On 16 August 2011, a 64-year-old male physician with no relevant co-morbidity was suspected for transversal colon cancer by colonoscopy. On 26 August 2011, seven likely secondary lesions were detected by abdominal ultrasound in different hepatic segments (the biggest lesion was 42 mm in the largest diameter) and 15 ng/mL was the serum CEA level. On 29 August 2011, he underwent hemicolectomy of the transversal colon, and adeno-carcinoma, G2/G4 was found in post-operative histology. pT3 N2a (6 regional lymph-nodes involved of 22 examined) M1 was the post-operative TNM classification. Kras was wild type. From 14 October 2011 to 20 July 2012, he received 1000 sqm/day capecitabine given orally and 130 mg/sqm oxaliplatin by i.v. infusion (the Xelox regimen) on days 1–14 every 21 days (one cycle) for six cycles, plus 5 mg/kg bevacizumab by i.v. infusion every two weeks followed by maintenance therapy with capecitabine and bevacizumab. His serum CEA level, which was 52 ng/mL at the beginning of chemotherapy, decreased to 25 ng/mL in July 2012, and the WB CT showed slight decreases in all hepatic metastases. On 11 September 2012, all detectable liver metastases were surgically removed following his demand and, in October 2012, his serum CEA level was in the normal range. In December 2012, a radiological assessment documented a suspected secondary lung nodule in addition to the recovery of metastatic liver disease; the serum CEA value was 5.9 ng/mL, which increased to 66 ng/mL in January 2013. From January to April 2013, he received seven cycles of 130 mg/sqm irinotecan by i.v. infusion and 500 mg/sqm cetuximab by i.v. infusion every two weeks. On 2 July 2013, he underwent surgical removal of the left liver lobe; contemporaneously, other secondary lesions were enucleated (overall, ten liver metastases were removed); post-operative histology confirmed the secondary origin of the liver lesions, while a subsequent abdominal MRI signaled three regions with necrotic features. WB positron emission tomography (PET) was negative for residual metastatic liver disease. On 28 February 2013 and 1 July 2013, the serum CEA level was in the normal range. On 21 August 2013, thoracic CT showed an increase in the previously detected nodule placed at the inferior left lung lobe, while liver ultra-sonography showed two small hypo-echogenic areas suspected to be surgical scars. On 29 August 2013, the patient underwent atypical resection of the inferior left lung lobe and post-operative histology confirmed that it was a secondary lesion compatible with primary colorectal cancer. The serum CEA level was 9 ng/mL at the end of September/beginning of October. On 24 October 2013, WB CT signaled a new focal liver lesion that was 57 mm in the largest diameter and a 16 mm nodule at the lower-basal region of the right lung: both were suspected for relapse. Following oncologic consultation, from November 2013 to January 2014, he received cycles with FOLFIRI plus cetuximab. In January 2014, the serum CEA level was in the normal range. In March 2014, he underwent surgical removal of the liver nodule and of the other two nodules in the right lung (one of them was a pleural lesion); they were all determined to be secondary lesions in the post-operative histology. He continued to receive the same FOLFIRI treatment for a total of six cycles until June 2014. In July 2014, WB CT showed multiple new bilateral lung nodules. On 19 September 2014, he accepted the invitation to be included in an experimental clinical trial that was recruiting previously treated patients who had progressed under cetuximab after an initial benefit. He was selected because of his high MET level, as assessed in a biologic sample; therefore, he was given 120 mg of tivantinib (a MET-inhibitor) orally twice daily and cetuximab until 25 October 2016, with an initial clinical-radiological partial response (PR) followed by a stable disease as documented by WB PET carried out on 27 May 2016. In addition, WB PET showed a likely metastatic lesion of the lateral eighth right rib; therefore, from 13 June 2016 to 17 June 2016, in addition to tivantinib and cetuximab, he underwent RT at the rib lesion (25 Gy as a total dose by five fractionated doses). During treatment with tivantinib plus cetuximab, the serum CEA value, which was measured every 2–3 months, was in the normal range until 21 September 2016, when it was found to be 12 ng/mL. On 04 November 2016, WB PET documented the progression of the secondary lesion of the eighth right rib. On 2 December 2016, the patient