On 9 October 2002, a 57-year-old male underwent nerve-sparing radical prostatectomy (RP), orchidectomy, vesiculectomy, and bilateral lymphadenectomy for prostate adenocarcinoma. The pre-operative serum PSA was >30 ng/mL. pT3a No Mo was the post-operative TNM classification, G2, 4-5 Gleason, stage III. On 27 January 2003, biochemical recurrence (BCR) (two consecutive values higher than 0.2 ng/mL) was detected [,] with a serum PSA level of 0.60 ng/mL. On 1 April 2003, a PSA level of 1.17 ng/mL was found. From 19 April 2003 to 3 June 2012, intermittent androgen deprivation therapy (IAD) was administered with 250 mg flutamide pills, three pills/day, and an luteinizing hormone-releasing hormone (LHRH) agonist was given subcutaneously once every four weeks. From 3 June 2012 to 12 October 2013, because of increasing serum PSA levels (on 29 May 2012, a PSA of 2.24 ng/mL was found), flutamide was replaced with 50 mg bicalutamide, one pill/day, and an LHRH agonist was given subcutaneously once every four weeks. Because PSA levels continued to increase (on 7 October 2013, a PSA value of 9.85 ng/mL was found), from 12 October 2013 to 15 April 2014, bicalutamide was replaced by 300 mg of cyproterone acetate, which was administered i.m. once a week, and an LHRH agonist was given subcutaneously once every four weeks. A trans-rectal ultrasound on 4 November 2013 and whole body (WB) computed tomography (CT) on 30 November 2013 detected a 27 × 26 mm nodule adherent to the bladder wall, and it was suspected to be local recurrence; this suspicion was confirmed by biopsy. On 17 December 2013, the serum PSA level was 18.28 ng/mL. From 18 April 2014 to 18 June 2014, he received external beam radiotherapy (EBRT; 7000 cGray in total). Following the fractioned EBRT, the serum PSA levels continuously decreased and, on 5 May 2016, the PSA value was 0.24 ng/mL. On 1 June 2016, the patient started cyclic IT, which was consistently administered according to the above-reported schedule. The serum PSA levels further and progressively decreased. On 27 August 2018, 50 months after EBRT, serum PSA was undetectable, and then it fluctuated between 0 and 0.01 ng/mL. The last PSA observation on 5 August 2019 was 0.01 ng/mL.\nA study [] recruited 35 prostate cancer patients submitted to RP. Ten of these patients were pT2a-b N0M0 and 24 pT3a-b N0M0. All 35 patients with a macroscopic histologically-proven local recurrence received 30 Gy (21 patients) or 40 Gy (14 patients) of intensity-modulated brachytherapy (IMBT), combined with 30 Gy of EBRT. In the subgroup of 21 patients, after a mean follow-up of 29 months, PSA progression-free survival (PFS) was 24%, and the mean time interval to a PSA increase was 16 months. In the other subgroup of 14 patients, the mean follow-up was 26 months, the PSA progression-free survival (PFS) was 43%, and the mean time interval to a PSA increase was 10 months. Rising PSA values of <2 to 4 ng/mL have been reported to be predictive factors for successful radiotherapy of local recurrences after RP [,]. In the above-mentioned study, the mean rising PSA prior to salvage radiotherapy was 5.02 ng/mL, while it was 18.28 ng/mL in our reported patient. Moreover, the serum PSA nadir has been reported in the literature to occur 12–24 months after radiotherapy (RT) []; in our patient, it was reached after 50 months and maintained at 62 months.
A 39-year-old female, in her 31st week of pregnancy, presented with a 5 cm breast nodule with inflammatory signs. From ultrasound, it was suspected to be invasive cancer; subsequent biopsy confirmed a diagnosis of invasive adeno-carcinoma. From 14 October 2015 to 18 February 2016, she received neo-adjuvant chemotherapy with four cycles of 90 mg/sqm epirubicin and 600 mg/sqm cyclophosphamide by i.v. infusion, with each cycle occurring every four weeks, followed by weekly 80 mg/sqm paclitaxel by i.v. infusion. This treatment was interrupted on 18 February 2016 because of disease progression. On 3 March 2016, she underwent a radical left mastectomy; post-operative histology showed infiltrating ductal carcinoma without lympho-vascular invasion. pT2 No Mo was the post-operative TNM classification, G3, ER+ (30%) Pr+ (10%), Ki67 90%, and HER2 negative. From 28 April 2016 to 04 July 2016, she received adjuvant chemotherapy with three cycles of CMF (600/40/600 mg/sqm on days 1, 8, and 28, by i.v. infusion) and, from 31 May 2016 to 08 July 2016, she received conventional radiotherapy on the chest wall and lymph-nodes at II–III–IV levels. From 29 July 2016 to 1 February 2017, 25 mg of exemestane daily plus an LHRH agonist every 28 days were administered. On 2 February 2017, exemestane was replaced by tamoxifen because a hormonal assessment showed the recovery of ovarian functionality. On 22 May 2017, diffusion whole body magnetic resonance imaging (MRI) was carried out at the European Institute of Oncology, in Milan, and it signaled an 8 mm nodule of the middle lung lobe, which was suspected for relapse. A 13 mm nodule in the same site of the suspected relapse was confirmed on 30 May 2017 by WB CT. The subsequent biopsy showed that the nodule had malignant characteristics. On 13 June 2017, the metastatic lung nodule was removed by atypical lung resection. The immunophenotype from post-operative histology confirmed that the primary breast cancer was the probable origin; ER, PR, and Ki67 were 30%, negative, and 50%, respectively. From 18 July 2017 to 24 August 2017, the patient received four cycles of liposomal doxorubicin. From 18 September 2017 to date, this patient received four consecutive cycles of IT twice, and the last cycle was followed by one month of rest and then four successive cycles of oral ChT with vinorelbine and capecitabine. In contrast to previous reports on the metronomic use of vinorelbine and capecitabine [,,] in breast cancer patients with detectable metastatic disease, one week of ChT interruption was planned because our patient did not show clinical-radiological evidence of metastatic disease. Vinorelbine at 30 mg was given every other day, and 500 mg of capecitabine was given three times a day continuously, on days 1–14 every 21 days. On 8 October 2018 and 16 October 2019, bone scanning (BS) and WB CT, respectively, were negative for relapse and circulating CEA-TPA-CA.15.3 levels were in the normal range on 14 October 2019.\nA study [] evaluated 103 breast cancer patients who underwent surgery for suspected pulmonary metastases. In this study, the median survival time (ST) was 29 months and the three-year survival was 43% in 14 patients with a disease-free interval (DFI) of less than 24 months. All patients had received complete resections of their lung metastases. Another study [] reported that, in 37 recruited breast cancer patients with completely resected pulmonary metastases (27 with a single pulmonary nodule (SPN) and 10 with two or more pulmonary nodules), the actuarial five-year survival was 59%. However, in five of them with a DFI of one year or less, the mean survival was only 15 ± 3.6 months, and all patients were dead at 26 months. Before, after, or both before and after thoracotomy, all 37 patients received ChT, tamoxifen, or both. Similarly, in another series [] of 40 patients (most of them with one or two pulmonary metastases) who had undergone complete pulmonary resection, the five-year survival rate was 35.6%, while the median DFI following complete pulmonary resection was 1.6 years. Most breast oncologists, even in SPN cases, prefer systemic medical treatment to surgery. In fact, pulmonary metastasis is considered a systemic disease, and poor survival rates have been reported for those with a DFI of <3 years or with discordance in the hormone receptor status between the primary cancer and the SPN [,].