Local control and patient survival.

Abstract Consideration is given to the concern that future improvements in radiation therapy which achieve increases of local control probabilities will fail to yield gains in survival, in that the new local control patients will ultimately fail because of the development of distant metastasis. The concept is that the local failure merely represents a marker of the exceptionally malignant nature of the tumor; hence, elimination of the local tumor will not affect the ultimate outcome, viz distant failure. This would mean that all tumors which fail locally after the current best radiation therapy will have established distant metastasis (subclinical) at the time of treatment of the primary tumor in stage M 0 patients. Thus, a more effective local treatment would not impact on the ultimate fate of the patient. Several lines of evidence are discussed which document that tumor free survival is greater after treatment which yields higher local control probabilities than those achieved by conventional external beam radiation therapy. That is, not all of the new local control patients develop distant metastasis. Consider the following points: (a) survival rates have increased during the history of radiation therapy as technical development provided the means of administering higher doses to the tumor involved tissues, for example, the shift from 140–180 kVp x-ray units of the 1920's to linear accelerators combined with complex treatment planning systems and modern imaging techniques of current standards of treatment; (b) the use of surgery in place of radiation for tumors for which conventional radiation therapy alone is quite ineffective has improved survival, for example, carcinoma of the gastrointestinal tract, kidney, ovary, squamous and adenocarcinoma of the lung, sarcoma of bone and soft tissues, etc.; (c) the addition of surgery to conventional external beam radiation therapy has also raised survival rates, for example, adenocarcinoma of the endometrium, Stage T III and IV carcinoma of the glottis and supraglottis; (d) the use of special techniques to administer higher radiation dose levels than is feasible with conventional fractionated radiation therapy alone have yielded higher survival rates in some instances, for example, external beam radiation therapy + brachytherapy for carcinoma of the uterine cervix, trans-anal 50 kVp x-ray beams for early stage carcinoma of the rectum (Papillon technique), proton beam therapy or radioactive plaques for uveal melanoma, proton beam techniques for sarcomas of the skull base, external beam radiation therapy + intraoperative electron beam radiation therapy for locally advanced carcinoma of the rectum, etc.; (e) long term disease free survivors are obtained by salvage surgery for local failures after radiation therapy in a worthwhile proportion of patients for many tumor categories; (f) the frequency of distant metastasis does not track "radiocurability" for example, seminoma versus glioblastoma multiforme; and (g) the limited evidence from laboratory studies shows no correlation between radiation sensitivity in vitro and spontaneous metastatic activity in vivo . These clinical findings do not suggest that the tumors which fail locally after conventional radiation therapy have established distant metastasis at the start of their local therapy.