underwent palliative surgical removal of the lateral arch of the VIII rib; post-operative histology confirmed the metastatic origin of the rib lesion with infiltration of the surgical edges. On 27 December 2016, surgical intervention for soft rib tissue radicalization and the removal of the middle lobe of the right lung was carried out; post-operative histology confirmed the metastatic origin of the residual disease. On 15 February 2017, WB CT showed multiple bilateral suspected secondary pulmonary lesions; the biggest was 7 mm in the largest diameter in the right lung. On 15 February 2017, he was given regorafenib, which he interrupted on 23 May 2017 because of strong side effects and the rising serum CEA level. On 17 August 2017, WB CT documented the progression of the disease at the level of the previously treated eighth rib lesion and the appearance of two new suspected lung lesions on the thoracic wall and lower right lobe (29 × 13 mm), respectively. The remaining multiple bilateral pulmonary lesions, the biggest of which was 8 mm in the largest diameter, were substantially stable. On 15 September 2017, WB PET signaled at least four suspected lung lesions and pathological activity of the VII, VIII, and IX right ribs. On 21 September 2017 and 20 November 2017, serum CEA values were 11.2 and 96 ng/mL, respectively. In November 2017, he again started treatment with the Xelox regimen plus cetuximab. After two cycles, oxaliplatin was interrupted because of strong side effects and he continued with capecitabine and cetuximab. On 13 February 2018, the serum CEA value was 46.3 ng/mL. In March 2018, WB PET confirmed the progression of metastatic disease in the right lung and right chest wall; on 20 March 2018, following transient ChT interruption, the patient underwent surgical removal of the lower right pulmonary lobe, multiple resections of the residual left lung, and thoracotomy of the VII, VIII, and IX right ribs with subsequent plastic surgery of the thoracic wall. The control with WB CT, which was carried out soon after surgery, showed that one metastatic lesion remained on the right lobe, in addition to the multiple repetitions of the left lung lobe. He started with capecitabine and cetuximab therapy, which he continued until March 2019. Serum CEA values, which were 4.1, 4.5, 3.6, 4, and 5.1 ng/mL on 6 April 2018, 24 May 2018, 1 August 2018, 10 October 2018, and 27 October 2018, respectively, increased to 12 ng/mL in December 2018. WB CT carried out in January 2019 signaled three new hepatic repetitions, the largest of which was about 2 cm, and two of them were close to the hepatic and cava veins, respectively, while the multiple lung repetitions were stable. At the beginning of April 2019, he underwent surgical removal of the hepatic lesions. Yet another WB CT carried out soon after surgery showed the persistence of metastatic liver disease in addition to the stable multiple lung repetitions. At the beginning of July 2019, he entered an experimental protocol with temozolomide that was interrupted at the end of August after two cycles because of the unresponsive metastatic disease. On 16 August, the serum CEA value was 86 ng/mL. On 2 September, following an oncologic consultation, he was given tas-102 therapy, which is ongoing. Although this patient is not disease-free, he is doing well with 0-1 ECOG PS 98 months after primary surgery.\nThis patient underwent an uncommon number of surgical interventions (nine) and, during a prolonged time of post-operative monitoring, serum CEA was often in the normal range. Therefore, in this patient, surgery, in addition to a systemic treatment, likely allowed for the maintenance of an undetectable or detectable, but relatively low metastatic tumor burden. Five-year OS rates of 30%–43% were reported in patients who were submitted to complete pulmonary metastasectomy following hepatic resection for colorectal metastases at an earlier stage []. Similarly, a 30% five-year OS rate and a median OS ranging from 29 to 40.5 months was reported in a study [] in which 206 inoperable patients with pulmonary oligo-metastases were treated with stereotactic body radiotherapy (SBRT). In 118 (57%) of these 206 patients, colorectal carcinoma was the primary site of pulmonary oligo-metastases. Moreover, Marudanayagam et al. [] reported a 53% five-year OS after combined liver and lung resections for patients in which the pulmonary metastases developed more than six months after liver resection (metachronous group). However, 0% was the four-year OS for those in which, as in our patient, lung metastasis developed within six months after liver resection (synchronous group).
