PSA level predicts prostate cancer risk in young men. Using a baseline PSA value to risk-stratify young men for their future risk of prostate cancer is increasingly recognized as clinically useful by both the NCCN and AUA guidelines. Tang et al studied over 9,500 men aged 50 or younger showing that a baseline PSA of 1.5 to 2.4 ng/mL increased the relative risk of prostate cancer by 9.3 for white men and 6- to 7-fold for black men. Overall, a PSA > 1.5 was a powerful predictor of subsequent prostate cancer (Tang P et al. J Urol. 2010;183:946-50).
RALP popular—but many questions remain. Robot-assisted laparoscopic prostatectomy (RALP) has become very popular in the US. A recent systematic review by Murphy et al showed the learning curve to be steep, and few published reports have reported outcomes in a standardized manner. The cost of the technology is substantial, and little is known of the cost-effectiveness compared to that of the open technique. (Murphy DG et al. Eur Urol. 2010;57:735-46).
Omission of post-lumpectomy radiation reasonable in women over 70 with stage I cancers. For nearly two decades there has been controversy as to the role of radiation therapy in women over the age of 70 years with small breast cancers. The CALGB 9343 trial enrolled women over age 70 with clinically node-negative disease, who had undergone lumpectomy with a clear margin (1-cm negative margin), had a tumor size of 2 cm or less, and were ER-positive or of indeterminate status. These women were randomized to either tamoxifen or tamoxifen plus radiation. The 631 eligible patients were followed for a median of 12 years. Radiation therapy was found to have an impact on breast tumor recurrence, with six events occurring in the 317 women who received tamoxifen plus radiation, compared with 27 events that occurred in 319 women who received tamoxifen alone (2% vs 9%, P < .0001). However, there were no benefits in terms of ultimate mastectomy (2% with radiation vs 4% without, P = .1779), axillary recurrence (0% with vs 3% without radiation), the frequency of second primary cancers (12% vs 9%, P = .7268), or overall survival at 10 years (33% of patients in each treatment arm had died at 10 years, P = .845). To date, approximately 50% of the women are still alive, 3% have died from breast cancer, and 46% have died due to other causes. It is notable that approximately 50% of women who were over 70 years of age upon enrollment in this study are still alive 12 years later. The investigators concluded that in older women the benefits of radiation after lumpectomy are small and that omitting radiation in women over 70 years of age with clinical stage I breast cancer is a reasonable alternative. (Hughes KS et al. J Clin Oncol. 2010;28:507.)
Radiation yields encouraging results in patients with smaller peripheral early-stage NSCLC who are not candidates for surgery. In 2010, Timmerman et al reported on a phase II North American multicenter study (RTOG 0236) of 59 patients with biopsy-proven, peripheral T1–2, N0, M0 NSCLC tumors (measuring < 5 cm in diameter) and medical conditions precluding surgical treatment. Patients were treated with a total of 54 Gy in three fractions over a 1- to 2- week period with a median follow-up of 34.4 months. The rates for disease-free survival and overall survival at 3 years were 48.3% (95% CI, 34.4%–60.8%) and 55.8% (95% CI, 41.6%–67.9%), respectively. The estimated 3-year primary tumor control was 97.6%, and the median overall survival was 48.1 months. The 2-year local control rate was excellent at 94% (Timmerman R et al. JAMA. 2010;303:1070-6).
Cisplatin-venorelbine has survival advantage over other adjuvant cisplatin regimens in patients with completely resected NSCLC. A meta-analysis by the LACE group found that in patients with completely resected NSCLC, the 5-year overall survival benefit of cisplatin-containing adjuvant regimens was 5.4% (hazard ratio = 0.89; P = .004). There appeared to be a survival advantage of 8.9% for cisplatin-vinorelbine, which was superior to other regimens containing cisplatin. The greatest benefit of adjuvant therapy was seen in patients having disease of a higher stage (14.7% for stage III, 11.6% for stage II, 1.8% for stage I; Douillard JY et al. J Clin Oncol. 2010;5:220-8).
Maintenance superior to break from chemotherapy in metastatic colon cancer. In patients with metastatic colorectal cancer responding to FOLFOX, a break from chemotherapy was compared with maintenance chemotherapy (5-FU, leucovorin) in the randomized trial OPTIMOX2. Control of disease was significantly longer with maintenance chemotherapy than with a break from chemotherapy (13.1 vs 9.2 months; Chibaudel B et al. J Clin Oncol. 2009;27:5757−5733).
Response to EGFR inhibitors poorer in patients with KRAS, BRAF. The genes KRAS and to some degree BRAF have been associated with a lack of response to the EGF receptor inhibitors cetuximab (Erbitux) and panitumumab (Vectibix). There is increasing retrospective evidence to show that mutations in KRAS or BRAF may significantly shorten overall survival. However, these mutations do not preclude a potential benefit from chemotherapy (Laurent-Puig P et al. J Clin Oncol. 2009;27:5924-30; Richman SD et al. J Clin Oncol. 2009;27:5931-37).
MYC a significant adverse prognostic indicator in DLBCL. MYC a significant adverse prognostic indicator in DLBCL. Two recent analyses showed the prognostic importance of MYC oncogene rearrangement in DLBCL. Savage et al reported that MYC+ DLBCL treated with R-CHOP was associated with an inferior 5-year progression-free survival (66% vs 31%) and overall survival (72% vs 33%). Further, MYC+ DLBCL was associated with a significantly increased risk of secondary CNS disease (Savage KJ et al. Blood. 2009;114:3533-7). A subsequent report confirmed the presence of MYC as a significant adverse prognostic factor in DLBCL (Barrans S et al. J Clin Oncol. 2010;28:3360-5).
For first-line therapy, bendamustine plus rituximab superior to R-CHOP in various kinds of lymphoma. Bendamustine (Treanda) plus rituximab (Rituxan) proved more effective than R-CHOP as first-line therapy in previously untreated patients with follicular, indolent, and mantle cell lymphomas, resulting in significantly longer median progression-free survival (54.8 months vs 34.8 months; P = .0002). In a multicenter, randomized phase III trial that enrolled 549 patients, bendamustine plus rituximab was less myelosuppressive than R-CHOP and resulted in fewer infections, less peripheral neuropathy, and fewer episodes of stomatitis (Rummel MJ et al. Blood. 2009;114:abstract 405).