Relationship between tumor size and the curability of metastatic prostatic cancer by surgery alone or in combination with adjuvant chemotherapy

The MAT-Lu subline of the Dunning R3327 system of rat prostatic adenocarcinomas universally metastasizes to the lungs of untreated recipient hosts. The MAT-Lu cancer was implanted into the hind leg of animals and the primary tumor was allowed to grow to various sizes before the tumor bearing leg was surgically removed. These studies demonstrated that there is a direct relationship between the size of the primary tumor at the time of surgical removal and the number of metastases already established in the lungs. Once the primary MAT-Lu reaches a size of ≥0.5 cc, ≥50% of all inoculated animals already have established lung metastases and are thus not cured by surgery alone. In an attempt to increase the cure rates, adjuvant chemotherapy (cytoxan given at a dose of 90 mg/kg body weight) was used in combination with surgery. These studies demonstrated that if chemotherapy was given by itself to animals bearing macroscopically established (≥0.5 cc) MAT-Lu cancers, no animals could be cured. In direct contrast, by combining the same intensity of adjuvant chemotherapy with the removal of the primary MAT-Lu cancer, cures could be produced in high (>90%) frequency, but only if this combinational approach was simultaneously initiated when the primary tumor was <2 cc in size. If the primary MAT-Lu cancer was allowed to grow to too large a size before surgery (>2 cc) or if the chemotherapy was delayed following surgery (both processes allowing the metastatic tumor burden to increase before initiating adjuvant chemotherapy), the ability of the adjuvant chemotherapy to cure the host of its metastatic tumor burden is lost. These results demonstrate that the MAT-Lu rat prostatic cancer, like human prostatic cancer, is not effectively treated by chemotherapy alone or by adjuvant chemotherapy combined with surgery if the treatment is given too late in the course of the disease. These studies emphasize the critical requirement of combining surgery and adjuvant chemotherapy as early as possible in the treatment of metastatic prostate cancer in order to minimize the total metastatic tumor burden and maximize the possibility of cure.