On 22 April 2010, a 65-year-old male underwent RP and vesiculectomy for prostate adeno-carcinoma. The pre-operative serum PSA was 13.66 ng/mL. pT3b No Mo was the post-operative TNM classification, G3, 4 + 4 Gleason, stage III. On 7 July 2010, the serum PSA was 0.01 ng/mL. On 10 April 2013, three months after RP, BCR was found to have occurred with two consecutive serum PSA values higher than 0.2 ng/mL (PSA level of 0.23 ng/mL). From 22 April 2013 to 10 May 2015, he received IAD therapy with 150 mg bicalutamide pills (once a day) and, on 9 February 2015, the serum PSA level was 0.02 ng/mL. From 11 May 2015 to 1 November 2015, no adjuvant therapy was given and, on 6 October 2015, the serum PSA level was 0.27 ng/mL. From 2 November 2015 to 29 October 2017, cyclic IT was administered. On 5 October 2017, the serum PSA level was 0.65 ng/mL. From 30 October 2017 to 13 May 2018, he received only 150 mg bicalutamide pills (once a day) and, on 9 May 18, the serum PSA level was 0.24 ng/mL. After that, as a result of a misunderstanding, the patient delayed the beginning of cyclic IT from 14 May 2018 to 11 June 2018. Moreover, during the first cycle of this new round of cyclic IT (from 11 June 2018 to 7 July 2018), he took one instead of four celecoxib pills a day. On 11 July 2018, the serum PSA level was 0.58 ng/mL. From 22 July 2018, he correctly underwent IT cycles and, on 11 May 19, the serum PSA was 0.99 ng/mL. He started on 50 mg bicalutamide pills (once a day), and an LHRH agonist was given subcutaneously once every three months. On 10 August 19, PSA was undetectable; therefore, he again started the IT schedule. On 10 October 19, the last PSA determination was 0.04 ng/mL.\nIn a study [], researchers examined 148 patients who prospectively enrolled in sequential Institutional Review Board approved vaccine protocols. The T stage was T1–T2 in 54% and T3–T4 in the remaining 46%; Gleason was 6–7 in 71% and 8–9 in the remaining 29%. All subjects had recurrent disease and no detectable radiological metastases. Recurrent disease manifested as BCR after surgery or as clinically localized disease at the sites for which they had undergone radiation therapy. The median PSA value at the time of protocol enrollment was 8.2 ng/mL and the median PSA double time (PSADT) was 4.7 months. Overall, 110 (74%) of the 148 patients showed metastatic progression at a median of 19 months and metastases were detected in 68% and 84% of them at 3 and 5 years, respectively. Patients with a T3 stage and Gleason score of 7 or more at the time of diagnosis were more likely to develop metastatic disease (log-rank test; p = 0.006), while the type of primary therapy and the presence of nodal disease were not predictive. In another study [], the researchers analyzed 1590 patients who developed recurrent disease, among 5277 patients who had undergone either RP (1003 patients) or EBRT (587 subjects). In the RP group, about 13% of the 1003 patients had received neo-adjuvant or adjuvant androgen deprivation therapy (ADT) and the mean time between primary treatment and recurrence was 34 months. PSA data after salvage therapy were available for 1050 patients (430 patients who had received initial EBRT and 620 patients from the RP group). In 367 patients (59.2%) in the RP group, ADT was the most common salvage treatment, followed by EBRT, which was carried out in the other 248 patients (40%). ADT was also administered to 402 subjects (93.5%) in the EBRT group. Failure after salvage therapy was defined as a PSA level of >0.2 ng/mL after treatment. Overall, 420 (68%) of the 620 patients in the RP group and 319 (74%) of the 430 patients in the EBRT group recurred after salvage therapy. Among these, 739 patients (24.8%) died. The mean survival was 81.1 months (median of 59.9 months) compared with 103.2 months (median of 101.2 months) for those who did not recur after salvage therapy. This difference in overall survival was statistically significant (p < 0.001). A report of a phase III randomized trial [] presented the long-term results of immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer. In a subgroup of 127 high-risk patients, eight-year clinical disease-free survival (DFS) was about 40%. The high-risk category was defined as having at least two of the following three risk factors: WHO performance status > 0, G3, and initial PSA > 10. Our patient, who shares these characteristics, is alive and in good health 114 months after RP.