Intraoperative electron radiation therapy (IOERT) in patients with locally recurrent renal cell carcinoma

Background: To analyze our experience with intraoperative electron radiation therapy (IOERT) followed by moderate doses of external beam radiation therapy (EBRT) in patients with locally recurrent renal cell carcinoma. Methods: From 1992 to 2010, 17 patients with histologically proven, locally recurrent renal cell carcinoma (median tumor size 7 cm) were treated by surgery and IOERT with a median dose of 15 Gy. All patients met the premise of curative intent including 7 patients with oligometastases at the time of recurrent surgery, which were resected and/or irradiated. The median time interval from primary surgery to local recurrence was 26 months. Eleven patients received additional 3D-conformal EBRT with a median dose of 40 Gy. Results: Surgery resulted in free but close margins in 6 patients (R0), while 9 patients suffered from microscopic (R1) and 2 patients from macroscopic (R2) residual disease. After a median follow-up of 18 months, two local recurrences were observed, resulting in an actuarial 2-year local control rate of 91%. Eight patients developed distant failures, predominantly to liver and bone, resulting in an actuarial 2-year progression free survival of 32%. An improved PFS rate was found in patients with a larger time interval between initial surgery and recurrence (> 26 months). The actuarial 2-year overall survival rate was 73%. Lower histological grading (G1/2) was the only factor associated with improved overall survival. Perioperative complications were found in 4 patients. No IOERT specific late toxicities were observed. Conclusions: Combination of surgery, IOERT and EBRT resulted in high local control rates with low toxicity in patients with locally recurrent renal cell cancer despite an unfavorable surgical outcome in the majority of patients. However, progression-free and overall survival were still limited due to a high distant failure rate, indicating the need for intensified systemic treatment especially in patients with high tumor grading and short interval to recurrence

Primary melanoma of the prostate: case report and review of the literature

Background: Primary melanoma of the prostate has an extremely rare incidence. Only five cases have been reported in the literature and prognosis is poor. The most likely origin of prostatic melanoma is the transitional epithelium of the prostatic urethra. Surgical care for primary melanoma of mucosal sites is less well established than for primary cutaneous melanoma, but excision of the primary is recommended if the patient has no systemic disease. Case presentation: Here, we describe a case of primary malignant melanoma of the prostate. A 37-year-old male patient with history of both chemo- and radiation therapy for Hodgkin’s disease was admitted to the University Hospital Heidelberg on suspicion of pleomorphic sarcoma of the bladder. In-house diagnostic work-up revealed a malignant melanoma of the prostate. We then performed radical prostatectomy with extended lymphadenectomy. Despite presumably curative surgery, the patient suffered from early relapse of disease with pulmonary metastasis. Systemic chemotherapy and subsequent immuno-oncologic treatment was thereafter initiated. Conclusion: Since prostatic melanoma is a rare disease and a melanoma metastasis of unknown primary is the differential diagnosis, a multidisciplinary approach including early imaging to rule out possible metastases and to search for another potentially existing primary is advisable. To prevent complications related to local tumor progression and to receive tissue for mutational analysis, we recommend complete surgical resection to reduce the tumor mass. Novel immune and targeted oncologic therapies can lead to an improved survival in some cases and support of clinical trials is needed

Quality of life and functional outcome after infravesical desobstruction and HIFU treatment for localized prostate cancer

Background: To evaluate quality of life, functional and oncological outcome after infravesical desobstruction and HIFU treatment for localized prostate cancer. Methods: One hundred thirty-one patients, treated with TURP and HIFU in a single institution were followed up for oncological and functional outcome. Oncological outcome was quantified by biochemical recurrence free survival using the Stuttgart and Phoenix criteria. Quality of life was assessed by usage of standardized QLQ-C30 and QLQ-PR25 questionnaires. In addition, functional questionnaires such as IPSS and IIEF-5 were used. Complications were assessed by the Clavien-Dindo classification. Results: One hundred thirty-one patients with a mean age of 72.8 years (SD: 6.0) underwent HIFU for prostate cancer (29.0% low risk, 58.8% intermediate risk, 12.2% high risk). PSA nadir was 0.6 ng/ml (SD: 1.2) after a mean of 4.6 months (SD: 5.7). Biochemical recurrence free survival defined by Stuttgart criteria was 73.7%, 84.4% and 62.5% for low-, intermediate- and high-risk patients after 22.2 months. Complications were grouped according to Clavien-Dindo and occurred in 10.7% (grade II) and 11.5% (grade IIIa) of cases. 35.1% of patients needed further treatment for bladder neck stricture. Regarding incontinence, 14.3%, 2.9% and 0% of patients had de novo urinary incontinence grade I°, II° and III° and 3.8% urge incontinence due to HIFU treatment. Patients were asked for the ability to have intercourse: 15.8%, 58.6% and 66.7% of patients after non-, onesided and bothsided nervesparing procedure were able to obtain sufficient erection for intercourse, respectively. Regarding quality of life, mean global health score according to QLQ-C30 was 69.4%. Conclusion: HIFU treatment for localized prostate cancer shows acceptable oncological safety. Quality of life after HIFU is better than in the general population and ranges within those of standard treatment options compared to literature. HIFU seems a safe valuable treatment alternative for patients not suitable for standard treatment

