Single-dose carboplatin followed by involved-node radiotherapy for stage IIA and stage IIB seminoma (SAKK 01/10): a single-arm, multicentre, phase 2 trial.

Background: Standard treatment options for patients with stage IIA or stage IIB seminoma include either para-aortic and pelvic radiotherapy or three to four cycles of cisplatin-based combination chemotherapy. These options result in 3-year progression free survival rates of at least 90%, but bear risks for acute and late toxic effects, including secondary malignancies. We tested a novel approach combining de-escalated chemotherapy with de-escalated involved node radiotherapy, with the aim of reducing toxicity while preserving efficacy.

Overcoming Immune Resistance With Radiation Therapy in Prostate Cancer.

Prostate cancer is the second most common cancer in men and represents a significant healthcare burden worldwide. Therapeutic options in the metastatic castration-resistant setting remain limited, despite advances in androgen deprivation therapy, precision medicine and targeted therapies. In this review, we summarize the role of immunotherapy in prostate cancer and offer perspectives on opportunities for future development, based on current knowledge of the immunosuppressive tumor microenvironment.

Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476).

Abiraterone acetate plus prednisolone (AAP) previously demonstrated improved survival in STAMPEDE, a multiarm, multistage platform trial in men starting long-term hormone therapy for prostate cancer. This long-term analysis in metastatic patients was planned for 3 years after the first results. Standard-of-care (SOC) was androgen deprivation therapy.

Incidence, Patterns, and Outcomes with Adjuvant Chemotherapy for Residual Disease After Neoadjuvant Chemotherapy in Muscle-invasive Urinary Tract Cancers.

Background: Patients with residual muscle-invasive urinary tract cancer after neoadjuvant chemotherapy (NAC) have a high risk of recurrence.

Objective: To retrospectively evaluate whether additional adjuvant chemotherapy (AC) improves outcomes compared with surveillance in patients with significant residual disease despite NAC.

Design, Setting, And Participants: We identified 474 patients who received NAC from the Retrospective International Study of Cancers of the Urothelium database, of whom 129 had adverse residual disease (≥ypT3 and/or ypN).

Impact of the Number of Cycles of Platinum Based First Line Chemotherapy for Advanced Urothelial Carcinoma.

Purpose: We evaluated the impact of the number of cycles of platinum based, first line chemotherapy (fewer than 6 cycles vs the conventional 6 cycles or more) on the survival of patients with metastatic urothelial carcinoma.

Materials And Methods: We used the RISC (Retrospective International Study of Invasive/Advanced Cancer of the Urothelium) database. The association of the number of cycles of chemotherapy with overall survival was investigated by Cox multiple regression analysis after controlling for recognized prognostic factors.

Bone Metastases as the Only Metastatic Site in Patients With Urothelial Carcinoma: Focus on a Special Patient Population.

Background: Patients with exclusive bone metastatic spread from urothelial carcinoma (UC) throughout their disease course represent a rare subgroup with unique clinical features. These patients deserved special consideration in a retrospective multicenter study.

Patients And Methods: Analyses were made from a pool of 1911 patients with a diagnosis of metastatic UC, from 23 centers.

Robot-assisted Versus Open Radical Cystectomy in Patients Receiving Perioperative Chemotherapy for Muscle-invasive Bladder Cancer: The Oncologist's Perspective from a Multicentre Study.

Background: Little is known about the outcomes of robot-assisted radical cystectomy (RARC) compared to open radical cystectomy (ORC) combined with perioperative chemotherapy for muscle-invasive urothelial bladder cancer (UBC).

Objective: To evaluate surgical and oncological outcomes for RARC and ORC in multimodal treatment.

Design, Setting, And Participants: Data from 28 centres were collected for cystectomies performed between January 2000 and July 2013.

Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy.

Background: Abiraterone acetate plus prednisolone improves survival in men with relapsed prostate cancer. We assessed the effect of this combination in men starting long-term androgen-deprivation therapy (ADT), using a multigroup, multistage trial design.

Methods: We randomly assigned patients in a 1:1 ratio to receive ADT alone or ADT plus abiraterone acetate (1000 mg daily) and prednisolone (5 mg daily) (combination therapy).

Nomogram-based Prediction of Overall Survival in Patients with Metastatic Urothelial Carcinoma Receiving First-line Platinum-based Chemotherapy: Retrospective International Study of Invasive/Advanced Cancer of the Urothelium (RISC).

Background: The available prognostic models for overall survival (OS) in patients with metastatic urothelial carcinoma (UC) have been derived from clinical trial populations of cisplatin-treated patients.

Objective: To develop a new model based on real-world patients.

Design, Setting, And Participants: Individual patient-level data from 29 centers were collected, including metastatic UC and first-line cisplatin- or carboplatin-based chemotherapy administered between January 2006 and January 2011.

Radiation Therapy after Radical Prostatectomy: Implications for Clinicians.

Depending on the pathological findings, up to 60% of prostate cancer patients who undergo radical prostatectomy (RP) will develop biochemical relapse and require further local treatment. Radiotherapy (RT) immediately after RP may potentially eradicate any residual localized microscopic disease in the prostate bed, and it is associated with improved biochemical, clinical progression-free survival, and overall survival in patients with high-risk pathological features according to published randomized trials. Offering immediate adjuvant RT to all men with high-risk pathological factors we are over-treating around 50% of patients who would anyway be cancer-free, exposing them to unnecessary toxicity and adding costs to the health-care system.

