The insightful article by Kramer and colleagues [1] and the accompanying editorial by Walsh [2] fail to recognize that the explanation for the success or failure of screening programs for cancer is its exquisite biology. The lessons from other malignancies can be translated to the investigation of prostatic carcinoma. Kramer and colleagues recognize that a cancer of one specific type is not monolithic but diverse in its biological behavior. The ubiquitous term "aggressive" should be replaced by more precise language about the potential for metastasis. The statistical term "lead time bias" would be converted into an understandable clinical paradigm that metastatic cancer cells in many situations emerge long before clinical diagnosis. Earlier is often not early enough. Conversely, some cancers never acquire the needed genetic abnormalities to be metastatic and thus represent biologically nonlethal cancer.

The incisive editorial by Sporn [3] points out that the oncology community has been slow to recognize the importance of detecting early precursor lesions and to use the enormous progress in the molecular biology of carcinogenesis that has yielded insights into the molecular aspects of tumor cell invasion and metastases [4].

The inevitable conclusion is that in many patients, the two separate processes of carcinogenesis and dissemination are more nearly simultaneous than sequential. This paradigm supports both clinical and cell kinetic observations regarding the potential for dissemination. Improved cure of any cancer can be distinguished in randomized trials and perhaps by rigorously controlled comparative case–control studies. The ongoing randomized national trial will probably help identify subsets of men likely to benefit from screening for prostate cancer and will set the scene for subsequent prospective trials.

In conclusion, it is time to move ahead into the next era by using clinical and molecular insights to decrease the rate of death from cancer. Specifically, the recognition of preneoplastic tissues that contain molecular abnormalities predisposing to cancer progression should be the goal of screening, especially if interruption or reversal by chemoprevention is possible.