SWITCH : A randomised, sequential, open-label study to evaluate the efficacy and safety of Sorafenib-sunitinib versus Sunitinib-sorafenib in the treatment of metastatic renal cell cancer

Background Understanding how to sequence targeted therapies for metastatic renal cell carcinoma (mRCC) is important for maximisation of clinical benefit. Objectives To prospectively evaluate sequential use of the multikinase inhibitors sorafenib followed by sunitinib (So-Su) versus sunitinib followed by sorafenib (Su-So) in patients with mRCC. Design, setting, and participants The multicentre, randomised, open-label, phase 3 SWITCH study assessed So-Su versus Su-So in patients with mRCC without prior systemic therapy, and stratified by Memorial Sloan Kettering Cancer Center risk score (favourable or intermediate). Intervention Patients were randomised to sorafenib 400 mg twice daily followed, on progression or intolerable toxicity, by sunitinib 50 mg once daily (4 wk on, 2 wk off) (So-Su), or vice versa (Su-So). Outcome measurements and statistical analysis The primary endpoint was improvement in progression-free survival (PFS) with So-Su versus Su-So, assessed from randomisation to progression or death during second-line therapy. Secondary endpoints included overall survival (OS) and safety. Results and limitations In total, 365 patients were randomised (So-Su, n = 182; Su-So, n = 183). There was no significant difference in total PFS between So-Su and Su-So (median 12.5 vs 14.9 mo; hazard ratio [HR] 1.01; 90% confidence interval [CI] 0.81–1.27; p = 0.5 for superiority). OS was similar for So-Su and Su-So (median 31.5 and 30.2 mo; HR 1.00, 90% CI 0.77–1.30; p = 0.5 for superiority). More So-Su patients than Su-So patients reached protocol-defined second-line therapy (57% vs 42%). Overall, adverse event rates were generally similar between the treatment arms. The most frequent any-grade treatment-emergent first-line adverse events were diarrhoea (54%) and hand-foot skin reaction (39%) for sorafenib; and diarrhoea (40%) and fatigue (40%) for sunitinib. Conclusions Total PFS was not superior with So-Su versus Su-So. These results demonstrate that sorafenib followed by sunitinib and vice versa provide similar clinical benefit in mRCC

Renal cell carcinoma with inferior vena cava involvement: Prognostic effect of tumor thrombus consistency on cancer specific survival: Tumor Thrombus Consistency and Survival

Renal cell carcinoma forming a venous tumor thrombus (VTT) in the inferior vena cava (IVC) has a poor prognosis. Recent investigations have been focused on prognostic markers of survival. Thrombus consistency (TC) has been proposed to be of significant value but yet there are conflicting data. The aim of this study is to test the effect of IVC VTT consistency on cancer specific survival (CSS) in a multi-institutional cohort

Neural Networks Modeling for Prediction of Required Resources for Personalized Endourologic Treatment of Urolithiasis

When scheduling surgeries for urolithiasis, the lack of information about the complexity of procedures and required instruments can lead to mismanagement, cancellations of elective surgeries and financial risk for the hospital. The aim of this study was to develop, train, and test prediction models for ureterorenoscopy. Routinely acquired Computer Tomography (CT) imaging data and patient data were used as data sources. Machine learning models were trained and tested to predict the need for laser lithotripsy and to forecast the expected duration of ureterorenoscopy on the bases of 474 patients over a period from May 2016 to December 2019. Negative predictive value for use of laser lithotripsy was 92%, and positive predictive value 91% before application of the reject option, increasing to 97% and 94% after application of the reject option. Similar results were found for duration of surgery at ≤30 min. This combined prediction is possible for 54% of patients. Factors influencing prediction of laser application and duration ≤30 min are age, sex, height, weight, Body Mass Index (BMI), stone size, stone volume, stone density, and presence of a ureteral stent. Neuronal networks for prediction help to identify patients with an operative time ≤30 min who did not require laser lithotripsy. Thus, surgical planning and resource allocation can be optimised to increase efficiency in the Operating Room (OR)

Harnessing the p53-PUMA Axis to Overcome DNA Damage Resistance in Renal Cell Carcinoma