Efficacy of cetuximab in metastatic castration-resistant prostate cancer might depend on EGFR and PTEN expression: results from a phase II trial (SAKK 08/07).

Purpose: The EGF receptor (EGFR) is overexpressed in the majority of metastatic castration-resistant prostate cancers (mCRPC) and might represent a valid therapeutic target. The combination of docetaxel and cetuximab, the monoclonal antibody against EGFR, has not been tested in patients with prostate cancer.

Experimental Design: Patients with mCRPC progressing during or within 90 days after at least 12 weeks of docetaxel were included in this phase II trial.

Pharmacotherapeutic management of locally advanced prostate cancer: current status.

Locally advanced prostate cancer (LAPC) is a heterogeneous entity usually embracing T3-4 and/or pelvic lymph-node-positive disease in the absence of established metastases. Outcomes for LAPC with single therapies have traditionally been poor, leading to the investigation of adjuvant therapies. Prostate cancer is a hormonally sensitive tumour, which usually responds to pharmacological manipulation of the androgen receptor or its testosterone-related ligands.

Neoadjuvant and adjuvant strategies in renal cell carcinoma: more questions than answers.

The current standard treatment for early stage (I-III) renal cell cancer (RCC) is surgery. While the prognosis of stage I tumors is excellent, stage II and particularly stage III have a high risk of relapse. The adjuvant treatment of patients with RCC remains an area of investigation, with patient selection being a key aspect.

Non-risk-adapted surveillance in clinical stage I nonseminomatous germ cell tumors: the Princess Margaret Hospital's experience.

Background: Since 1981 Princess Margaret Hospital has used initial active surveillance (AS) with delayed treatment at relapse as the preferred management for all patients with clinical stage I nonseminomatous germ cell tumors (NSGCT).

Objective: Our aim was to report our overall AS experience and compare outcomes over different periods using this non-risk-adapted approach.

Design, Setting, And Participants: Three hundred and seventy-one patients with stage I NSGCT were managed by AS from 1981 to 2005.

[New drugs at the horizon for men with prostate cancer].

Despite major progress in the understanding of biological mechanisms underlying metastatic prostate cancer, the treatment of men with advanced prostate cancer remains challenging. Several randomized controlled trials with promising or positive results are underway or just released. Here we discuss new treatments which might be used in clinic in the near future: hormonal treatments (Abiraterone and MDV3100), a new chemotherapy (Cabazitaxel), a cellular vaccine (Sipuleucel-T), anti-angiogenic drugs (Bevacizumab, Aflibercept), a new radioactive treatment (Alpharadin) and a new bone-protective agent (Deno-sumab).

Docetaxel in the management of prostate cancer: current standard of care and future directions.

Background: Advanced and metastatic prostate cancer continues to represent a significant healthcare burden. Since the publication of two randomized trials that showed significant survival and palliative benefits for men treated with docetaxel, this drug has become the treatment of choice for patients with metastatic castration resistant prostate cancer (CRPC).

Objective: This review discusses the development and current use of docetaxel in metastatic CRPC, as well as future clinical applications.

Treatment of hormone-refractory prostate cancer with docetaxel or mitoxantrone: relationships between prostate-specific antigen, pain, and quality of life response and survival in the TAX-327 study.

Purpose: The TAX-327 study randomized 1,006 men with metastatic hormone-refractory prostate cancer to receive 3-weekly docetaxel, weekly docetaxel, or mitoxantrone, each with prednisone.

Experimental Design: We used the TAX-327 database to address (a) the relationship between quality of life (QoL) and pain; (b) whether minimally symptomatic patients benefit from treatment or have treatment-related decline in QoL; (c) the relationships between prostate-specific antigen (PSA) response, pain response, and QoL response; (d) the times at which these responses are first observed; and (e) whether PSA, pain, and/or QoL response predict for overall survival.

Results: At baseline, 374 of 815 men assessed for QoL had major pain; of these, 92% had substantial impairment of QoL compared with 75% without major pain (P < 0.

Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study.

Purpose: The TAX 327 study compared docetaxel administered every 3 weeks (D3), weekly docetaxel (D1), and mitoxantrone (M), each with prednisone (P), in 1,006 men with metastatic hormone-resistant prostate cancer (HRPC). The original analysis, undertaken in August 2003 when 557 deaths had occurred, showed significantly better survival and response rates for pain, prostate-specific antigen (PSA), and quality of life for D3P when compared with MP. Here, we report an updated analysis of survival.

Targeting metastatic prostate cancer: the search for innovative systemic therapies.

Metastatic hormone-resistant prostate cancer has proven largely resistant to cytotoxic therapy. Since 2004, docetaxel (Taxotere)/prednisone has become the standard chemotherapy used to treat advanced hormone-resistant prostate cancer. However, the survival advantage is modest and a significant number of patients do not respond to chemotherapy.

Novel targets in prostate cancer.

Despite recent advances in the understanding of the cellular and molecular biology of prostate cancer, new options for the treatment of prostate cancer remain elusive. Targeted therapies have shown promising activities in many solid tumours and the growing number of targets and targeted agents is creating numerous opportunities for clinical research in advanced prostate cancer. At ASCO 2006 in Atlanta, a clinical science symposium on novel targets in prostate cancer was presented.