, named self-assembly nanoparticles (NP_ZOL), were prepared using standard protocols already described. The prostate carcinoma cell lines PC-3, DU-145 and LNCaP were cultivated in 96-well MTP9s and as Spheroids on agarose coated 96-well MTP9s. Heterologous spheroids were prepared by mixing tumor cells with different ratios of normal (NAF) or tumor-associated (CAF) fibroblasts. Cell cultures/spheroids were incubated with ZOL, NP_ZOL/PGNP_ZOL for up to 120 h. Changes in growth behavior and toxicity (apoptosis/necrosis) were quantified from spheroid-cultures by modifications of standard assays (CDD+, LDH+). The adaptability of these techniques for 3D- cultures was assessed using thapsygargin/tunicamycin as apoptosis-inducing agents. Results: Standard-viability assays revealed a significant enhancement of antitumor activity of NP_ZOL/PGNP_ZOL as compared to the free drug in cell cultures of DU-145 and LNCaP, whereas these effects were less pronounced in PC-3 cells. The antitumor efficacy of NP_ZOL/PGNP_ZOL was caused by a strong inhibition of tumor cell proliferation as revealed by the BrDU-assay; on the other hand, both CDD+ and LDH+ failed to detect both apoptosis and necrosis after drug treatment for up to 120 h. The average IC 50 values in the tumor cells ranges from 10-20µM/L, but the fibroblasts exhibit complete growth inhibition at concentrations between 2-5µm/L ZOL. Conclusion: These results confirm the hypothesis that the use of nanomedicine enables the extension in therapeutic applications of drugs such as bisphosphonates. In this context, ZOL seems to exert benefits even onto the primary tumor cells. Homo-/heterologeous 3D-spheroids offer advanced models mimicking the microenvironment within a tumor tissue grows thus bridging the gap between cell culture and live tissue. Moreover, the rapid generation of single-tumor spheroids allows for a high-throughput cell function and toxicity analysis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5231. doi:1538-7445.AM2012-5231