Resistance to DNA damage–induced apoptosis is a hallmark of cancer and a major cause of treatment failure and lethal disease outcome. A tumor entity that is largely resistant to DNA-damaging therapies including chemo- or radiotherapy is renal cell carcinoma (RCC). This study was designed to explore the underlying molecular mechanisms of DNA damage resistance in RCC to develop strategies to resensitize tumor cells to DNA damage–induced apoptosis. Here, we show that apoptosis-resistant RCC cells have a disconnect between activation of p53 and upregulation of the downstream proapoptotic protein p53 upregulated modulator of apoptosis (PUMA). We demonstrate that this disconnect is not caused by gene-specific repression through CCCTC-binding factor (CTCF) but instead by aberrant chromatin compaction. Treatment with an HDAC inhibitor was found to effectively reactivate PUMA expression on the mRNA and protein level and to revert resistance to DNA damage–induced cell death. Ectopic expression of PUMA was found to resensitize a panel of RCC cell lines to four different DNA-damaging agents tested. Remarkably, all RCC cell lines analyzed were wild-type for p53, and a knockdown was likewise able to sensitize RCC cells to acute genotoxic stress. Taken together, our results indicate that DNA damage resistance in RCC is reversible, involves the p53-PUMA axis, and is potentially targetable to improve the oncological outcomes of RCC patients

Decision-making in localized prostate cancer: lessons learned from an online support group

Huber J, Ihrig A, Peters T, et al. Decision-making in localized prostate cancer: lessons learned from an online support group. BJU International. 2011;107(10):1570-1575.Study Type – Patient (preference/ecological) Level of Evidence 2c What's known on the subject? and What does the study add? Social support plays a major role for decision-making in localized prostate cancer and the importance of online resources has become increasingly recognized. However, so far most of the knowledge has been generated on formal and stylistic aspects. The study adds to understanding the content and the dynamics of peer-to-peer counselling in an online support group. OBJECTIVE • To investigate patient-to-patient communication with regard to decision-making in localized prostate cancer; as most of it is done in private, online support groups are a unique means for this task. PATIENTS AND METHODS • Over a 32-month period, we screened 501 threads in the largest German online support group for prostate cancer. • Threads started by questioners newly diagnosed with localized prostate cancer and stating decision-making as the key topic were included; in all, 82 (16.4%) threads met these criteria. • Two independent investigators characterized every thread following a standardized protocol. • Fisher’s exact test and Mann–Whitney U-test were applied for group analyses. A complementary qualitative linguistic approach was chosen. RESULTS • Threads were most commonly started to ask for therapy recommendations (66%), information on the course of treatment (46%) and emotional support (46%). • Answers consisted of treatment recommendations (40%), emotional support (37%) and personal experiences (28%). • A second opinion on the biopsy cores (51%) and additional imaging (40%) were common suggestions. • The rate of advice for radical prostatectomy (RP) vs radiotherapy was 67 vs 82%. Thus, surgery was less recommended in our sample (P= 0.01); 75% of the men with an initial therapeutic preference were finally confirmed herein. • Linguistic analysis showed that posters frequently use a tentative language style and that common language is avoided. CONCLUSIONS • Patients readily receive information, advice and emotional support as part of an online support group. • The scientific evaluation of an online support group is a complementary way of getting to know our patients’ needs and worries. • Patient–physician contact can benefit from this knowledge

External validation of two MRI-based risk calculators in prostate cancer diagnosis

Background: The diagnosis of (significant) prostate cancer ((s)PC) is impeded by overdiagnosis and unnecessary biopsy. Risk calculators (RC) have been developed to mitigate these issues. Contemporary RCs integrate clinical characteristics with mpMRI findings. Objective: To validate two of these models—the MRI-ERSPC-RC-3/4 and the risk model of van Leeuwen. Methods: 265 men with clinical suspicion of PC were enrolled. Every patient received a prebiopsy mpMRI, which was reported according to PI-RADS v2.1, followed by MRI/TRUS fusion-biopsy. Cancers with ISUP grade ≥ 2 were classified as sPC. Outcome measurements and statistical analysis: Statistical analysis was performed by comparing discrimination, calibration, and clinical utility Results: There was no significant difference in discrimination between the RCs. The MRI-ERSPC-RC-3/4-RC showed a nearly ideal calibration-slope (0.94; 95% CI 0.68–1.20) than the van Leeuwen model (0.70; 95% CI 0.52–0.88). Within a threshold range up to 9% for a sPC, the MRI-ERSPC-RC-3/4-RC shows a greater net benefit than the van Leeuwen model. From 10 to 15%, the van Leeuwen model showed a higher net benefit compared to the MRI-ERSP-3/4-RC. For a risk threshold of 15%, the van Leeuwen model would avoid 24% vs. 14% compared to the MRI-ERSPC-RC-3/4 model; 6% vs. 5% sPC would be overlooked, respectively. Conclusion: Both risk models supply accurate results and reduce the number of biopsies and basically no sPC were overlooked. The van Leeuwen model suggests a better balance between unnecessary biopsies and overlooked sPC at thresholds range of 10–15%. The MRI-ERSPC-RC-3/4 risk model provides better overall calibration