Progression-free survival as a clinical trial endpoint in advanced renal cell carcinoma.

Traditionally, overall survival (os) has been considered the "gold standard" for evaluating new systemic oncologic therapies, because death is easy to define, is easily compared across disease sites, and is not subject to investigator bias. However, as the available options for continuing therapy increase, the use of os as a clinical trial endpoint has become problematic because of the increasing crossover and contamination of trials. As a result, the approval of promising new therapies may be delayed.Many clinicians believe that progression-free survival (pfs) is a more viable option for evaluating new therapies in metastatic and advanced renal cell carcinoma. As with all endpoints, pfs has inherent biases, and those biases must be addressed to ensure that trial results are not compromised and that they will be accepted by regulatory authorities. In this paper, we examine the issues surrounding the use of pfs as a clinical trial endpoint, and we suggest solutions to ensure that data integrity is maintained.

Management of stage I seminomatous testicular cancer: a systematic review.

The treatment options available for the management of stage I seminoma consist of either a surveillance strategy or adjuvant therapy after orchidectomy. A systematic review was undertaken to identify the optimal management strategy. The MEDLINE and EMBASE databases, in addition to the American Society of Clinical Oncology Meeting Proceedings, were searched for the period 1981 to May 2007. Studies were eligible for inclusion if they discussed at least one of survival, recurrence, second malignancy, cardiac toxicity, or quality of life for patients with stage I seminoma. A search update was carried out in June 2009. Fifty-four reports satisfied the eligibility criteria, including seven clinical practice guidelines, one systematic review, three randomised controlled trials focused on treatment options, 26 non-randomised studies of treatment options, and 15 non-randomised long-term toxicity studies. The existing data suggest that virtually all patients with stage I testicular seminoma are cured regardless of the post-orchidectomy management. The 5-year survival reported in all the studies identified in this systematic review was over 95%, regardless of the management strategy, including surveillance alone with no adjuvant therapy. In conclusion, to date, the optimal management of stage I seminoma remains to be defined. Surveillance seems to be the preferable option, as this strategy minimises the toxicity that might be associated with adjuvant treatment, while preserving high long-term cure rates. The currently available evidence should be presented to patients in order to select the most appropriate option for the individual.

Management of stage I non-seminomatous testicular cancer: a systematic review and meta-analysis.

After orchidectomy and staging, patients with clinical stage I (CS I) non-seminomatous testicular cancer (NSTC) may be offered chemotherapy, surgery or active surveillance. The optimal postoperative approach is undefined. Therefore, a systematic review was carried out to assess these management approaches. Eligible studies, systematic reviews and clinical practice guidelines included patients with CS I NSTC or a mixed seminoma/non-seminoma diagnosis. The primary outcomes of interest included cancer cure, long-term toxicity and quality of life. In total, 32 unique reports met the selection criteria. Cancer cure rates were excellent regardless of the management option selected. Overall and disease-free survival rates were over 95% for all management approaches; recurrence rates were higher in the patients managed by surveillance. In conclusion, patients with CS I NSTC should be assessed and managed at multidisciplinary centres by health care professionals experienced in the treatment of testicular cancer. On the basis of the available evidence, the Genitourinary Disease Site Group recommended primary surveillance for all patients with CS I NSTC, with treatment if relapse occurs. As cancer cure rates are similar with primary surveillance, adjuvant chemotherapy and retroperitoneal lymphadenectomy, patient preference with respect to the risk of recurrence and the timing and toxicities of treatment must be considered. For patients who prefer immediate treatment, or who are unsuitable for primary surveillance, adjuvant chemotherapy with two cycles of bleomycin, etoposide (500mg/m(2)/cycle) and cisplatin was recommended. Surgeons involved in the development of this guideline suggested that retroperitoneal lymphadenectomy may be a useful option for patients at high risk of relapse. There is currently insufficient evidence from prospective trials to support or refute this position.